Term
| What are the 2 arms of the immune system? |
|
Definition
1) innate (natural)
2) adaptive (specific) |
|
|
Term
| What are the 4 components of innate immunity? |
|
Definition
1) Skin & mucosal barriers
2) Phagocytes (neutrophils & macrophages)
3) NK cells (Natural Killer)
4) Plasma Proteins (s.a. complement, CRP, mannose binding lectin, etc) |
|
|
Term
| *What stimulates the phagocytes on innate immunity? |
|
Definition
| microbial products & a variety of chemical mediators (s.a. CCCLLIP) |
|
|
Term
| What is the order of events from margination to phagocytosis? |
|
Definition
1) Margination (blood stasis)
2) rolling (selectins & ligands)
3) adhesion (integrins & ligands)
4) transmigration (leukocyte adhesion molecules)
5) chemotaxis
6) activation & attachment (usually receptor mediated)
7) phagocytosis |
|
|
Term
|
Definition
large granular lymphocytes that
1) lyse target cells
2) secrete cytokines |
|
|
Term
| What regulates the cellular killing of NK cells? |
|
Definition
| balance b/w signals from activating receptors (viral/stress-induced proteins) & inhibitor receptors (MHC I) |
|
|
Term
| What are the components of adaptive immunity? |
|
Definition
1) T lymphocytes
2) B lymphocytes
3) Dendritic Cells
4) Macrophages
5) NK Cells |
|
|
Term
| What are the 2 parts of adaptive immunity? |
|
Definition
|
|
Term
| *What is cell-mediated (cellular immunity) effective against? |
|
Definition
|
|
Term
| *What is anti-body mediated (humoral immunity) targeted towards? |
|
Definition
|
|
Term
| How much of circulating T cells are mature, yet naive? |
|
Definition
|
|
Term
| What attracts mature, naive T cells to lymphoid organs? |
|
Definition
|
|
Term
| Where are T cells produced? |
|
Definition
| thymus *where unique TCR gene rearrangments occur) |
|
|
Term
What are mature T cells with Ag-specific TCRs linked to?
Why? |
|
Definition
| molecular complexes for T cell activation |
|
|
Term
| What does T cell activation require? |
|
Definition
1) presentation of membrane-bound Ags in association with MHC (major histocompatibility)
2) interaction b/w costimulatory molecules on cell membranes of APCs (Ag presenting cells) & T cells |
|
|
Term
Function
activated T cells |
|
Definition
1) secretion of cytokines
2) cellular proliferation
3) differentiation into effector or memory cells |
|
|
Term
| What are the 2 types of T cells? |
|
Definition
CD4+ (helper)
CD8+ (cytotoxic) |
|
|
Term
| Which MHC class type do CD4+ & CD8+ T cells bind to? |
|
Definition
|
|
Term
|
Definition
| secrete cytokines to modulate all aspects of the immune response |
|
|
Term
| What are the 3 types of CD4+ T cells? |
|
Definition
| 1) TH1
2) TH2
3) Regulatory T cells |
|
|
Term
|
Definition
| secrete IL-2 & IFN-γ => T cell proliferation, macrophage activation, & Ab production |
|
|
Term
|
Definition
| secrete IL-4, IL-5, IL-13 => eosinophil activation & IgE synthesis |
|
|
Term
Function
Regulatory T cells |
|
Definition
| suppress APCs &/or effector T cells by mechanisms s.a. secretion of immunosuppressive factors, cell contact mediated regulation, & cell lysis |
|
|
Term
| What are the 2 types of regulatory T cells? |
|
Definition
1) Tregs (natural regulatory cells)
2) Adaptive regulatory T cells (induced by inflammation) |
|
|
Term
|
Definition
| CD4+, CD25+, Foxp3+ T cells that develop in the thymus & suppress autoreactive T cells |
|
|
Term
def
adaptice regulatory T cells |
|
Definition
| non-regulatory CD4+ T cells that upregulate CD25 expression in the periphery |
|
|
Term
|
Definition
|
|
Term
| How much of all circulating lymohotcytes are B cells? |
|
Definition
|
|
Term
| What attracts B cels to specific lymphoid organs? |
|
Definition
|
|
Term
| Where are B cells produced? |
|
Definition
| Bone marrow (unique Ig gene arrangements occur) |
|
|
Term
| What are mature B cells BCRs linked to that is necessary for activation? |
|
Definition
cell memebrane proteins
(CD4+ T cells are required for some) |
|
|
Term
|
Definition
|
|
Term
Function
Activated B cells |
|
Definition
| differentiate to plasma cells => Ab secretion |
|
|
Term
| What are the 2 types of dendritic cells? |
|
Definition
1) dendritic cells
2) follicular dendritic cells |
|
|
Term
| Where are dendritic cells found? |
|
Definition
1) epithelial surfaces & interstitium of tissues
2) recruited to T cell regions of lymphoid organs via chemockine receptor |
|
|
Term
|
Definition
| present Ags to CD4+ T cells => activation |
|
|
Term
| Where are follicular dendritic cells found? |
|
Definition
| germinal centers of lymphoid follicles |
|
|
Term
Function
follicular dendritic cells |
|
Definition
| present Ags to B lymphocytes => activation of B cells |
|
|
Term
| How do macrophages affect the adaptive immunity? |
|
Definition
Function as:
1) APCs for T cells
2) Effector cells for cellular & humoral immunity |
|
|
Term
| How do NK cells affect the adaptive immunity? |
|
Definition
| participate in Ab-dependent, cell-mediated cytotoxicity |
|
|
Term
*def
MHC Complex/HLA Complex |
|
Definition
| group of closely linked, markedly polymorphic genes found on chromosome 6 |
|
|
Term
*Function
MHC I & II products |
|
Definition
| bind & present peptide fragments of foreign proteins to Ag-specific T cells |
|
|
Term
| *What does the reactivity of T cell immunity depend on? |
|
Definition
| MHC molecule exposure during development & MHC genetic inheritance |
|
|
Term
|
Definition
| cell surfaces of all nucleated cells & platelets |
|
|
Term
| What 3 loci encode the variable chain of MHC I? |
|
Definition
|
|
Term
|
Definition
| in ER, bind to peptide fragments of foreign cytoplasmic Ags => relocation of MHC I to cell surfaces to present peptides to CD8+ T cells |
|
|
Term
|
Definition
cell surface of APCs
induced expression on other cell types |
|
|
Term
| What 3 subreigons of the HLA-D loci encode the 2 variable chains of MHC II? |
|
Definition
|
|
Term
|
Definition
| bind to peptide fragments of exogenous Ags => MHC II relocation to cell surface => presenation to CD4+ T cells |
|
|
Term
| How many different types of hypersensitivity reactions are there? |
|
Definition
|
|
Term
def
Type I Hypersensitivity |
|
Definition
|
|
Term
| What causes type I hypersensitivity? |
|
Definition
| Initial exposure followed by subsequent exposures |
|
|
Term
| What occurs during an initial exposure in a type I hypersensitivity reaction? |
|
Definition
| Ag presentation by dendritic cells to pre-TH2 cells => activation of TH2 cells => differentiation of IgE-secreting B cells => increased igE (via IL-4) & increased eosinophil longevity (via IL-3, IL-5, GM-CSF) => IgE attachment to mast cells & basophils (via Fc receptors) |
|
|
Term
| What occurs in subsequent Ag exposure in Type II hypersensitivity reactions? |
|
Definition
| Same as initial exposure + Ag binds to attached IgE Abs => IgE cross-linking on mast cells/basophils => mast cell/basophil activation/degranulation |
|
|
Term
| What are the effects of mast cell/eosinophil degranulation? |
|
Definition
1) release of primary (preformed) mediators - within 1 hr
follow by eventual
2) release of secondary (newly synthesized) medaitors - within several hrs |
|
|
Term
| What are the 4 primary mediators released for the early manifestations of type 1 hypersensitivity reactions? |
|
Definition
1) biogenic amines (histamine, adenosine)
2) chemotactic factors
3) enzymes
4) proteoglycans (=> metachromatic staining of intact mast cells/basophils) |
|
|
Term
| What are the effects of the release of the secondary mediators of the later response of type 1 hypersensitivity reactions? |
|
Definition
| 1) activation of phospholipase A2 within mast cell phospholipid membranes
a) arachidonic acid production (=> LTs & prostaglandins)
b) PAF production
2) cytokine & chemokine secretion |
|
|
Term
| What are the histological effects seen in type 1 hypersensitivity? |
|
Definition
1) vascular change (VD & increased perm => edema)
2) bronchial s. muscle contraction (=> hyperplasia)
3) increased glandular secretions (=> mucinous metaplasia)
4) infiltration & activation of inflammatory cells (esp. eisinophils & chronic inflammatory cells)
5) mucosal epithelial injury (due to inflammatory cells) |
|
|
Term
| *What helps prolong the type 1 hypersensitivity reaction? |
|
Definition
| infiltration & activation of inflammatory cells that produce additional mediators |
|
|
Term
Sx
Type 1 Hypersensitivity Rxn |
|
Definition
1) localized erythema => shock (due to VD)
2) edema (due to increased vasc. perm.) s.a. hives, nasal & laryngeal edema
3) wheezing & airway constriction (due to bronchospasm)
4) rhinorrhea & bronchial mucous plugs (due to increased glandular & mucinous secretions) |
|
|
Term
*def
Type II Hypersensitivity Reaction |
|
Definition
| Abs bind to cell surface or tissue Ags => cell death or cell/tissue dysfunction |
|
|
Term
| What are the 3 mechanisms of type II hypersensitivity reactions? |
|
Definition
1) Complement-dependent reactions
2) Ab-dependent cell-mediated cytotoxicity (ADCC)
3) Ab-mediated cellular dysfunction |
|
|
Term
MOA
type II hypersensitivity
via complement dependent reactions |
|
Definition
1) Ab + cell surface/tissue Ag => complement activation => formation of MAC => cell lysis/tissue injury
2) Ab + cell surface Ag =>
a) phagosytosis by inflammatory cells via Fc
b) if complement is fixed, C3b receptors |
|
|
Term
Examples
Type II hypersensitivity
via complement-dependent reactions |
|
Definition
1) autoimmune rxns to normal/altered blood cells
2) autoimmune hemolysis
3) autoimmune blistering skin diseases
4) Good pasture syndrome (Abs directed against glomerular & pulmonary basement membrane) |
|
|
Term
MOA
type II hypersensitivity
via ADCC |
|
Definition
| Ab (IgG or IgE) + cell surface Ag => binding to sensitized inflammatory cells via Fc receptors => target cell death (NO phagocytosis or complement activation) |
|
|
Term
Example
type II hypersensitivity
via ADCC |
|
Definition
| host immune respinse to parasite & malignant cells |
|
|
Term
MOA
type II hypersensitivity
via Ab-mediated cellular dysfunction |
|
Definition
| Ab + cell surface receptor => impaired cell function (NO cell death) |
|
|
Term
Examples
type II hypersensitivity reactions
via Ab-mediated cellular dysfunction |
|
Definition
1) myasthenia gravis (Ab to AchR of skeletal muscle motor end plates)
2) Graves disease (Abs directed against TSH receptors of thyroid follicular epithelial cells) |
|
|
Term
*def
Type III hypersensitivity reactions |
|
Definition
| immune complex formation & tissue deposition => activation of complement, acute inflammatory cells & coagulation system => tissue injury |
|
|
Term
| *What is the immune complex composed of in type III hypersensitivity reactions? |
|
Definition
| circulating Ab + Ab (fixed or circulating) |
|
|
Term
| How does the immune complex form in type III hypersensitivity reactions? |
|
Definition
1) Ag can be fixed or circulating, exogenous (s.a. microbial Ags, drugs, animal sera) or endogenous (s.a. nuclear Ags, Igs, Ags of malignant cells)
2) Ab is produced by differentiation of Ag-specific B cells with formation of complement-fixing IgG, IgM, or IgA |
|
|
Term
| How does the immune complex deposition occur in type III hypersensitivity reactions? |
|
Definition
1) locally via in-situ immune complex formation at Ag tissue site
2) systemically via circulating immune complexes => complex deposition within tissues |
|
|
Term
| What does systemic immune complex deposition depend on? |
|
Definition
| immune complex & host factors s.a. size, charge, structure, & adequacy of immune complex clearance |
|
|
Term
| Where are frequent sites of systemic tissue deposition of immune complexes? |
|
Definition
| sm. to med. sized blood vessels, renal glomeruli, joints, & skin |
|
|
Term
| What 3 things are activated by immune complex deposition => tissue injury in type III hypersensitivity? |
|
Definition
1) complement
2) acute inflammatory cell (infiltration & activation)
3) coagulation system |
|
|
Term
| What parts of the complement system are activated via immune complex deposition and aid in tissue injury? |
|
Definition
1) C3a & C5a => VD & increased vasc. perm => enhanced tissue deposition
2) C3b => enhanced phagocytosis of immune complexes & inflammatory cell activation
3) C5a => chemotaxis or acute inflammatory cells
4) C5-9 => MAC formation => cell lysis |
|
|
Term
| How does acute inflammtory cell infiltration & activation (PMNs & macs)by immune complex deposition aid in tissue injury? |
|
Definition
1) additional vasoactive/chemotactic substances
2) proteolytic enzymes
3) oxygen-derived free radicals |
|
|
Term
| How does activation of the coagulation system by immune complex deposition aid in tissue injury? |
|
Definition
1) platelets
2) coagulation factor cascade |
|
|
Term
| *What pathological finding characterizes type III hypersensitivity? |
|
Definition
| acute necrotizing vasculitis of sm. to med. sized blood vessels |
|
|
Term
| What are the histological findings of type III hypersensitivity? |
|
Definition
1) fibrinoid necrosis of vessel wall (due to vascular necrosis by MAC & inflam. cell ezymes => endo. disruption & activation of coag. system => fibrin deposition)
2) acute inflammatory infiltrate
3) edema & hemorrhage in surrounding tissue
4) vascular luminal thrombosis => ischemic necrosis of tisse (depends on vascular supply) |
|
|
Term
| What are the immunofluorescent microscopic features (of involved vessels) of type III hypersensitivity reactions? |
|
Definition
| granular, "lumpy-bumpy" direct immunofluorescence pattern, using Abs to immunoglobulin & complement components |
|
|
Term
| What are the electron microscopic features (of involved vessels) of type III hypersensitivity? |
|
Definition
| presence of electron dense deposits (immune complexes) |
|
|
Term
Examples
type III hypersensitivity reactions |
|
Definition
1) acute post-steptococcal glomerulonephritis
2) SLE
3) plyarthritis nodosa
4) RA |
|
|
Term
| *What are the 2 variatns of type IV hypersensitivity reactions? |
|
Definition
1) delayed-type hypersensitivity
2) cytotoxic T cell-mediated hypersensitivity |
|
|
Term
| What causes delayed-type hypersensitvity? |
|
Definition
| similar to type I in that an initial exposure preceeds subsequent Ag exposure |
|
|
Term
| What happens in the initial Ag exposure of delayed-type hypersensitivity reactions? |
|
Definition
| Ag + MHC II molecules of APCs => differentiation of CD4+ T cells to sensitized TH1 cells |
|
|
Term
| hat happens in the subsequent Ag exposures of delayed-type hypersensitivity reactions? |
|
Definition
| 1) activation & proliferation of preveiously sensitized memory TH1 cells => cytokine secretion
2) activation of macrophages => enhanced Ag presentation, killing, & cytokine secretion |
|
|
Term
| What cytokines are secreted by TH1 cells in delayed type hypersensitivity reactions?
What are their functions? |
|
Definition
1) IL-2 => amplification of T cell response
2) TNF-α => endothelial cell activation => production of pro-inflam. mediators
3) IFN-γ => accumulation & activation of macs |
|
|
Term
What cytokines are secreted by activated macrophages in delayed type hypersensitivity?
What is their function? |
|
Definition
| 1) IL-12 => differentiation & activation of TH1 cells
2) PDGF & TGF-β => fibroblast proliferation |
|
|
Term
| What histological findings are seen in delayed-type hypersensitivity? |
|
Definition
| Initially: lyphocyte infiltration (CD4+ TH1 cells) - perivascular => diffuse
later: collections of activated macs - granulomatous inflammation |
|
|
Term
Examples
Delayed-Type (IV) hypersensitivity |
|
Definition
1) TB & tuberculin skin test
2) fungal inf.
3) contact dermatitis |
|
|
Term
| What causes cytotoxic T cell-mediated hypersensitivity? |
|
Definition
| Ag + MHC I => sensitization of CD8+ T cells => apoptotic death of target cells (via perforin-granzyme and Fas-Fas ligand mech.) |
|
|
Term
Examples
Cytotoxic T cell-mediated (IV) hypersensitivity |
|
Definition
1) viral inf.
2) tumor immunity
3) acute graft rejection |
|
|
Term
| What type(s) of immunity are involved in solid organ transpant rejection? |
|
Definition
|
|
Term
| What are the 2 T cell-mediated response pathways in solid organ transplant rejection? |
|
Definition
|
|
Term
| When are the direct & indirect pathways of cellular response more prominent in solid organ transplant rejection? |
|
Definition
Direct: acute cellular rejection
Indirect: chronic rejection |
|
|
Term
| What are the 2 parts of the direct pathway of cellular response in solid organ transplant rejection? |
|
Definition
1) graft recogition
2) graft rejection |
|
|
Term
| What happens in graft recoginition in direct cellular response in solid organ transplant rejection? |
|
Definition
| foreign (mismatched) MHC molecules on donor's APCs are recognized by recipiant's CD4+ & CD8+ T cells |
|
|
Term
| What happens in graft rejection in direct cellular response in solid organ transplant rejection? |
|
Definition
| 1) cytotoxic T cell-mediated hypersensitivity (differentiation of sensitized CD8+ T cells => graft apoptosis)
2) delayed-type hypersensitivity (proliferation & differentiation of sensitized CD4+ T cells to TH1 cells => cytokine production => mac activation & amplification of inflam. response) |
|
|
Term
| What are the 2 parts of the indirect pathway of cellular response in solid organ transplant rejection? |
|
Definition
1) graft recognition
2) graft rejection |
|
|
Term
| What happens in graft recoginition in indirect cellular response in solid organ transplant rejection? |
|
Definition
| foreign (mismatched) MHC molecules are processed & presented by recipiant's APCs to the recipiant's CD4+ T cells |
|
|
Term
| What happens in graft rejection in indirect cellular response in solid organ transplant rejection? |
|
Definition
| delayed-type hypersensitivity |
|
|
Term
Effect
Humoral response in solid organ transplant rejection |
|
Definition
|
|
Term
| What causes rejection vasculitis in humoral response in solid organ transplant rejection? |
|
Definition
1) preformed recipiant Abs to donor Ags => hyperacute rejection
2) induced recipiant Abs to donor Ags => acute humoral rejection (complement-dependent cytotoxicity or Ab-dependent cell mediated cytotoxicity) |
|
|
Term
| What are the 3 types of rejection that can occur in renal transplant rejection? |
|
Definition
1) Hyperacute rejection
2) Acute rejection
3) Chronic rejection |
|
|
Term
| What causes hyperacute rejection? |
|
Definition
| preformed recipiant Abs to donor Ags (can be due to previous transplants, blood transfusions, pregnancies, etc) |
|
|
Term
| *How quickly does hyperacute rejection occur in kidney transplant? |
|
Definition
| minutes to hours after transplant => discolored & non0functioning kidney => immediate removal |
|
|
Term
| *What forms on the renal transplant vascular endothelium in hyperacute rejection? |
|
Definition
immune complex formation => compliment activation =>
a) VD & increased vasc. perm (=> edema)
b) acute inflam. cell infiltrate
c) endothelial cell damage => fibrinoid necrosis, hemorrhage & thrombosis
d) tissue infarct |
|
|
Term
| *How soon after renal transplant does acute rejection occur? |
|
Definition
| days to weeks after transplant OR reduction in immunosuppression |
|
|
Term
*Effect
Acute renal transplant rejection |
|
Definition
1) increased serum creatinine
2) decreased urin output
3) development of renal failure |
|
|
Term
| What are the 2 types of acute rejection seen in renal transplant rejection? |
|
Definition
1) acute cellular rejection
2) acute humoral rejection (acute rejection vasculitis) |
|
|
Term
Tx
acute cellular rejection |
|
Definition
| increased immunosuppression |
|
|
Term
| What causes acute cellular renal transplant rejection? |
|
Definition
| interstitial mononuclear inflammatory cell infiltrate => tubulitis, endothelitis & edema |
|
|
Term
| What causes acute humoral renal transplant rejection? |
|
Definition
1) complement activation => vascular fibrinoid necrosis, acute inflam. & thrombosis => tissue infarct
2) vascular intimal thickening by foamy macs & proliferating fibroblasts & s. muscle cells (sue to cytokine production) => tissue atrophy |
|
|
Term
| *When does chronic renal transplant recjection occur? |
|
Definition
| years after transplantation |
|
|
Term
*Effect
Chronic renal transplant rejection |
|
Definition
| slowing increasing creatinine levels |
|
|
Term
| What causes chronic renal transplant rejection? |
|
Definition
| vascular fibrosis, associated with renal atrophy, insterstitial fibrosis & a mononuclear inflam. cell infiltrate |
|
|
Term
Prevention/Tx
Solid Organ Transplant Rejection |
|
Definition
1) HLA Matching
2) Immunosuppression
3) Induction of immunological tolerance |
|
|
Term
| *What usually occurs prior to allogenic hematopoietic stem cell transplants? |
|
Definition
| recipiant's immune system is ablated (irradiation) |
|
|
Term
| What are the 3 effects possibly seen after allogenic hematopoietic stem cell transplantation? |
|
Definition
1) immunodeficiency (=> susceptibility to inf.)
2) transplant rejection (mediated by recipiant's survivint T cells & NK cells)
3) Graft vs. Host Disease (GVH) |
|
|
Term
| What are the 2 forms of GVH? |
|
Definition
|
|
Term
|
Definition
| donor's immunocompetent CD4+ & CD8+ T cells react against recipiant's cells => beneficial anti-rejection & graft-vs-tumor effect |
|
|
Term
| What are the 4 major affected tissues in GVH? |
|
Definition
1) Skin
2) Mucosal surfaces
3) Liver
4) Lymphoid organs |
|
|
Term
|
Definition
maculopapular rash (desquamate - acute, or dermal fibrosis - chronic)
GI - N/V/D
eyes/mouth - dryness/irritation (chronic)
jaundice (due to injured bile ducts)
lympoid organs affected => compounds recipiant's immunodeficiency & can lead to autoimmune complications |
|
|
Term
|
Definition
| organ specific & systemic disorders that re primary autoimmune reactions, T &/or B cell-mediated |
|
|
Term
| What are the 2 mechanisms for immunologic self-tolerance (prevention of autoreactivity)? |
|
Definition
|
|
Term
|
Definition
| immature self-reactive T cells (thymus) & B cells (bone marrow) elimiated by apoptosis - imperfect |
|
|
Term
| What are the 4 "back up systems" (peripheral tolerance) to the imperfect central tolerance? |
|
Definition
1) anergy
2) suppression
3) deletion (activation0induced cell death)
4) Ag sequestration |
|
|
Term
def
anergy
peripheral tolerance |
|
Definition
| presentation of self-Ags to T cells => prolonged Ag-specific T cell anergy (inactivation) due to lack of expression of, or binding of inhibitory T cell receptors to, costimulatory molecules => B cell anergy due to lack of self-reactive helper T cells |
|
|
Term
def
suppression
peripheral tolerance |
|
Definition
| cytokine secretion by regulatory T cells => suppression of autoreactivity |
|
|
Term
def
deletion (activation-induced cell death)
peripheral tolerance |
|
Definition
| repeated activation of Ag-specific T cells by self-Ags => eventual binding of Fad (widespread cellular expression) to FasL (Fas Ligand) on the activated T cells => elimination of autoreactive T cells by apoptosis |
|
|
Term
def
Ag sequestration
peripheral tolerance |
|
Definition
| "hidden" self-Ags within certain immune-privileged tissues |
|
|
Term
| What are the 2 causes of autoimmune disease (loss of self-tolerance)? |
|
Definition
1) genetic
2) environment (inf.) |
|
|
Term
| What 2 environmental factors cause autoimmune disease? |
|
Definition
1) initiation of the autoimmune reaction - via microbial-induced increased expression of costimulatory molecules on APCs &/or immunologic cross-reaction with self-Ags => activation of autoreactive lymphocytes
2) presistance & progression of disease process - tissue damage secondary to inf. => release & alteration of self-Ags (inc. exposure of normally concealed epitopes) => continuing lymphocyte activation |
|
|
Term
*def
SLE (systemic lupus erythematosus) |
|
Definition
| relatively common, clinically & pathologically heterogeneous, relapsing & remitting autoimmune disease affecting mutliple organ systems (esp. the skin, kidneys, joints, & serosal surfaces) |
|
|
Term
| When is SLE usually diagnosed? |
|
Definition
|
|
Term
| Who is usually more affected by SLE? |
|
Definition
F>M
more frequent/severe in african american women particularly |
|
|
Term
*Examples
genetic susceptibility
SLE |
|
Definition
1) association b/w specific HLA alleles & production of certain auto-Abs
2) inherited deficiencies in the early complement factors found in a minority of patients with SLE, perhaps causing impaired clearance of immune complexes &/or apoptotic cells |
|
|
Term
*Examples
environmental triggers
SLE |
|
Definition
1) levels of sex hormones
2) administration of certain medications
3) exposure to UV radiation |
|
|
Term
| What is the pathogenesis of SLE? |
|
Definition
| genetically predisposed individual exposed to appropriate environmental trigger => loss of self-tolerance & activation of autoreactive CD4+ T cells => stimulation of self-Ag-specific B cells => production of variety of auto-Abs => immune complex & Ab-mediated tissue damage |
|
|
Term
| What types of autoantibodies are formed in SLE? |
|
Definition
1) antinuclear Abs (ANAs)
2) antiphospholipid Abs
3) Abs to formed elements of the blood |
|
|
Term
|
Definition
| bind to exposed nuclear Ags => immune complex formation in sm. blood vessels => type III hypersensitivity reaction |
|
|
Term
| How do antiphospholipid Abs work? |
|
Definition
bind to exposed epitopes of proteins complexed to phospholipids =>
1) delayed coagulation - lupus anticoagulant Abs
2) hypercoagulability - secondary to antiphospholipid Ab syndrome |
|
|
Term
| How do Abs to formed elements of the blood work? |
|
Definition
| bind to RBCs, platelets, &/or WBCs => opsonization & phagocytosis => anemia, thrombocytopenia &/or leukopenia |
|
|
Term
| What happens to small arteries & arterioles in SLE? |
|
Definition
1) fibrinoid necrosis & acute inflam. => fibrous scarring (multiple organs)
2) non-inflam. occlusion, thrombotic &/or fibrotic |
|
|
Term
| What do kidney glomeruli look like in light microscopy in Class I & Class II SLE? |
|
Definition
I: minimal to no abnormalities
II: mesangial lupus glomerulonephritis
expansion of the mesangium due to an increased number of mesangial cells & increased matrix |
|
|
Term
| What do kidney glomeruli look like in light microscopy in Class III SLE? |
|
Definition
focal proliferative glomerulonephritis
scattered glomeruli w/ increased cellularity as well as occasional fibrinoid necrosis & thrombosis |
|
|
Term
| *What do kidney glomeruli look like in light microscopy in Class IV SLE? |
|
Definition
diffuse proliferative glomerulonephritis
majority of glomeruli w/ increased cellularity frequently accompanied by fibrinoid necrosis & thrombosis |
|
|
Term
| What do kidney glomeruli look like in light microscopy in Class V SLE? |
|
Definition
membranous glomerulopathy
widespread thickening of the glomerular capillary walls |
|
|
Term
| What is observed in kidney glomeruli in SLE via direct immunofluorescent mincroscopy? |
|
Definition
| granular pattern of fluorescence within the mesangium ± glomerular capillary walls using anti-Ig & anti-complement fluorescent probes |
|
|
Term
| What is observed in kidney glomeruli in SLE via electron microscopy? |
|
Definition
| electron-dense immune complexes within the mesangium ± deposition in a subepithelial (class V) &/or subendothelial (class III & IV) |
|
|
Term
| *What can be seen via ligh microscopy when there's extensive immune complex deposition in SLE? |
|
Definition
| substanatial thickening of capillary walls (wire loops) |
|
|
Term
| What happes to the tubulointerstitium of the kidney in SLE? |
|
Definition
| immune complex deposition within tubular basement membranes |
|
|
Term
| *What is the most common skin Sx of SLE? |
|
Definition
| erythematous rash (esp. in a butterfly or malar pattern on face) |
|
|
Term
| *What exacerbates the erythematous rash of SLE? |
|
Definition
|
|
Term
| What is seen in the skin via light microscopy in SLE? |
|
Definition
| edemaa & degeneration of the basal cells along the dermoepidermal junction (frequently accompanied by dermal vasculitis) |
|
|
Term
| What is seen in the skin via direct immunofluorescent mircoscopy in SLE? |
|
Definition
| granular pattern of fluorescence at the dermoepidermal junction using anti-Ig & anti-complement fluorescent probes (leisonal & non-leisonal skin) |
|
|
Term
| What is seen in the joints in SLE? |
|
Definition
| synovial inflammation w/o articular erosion |
|
|
Term
| What is seen in the serosal surfaces in SLE? |
|
Definition
| acute fibrinous inflammation => chronic inflammation & fibrosis |
|
|
Term
| What is seen in the heart in SLE? |
|
Definition
1) Libman-Sacks endocarditis (sm. vegetations which can be on either side of the leaflets of any valve)
2) myocarditis
3) *pericarditis |
|
|
Term
| What is seen in the coronary arteries in SLE? |
|
Definition
| accelerated atherosclerosis |
|
|
Term
| What happens to the lymphoid organ in SLE? |
|
Definition
| follicular hyperplasia with an increased number of plasma cells |
|
|
Term
| *What evidence is there for ANAs as autoimmunity in SLE? |
|
Definition
1) detection & quantification by indirect immunofluorescence
2) specific ANA charaterization |
|
|
Term
| *Is ANA detection/quantification by indirect immunofluorescence sensitive or specific? |
|
Definition
| sensitive, but not specific |
|
|
Term
| *What 5 patterns of nuclear fluorescence can be seen with positive ANA tests? |
|
Definition
1) homogeneous (diffuse) pattern
2) rim (peripheral) pattern
3) speckled pattern
4) nucleolar pattern
5) centromere pattern |
|
|
Term
*def
homogeneous (diffuse) pattern
positive ANA test |
|
Definition
common, but nonspecific
reflects Abs to diverse nuclear constituents |
|
|
Term
*def
rim (peripheral) pattern
positive ANA test |
|
Definition
most specific pattern for SLE
reflects Abs to dsDNA |
|
|
Term
*def
speckled pattern
positive ANA test |
|
Definition
common, but nonspecific
reflects Abs to various non-DNA nuclear components |
|
|
Term
*def
nucleolar pattern
positive ANA test |
|
Definition
most commonly seen with systemic sclerosis
reflects Abs to nucleolar RNA |
|
|
Term
*def
centromere pattern
positive ANA test |
|
Definition
| most frequently seen with limited systemic sclerosis |
|
|
Term
| *What tests are done for specific ANA characterization? |
|
Definition
|
|
Term
| *What evidence is there for antiphospholipid Abs autoimmunity in SLE? |
|
Definition
1) prolonged aPTT due to lupus anticoagulant Abs
2) anticardiolipin Abs |
|
|
Term
| *What evidence is there for Abs to formed blood elements in autoimmunity in SLE? |
|
Definition
| anemia, thrombocytopenia, &/or leukopenia |
|
|
Term
| *What are lupus erythematosus (LE) cells or hematoxylin bodies in SLE? |
|
Definition
| neutrophils or macs which have phagocytosed the nuclei of injured cells |
|
|
Term
|
Definition
variable
1) chronic, relapsing & remitting with common signs/Sx inc. fever, malaise, malar rash worsened by sun exposure, joint pain
2) lab abnormalities typical of SLE + those related to renal involvement & immune complex deposition |
|
|
Term
|
Definition
| immunosuppresive medications (=> incerased susceptibility to inf.) |
|
|
Term
| What are the 3 lupus "variants?" |
|
Definition
1) chronic discoid lupud erythematosus
2) subacute cutaneous lupus erythmatosus
3) drug-induced lupus erythematosus |
|
|
Term
Sx
chronic discoid lupus erythematosus |
|
Definition
(scarring dermatosis)
only involvement of skin, particularly areas exposed to sunlight
scaling, skin plaques with raised, red border |
|
|
Term
| What microscopic findings will be seen in chronic discoid lupus erythematosus? |
|
Definition
| epidermal atophy, vacuolar change of basal cells, follicular plugging, dermal chronic inflam. w/ similar immunofluorescent findings as SLE |
|
|
Term
Sx
subacute cutaneous lupus erythematosus |
|
Definition
(nonscarring dermatosis)
photosensitive erythematous rash dominates
mild systemic manifestations are often present |
|
|
Term
| What microscopic findings will be seen in subacute cutaneous lupus erythematosus? |
|
Definition
| positive ANAs, esp ant-Ro (SS-A) Abs |
|
|
Term
| What causes drug-induced lupus erythematosus? |
|
Definition
| multiple medications implicated (withdrawl of drug => disease remission) |
|
|
Term
| What microscopic findings are seen in drug-induced lupus erythematosus? |
|
Definition
| positive ANAs, esp. antihistone Abs (more common than clinical Sx of SLE) |
|
|
Term
|
Definition
| chronic autoimmune disorder affecting predominately the lacrimal & salivary glands |
|
|
Term
| *Who is most likely diagnosed with Sjögren syndrome? |
|
Definition
| middle-aged women (50-60 y/o) |
|
|
Term
| *What are the 2 forms of Sjögren Syndrome? |
|
Definition
1) primary - sicca syndrome
2) secondary - associated with another autoimmune disease (most frequently RA) |
|
|
Term
| What causes Sjögren syndrome? |
|
Definition
1) genetic predisposition
2) environmental triggers |
|
|
Term
| What is the pathogenesis of Sjögren Syndrome? |
|
Definition
| genetically susceptible individual exposed to environmental trigger => loss of tolerance & activation of autoreactive CD4+ T cells => stimulation of self-Ag-specific B cells => production of various auto-Abs => immunologically-mediated damage primarily to lacrimal & salivary glands |
|
|
Term
| How are exocrine glands (esp. lavrimal & salivary glands) affected in Sjögren Syndrome? |
|
Definition
lymphocytic & plasma cell infiltration
ductal epithelial hyperplasia
eventual glandular fibrosis & acinar atrophy |
|
|
Term
| How are mucosal surfaces affected in Sjögren Syndrome? |
|
Definition
| drying with secondary ulceration & inflam. |
|
|
Term
| How often are other organs affected in Sjögren Syndrome? |
|
Definition
| occasionally (i.e. renal tubulointerstitium) |
|
|
Term
| What is the evidence of autoimmunity in Sjögren Syndrome? |
|
Definition
| detection of auto-Abs, esp. rheumatoid factor & ANAs directed against 2 ribonucleoprotein Ags (SS-A [Ro] & SS-B [La]) |
|
|
Term
|
Definition
chronic condition characterized by dry eyes (keratoconjunctivitis sicca) with resultant blurred vision & dry mouth (xerostomia)
other upper airway mucosal surfaces may also be affected
frequently: parotid gland enlargement, associated RA, & lymphadenopathy (incerased risk of B cell lymphoma) |
|
|
Term
*def
systemic sclerosis (scleroderma) |
|
Definition
| chronic disease characterized by excessive fibrosis |
|
|
Term
| *Who is most often affected by systemic scleroderma? |
|
Definition
| middle-aged women (50-60 y/o) |
|
|
Term
| What are the 2 classifications of systemic sclerosis? |
|
Definition
1) diffuse systemic sclerosis
2) limited systemic sclerosis |
|
|
Term
Sx
diffuse systemic scleroderma |
|
Definition
rapidly progessive variant
initial involvement of extensive areas of the skin followed by abnormalities in multiple visceral organs (s.a. GI, joints, kidneys, lungs, heart, sk. muscle) |
|
|
Term
Sx
limited systemic scleroderma |
|
Definition
slowly progressive variant
frequently confined to skin of face & distal upper extremities |
|
|
Term
|
Definition
| subset of limited systemic sclerosis |
|
|
Term
|
Definition
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia |
|
|
Term
| What causes systemic sclerosis? |
|
Definition
1) abnormal activation of the immune system
2) microvascular damage |
|
|
Term
| What happens in systemic scerloderma when cell-mediated immunity is abnormally activated? |
|
Definition
| inappropriate stimulation of Ag-specific CD4+ T cells => secretion of variety of cytokines (inc. several GFs for fibroblasts) => excessive collagen production |
|
|
Term
| What happens in systemic scerloderma when humoral immunity is abnormally activated? |
|
Definition
presence of ANAs s.a.:
1) anti-Scl 70 (fairly specific for diffuse systemic sclerosis)
2) anticentromere Ab (found primarily in patients with CREST syndrome) |
|
|
Term
| What happens due to microvascular damage in systemic sclerosis? |
|
Definition
| persistance injury to microvascular endothelium => platelet activation => release of GFs for fibroblasts => excessive collagen production |
|
|
Term
| What happens to the skin in systemic sclerderma? |
|
Definition
intital involement of upper extremeties first, followed by the face, proximal upper extremeties & upper trunk
sm. vessel damage with luminal restriction, edema, collagen degeneration, & lymphocytic infiltrated within the dermis => dermal fibrosis with deposition of dense collagen, epidermal atrophy & microvascular hyalinization => occasionally calcifications, ischemic ulcerations, & even autoamputation |
|
|
Term
| What happens to the GI tract in systemic sclerosis? |
|
Definition
| mucosal atrophy & collagenization of the wall (esp. in esophagus) => complications s.a. dysmotility, gastroesophageal reflux & malabsorption (with involvement of the sm. intestine) |
|
|
Term
| What happens to the joints in systemic sclerosis? |
|
Definition
| synovial inflam. & fibrosis (NO joint distruction) |
|
|
Term
| What happens to the kidneys in systemic scleroderma? |
|
Definition
| arterial intimal cell proliferation & deposition of ECM |
|
|
Term
| What happens to the lungs in systemic sclerosis? |
|
Definition
pulmonary interstitial fibrosis
vascular abnormalities of pulmonary HTN |
|
|
Term
| What happens to the heart in systemic scleroderma? |
|
Definition
fibrosis of the myocardium & its arterioles
occasional pericarditis |
|
|
Term
| What happens to sk. muscles in systemic sclerosis? |
|
Definition
|
|
Term
|
Definition
range of organ involvement, usually beginning with prominent skin changes that may progress to involve multiple other organs s.a:
1) GI: dysphagia, gastroesophageal reflux, malabsorption
2) kidneys: proteinuria, malignant HTN, renal failure
3) lungs/heart: cardiac failure |
|
|
Term
| What 3 things characterize mixed connective tissue disease? |
|
Definition
1) overlapping clinical features of SLE, polymyositis, RA, & systemic sclerosis
2) high titers of anti-U1 RNP Abs
3) minimal renal disease |
|
|
Term
|
Definition
|
|
Term
*def
inherited (primary) immunodeficiencies |
|
Definition
| heterogeneous disease that may affect specific immunity and are being diagnoses with increased frequency |
|
|
Term
| *What type of immune deficiency is more commonly seen in primary immunodeficiency? |
|
Definition
| disorders of humoral immunity => decreased Ab production |
|
|
Term
| *How do primary immunodeficiencies usually present? |
|
Definition
| recurrent &/or chronic inf. in infancy or young adulthood, with increased susceptibility to certain malignancies & autoimmune disorders |
|
|
Term
| *How do B cell immunodeficiencies present? |
|
Definition
| deficient humoral immunity => inf. by pyogenic bacteria (often encapsulated), certain viruses (esp. enteroviruses), & intestinal parasites |
|
|
Term
| *How do T cell immunodeficiencies present? |
|
Definition
| deficient cell-mediated immunity => inf. by viruses, fungi, intracellular bacteria, & protozoa |
|
|
Term
def
SCID (severe combined immunodeficiency diseases) |
|
Definition
| profound deficiency in BOTH cell-mediated & humoral immunity |
|
|
Term
| In SCID, which immunity is usually at a greater deficit? |
|
Definition
|
|
Term
| What causes impaired T cell immunity in SCID? |
|
Definition
| abnormal T cell differentiation or abnormal T cell activation |
|
|
Term
| What causes impaired humoral immunity in SCID? |
|
Definition
| bone marrow stem cell defect or nonfunctional B cells secondary to abnormal T cell function (more common) |
|
|
Term
|
Definition
| abnormal development &/or activation of both T & B cells by diverse cellular, molecular & genetic mech. |
|
|
Term
| What are the 2 types of SCID? |
|
Definition
1) *X-linked recessive (most common)
2) autosomal recessive |
|
|
Term
| *What causes X-linked SCID? |
|
Definition
| abnormal IL receptor protein |
|
|
Term
| What causes autosomal recessive SCID? |
|
Definition
1) abnormal receptor or signaling protein
2) impaired expression of MHC II
3) PNP deficiency
4) *adenosine deaminase deficiency (ADA) |
|
|
Term
|
Definition
| accumulation of alternative metabolites which inhibit DNA synthesis => cellular toxicity, particularly to developing T cells |
|
|
Term
| *What is special about ADA? |
|
Definition
| one of the first disorders to be treated with gene therapy |
|
|
Term
| What happens to systemic lympoid tissue in SCID? |
|
Definition
| virtually absent or hypoplastic |
|
|
Term
| What happens to the thymus is SCID? |
|
Definition
sm. & nondescended, lacks lymphoid cells
Hassall's corpuscles are decreased or fetal in appearance |
|
|
Term
|
Definition
1) severe lymphopenia with decreased mature T & B cells
2) deficienct cell-mediated immunity (no lymphoproliferative response to mitogens or allogeneic cells, no delayed-type hypersensitivity reaction or allograft rejection)
3) deficient humoral immunity (scant IgG, absent IgM & IgA, no Ab response to vaccination)
=> failure to thrive & infections & GVH (usually death by age 1 if untreated) |
|
|
Term
| What infections are commonly seen in SCID? |
|
Definition
1) pyogenic bacteria
2) fungi & protozoa
3) viruses
4) viable attenuated vaccines |
|
|
Term
| When is GVH disease seen in SCID? |
|
Definition
1) transplacental transfer of maternal T cells
2) blood transfusion |
|
|
Term
|
Definition
| early allogenic stem cell transplant => full immunologic function & good chance of a allograft success with high risk of GVH |
|
|
Term
|
Definition
| partial or complete thymic hypoplasia => selective deficiency of T cells & T cell-mediated immunity |
|
|
Term
| What causes DiGeorge Syndrome? |
|
Definition
1) defective development of the 3rd & 4th pharyngeal pouches
2) majority: chromosome 22q11 deletion |
|
|
Term
| What 4 things are defective/absent in DiGeorge Syndrome? |
|
Definition
1) Thymus
2) Parathyroid gland
3) Congenital defects of heart & great vessels
4) facial deformities |
|
|
Term
| What does the hypoplastic/absent thymus in DiGeorge cause? |
|
Definition
defective T cell maturation =>
1) low-normal lymphocyte count
2) paracortical areas of lymph nodes & pariarteriolar lymphoid sheaths of spleen depleted
3) deficient cell-mediated immunity (no delayed hypersensitivity rxns or graft rejection) |
|
|
Term
| What does the absent or rudimentary parathyroid gland in DiGeorge Syndrome cause? |
|
Definition
| hypocalcemia => tetany (often in first few days of life) |
|
|
Term
| What infections are seen in DiGeorge? |
|
Definition
| viral, fungal, & mycobacterial |
|
|
Term
|
Definition
| transplantation of fetal thymus or thymic epithelium (often not needed) |
|
|
Term
def
Bruton (X-linked) Agammaglobuminemia (XLAG) |
|
Definition
| delective deficiency of B cells & plasma cells & humoral immunity |
|
|
Term
|
Definition
1) defect due to block in the maturation of pre-B cells to B cells
2) X-linked recessive (males only) |
|
|
Term
| Where are B cells (& their products) lacking in XLAG? |
|
Definition
1) blood/lymphoid tissue
2) germinal centers in lymph nodes & spleen
3) no plasma cells in tissue
4) no serum Ig's |
|
|
Term
| *What infections are seen in XLAG? |
|
Definition
severe recurrent inf. beginning at 6-12 mo.
1) pyogenic bacteria
2) certain viruses
3) Giardia lamblia |
|
|
Term
| *Why do the recurrent infections begin at 6-12 months in XLAG? |
|
Definition
| maternal Ig's become depleated |
|
|
Term
|
Definition
| periodic γ globulin infusions (passive immunity) |
|
|
Term
| What disorders are frequently associated with XLAG? |
|
Definition
| arthritis & autoimmune diseases |
|
|
Term
| *What is the most common primary immunodeficiency? |
|
Definition
|
|
Term
def
isolated IgA deficiency |
|
Definition
| selective deficiency for IgA |
|
|
Term
| What causes isolated IgA deficiency? |
|
Definition
| congenital or acquired defect due to a block in the differentiation of IgA B cells to plasma cells |
|
|
Term
| How does isolated IgA deficiency affect body IgA levels (& it's derivatives)? |
|
Definition
1) absence of both IgA & sIgA
2) normal # IgA B cells, tho mostly immature
3) ~40% of patients also have serum Abs to IgA (*=> may be suceptible to anaphylactic shock when transfused with blood containing IgA) |
|
|
Term
| What infections are seen in isolated IgA deficiency? |
|
Definition
frequently asymptomatic
may have recurrent sinopulmonary inf. & diarrhea |
|
|
Term
| What disorders are often associated with isolated IgA deficiency? |
|
Definition
| resp. allergies, celiac disease, & autoimmune disease |
|
|
Term
*def
common variable immunodeficiency disease |
|
Definition
| relatively common heterogeneous group of disorders that may be congenital or acquired |
|
|
Term
| *Who is often diagnosed with common variable immunodeficiency disease? |
|
Definition
|
|
Term
| What is the common variable in common variable immunodeficency disease? |
|
Definition
| hypogammagloulinemia - usually all Igs, occasionally only IgG |
|
|
Term
| What causes common variable immunodeficiency disease? |
|
Definition
intrinsic B cell defect (*usually present), where B cells can proliferate in response to Ags, BUT fail to differentiate to plasma cells to produce Abs
± immunoregulatory T cell disorder, with deficient T helper cell function OR excessive T suppressor cell activity |
|
|
Term
Sx
common variable immunodeficiency disease |
|
Definition
1) normal # circulating B cells
2) hyperplastic B cells areas in lymph nodes, spleen, & GI
3) no plasma cells
4) recurrent inf.
5) noncaseating granulomas |
|
|
Term
| What recurrent infections are seen in common variable immunodeficiency? |
|
Definition
pyogenic bacteria
intestinal inf. with Giardia lamblia & c. diff |
|
|
Term
| What disorders are often associated with common variable immunodeficiency disease? |
|
Definition
| autoimmune idsease & lymphoma |
|
|
Term
Tx
common variable immunodeficiency disease |
|
Definition
|
|
Term
| What is the diagnostic triad for Wiskott-Aldrich Syndrome? |
|
Definition
1) immunodeficiency
2) thrombocytopenia
2) eczema |
|
|
Term
| What leads to early death (6-8 y/u) in Wiskott-Aldrich Syndrome? |
|
Definition
| recurrent inf, bleeding complications or malignancies |
|
|
Term
| What causes Wiskott-Aldrich Syndrome? |
|
Definition
| X linked recessive genetic defect in WASp (Wiskott-Aldrich Syndrome protein) which seems to function in cytoskeletal actin polymerization |
|
|
Term
| What is the pathology of Wiskott-Aldrich Syndrome? |
|
Definition
Early: lymphocyte & thymus - normal, BUT poor Ab response to polysaccharide Ags
With increasing age: progressive depletion of lymphocytes in blood & T cell areas of lymph nodes => variable loss of cellular immunity |
|
|
Term
| What commonly happens to Ig levels in Wiskott-Aldrich Syndrome? |
|
Definition
decreased IgM
normal IgG
increased IgA & IgE |
|
|
Term
| What disorder is often associated with Wiskott-Aldrich Syndrome? |
|
Definition
|
|
Term
Tx
Wiskott-Aldrich Syndrome |
|
Definition
|
|
Term
|
Definition
| autosomal recessive, multisystem disorder |
|
|
Term
| What characterizes ataxia-telangiectasia? |
|
Definition
| progressive neurologic dysfunction, cereballar ataxia, oculocutaneous telangiectasia, abnormal sensitivity to X-rays, impaired organ development, & variable immunodeficiency with an increased frequency of malignancies |
|
|
Term
| *What are many membrane-associated proteins necessary for in WBC function? |
|
Definition
| WBC functions involving cell-to-cell interactions |
|
|
Term
| What are the 2 types of deficiencies of cell membrane molecules/receptors? |
|
Definition
1) leukocyte adhesion deficiencies
2) bare lymphocyte syndrome |
|
|
Term
def
leukocyte adhesion deficiencies |
|
Definition
| rare genetic deficiencies of leukocyte adhesion molecules => impaired leukocyte adhesion to endothelium in inflam., neutrophil aggregation & chemotaxis, phagocytosis, lymphocyte-mediated cytotoxicity, &/or T & B cell interactions |
|
|
Term
Sx
leukocyte adhesion deficiencies |
|
Definition
recurrent bacterial & fungal inf.
poor wound healing
periodontal disease |
|
|
Term
def
bare lymphocyte syndrome |
|
Definition
| deficiency of MHC II Ags on cell surfaces => failure of Ag presentation to & impaired development of CD4+ T cells => immunodeficiency BOTH cellular & humoral |
|
|
Term
| What infections are common in bare lymphocyte syndrome? |
|
Definition
| bacterial, viral, fungal, & protozoal inf. |
|
|
Term
| What are the 3 disorders of nonspecific host disease? |
|
Definition
1) CGD (chronic granulomatous disease)
2) Chediak0Higaski syndrome
3) Genetic deficiencies of the complement system (rare) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| lack of "resp. burst" with phagocytosis
1) defective activation of membrane NADPH-oxidase => impaired production of superoxide anion during phagocytosis => deficient H2O2 production => failure of H2O2-MPO-halide killing system
2) ~2/3 are X linked recessive; the rest are autosomal recessive |
|
|
Term
| What infections are seen in CGD? |
|
Definition
can be fatal
1) frequent, severe, chronic bacterial inf. with abscesses & granulomas of subcutaneous tissue, lymph nodes, lyngs, liver, etc.
2) catalase-positive bacterial & fungi |
|
|
Term
|
Definition
|
|
Term
def
Chediak-Higashi syndrome |
|
Definition
| rare autosomeal recessive disease with defective lysosomal trafficking regulator protein => probably abnormal organella synthesis, trafficking &/or fusion |
|
|
Term
Sx
Chediak-Higaski syndrome |
|
Definition
1) generalized increased fusion of cytoplasmic granules (giant)
2) progressive neurologic dysfunction
3) eventual accelerated phase: life-threatening lymphoproliferative infiltrates |
|
|
Term
| What happens to leukocytes (particularly neutophils) in Chediak-Higaski syndrome? |
|
Definition
| enlarged lysosomes => neutropenia & impaired neutrophil function => recurrent inf. |
|
|
Term
| What happens to NK cells in Chediak-Higaski syndrome? |
|
Definition
|
|
Term
| What happens to melanocytes in Chediak-Higaski syndrome? |
|
Definition
| giant melanosomes => partial oculocutaneous albinism (due to melanin trapping) |
|
|
Term
| What happens to platelets in Chediak-Higaski syndrome? |
|
Definition
| abnormal dense bodies => mild bleeding tendency |
|
|
Term
| What are the 3 rare genetic deficiencies of the complement system? |
|
Definition
1) C1 (q,r, or s), *C2 & C4 deficiencies
2) C3 deficiency
3) C5-9 deficiencies |
|
|
Term
Effect
C1(q,r, or s), *C2 & C4 deficiencies |
|
Definition
| autoimmune &/or immune complex diseases |
|
|
Term
|
Definition
| frequent, serious, pyogenic bacterial inf. |
|
|
Term
|
Definition
| recurrent disseminated inf. by neisseria |
|
|
Term
|
Definition
1) ADA deficiency
2) XLAG
3) Hyper IgM Syndrome
4) DiGeorge
5) X linked SCID
6) MHC II Deficiency |
|
|
Term
|
Definition
| abnormal mass of tissue, the growth of which exceed & is uncoordinated with that or normal tissues and persists in the same excessive manner after a cessation of the stimuli which evoked the change |
|
|
Term
| What are the 2 types of neoplasms? |
|
Definition
|
|
Term
| What are the 2 components of a neoplasm? |
|
Definition
1) parenchymal cells (neoplastic)
2) stroma (supportive CT w/ blood vessels) |
|
|
Term
|
Definition
| dense collagenous stromal response frequently induced by malignamt neoplasms, esp. carcinomas |
|
|
Term
| *How are tumor suffixes determined? |
|
Definition
| based on the biologic potential of the neoplastic cells (benign vs. malignant) |
|
|
Term
|
Definition
|
|
Term
Suffix
malignant neoplasms |
|
Definition
1) epithelial: -carcinoma
2) mesenchymal: -sarcoma |
|
|
Term
| How are tumor prefixes determined? |
|
Definition
| based on the differentiating parenchymal cell type |
|
|
Term
|
Definition
| epithelial neoplasm showing differntiation toward glandular epithelium |
|
|
Term
|
Definition
| epithelial neoplasm showing differntiation toward squamous epithelium |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward fibrous tissue |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward cartilage |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward bone |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward adipose tissue |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward s. muscle |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward sk. muscle |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward vascular tissue |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward blood vessels |
|
|
Term
|
Definition
| mesenchymal neoplasm showing differentiation toward lymphatic vessels |
|
|
Term
| *What 3 additional tumor prefixes may be used based on the parenchymal cell growth pattern? |
|
Definition
1) Cyst-
2) Papillary
3) Polypoid |
|
|
Term
|
Definition
| neoplastic cells forming cystic structures |
|
|
Term
|
Definition
| neoplastic cells forming multiple finger-like projections extending into a cystic space |
|
|
Term
|
Definition
| neoplastic cells forming a mass that projects above a mucosal surface |
|
|
Term
| *What does the prefix of a neoplasm tell you? |
|
Definition
| differentiates b/w parenchymal cell type ± neoplastic growth pattern |
|
|
Term
| *What does the suffix of a neoplasm tell you? |
|
Definition
|
|
Term
|
Definition
| benign neoplasm showing differentiation toward smooth muscle |
|
|
Term
|
Definition
| malignant mesenchymal neoplasm showing differentiation toward s. muscle |
|
|
Term
|
Definition
| benign neoplasm showing differentiation toward glandular epithelium with a cystic growth pattern |
|
|
Term
def
polypoid adenocarcinoma |
|
Definition
| malignant neoplasm showing differentiation toward glandular epithelium |
|
|
Term
| What would you expect the name of a benign neoplasm showing differentiation toward bone to be? |
|
Definition
|
|
Term
| What would you expect the name of a malignant neoplasm showing differentiation toward squamous epithelium to be? |
|
Definition
|
|
Term
| What would you expect the name of a malignant neoplasm showing differentiation toward adipose tissue to be? |
|
Definition
|
|
Term
|
Definition
| malignancy showing differentiation toward melanocytic cells |
|
|
Term
|
Definition
| malignancy showing differentiation toward lymphocytic cells |
|
|
Term
|
Definition
| specific type of germ cell malignancy of the testis |
|
|
Term
|
Definition
| malignancy of hematopoietic stem cells |
|
|
Term
|
Definition
| neoplasm showing differentiation toward more than one cell type |
|
|
Term
|
Definition
| neoplasm showing differentiation toward cell types from more than one germ cell layer |
|
|
Term
|
Definition
| ectopic rest of normal tissue |
|
|
Term
|
Definition
| disorganized mass of mature tissue comprised of various cell types normally found at its location - benign |
|
|
Term
|
Definition
| extent to which parenchymal cells resemble comparable to normal cells, both morphologically & functionally |
|
|
Term
| How differentiated are all benign neoplasms? |
|
Definition
|
|
Term
| How differentiated are malignant neoplasms? |
|
Definition
Can be:
1) well-differentiated
2) moderately-differentiated
3) poorly-differentiated
4) undifferentiated |
|
|
Term
def
well-differentiated malignant neoplasms |
|
Definition
| neoplastic cells show a considerable degree of maturation toward a normal tissue type |
|
|
Term
def
moderately-differentiated malignant neoplasms? |
|
Definition
| neoplastic cells show a moderate degree of maturation toward a normal tissue type |
|
|
Term
def
poorly-differentiated malignant neoplasms |
|
Definition
| neoplastic cells show little maturation toward a normal tissue type |
|
|
Term
def
undifferentiated malignant neoplasms |
|
Definition
| neoplastic cells show no perceptible differentiation toward a normal tissue type |
|
|
Term
| What 8 morphological alterations are seen with loss of differentiation (anaplasia)? |
|
Definition
1) pleomorphism
2) hyperchromatic nuclei
3) increased nuclear:cytoplasmic ratio
4) abnormal nucleoli
5) atypical mitotic activity
6) tumor giant cells
7) disorganized tissue architecture & abnormal cellular orientation
8) ischemic (coagulative) necrosis |
|
|
Term
|
Definition
| variation in the size and shape of neoplastic cells & their nuclei |
|
|
Term
| What causes the hyperchromatic nuclei seen in loss of differentiation? |
|
Definition
| increased DNA in neoplastic cells |
|
|
Term
| How are nucleoli abnormal in anaplasia? |
|
Definition
| large, irregular &/or multiple nucleoli in neoplastic cells |
|
|
Term
| What atypical mitotic activity is seen in anaplasia? |
|
Definition
| increased &/or aberrant mitosis |
|
|
Term
| What functional alterations are seen with loss of differentiation? |
|
Definition
1) loss of normal function
2) acquisition of atypical function |
|
|
Term
| What atypical functions can be acquired with loss of differentiation? |
|
Definition
1) aberrant hormone synthesis (hormone production by nonendocrine neoplasms or abnormal hormone production by endocrine neoplasms)
2) synthesis of fetal proteins |
|
|
Term
|
Definition
potentially premalignant condition characterized by failure of normal maturation, loss of polarity, and cytologic features of anaplasia, confined to an epithelial surface
(NO invasion thru the basement membrane) |
|
|
Term
| How severe can dysplasia be? |
|
Definition
| mild, moderate, and severe |
|
|
Term
*How much variation is seen b/w tumors & within one tumor over time in regards to rte of neoplastic growth?
*What does it depend on? |
|
Definition
| great variation due to modifying factors |
|
|
Term
| Do malignant or benign neoplasms tend to grow more rapidly? |
|
Definition
|
|
Term
| Which types of malignant tumors seem to have the fastest neoplastic growth? |
|
Definition
| poorly-differentiated > moderately-differentiated > well-differentiated |
|
|
Term
| What is the pattern of benign neoplastic growth? |
|
Definition
cohesive & well-circumscribed
surrounded by a fibrous capsule
easily demarcated surgically |
|
|
Term
| What is the pattern of malignant neoplastic growth? |
|
Definition
poorly delineated
infiltrative & invasive
difficult to determine margins surgically |
|
|
Term
|
Definition
| tumor implantation distant from the primary neoplasm |
|
|
Term
| What is the significance of metastsis? |
|
Definition
1) definintively identifies a neoplasm as being malignant
2) presence generally worsens the patient's prognosis |
|
|
Term
| What 3 factors determine probability of metastasis? |
|
Definition
1) hystologic type of malignancy
2) degree of differentiation of the neoplasm
3) host immune response to the tumor |
|
|
Term
| What are the 3 routes of metastatic spread? |
|
Definition
1) lymphatic dissemination
2) hematogenous spread
3) seeding of body cavities & surfaces |
|
|
Term
| *What characteristic malignancies use lymphatic dissemination? |
|
Definition
| carcinomas - initial pathway |
|
|
Term
| What causes lymphatic dissemination? |
|
Definition
| malignant cell penetration of lymphatic channels |
|
|
Term
| What are the sites of metastatic involvement in lymphatic disseminiation? |
|
Definition
reflect normal lymphatic drainage
1) *regional lymph nodes
2) "skip" metastases |
|
|
Term
Sx
lymphatic disseminiation |
|
Definition
|
|
Term
| What causes hematogenous metastatic spread? |
|
Definition
malignant cell invasion of blood vesssels
venous > arterial |
|
|
Term
| What characteristic malignancies use hematogenous spread? |
|
Definition
carcinomas (after lymph node metastases)
sarcomas |
|
|
Term
| What are the sites of metastatic involvement in hematogenous spread? |
|
Definition
reflect normal vascular flow
1) via venous penetration (initial)
2) via arterial penetration (eventual) |
|
|
Term
Which 3 sites of initial neoplasms tend to spread hematogenous via venous penetration?
Where? |
|
Definition
1) *liver => port vein invasion
2) *lungs => systemic vein invasion
3) vertebral bodies => infiltration of paraverterbral plexus |
|
|
Term
| What causes arterial penetration in hematogenous spread? |
|
Definition
| systemic, multiple oran involvement |
|
|
Term
|
Definition
| multiple, variably sized tumor nodules |
|
|
Term
| What causes seeding of body cavities & surfaces? |
|
Definition
| malignant cell infiltration into a body cavity |
|
|
Term
| *What characteristic malignancies use seeding of body cavities and surfaces? |
|
Definition
| ovarian carcinoma, lung carcinoma, breast carcinoma, medulloblastoma |
|
|
Term
| What are the sites of metastatic involvement in seeding of body cavities and surfaces? |
|
Definition
| peritoneal cavity, pleural space, pericardial sac, subarachnoid space |
|
|
Term
Sx
seeding of body cavities & surfaces |
|
Definition
1) *collection of fluid
2) accumulation of mucinous material |
|
|
Term
| *What is staging a greater clinical value for? |
|
Definition
|
|
Term
|
Definition
extent of differentiation
grades I to III/IV (well-differentiated to poorly-differentiated) |
|
|
Term
|
Definition
extent of its growth & spread
uses TNM system (tumor size, lymph node involvement, hematogenous metastases)
stages 0-IV |
|
|
Term
| What are the 4 clinical features of tumors? |
|
Definition
1) local effects of tumors
2) cachexia due to malignancies
3) hormonal effects due to endocrine tumors
4) paraneoplastic syndromes |
|
|
Term
| What causes cachexia due to malignancies? |
|
Definition
| cytokines by macs &/or tumor cells |
|
|
Term
*def
paraneoplastic syndromes |
|
Definition
| symptoms occuring in a minority of patients with malignancies that cannot be attributed tumor growth & spread or endogenous hormone synthesis |
|
|
Term
| What 5 paraneoplastic syndromes are seen with tumors? |
|
Definition
1) endocrinopathies
2) neuromyopathies
3) dermatologic disorders
4) hypertrophic osteoarthropathy
5) hypercoagulability |
|
|
Term
| What causes endocrinopathies? |
|
Definition
| production of an ectopic hormone or hormone-like substance |
|
|
Term
| What are the 5 possible endocrineopathies? |
|
Definition
1) Cushing Syndrome
2) Syndrome of inappropriate ADH secretion
3) Hypercalcemia
4) Carcinoid Syndrome
5) Polycythemia |
|
|
Term
| What causes Cushing Syndrome endocrinopathy? |
|
Definition
| synthesis of ectopic ACTH or ACTH-like compund |
|
|
Term
| What causes hypercalcemia endocrinopathy? |
|
Definition
| synthesis of ectopic PTH or PTH-related protein |
|
|
Term
| What causes carcinoid syndrome endocrinopathy? |
|
Definition
| ectopic production of 5-HT |
|
|
Term
| What causes polycythemia endocrinopathy? |
|
Definition
| ectopic synthesis of erythropoietin |
|
|
Term
| What causes neuromyopathy paraneoplastic syndrome? |
|
Definition
|
|
Term
def
hypertrophic osteoarthopathy |
|
Definition
| periosteal new bone formation of distal long bone formation of distal long bones with accompanying arthritis & clubbing of the fingertips |
|
|
Term
| What 3 hypercoagulability paraneoplastic syndromes are seen? |
|
Definition
1) migratory thrombophlebitis (Trousseau syndrome)
2) nonbacterial thrombotic endocarditis (NBTE)
3) disseminated intravascular coagulation (DIC) |
|
|
Term
| What are the 4 most common cancers in men? |
|
Definition
1) prostate
2) lung
3) colon
4) UT |
|
|
Term
| What are the 4 most common cancers in women? |
|
Definition
1) breast
2) lung
3) colon
4) uterus |
|
|
Term
| What is the overall mortality rate of cancer? |
|
Definition
|
|
Term
| What are the 3 cancers of highest mortality in men? |
|
Definition
1) lung
2) prostate
3) colon |
|
|
Term
| What are the 3 cancers of highest mortality in women? |
|
Definition
|
|
Term
| What age-adjusted death rate changes have occured in both men & women over the past century? |
|
Definition
1) lung carcinoma - dramatic increase
2) gastric carcinoma (uterine & cervical carcinomas - women) - substantial decrease |
|
|
Term
Do gastric/hepatocellular carinomas have greater cancer death rates than the USA?
What about colon/prostate carcinomas? |
|
Definition
gastric/hepatocellular: Japan > USA
colon/prostate: Japan < USA |
|
|
Term
| What 4 environmental exposures increase the risk of cancer? |
|
Definition
1) cigarrete smoke
2) EtOH abuse
3) sexual promiscuity
4) sun exposure |
|
|
Term
| What age has the greatest risk of cancer death? |
|
Definition
|
|
Term
| What 3 cancers are the greatest killers in men <34 y/o? |
|
Definition
1) leukemia
2) nervous system malignancies
3) non-Hodgkin lymphomas |
|
|
Term
| What 3 cancers are the greatest killers in women <34 y/o? |
|
Definition
1) leukemia
2) breast carcinoma (*15-34 y/o)
3) nervous system malignancies |
|
|
Term
| What 3 cancers are the greatest killers in men >55 y/o? |
|
Definition
1) lung carcinoma
2) prostate carcinoma
3) colon carcinoma |
|
|
Term
| What 3 cancers are the greatest killers in women >55 y/o? |
|
Definition
1) lung carcinoma
2) breast carcinoma
3) colon carcinoma |
|
|
Term
|
Definition
| multistage process arising from the accumulation of genetic abnormalities withing a single clone |
|
|
Term
| What is the effect of a mutation? |
|
Definition
| altered biochemical properties s.a. proliferation, motilitiy, invasion, angiogenesis |
|
|
Term
|
Definition
1) Mutation
2) Monoclonal expansion
3) Addistional mutations
4) Altered biochemcical properties |
|
|
Term
| What are the 3 most important abnormal molecular features of cancer cells? |
|
Definition
1) monoclonality
2) presense of multiple genetic abnormalities
3) altered growth |
|
|
Term
|
Definition
normal tissue, random inactivation occurs so on avg. ~ 50% of cells will express one of 2 alleles.
(in contrast to cancer where tissues expresses one allele only) |
|
|
Term
| Does monoclonality characterize benign, malignant, or both tumors? |
|
Definition
|
|
Term
| Since all malignant tumors are monoclonal, does that mean all benign tumors are polyclonal? |
|
Definition
|
|
Term
| What causes malignant tumors? |
|
Definition
| multiple genetic abnormalities in multiple genes |
|
|
Term
| How do we know malignant tumors stem from multiple genetic abnormalities? |
|
Definition
1) molecular analysis of of malignant tissue
2) experimental models to manipulate a cell to become malignant |
|
|
Term
| How do we know that cancer is a disease of multiple abnormal genes? |
|
Definition
in vitro models
the gene abnormalities must be in connection with controlling key cell processes s.a. proliferation, adhesion, motility, etc. |
|
|
Term
| What causes cancer's abnormal growth? |
|
Definition
secondary to an increase in the ratio of proliferation:[differentiation+death] (apoptotsis) due to either:
1) increased proliferation & reduced differentiation (predominately the case)
2) decreased apoptosis (unusual) |
|
|
Term
| What 3 cell proliferative properties are tightly regulated? |
|
Definition
1) cell division
2) cell (gradual) differentiation
3) apoptosis (once fully differentiated) |
|
|
Term
|
Definition
| contingent of cells continuously proliferating to replace dead, differentiated cells |
|
|
Term
| What happens to the size of the nucleus in regards to proliferative potential of the cell? |
|
Definition
| nucleus:cytoplasm ration increases |
|
|
Term
| What is usually key to determining a differentiated cell? |
|
Definition
|
|
Term
| What are some examples of proof of differentiation? |
|
Definition
1) presence of mucous
2) surface cilia
3) keratin production |
|
|
Term
| How can apoptotic cells be identified morphologically? |
|
Definition
| as bluish dots, representing fragmented chromatin |
|
|
Term
| What assures the blanace of proliferation & differentiation/apoptosis? |
|
Definition
|
|
Term
| How can extent of cell proliferation be evaluated? |
|
Definition
1) tissue sections - measuring mitosis
2) immunohistochemistry - tests for presence of ki-67 Ag only expressed in proliferating cells |
|
|
Term
| How do the cells of cancer vs. normal tissue differ? |
|
Definition
| proliferating undifferentiated basal-like cells predominate |
|
|
Term
| If a tumor has less differentiation, what seems to be the problem? |
|
Definition
| stem cells fail to produce committed daughter cells |
|
|
Term
| If a tumor had more differentiation, what seems to be the problem? |
|
Definition
| prolonged life span of cells committed to differentitation, but still endowed with proliferative potential |
|
|
Term
What should cancer treatment target?
Why? |
|
Definition
| stem cell proliferation b/c survival of the tumor depends on the presence of cancer stem cells |
|
|
Term
| What unusual type of cancer is due to decreased apoptosis (as opposed to increased proliferation with decreased |
|
Definition
|
|
Term
| What mutation causes follicular lymphoma? |
|
Definition
| over-expression of bcl-2 (inhibits apoptosis) |
|
|
Term
| What directly regulates cell growth? |
|
Definition
| GFs & growth inhibitors & their specific pathways by regulating transition thru the cell cycle |
|
|
Term
| What indirectly regulates cell growth? |
|
Definition
| molecules involved in sensing availability of nutrients & mediating cell to cell contact |
|
|
Term
| *What is included in the cascade of events linking binding of a cell to a GF to stimulation? |
|
Definition
1) phosphorylation of Tyrosine & Serine/Threonine aa
2) activation of a cyclic nucleotide binding protein
3) activation of transcription
4) activation of translation
(if the first occurs, the others will follow...like a domino effect) |
|
|
Term
|
Definition
1) Tyrosine - autophosphorylation of GFR
2) Activation of GTPase protein Ras
3) Activation of Ser/Thr kinases
4) Increased Cyclins D & E => activated CDK's
5) Rb phosphorylation => Rb inactivation => activation of transcription |
|
|
Term
| In general, is GDP-GTP exchange (GTPase) pro-proliferative or anti-proliferative? |
|
Definition
|
|
Term
| In general, is kinase activity pro-proliferative or anti-proliferative? |
|
Definition
|
|
Term
| What factors are anti-proliferative? |
|
Definition
1) growth inhibitors
2) CDKIs |
|
|
Term
| What controls GF growth stimulation? |
|
Definition
|
|
Term
|
Definition
| prototype tyrosine kinase GFR |
|
|
Term
| What does binding of GF to GFR stimulate? |
|
Definition
| receptor dimerization & autophosphorylation of GFRs own TK => Ras activation => initiation of cascade of intracellular Ser/Thr kinase reaction => increased transcription & translation => phosphorylation of RB => stimulation of DNA synthesis |
|
|
Term
| What are the 3 most importent events that lead to DNA synthesis? |
|
Definition
1) binding of a GF to it's receptor
2) TK autophosphorylation
3) activation of Ras |
|
|
Term
| What are the most important GFRs? |
|
Definition
|
|
Term
| In what cancers are EGFR frequently activated? |
|
Definition
squamous cell carcinoma of head/neck
non-small lung cancer
colon carcinoma |
|
|
Term
| In what cancers are HER-2 frequently activated? |
|
Definition
|
|
Term
|
Definition
extracellular domaine, transmembrane domain, & cytoplasmic domain.
ECD: binds to GFs
Inta/cytoD: catalytic site |
|
|
Term
| When GFR receptors dimerize, is it to form homo- or hetero- dimers? |
|
Definition
either
i.e. EGFR-EGFR or EGFR-HER-2 |
|
|
Term
| What causes activation of the Ras gene? |
|
Definition
| autophosphorylation of TK of GFR dimer |
|
|
Term
| What 4 mechanisms allow activation of GFR pathway in cancer? |
|
Definition
1) autocrine loop
2) increased level of normal GRF
3) GFR mutations
4) mutations downstream of GFR, within same pathway |
|
|
Term
| How can cancer cells use autocrine signaling? |
|
Definition
| cells become autonomous & secrete their own GFs |
|
|
Term
| What are the 2 ways levels of structurally normal GFRs can increase? |
|
Definition
1) structurally normal receptor becomes activated in the absence of GFs (i.e. HER-2)
2) increased levels due to gene amplification (primarily) or transcriptional degrulation AND secrete their own GFs (i.e. EGFR) |
|
|
Term
| What happens when the GFR is mutated? |
|
Definition
| becomes constitutively active => frees neoplastic cell from need to a GF in order to proliferate |
|
|
Term
| Where in the GFR can the point mutation occur? |
|
Definition
1) in the TK domain (i.e. c-Kit in GIST)
2) ECD, truncating it (EGFR in glioblastoma) |
|
|
Term
def
GIST (Gastro Intestinal Stromal Tumors) |
|
Definition
most common stromal neoplasm of GI, mesentary or omentum
-express c-Kit |
|
|
Term
| What cancer therapies are currently out there that target GRFs? |
|
Definition
|
|
Term
|
Definition
1) displace GF (inhibit GF binding)
2) stimulate tumor cell lysis via activation of complement or faciliation of receptor degradation (immune system activation)
3) stimulate internalization via endocytosis (activation of receptor endocytosis) |
|
|
Term
|
Definition
|
|
Term
| What does Ras couple GFR with? |
|
Definition
|
|
Term
|
Definition
| exchange GDP for GTP(Ras-GTP is active) |
|
|
Term
| How is constitutive activation of Ras achieved? |
|
Definition
1) Ras mutation
2) Inactivation of Neurofibromin 1 |
|
|
Term
| What other mutation exert the same effect as a constitutive Ras activation, but doesn't involve Ras? |
|
Definition
| mutations in downstream Ser/Thr kinase |
|
|
Term
| What facilitates the return of Ras to it's inactive state |
|
Definition
|
|
Term
| In what cancers are Ras mutations most common? |
|
Definition
| pancreas, lung, colon adenocarcinoma |
|
|
Term
Will anti-GFR cancer therapies be effective in Ras mutations?
Ser/Thr mutations? |
|
Definition
|
|
Term
| In which cancer is neurofibromin 1 inactivated? |
|
Definition
|
|
Term
|
Definition
1) multiple benign nerve sheath tumors prone to malignant transformation
2) overall increased incidence of malignant tumors s.a. CML, brain tumors, & pheochromocytoma
3) cafe au lait spots
4) nodules in iris |
|
|
Term
|
Definition
| a gene that has a cancer promoting activity even in the heterozygotic state (i.e. dominant) |
|
|
Term
| What are 3 examples of oncogenes that have been discussed previously? |
|
Definition
|
|
Term
|
Definition
| inhibits a function that promotes cancer formation (i.e. growth) |
|
|
Term
| What is required of tumor suppressor genes for cancer development? |
|
Definition
| homozygous inactivation (i.e. recessive) |
|
|
Term
| What is an example of a tumor supressor gene previously discussed? |
|
Definition
neurofibromin
(also Rb, but hasn't been discussed yet) |
|
|
Term
| What must occur to oncogenes & tumor suppressor genes for cancer to arise? |
|
Definition
oncogene activation
TSG inactivation |
|
|
Term
Mechanisms for stimulating growth include all of the following EXCEPT:
A) increased production of EGFR
B) overexpression of EGFR
C) mutated GFR
D) inactivation of EGFR |
|
Definition
|
|
Term
| What does the cascade activated by Ras culminate in? |
|
Definition
| increaed level of cyclins D & E (G1 cyclins) => CDK complexes => phosphorylation of Rb |
|
|
Term
Function
specific complexes of cyclins & CDKs |
|
Definition
| control differnt phases of the cell cycle |
|
|
Term
| What controls the activity of CDKs? |
|
Definition
| cyclin levels (which are tightly controlled by CDKIs) |
|
|
Term
|
Definition
| growth inhibitors s.a. TGF-β |
|
|
Term
| How can CDK, cyclin, or CDKI mutations => altered growth in cancer? |
|
Definition
1) increased CDK & cyclin activity
2) inhibition of CDKI activity |
|
|
Term
def
CDKs (cyclin dependent kinases) |
|
Definition
| Ser/Thr kinase enxymes that phosphorylate Retinoblastoma gene (Rb) |
|
|
Term
Function
Ser/Thr phosphatase |
|
Definition
|
|
Term
| How does Rb phosphorylation lead to activation of transcription? |
|
Definition
| release/activation of transcription factors |
|
|
Term
| Why are increased levels of G1 cyclins(particularly D1) crucial? |
|
Definition
| allows passage thru restriction point |
|
|
Term
| Why is the restriction point considered the point of no return in the cell cycle? |
|
Definition
| the cell cycle is no longer influcenced by EC signals past this point and is irreversibly commited to progression thru the cell cycle |
|
|
Term
| How is the cascade of G1 to S to G2 to M achieved? |
|
Definition
| activation of additional proten complexes of cyclins & CDKs that are cell cycle specific and are only activated for a limited window |
|
|
Term
| What controls orderly & timely cell cycle progression? |
|
Definition
| rapid degradation of cyclins |
|
|
Term
| What happens if the cyclin-CDK complexes are over-expressed/over-activated? |
|
Definition
|
|
Term
| What is the inhibitory arm on CDK activity & the end point of growth factor inhibition? |
|
Definition
|
|
Term
|
Definition
| growth inhibitors s.a. TGF-β & p53 (=> increased levels of CDKIs) |
|
|
Term
|
Definition
| inhibit CDKs => cell cycle arrest |
|
|
Term
| Are CDKs & cyclins oncogenes or tumor suppressor genes? |
|
Definition
|
|
Term
| What happens if CDKIs are inactivated? |
|
Definition
|
|
Term
| Are CDKIs oncogenes or tumor suppressor genes? |
|
Definition
|
|
Term
| Is homo- or hetero- zygous inactivation of CDKIs necessary? |
|
Definition
|
|
Term
| What can cause CDKI inactivation? |
|
Definition
| Inactivation of CDKI itself or of upstream events s.a. TGF-β |
|
|
Term
| What is the over-expression of cyclins & CDKs secondary to? |
|
Definition
|
|
Term
| In which cancer is cyclin E frequently over-expressed in? |
|
Definition
|
|
Term
| In which cancer is CDK4 over-expressed in? |
|
Definition
|
|
Term
| What are reduced levels of CDKIs secondary to? |
|
Definition
| inactivation of the gene or its upstream pathway |
|
|
Term
| Which CDKI nuclear loss is associated with reduced survival in breast cancer? |
|
Definition
|
|
Term
| What is the guardian of the G1-S transition & bottle neck of the pathway? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| phosphorylation => irreversible progress to S phase |
|
|
Term
| Does homo- or hetero- zygous inactivation of Rb need to occur for cancer development? |
|
Definition
|
|
Term
| Why is famililar retinoblastoma considered autosomal dominant? |
|
Definition
it's aheterozygous mutation of the gene.
only inactivation of one allele (the normal allele) is needed to cause the disease |
|
|
Term
| What is the general model of activation of a tumor suppressor gene? |
|
Definition
| Deletion of one allele + inactivation of normal allele with loss of heterozygositiy (LOH) |
|
|
Term
| What is the most common mech. for achieving LOH? |
|
Definition
| DNA methylation => inhibition of transcription of normal allele |
|
|
Term
| What is the target of both CDKIs & CDKs? |
|
Definition
|
|
Term
| How is Rb phosphorylated? |
|
Definition
| G1 cyclins & associated kinases |
|
|
Term
| How does activated Rb (hypophosphorylated) exert it's inhibitory influence on proliferation? |
|
Definition
| binding to transcription factors (s.a. E2F) that stimulate transcription of genes in DNA synthesis |
|
|
Term
Function
chromatin remodeling factors |
|
Definition
| allow the opening up of DNA for gene transcription |
|
|
Term
| In what cancer is Rb frequently inactivated? |
|
Definition
sporadic malignancies s.a. small cell carinoma of lung, breast cancer, & glioblastoma
inherited (rare) => retinoblastoma & predisposition to other tumors |
|
|
Term
| When is sporadic vs. familial retinoblastoma diagnosed? |
|
Definition
Sporadic (unilateral tumor) by 24 mo.
Familial (bilateral tumor) by 8 mo. |
|
|
Term
| How is familial retinoblastoma transmitted? |
|
Definition
| clinically dominant (tho molecular recessive) |
|
|
Term
| What is the most common presentation of retinoblastoma? |
|
Definition
| leukocoria (white reflection of eye) |
|
|
Term
| What characterizes retinoblastoma microscopically? |
|
Definition
| proliferation of primitive cells focally arranged around a central lumen |
|
|
Term
| What further increases patients with retinoblastoma to other tumors? |
|
Definition
|
|
Term
|
Definition
both genes need to be inactivated for the tumor to arise.
What this means for retinoblastoma:
familial - one mutation is inherited & the other is a somatic mutation later in life
sporadic: both mutations are acquired
either case: BOTH ALLELES are inactived
(same is true for ALL tumor suppressor genes) |
|
|
Term
| What (again) is the general mechanism to achieve homozygous inactivation? |
|
Definition
1st allele lost by point mutation/deletion
2nd allele inactivated by LOH (commonly methylation) |
|
|
Term
|
Definition
| analysis of DNA by restriction digestion with endonucleases |
|
|
Term
| Why is LOH selected out by cancer cells? |
|
Definition
| it's a more frequent alteration in human tumors than point mutations |
|
|
Term
| What mechanisms, besides methylation, can cause LOH? |
|
Definition
| gene conversion, gene deletion, non mitotic disjunction, mitotic recombination |
|
|
Term
|
Definition
|
|
Term
| What causes gene methylation? |
|
Definition
| specific DNA mathylases that are transmitted as a genetic trait |
|
|
Term
| What is gene methylation used for in cancer? |
|
Definition
| inactivate tumor suppressor genes |
|
|
Term
| Why are tumors formed in the retina in retinoblastoma & not other tissues where more proliferation occurs? |
|
Definition
some tissues are more sensitive to the effect of the mutation on the post-natal retina has peculiar biological features.
Not to mention, if a patient survives to adulthood, carcinomas are more common |
|
|
Term
| Why is there different penetrance & expressivity of retinoblastoma? |
|
Definition
different Rb families exist
biochemical alterations are different depending on specific mutations |
|
|
Term
|
Definition
| % of individuals with mutation developing clinically |
|
|
Term
|
Definition
| severity of the disease in those who have it |
|
|
Term
| If a child inherits one mutates gene, is it possible that s/he will never acquire the second mutation and/or disease? |
|
Definition
| depends on the severity of the mutation, but it is virtually inevitable due to 80-90% penetrance and the fact that most will develop tumors EVEN WITH retention of normal allele |
|
|
Term
| What cancers are adults with retinoblastoma at an increased risk for? |
|
Definition
soft-tissue sarcomas
osteosarcomas |
|
|
Term
| Why does heterozygous retention of Rb allele also lead to increased tumor formation risk? |
|
Definition
Rb plays a role in apoptosis => prevention of propagation of mutations.
Thus in a cell that's heterozygous this activity is impaired facilitating propagation of mutations |
|
|
Term
| Are there forms of RB that are less clinically severe? |
|
Definition
| yes, but they're more rare |
|
|
Term
| What could cause a Rb mutation to be less clinically severe? |
|
Definition
| reduced levels or reduced biochemical efficiency of gene (as opposed to complete inactivation/loss) via mutations involving regulatory sites in Rb sequence => partial functioning Rb or decreased normally functioning Rb |
|
|
Term
|
Definition
eyes containing tumors:# of carriers
2: every carrier has disease in both eyes
1: on average, each carrier has one affected eye
<1: only some carriers have the disease |
|
|
Term
| What is there a vicious cycle b/w in cancer? |
|
Definition
| abnormal proliferation & accumulation of mutations |
|
|
Term
| What does the mutagenic activity of carcinogens target? |
|
Definition
1) molecules directly controlling proliferation
2) pathways that control the development & propagation of mutations (indirect) |
|
|
Term
| What is the hallmark of malignant tumors compared to normal tissues? |
|
Definition
| high number of mutations => biochemical alterations |
|
|
Term
| Why are most mutations inconsequential? |
|
Definition
| mutations occur randomly & most of the genome is made of noncoding sequences |
|
|
Term
| What mutations are selected out over the time it takes cancer to develop? |
|
Definition
| genes affecting proliferation |
|
|
Term
| What are spontaneous mutations secondary to? |
|
Definition
| errors in DNA replication |
|
|
Term
| What increases a cell's chance of mutation accumulation? |
|
Definition
| the higher the proliferative rate of a cell |
|
|
Term
| How do mutations in pathways that control development & propagation of mutations indirectly facilitate cancer growth? |
|
Definition
| facilitating the development or propagation of mutations in other genes |
|
|
Term
| What are the 2 pathways that control the development & propagation of DNA? |
|
Definition
house-keeping genes:
1) DNA repair enzymes that chemically fix damaged DNA (tagets of p53)
2) enzymes that metabolize carcinogens |
|
|
Term
| What malignancy types are mutations of housekeeping genes associated with? |
|
Definition
| inherited & sporadic malignancies |
|
|
Term
|
Definition
1) endogenous products generated by oxidative stress
2) exogenous products |
|
|
Term
| What is the cacinogenic potential of an agent entirely secondary to? |
|
Definition
| ability to create mutations, which is secondary to the ability to oxidize DNA |
|
|
Term
| What is required for chemicals to acquire it's mutagenic activity? |
|
Definition
| metabolic conversion of an inactive exogenous precursor |
|
|
Term
| What is there for disposal or chemical inactivation of carcinogens? |
|
Definition
|
|
Term
| What happens after a carcinogen is absorbed? |
|
Definition
distributed to body &
1)metabolized to form either an inactive or more toxic compound
or
2) inactivated by conjugation to other products & excreted
If a more toxic metabolite is formed, they are re-distributed to the body & interact with other molecules. They then can cause mutations. |
|
|
Term
| What is required for benzopyrene (of cigarette smoke) to become carcinogenic? |
|
Definition
| metabolic conversion via oxidation |
|
|
Term
| What is the carcinogenic activity of benzopyrene secondary to? |
|
Definition
| presence of a highly reactive oxygen species (electrophilic - therefore can react with molecules containing a free e- pair) |
|
|
Term
| What does the ultimate carcinogen of benzopyrene interact with? |
|
Definition
| with DNA to form large 3D complex (DNA adduct) => distortion of DNA helix & facilitates mutations |
|
|
Term
| When are oxidative compounds a normal by product of metabolism? |
|
Definition
|
|
Term
| *What causes oxidative stress? |
|
Definition
| an imbalance b/w endogenous oxidative compunds (ROS) & scavenging systems that have the potential of metabolizing these products |
|
|
Term
|
Definition
| wide spectrum of pathological conditions from aging to cancer |
|
|
Term
| What incrases production of ROS? |
|
Definition
|
|
Term
Why is there a link b/w gastroesophageal reflux & cancer?
ulcerative colitis & cancer? |
|
Definition
|
|
Term
| What cancer is linked to gastroesophageal reflux? |
|
Definition
| esophageal adenocarcinoma |
|
|
Term
| What cancer is associated with ulcerative colitis? |
|
Definition
|
|
Term
| Why do drugs s.a. aspirin & other NSAIDs decrease risk of cancer? |
|
Definition
|
|
Term
| How are ROS & exogenous carcinogens related? |
|
Definition
| electrophilic & highly reactive compunds |
|
|
Term
| What is the most important pathway in removal of oxidative species? |
|
Definition
|
|
Term
|
Definition
| acts are a reducing agent => donates electrons to a ROS & reduces it to OH |
|
|
Term
|
Definition
|
|
Term
| With which cancer is GSH loss common? |
|
Definition
|
|
Term
| What doe individuals with polymorphic variants of GSH with reduced activity have an increased risk of? |
|
Definition
|
|
Term
Function
DNA repiar enzymes |
|
Definition
|
|
Term
| What happens if there is a mutation in DNA repair enzymes? |
|
Definition
severe function impiarment => high cancer incidence
(inherited variants with slightly reducded activity => only slight increase in susceptibility) |
|
|
Term
| What cancers are associated with DNA repair enzyme mutations? |
|
Definition
|
|
Term
| What 3 familial syndromes are involved in alterations of DNA repair pathways? |
|
Definition
1) HNPCC (Heriditary Non-Polyposis Colon Cancer)
2) Xeroderma Pigmentosum
3) BRCA syndrome |
|
|
Term
|
Definition
| mutagens & by hypoxia (conditions that signal the possible development of malignancy) |
|
|
Term
|
Definition
| prevents the development & propagation of mutations by controlling apoptosis, DNA repair & cell cycle |
|
|
Term
| What are inherited mutations in p53 (s.a. Li Fraumeni syndrome) associated with? |
|
Definition
|
|
Term
| What type of cancer is p53 mutations common in? |
|
Definition
|
|
Term
| How can functional inactivation of p53 occur? |
|
Definition
| interaction with other molecules (i.e. proteins produced by HPV) |
|
|
Term
| What does cancer depend on crucially? |
|
Definition
|
|
Term
| What is a tumor's ability to induce angiogenesis directly proportional to? |
|
Definition
|
|
Term
| Why does p53 sense hypoxia? |
|
Definition
| it's a sign of possible impending malignancy |
|
|
Term
|
Definition
1) p21 (CDKI)
2) GADD 45 (DNA repair enzyme)
3) BAX (pro-apoptotic gene) |
|
|
Term
| What induces cell cycle arrest? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the biological significance of p53 activating p21 & GADD45? |
|
Definition
| prevent cell from centering S phase & therefore from propagating it's mutation & allows time to repair DNA damage |
|
|
Term
| When would p53 activate BAX? |
|
Definition
| if the repair pathway fails => prevention of cell passing on mutations by undergoing death |
|
|
Term
| is p53 an oncogene or tumor suppressor gene? |
|
Definition
| TSG (meaning subject to 2 hit model) |
|
|
Term
| What is the most commonly altered tumor suppressor gene? |
|
Definition
| p53 (~50% of all malignant tumors) |
|
|
Term
|
Definition
| development of wide spectrum of tumors |
|
|
Term
| What alternative mechanisms are used to inactivate p53 are selected out in cancer? |
|
Definition
1) Binding HPV oncogenic proteins (cervical cancer)
2) binding to other proteins (MDM2) that target p53 for proteolytic degradation (sarcomas) |
|
|
Term
| What other key player in tumor biology does HPV oncoproteins bind to & inactive? |
|
Definition
|
|
Term
| What lessons are learned from studying inherited cancer syndromes? |
|
Definition
are inherited mutations exist that are linked to malignancies with high percentage of affected carriers with inactivating mutations in genes with crucial roles in DNA repair &/or cell cycle control
(high penetrance, high expressivity, low frequency)
and are transmitted as mendelian traits |
|
|
Term
| *What does it mean that inherited cancers are transmitted as Mendelian traits? |
|
Definition
| one gene corresponds to one disease where the contribution of genotype to phenotype is overwhelming |
|
|
Term
| How much of all cancer is 100% inherited? |
|
Definition
|
|
Term
| What are the 3 types of etiologic agents of malignancies? |
|
Definition
1) 100% genetic
2) 100% environmental
3) multi-factorial: genetic predisposition & given a specific environmental exposure |
|
|
Term
| What happens to the cancer risk for those with a genetic predisposition? |
|
Definition
| small increased risk (low expressivity with low penetrance) |
|
|
Term
| Are those with genetic predisposition inherited mendelianly? |
|
Definition
| No. They're polymorphic with a high frequency in the population |
|
|
Term
|
Definition
| 1% or more of the population |
|
|
Term
| What genes display genetic polymorphisms for cancer? |
|
Definition
1) detoxification
2) DNA repair
3) cell cycle regulation |
|
|
Term
| What can polymorphic varients in detoxification, DNA repiar & cell cycle regulation result in? |
|
Definition
proteins with altered activity that may confer slightly increased risk of cancer
(an environmental exposure is needed to cause malignant tumor, but the threshold is lower) |
|
|
Term
| What explains why persons with similar environmental carcinogenic exposures have a wide variation in incidence & severity of cancers? |
|
Definition
|
|
Term
| *What is there an interplay between in the multifactorial model? |
|
Definition
polymorphic variants of enzymes
additive effects of mutiple genetic variants
environmental exposure |
|
|
Term
| What other factors may potentially affect development of cancer? |
|
Definition
1) general clinical conditions of the patient
2) nutritional status
3) early detection
4) co-morbid conditions
5) *his/her immune competence |
|
|
Term
| What is the premalignant phase of cancer? |
|
Definition
|
|
Term
| Does metastases ever occur in premalignant phases? |
|
Definition
|
|
Term
def
molecular model of cancer |
|
Definition
| inherited &/or acquired factors contribute (in varying degrees) to allow the expansion of a clone & it's accumulation of genetic abnormailities => alterations of cell biology (esp. proliferation) |
|
|
Term
| What parallels the molecular model? |
|
Definition
|
|
Term
|
Definition
2 phases:
1) premalignant/dysplastic (accumulation of normal cells within an epi)
2) malignant (local invasion &/or distant spread) |
|
|
Term
|
Definition
| increase in # of NORMAL cells |
|
|
Term
| is hyperplasia a precursor for malignancy? |
|
Definition
|
|
Term
| Is hyperplasia reversible? |
|
Definition
|
|
Term
|
Definition
| tissue response to specific stimulus (usually hormone or inflammation) |
|
|
Term
| When can hyperplasia be a premalignant condition? |
|
Definition
| when preceeded by a modifying adjuctive s.a. atypical, complex |
|
|
Term
|
Definition
| for of dysplasia in uterus or breast |
|
|
Term
|
Definition
| dysplasia of uterus & is premalignant |
|
|
Term
|
Definition
replacement of one differentiated epi with another
(cells look NORMAL, but are not the type normally seen in that location) |
|
|
Term
| Can metaplasia be a premalignant condition? |
|
Definition
|
|
Term
|
Definition
| epi. leison characterized by the accumulation of ABNORMAL cells (cancer-like, at the architectural & cellular level) in the epithelium WITHOUT invasion |
|
|
Term
| Can dysplasia lead to malignancy? |
|
Definition
|
|
Term
| What are the abnormal achritectural & cellular features of dysplasia? |
|
Definition
1) increased cellularity
2) accumulation of abnormal cells
3) increased ratio of proliferation:differentiating cells
4) altered polarity
5) abnormal nuclear morphological features
6) increased N:C ratio |
|
|
Term
| What is grading of dysplasia based on? |
|
Definition
| extend of distribution of abnormal/dysplastic cells within epi. |
|
|
Term
| What is the potential of dysplasia developing into overt invasive carinoma proportional to? |
|
Definition
|
|
Term
| Where is proliferation normally limited to? |
|
Definition
|
|
Term
| Is the N:C ratio high or low in basal cells? |
|
Definition
|
|
Term
| What happens to the N:C ratio as you approach the surface in normal tissue? |
|
Definition
|
|
Term
| What intermediate filaments accumulate in the cytoplasm close to the surface in normal squamous epi? |
|
Definition
|
|
Term
| What is accumulation of keratin evidence of? |
|
Definition
|
|
Term
Where in normal squamous epithelium is proliferation highest?
differentiation? |
|
Definition
pro: basal cells
dif: surface |
|
|
Term
| What happens to overall cellularity in dysplasia? |
|
Definition
|
|
Term
| What cell types are increased and spread across the epi. in dysplasia? |
|
Definition
| mitoses & abnormal, basal-like cells with high N:C ratios |
|
|
Term
| When can mitoses & abnormal cells be found at the surface in dysplasia? |
|
Definition
|
|
Term
| What does increased number & spread of mitoses & abnormal cells imply? |
|
Definition
| reduced differentiation & increased proliferation |
|
|
Term
| Where can kertatinization occur in dysplasia? |
|
Definition
| not in the surface, per normal, but midway or at its base |
|
|
Term
| What does abnormal placesment of keratinization in dysplasia imply? |
|
Definition
| abnormal orientation of cells (i.e. abnormal polarity) |
|
|
Term
| What happens to nuclei in dysplasia? |
|
Definition
pleomorphism (variation in size & shape) - even giant cells
hyperchromasia (increased density of chromatin) |
|
|
Term
| What is the grading of dysplasia based on? |
|
Definition
extent of distribution of the abnormal cells in
1) 4 tiers
(mild, moderate, secere, CIS)
2) 2 tiers
(low, high) |
|
|
Term
| How is severe vs. CIS determined? |
|
Definition
| more extensive cytological atypia present in CIS |
|
|
Term
| How can dysplasia be graded? |
|
Definition
1) tissue biopsy
2) examination of isolated smears (PAP smear) |
|
|
Term
| Which cancers are easily screened/have earlier detection? |
|
Definition
| Those with easy access for sampling s.a. uterine cervix, URT, colon |
|
|
Term
| What does it mean that a molecular progression mirrors the morphological progression of cancer? |
|
Definition
| cells accumulate genetic abnormalities |
|
|
Term
| What 2 sites is dysplasia rather peculiar? |
|
Definition
|
|
Term
| Where is the lamina propria in the colon? |
|
Definition
| in the mucosa, surrounding crypts |
|
|
Term
| What separated the mucosa from the submucosa in the colon? |
|
Definition
|
|
Term
| *Why can't cells of the mucosa in the colon metastasize? |
|
Definition
no lymphatics or venules in lamina propria
(note: it can in the stomach) |
|
|
Term
| When does colon cancer become invasive? |
|
Definition
| once it trespasses into the muscularis mucosae |
|
|
Term
| What is invasive carcinoma of the colon often associated with? |
|
Definition
|
|
Term
|
Definition
| deposition of dense fibrous tissue |
|
|
Term
| What happens in adenomas of the colon? |
|
Definition
abnormal cells accumulate withing the crypts that retain overall shape & remain separated by the stroma of lamina propria.
underlying muscularis mucosae is intact |
|
|
Term
| Are adenomas of the colon that spread into the lamina propria considered fully malignant? |
|
Definition
| no b/c unable to metastasize |
|
|
Term
| What are the cytological & histological features of colon adenomas? |
|
Definition
| ~to other hysplastic tissue |
|
|
Term
| What histological border is tresspassed in progression from dysplasia to cancer in squamous epithelium? |
|
Definition
|
|
Term
What histological border is tresspassed in progression from dysplasia to cancer in the colon?
in the breast? |
|
Definition
colon: muscularis mucosae - trespassed
breast: myoepithelial cell - lost |
|
|
Term
| Where are breast myoepithelial cells normally found? |
|
Definition
| outer layer in normal ducts |
|
|
Term
| Is the myoepithelial layer of breast preserved in dysplasia? |
|
Definition
|
|
Term
| What is the lower & higher risk dysplastic conditions of the breast? |
|
Definition
lower: atypical ductal hyperplasia
higher: ductal carcinoma in situ |
|
|
Term
| Where is the site of origin of the most common type of invasive breast cancer? |
|
Definition
mammary ducts
(second most common is lobular carcinoma in lobules) |
|
|
Term
Fuction
myoepithelial cells of ducts |
|
Definition
| allow breast sevretions to be propelled into the excretory system with features of both wpithelial cells & contractile cells |
|
|
Term
| What is the DCIS subtype with the highest malignancy potential? |
|
Definition
comedo-type DCIS with a necrotic, pus-like center
(comedone = zit) |
|
|
Term
| Which oncogene overexpression is often seen in comedo-type DCIS? |
|
Definition
|
|
Term
| Does ADH or DCIS have a higher postential to become breast cancer? |
|
Definition
|
|
Term
| What does cancer often arise in the background of? |
|
Definition
multifocal precursor leisons
(i.e. patients with one leison are like to to develop more than one)
[this implies cancer Tx should cover a wide range] |
|
|
Term
| Is progressive dysplasia into invasive carcinoma a slow or fast process? |
|
Definition
| slow (decades, but varies among patients) |
|
|
Term
| Do all dysplastic leisons become carinomas given enough time? |
|
Definition
| no, they may arrest or regress |
|
|
Term
| Do all dysplastic leisons have a known/detectible pre-invasive phase? |
|
Definition
| no, s.a. small cell carinoma of the lung |
|
|
Term
| Why is early detection of some cancers more important than others? |
|
Definition
| some are more aggressive & more likely to kill |
|
|
Term
| What 3 factors influence progression from dysplasia to overt cancer? |
|
Definition
1) early detection/Tx
2) potency of carinogenic agent(s)
3) biological features of the host (s.a. genetic polymorphisms, immune competence/surceillance, exercise, diet, etc) |
|
|
Term
| Specifically, what 5 factors influcence the pregression of cervical intraepithelial neoplasia (CIN)? |
|
Definition
1) access to early detection/Tx/vaccination
2) viral serotype (low/high risk)
3) immunocompetence
4) polymorphism of p53
5) others (s.a. smoking, oral contraception, HLA type, genital inf. promiscuity, age of first intercourse) |
|
|
Term
| Which serotypes of HPV are high risk for cervical cancer? |
|
Definition
|
|
Term
| Why do HPV serotypes 16 & 18 have a higher carcinogenic capability? |
|
Definition
| they have an ability to bind with high affinity & thus inactivate p53 & Rb |
|
|
Term
| How do the polymorphic variations of p53 influence cervical cancer risk? |
|
Definition
| some p53 polymorphisms are more susceptible to HPV serotypes 16 & 18 than others |
|
|
Term
| What is the evidence of the link of immunocompetence to cancer? |
|
Definition
| AIDS paitents & iatrogenic immunocompetence (transplant patients) are more likely to develop cancer |
|
|
Term
| What are the 2 AIDS defining malignancies? |
|
Definition
1) Non-Hodgkin lymphompa
2) Kaposi sarcoma
(increased risk for cervical carcinoma) |
|
|
Term
| What is related to better prognosis in some cancers in regards to immunity? |
|
Definition
|
|
Term
| How do the cancer & the immune system interplay? |
|
Definition
|
|
Term
| When do clinical presentation & Dx occur with most cancer? |
|
Definition
when the tumor has developed large size & accumulated multiple genetic abnormalities, spread locally/systemically
(high stage) |
|
|
Term
| What causes the differences in aggressiveness & intrinsic potential to progress of cancers? |
|
Definition
1) tissue organ
2) individual variations among individuals |
|
|
Term
| When can patient's recieve cancer Tx? |
|
Definition
|
|
Term
| How is the initial stage evaluation done? |
|
Definition
| combination of pathological evaluation & non-invasive imaging procedures, but finalized with pathological tissue examination (& local lymph nodes resected and examined) |
|
|
Term
|
Definition
tumor, nodes, metastases
most commonly used system to indicate tumor burden & represents overall the best predictor/prognosis of cancer |
|
|
Term
| What does increasing stage indicate? |
|
Definition
|
|
Term
| What is the difference b/w tumor stage & grade? |
|
Definition
stage: WHERE the tumor's been
grade: WHAT the tumor's like |
|
|
Term
| What does the T stage indicate? |
|
Definition
|
|
Term
| What does the N stage indicate? |
|
Definition
| extent of lymph node involvement |
|
|
Term
| What does the M stage indicate? |
|
Definition
| metastases are either present (1) or absent (0) and is an ominous sign regardless of the T or N stage |
|
|
Term
| How is the classification of tumors primarily done? |
|
Definition
histological examination:
HE, immunohistochemistry, special stains, ultra structure |
|
|
Term
| How is cancer type determined? |
|
Definition
| pattern recognition s.a. architectural & cellular features |
|
|
Term
| How is extent of differentiation determined? |
|
Definition
| how reminescent it is of a specific tissue type |
|
|
Term
| How is subtyping determined? |
|
Definition
distinctive morphological features
refined observing growth pattern & fatures of individual cells |
|
|
Term
| What among architectural patterns are the most important features evaluated to distinguish benign from malignant? |
|
Definition
| invasiveness & orderliness of cells |
|
|
Term
| What is seen in squamous cell carcinoma? |
|
Definition
| keratinization &/or intracellular bridges |
|
|
Term
| What binds intracellular bridges? |
|
Definition
|
|
Term
|
Definition
| malignant tumor showing evidence of glandular differentiation |
|
|
Term
| How is differentiation evident in an adenocarcinoma? |
|
Definition
architectural level: arrangement of cells around a central lumen
cellular level: presence of intracellular mucin |
|
|
Term
| What is a common feature of all carcinomas |
|
Definition
| they are surrounded by very dense fibroblastic stroma (desmoplasia) => makes them firm & fixed to underlying tissue planes at palpatation, intraoperatively, & gross examination of removed specimen |
|
|
Term
| What is a common feature of sarcomas? |
|
Definition
| spindle cell morphology (enlongated, cigar shaped) |
|
|
Term
| What is a common feature of lymphomas? |
|
Definition
| lack a stromal response & are characterized by polygonal or round cells with high N:C ratios that frow in a large solid sheet (cells more likely to accumulate in lymph nodes, bone marrow) |
|
|
Term
| What is the most common ancillary technique used to classify tumors in pathology & to direct therapy? |
|
Definition
| Immunohistochemistry (IHC) |
|
|
Term
| How is IHC used to direct therapy? |
|
Definition
| testing presence in a tumor of molecules |
|
|
Term
|
Definition
| lab technique based on Ag-Ab reaction linked to a chromagen - used to identify origin of metastases & therapeutic targets |
|
|
Term
What are the results of IHC linked to?
Why? |
|
Definition
morphological features by the pathologist & clinical info from the physician since no test is 100% specific or sensitive
(and origination still might not be able to be determined) |
|
|
Term
| What diagnostic aid has veen used recently to complement & aid pathological evaluation of tumors? |
|
Definition
| tumor-specific genetic abnormalities |
|
|
Term
| What does histological differences (morphologically) b/w tumors represent? |
|
Definition
| biological differenes of the individual, organ type, cancer type |
|
|
Term
| Why is ID of gene ecpression profile of tumors being studied? |
|
Definition
| to provide novel tumor classification |
|
|
Term
| What is used clinically to Dx & classify tumors? |
|
Definition
|
|
Term
|
Definition
| the degree of differentiation of a tumor (how much does tumor resemble its normal counterpart) |
|
|
Term
| Wgere us tumor grade reflected? |
|
Definition
| in the architecture (how orderly, cytological features, how abnormal do individual cells look) |
|
|
Term
| What determines the grade in squamous cell carcinoma? |
|
Definition
| how much keratinization is present |
|
|
Term
| What determines grade in adenocarcinoma? |
|
Definition
| extend of glandular formation |
|
|
Term
|
Definition
| no resemblance of the tumor to any normal organs (i.e. undifferentiated) |
|
|
Term
| When is grade a good prognostic tool? |
|
Definition
1)limited stage cancers
2)cancers with specific/quantifiable criteria (prostate/breast)
3)sarcoma (part of staging)
4)within same stage |
|
|
Term
| Why is there inter and intra observer variability in grading tumors? |
|
Definition
| lack of clearly indentified, standard, & quantifiable criteria |
|
|
Term
|
Definition
score in prostate cancer
sum of major & minor growth pattern grades |
|
|
Term
|
Definition
| system for grading breast cancer |
|
|
Term
The prognosis of a patient with well differentiated (low grade) adenocarcinoma of the breast & liver metastasis compared to a patient with a larger poorly differentiated (high grade) carcinoma & no liver metabolism is:
A) depends on the presence of metastases to axillary lymph nodes
B) depends on the ER status
C) Better
D) Worse |
|
Definition
|
|
Term
| How is grade of sarcomas determined? |
|
Definition
degree of differentiation (~ to that of carcinomas), mitotic rate, & extent of necrosis
degree of vessel formation helps |
|
|
Term
| Why is grading included in the staging process of sarcomas? |
|
Definition
| good prognostic indicator |
|
|
Term
| Can sarcomas also be undifferentiated? |
|
Definition
| yes, some are always high grade |
|
|
Term
|
Definition
| high grade sarcoma by definition of childhood |
|
|
Term
| What exception is there to the aggressiveness-differentiation coorelation in sarcomas? |
|
Definition
| Nasopharyngeal angiofibroma is a stromal tumor endowed with potential to recur & widely invade locally, in spite of being well differentiated, with bland morphology (tho no potential for metastaes) |
|
|
Term
What is the normal epithelium of endocervix?
ectocervix? |
|
Definition
endo: simple columnar mucinous
ecto: stratified squamous |
|
|
Term
What is the endocervix connected to?
What is the ectocervix connected to? |
|
Definition
endo: lower uterus
ecto: vagina |
|
|
Term
| What part of the cervix have you reached when you find submucosal glands? |
|
Definition
|
|
Term
What is it called if endocervix simple columnar epithelium is coverted to stratified squamous?
What causes it? |
|
Definition
| squamous metaplasia caused by chronic irritation |
|
|
Term
|
Definition
potentially premalignant condition with failure of normal maturation, loss of polarity and cytological features of atypia, confined to an epithelial surface (NO invasion)
(looks abnormal) |
|
|
Term
|
Definition
replacement of one mature cell by another without cytological atypia or premalignant potential
(looks normal, but isn't) |
|
|
Term
| Where are mitotic figured usually found in epithelium? |
|
Definition
|
|
Term
| What does dysplasia look like? |
|
Definition
enlarged, pleomorphic, hyperchromatic nuclei
high N:C ratio
loss of polarity
more basophilic
mitosis near surface
loss of differentiation |
|
|
Term
| What is the gross apprearance of a malignant tumor? |
|
Definition
poorly circumscribed
irregular, infiltrative border |
|
|
Term
|
Definition
|
|
Term
What product is seen in epithelial dysplasia indicating some differentiation?
What does it look like? |
|
Definition
keratinization
large, pink, polygonal cells in a mosaic pattern |
|
|
Term
| How do you differentiate b/w a benign & malignant tumor grossly? |
|
Definition
benign: well circumscribed, homogeneous-appearing, often surrounded by fibrous capsule
malignant: poorly delineated, infiltrative, areas of necrosis & hemorrhage |
|
|
Term
def
benign glandular neoplasm |
|
Definition
|
|
Term
|
Definition
| soild leison that protrudes from a surface, frequently a mucosal surface |
|
|
Term
| What are the 2 types of polyps? |
|
Definition
|
|
Term
| What is the difference b/w pedunculated & sessile polyps? |
|
Definition
pedunculated: round & connected to mucosa by thin stalk
sessile: boradbased & rather flat |
|
|
Term
|
Definition
| loss of cellular differentiation |
|
|
Term
| If someone develops a pedunculated colonic polyp, are they more likely to develop an invasive glandular malignancy? |
|
Definition
yes, since these glandular epithelial cells have already undergone mutations and other areas of the colon could have been exposed to the same carcinogens
at risk for adenocarcinoma |
|
|
Term
| What Tx regimen should be recommended for a patient with pendunculated polyps of the colon? |
|
Definition
dietary modification
follow up colonoscopies (frequency determined by # of polyps, size, degree of dysplasia, family Hx) |
|
|
Term
def
invasive glandular malignancy of the colon |
|
Definition
|
|
Term
|
Definition
| determining extent of growth & spread for Tx & prognosis |
|
|
Term
| What happens to the proximal colon in an adenocarcinoma? |
|
Definition
| distention from obstruction |
|
|
Term
|
Definition
| determinging extent of differentiation |
|
|
Term
| What infiltrative nests surround the tumors in carcinomas? |
|
Definition
chronic inflammatory cells
desmoplasia |
|
|
Term
|
Definition
| fibroblastic proliferation with production of collagen |
|
|
Term
| Why might colonic tissue be found in the liver? |
|
Definition
| metastases enter portal system |
|
|
Term
def
benign smooth muscle neoplasm |
|
Definition
|
|
Term
| What are the 3 categories that human disease cause can be classified into? |
|
Definition
1) environmental
2) genetically
3) both genetics & environment |
|
|
Term
| What are the 5 categories of genetic diseases? |
|
Definition
1) resulting from expressed mutation in single gene of large effect w/ Mendelian inheritance
2) complex multifactorial disease that results from interaction of multiple genes & environmental factors
3) chromosomal disorders
4) resulting from single gene disorders w/ non-classic patterns of inheritance
5) resulting from mitochondrial disorders |
|
|
Term
|
Definition
| derived from parents & are transmitted in the germline & therefore familial |
|
|
Term
|
Definition
| born with a disease (not necissarily genetic disease) |
|
|
Term
| How much of the DNA is shared b/w individuals? |
|
Definition
|
|
Term
| What does the .1% difference in genomes in individuals allow? |
|
Definition
|
|
Term
| What is the most common form of DNA variation? |
|
Definition
| single nucleotide polymorphism (SNP) |
|
|
Term
|
Definition
|
|
Term
| What can a mutation in germ cells lead to? |
|
Definition
| progeny => inherited disease |
|
|
Term
| What can a mutation in somatic cells lead to? |
|
Definition
| cancer & some congenital malformations |
|
|
Term
| What can increase the rate of spontaneous DNA mutations? |
|
Definition
1) radiations
2) chemicals
3) viruses |
|
|
Term
| What are the 3 classifications of mutations? |
|
Definition
1) gene mutations
2) genome mutations
3) chromosome mutations |
|
|
Term
| What can cause gene mutations? |
|
Definition
1) point mutations
2) framshift mutations
3) trinucleotide repeats |
|
|
Term
| what can cause alterations in chromosomes (cytogenic or karyotypic abnormalities)? |
|
Definition
1) genome mutations
2) chromosome mutation |
|
|
Term
| Which mutations can be detected by karyotype analysis? |
|
Definition
| alterations in chromosomes |
|
|
Term
| What is the link b/w mutation & disease? |
|
Definition
1) predisposition
2) direct cause
3) manifestation |
|
|
Term
| What do all Mendelian disorders result from? |
|
Definition
| expressed mutation in single genes of large effect |
|
|
Term
| What are the 3 transmission patterns of single gene disorders? |
|
Definition
1) Autosomal dominant
2) autosomal recessive
3) x-linked |
|
|
Term
| What can modify the clinical features of an autosomal dominant disorder? |
|
Definition
| penetrance & expressivity |
|
|
Term
| Which tranmission pattern is usually mutations to enzymatic proteins? |
|
Definition
|
|
Term
| What 6 mechanisms are involved in the pathogenesis of single gene disorders? |
|
Definition
1) lysosonal storage diseases
2) non-lysosomal enzyme defects
3) defects in membrane receptors
4) defects in transport proteins
5) defects in structural proteins
6) defects in regulatory proteins of cell growth & differentiation |
|
|
Term
|
Definition
1) abnormal accumulation of metabolites
2) decreased amount of end product necessary for normal function
3) failure to inactivate a tissue damaging substance |
|
|
Term
|
Definition
single membrane bound organelles that contain degradative hydrolases that function in the acid milieu of the lysosome.
They are considered the "intracellular digestive tract" involved in the turnover of macromolecules |
|
|
Term
| Where are lysosomal enzymes synthesized? |
|
Definition
| ER & transported to golgi for post-translational modifications (inc. attachment of terminal mannose-6-phosphate) => golgi recognition of this modification => bind to receptor & pinch off to fuse with lysosomes |
|
|
Term
| What causes lysosomal storage diseases (LSDs)? |
|
Definition
| lack of any protein essential for the normal function of lysosomes |
|
|
Term
| What determines the distribution of non-degraded material in a LSD? |
|
Definition
1) tissue where most of the material to degrade is found
2) tissue when most of the degradation takes place |
|
|
Term
|
Definition
| by macromolecule undergoing degradation (or lacking) |
|
|
Term
def
mucopolysaccharides (MPSs) |
|
Definition
| heterogeneous group of macromolecules composed of GAGs |
|
|
Term
def
GAGs
(glycosaminoglycans) |
|
Definition
long chain CHOs with disaccharide repeating units that include:
dermatan sulfate (heart, vessels, skin)
heparin sulfate (lung, arteries, cell surfaces)
ketatan sulfate (carilage, cornea, discs)
chondroitin sulfate
hyaluronic acid |
|
|
Term
|
Definition
| GAGs attached to proteins |
|
|
Term
|
Definition
| structural integrity of ECM |
|
|
Term
| What secrete proteoglycan? |
|
Definition
| GAG-synthesizing cells (fibroblasts, endothelial cells, leukocytes) |
|
|
Term
| What happens to proteoglycans not secreted? |
|
Definition
| degraded by lysosomal hydrolases |
|
|
Term
| What happens when there's an accumulation of proteoglycans due to a lysosomal enzyme deficiency? |
|
Definition
accumulation in lysosomes
free GAGs appear in urine |
|
|
Term
| Are MPS disorders static or progressive? |
|
Definition
|
|
Term
| What clinical features are common to most MPS disorders? |
|
Definition
1) multisystem involvement
2) organomegaly
3) abnormal facies
4) joint stiffness/deformity
5) MR
6) autosomal recessive |
|
|
Term
What is the only MPS that is NOT autosomal recessive?
What inheritance pattern is it? |
|
Definition
| Hurler's syndrome - X-linked recessive |
|
|
Term
|
Definition
1) Onset: 6-8 mo
2) severe motor & mental retardation
3) common: resp. disease, coarse facial features, ophthalmic disease (early corneal clouding), dwarfing, stiff joints, hepatosplenomegaly, CNS disease, deafness
4) death by age 10
5) urinary excretion of dermatan & heparan sulfate |
|
|
Term
| What enzyme is deficient in Hurler's syndrome? |
|
Definition
|
|
Term
|
Definition
1) Onset: early infancy/childhood
2) Sx: similar to Hurler but less severe
3) common: dwarfing, coarse facial features, progressive deafness, stiff joints
4) NO corneal clouding
5) urinary excretion of dermatan & heparan sulfate |
|
|
Term
| What lysosomal enzyme is deficient in Hunter syndrome? |
|
Definition
|
|
Term
| What are the 2 MPS diseases we need to know? |
|
Definition
|
|
Term
|
Definition
| diseases that result from a defect in metabolism of sphingolipids |
|
|
Term
|
Definition
| long-chain amino alcohols (sphingosine) attached to a fatty acid to produce a complex lipid (ceremide). |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| ceramide + plysaccharide + 1 or more N-acetylneuraminic acid |
|
|
Term
| What are the 3 sphingolipidoses we need to know? |
|
Definition
| 1) Niemann-Pick
2) GM1 gangliosidoses
3) GM2 gangliosidoses |
|
|
Term
|
Definition
| lipids distributed throughout the body as a structural component of cell membranes |
|
|
Term
| What enzyme is deficient in Niemann-Pick disease? |
|
Definition
|
|
Term
| What is the result of sphingomyelinase deficiency in Niemann-Pick disease? |
|
Definition
| lysosomal accumulation of sphingomyelin in reticuloendothelial cells & other cells in the body |
|
|
Term
| What are the different types of Niemann-Pick disease? |
|
Definition
I (A & B) - caused by deficiency in sphingomyelinase
II (C & D) - caused by a defect in cholesterol esterification |
|
|
Term
Which type of Niemann-Pick is the severe infantile form?
the chronic visceral form?
the more common form? |
|
Definition
A- severe infantile
B- chronic visceral
C- more common |
|
|
Term
| Of the type I Niemann-Pick diseases, which is more common, A or B? |
|
Definition
|
|
Term
Sx
Type A Niemann-Pick Disease |
|
Definition
1) Onset: w/in 1st weeks of life
2) severe neurologic impairment (hypotonia, progrssive psychomotor retardation)
3) failure to thrive
4) marked hepatosplenomegaly
5) 50% will have macular cherry red spot
6) brain becomes atrophic
7) death by 3-4y |
|
|
Term
| What will be seen accumulating in many tissues (esp. liver, lymph nodes, kidney, bone marrow, PNS & CNS neurons) in Type A Niemann-Pick? |
|
Definition
|
|
Term
| Which ancestry is Type A Niemann-Pick more common? |
|
Definition
|
|
Term
Sx
Type B Niemann-Pick disease |
|
Definition
1) Onset: infancy/childhood
2) organomegaly, NO CNS involvement
3) usually survive to adulthood |
|
|
Term
| Which ancestry is Type B Niemann-Pick more common? |
|
Definition
|
|
Term
| What gene is affected in Type C Niemann-Pick? |
|
Definition
|
|
Term
|
Definition
| encodes a protein that is involved in the cellular trafficking of exogenous cholesterol |
|
|
Term
| What is accumulated due to the defect in NPC-1 in Type C Niemann-Pick? |
|
Definition
| lysosomal accumulation of unesterified cholesterol |
|
|
Term
|
Definition
variable disease that affects viscera & CNS
Classic form:
1) Onset: 2-4y
2) seizures, ataxia, supranuclear palsy, mental deterioration
3) bone marrow contains Niemann-Pick cells & sea blue histiocytes
4) death b/w 5-15y |
|
|
Term
| What are the 2 types of GM1 gangliosidoses? |
|
Definition
I: infantile, generalized
II: juvenile |
|
|
Term
| Sx
GM1 infantile, generalized gangliosidosis |
|
Definition
1) Onset: early infancy
2) developmental arrest a few months after birth, progressive neurological deterioration, seizures
3) course facial features, hepatosplenomegaly, dysostosis multiplex
4) 50% have macular cherry red spot
5) death by 2y |
|
|
Term
| Which enzyme is deficient in GM1 infantile gangliosidosis? |
|
Definition
|
|
Term
| What happens when β-galactosidase is deficient in GM1 infantile gangliosidoses? |
|
Definition
| accumulation of ganglioside in neurons resulting in progressive atrophy & neuronal swelling with subsequent loss of neurons & gliosis |
|
|
Term
| What role do β-galactosidases have in tissues other than neurons? |
|
Definition
role in degradation od MPSs
widespread visceral storage
cardiac involvement with cardiomegaly
nodular thickening of mitral & tricuspid valves (esp. at free margins) |
|
|
Term
| How is a presumptive Dx of GM1 infantile gangliosidosis made? |
|
Definition
|
|
Term
| Sx
GM1 juvenile gangliosidosis |
|
Definition
1) Onset: ~1 yr
2) Sx ~ to type I (infantile)
3) death by 5y |
|
|
Term
| What are the 3 types of GM2 gangliosidoses? |
|
Definition
| 1) Tay-Sachs
2) Sandhoff's
3) GM2 Activator Deficiency Gangliosidosis |
|
|
Term
| What causes GM2 gangliosidoses? |
|
Definition
| inability to catabolize GM2 gangliosides that requires 3 polypeptides encoded by 3 different loci
(a different enzyme at 3 different loci => 3 different possible deficiencies => 3 different diseases) |
|
|
Term
| What enzyme is deficient in Tay-Sachs? |
|
Definition
| α subunit of Hexaminidase A |
|
|
Term
| What enzyme is deficient in Sandhoff's? |
|
Definition
| β subunit of Hexaminidase A |
|
|
Term
| What is deficient in GM2 Activator deficiency gangliosidosis? |
|
Definition
|
|
Term
|
Definition
1) normal at birth => rapidly progressive neurodegenerative disease with dementia & blindness
2) macular cherry red spot
3) death by 2-3y |
|
|
Term
| Where do GM2 gangliosides accumulate in GM2 gangliosidoses? |
|
Definition
many tissues, but neurons & retina dominate
neurons: ballooned & contain cytoplasmic vacuoles. EM shows lysosomes containing whorled material. Brain initially becomes large, then atrophic |
|
|
Term
| What ancestry is seen to more affected by GM2 gangliosidoses? |
|
Definition
Ashkenazi Jewish
French Canadians
Cajuns |
|
|
Term
| What are the 2 major sulfatidoses? |
|
Definition
1) metachromatic leukodystrophy
2) multiple sulfatase deficiency |
|
|
Term
| What enzyme is deficient in metachromatic leukodystrophy? |
|
Definition
|
|
Term
|
Definition
| hydrolyses galactocerebroside sulfate to galactocerebroside (found in myelin membranes) |
|
|
Term
| What is required for arylsulfatase A to function properly? |
|
Definition
|
|
Term
|
Definition
| solubilizes the hydrophobic lipid => accessible to arylsulfatase A |
|
|
Term
| What happens if SAP (saposin B) is deficient? |
|
Definition
| a disease phenotypically similar to metachromatic leukodystrophy |
|
|
Term
| What are the 3 forms of metachromatic leukodystrophy? |
|
Definition
1) infantile
2) juvenile
3) adult |
|
|
Term
Sx
late infantile metachromatic leukodystrophy |
|
Definition
1) Onset ~2y
2) hypotonia, muscle weakness
3) mental disoration w/ loss of milestones
4) peripheral nerve involvement (prolonged nerve conduction time)
5) death by 5y |
|
|
Term
What accumulates when arylsulfatase A is deficient?
Where? |
|
Definition
| galactocerebroside sulfate accumulates in the CNS & extraneural sites (excreted in urine) |
|
|
Term
| What happens due to arylsulfatase A deficiency? |
|
Definition
1) progressive myelin loss in cerebral & cerebellar white matter
2) accumulation of metachromatic material (stains brown with cresyl-violet stain)
3) gliosis
4) cytoplasmic inclusions in the white matter oligodendrocytes & astrocytes
5) metachromatic material in peripheral nerves, renal epithelial cells, bile ducts, Kupffer cells, gallbladder mucosal cells
6) EM - cytoplasmic inclusions w/ herringbone pattern |
|
|
Term
When is the onset of juvenile metachromatic leukodystrophy?
adult form? |
|
Definition
juvenile: 3-16y
adult: after 16y, usually in 30s. Psychiatric Sx appear before neurologic Sx |
|
|
Term
Sx
multiple sulfatase deficiency |
|
Definition
| metachromatic leukodystrophy Sx + MPS disease Sx |
|
|
Term
| What causes multiple sulfatase deficiency? |
|
Definition
| reduction in the activities of several sulfatidases (arylsulfatidase A, B, C) => accumulation of sulfatides, sulfated GAGs, sphingolipids, & steroid sulfates |
|
|
Term
| *What is the most common lysosomal storage disease? |
|
Definition
|
|
Term
| What type of lysosomal storage disease is Gaucher disease? |
|
Definition
|
|
Term
| What enzyme is defective in Gaucher disease? |
|
Definition
|
|
Term
Function
glucocerebrosidase |
|
Definition
| enzyme important in complex catabolic pathways of gangliosides |
|
|
Term
| What accumulates in Gaucher disease? |
|
Definition
| glucocerebroside & other glycolipids |
|
|
Term
| Where do glycocerebrosides derive from? |
|
Definition
| breakdown of senescent leukocyte & RBC membranes |
|
|
Term
| Where are the incompletely metabolized sunbrates in Gaucher disease stored? |
|
Definition
| monocytes/macs aka Gaucher cell (fibrillary, crumpled paper appearance to cytoplasm with eccentrically displaced nucleus) |
|
|
Term
| What special stain IDs Gaucher cells? |
|
Definition
|
|
Term
| What are the 3 clinical subtypes of Gaucher disease? |
|
Definition
1) type 1: chronic non-neuronopathic form (most common)
2) type 2: acute neuropathic form
3) type 3: subacute, intermediate, juvenile form |
|
|
Term
| What accounts for the 3 types of Gaucher disease? |
|
Definition
| different allelic disorders with different mutations in the gene encoding for β-glucocerebrosidase |
|
|
Term
Sx
Type 1 Gaucher disease
chronic non-neuronopathic form |
|
Definition
1) bone disease (osteopenia, focal lytic or sclerotic leisons, osteonecrosis)
2) hepatosplenomegaly
3) absense of primary neurologic disease
4) decreased levels of glucocerebrosidase activity
5) storage of glucocerebroside in mononuclear phagocytes thry body, except brain
(no CNS involvement) |
|
|
Term
Sx
Type 2 Gaucher disease
acute, neuropathic form |
|
Definition
1) absent glucocerebrosidase
2) progressive CNS involvement
3) hepatosplenomegaly
4) cytopenias secondary to hypersplenemia
5) death by 2y
(no bone involvement) |
|
|
Term
Sx
Type 3 Gaucher disease
aubacute, intermediate, juvenile form |
|
Definition
1) reduced glycocerebrosidase
2) progressive CNS involvement; Onset: 10s-20s
3) hepatosplenomegaly
4) cytopenias secondary to hypersplenism
5) bone involvement |
|
|
Term
| Which Gaucher type is common in Ashkenaszi Jewish ancestry? |
|
Definition
|
|
Term
| How is Gaucher disease Dx made? |
|
Definition
| measurement of glucocerebroside activity (peripheral blood leukocytes or fibroblast culture) |
|
|
Term
|
Definition
1) replacement therapy with recombinant enzymes
2) bone marrow transplant
3) future: gene therapy |
|
|
Term
| What do non-lysosomal enzyme defects involve? |
|
Definition
| various pathways of intermediary metabolism |
|
|
Term
| How are non-lysosomal enzyme defects groups? |
|
Definition
| major kind of molecule implicated |
|
|
Term
| What are the 2 types of non-lysosomal enzyme defects? |
|
Definition
1) disorders of CHO metabolism
2) disorders of aa metabolism |
|
|
Term
| What are the 2 types of disorders of CHO metabolism? |
|
Definition
1) disorders of galactose metabolism
2) disorders of glycogen metabolism |
|
|
Term
| What is a disorder of galactose metabolism? |
|
Definition
|
|
Term
| What is the inheritance pattern of classic galactosemia? |
|
Definition
|
|
Term
| What enzyme is deficient in classic galactosemeia? |
|
Definition
| galactose-1-phosphate uridyltransferase |
|
|
Term
Function
gal-1-P uridyltransferase |
|
Definition
| conversion of gal-1-P & UDP-glucose to UDP-galactose & glucose-1-P |
|
|
Term
| What organ systems are most affected by classic galactosemia? |
|
Definition
|
|
Term
|
Definition
1) Onset: few days following ingestion of milk
2) failure to thrive
3) V/D
4) liver dysfunction (jaundice &/or hepatomegaly)
5) cataracts resulting from punctate leisons on the lens (within few days of life)
6) increased susceptibility to inf. (esp. E. coli)
7) if untreated, irreversible MR
8) steatosis of hepatocytes => cirrosis
9) brain edema, gliosis, neuronal necrosis
10) galactosuria
11) generalized aminoaciduria, proteinuria, hyperchloremic acidosis |
|
|
Term
| How is classic galactosemia Dx? |
|
Definition
| newborn screening test with confirmation by red cell galactose-1-P uridyltransferase level |
|
|
Term
| What 2 other enzyme deficiencies can lead to elevated levels of galactose? |
|
Definition
1) galactokinase
2) UDP-gal-4-epimerase |
|
|
Term
| What are the 3 forms of glycogen metabolism disorders? |
|
Definition
1) hepatic form
2) myopathic form
3) systemic form |
|
|
Term
| What is the principal storage form of glycose? |
|
Definition
|
|
Term
| What is glycogen composed of? |
|
Definition
| glucose molecules linked together to form a highly branched structure (synthesized by a series of enzymatic steps) |
|
|
Term
| What causes GSDs (glycogen storage disorders)? |
|
Definition
dfects in enzymes involved in degrading & synthesizing glycogen
(its also degraded in lysosomes by acid maltase) |
|
|
Term
| What is an example of the hepatic GSD? |
|
Definition
|
|
Term
| What enzyme is deficient in von Gierke disease? |
|
Definition
| G-6-P (glucose-6-phosphatase) |
|
|
Term
|
Definition
1) failure to thrive
2) hepatomegaly
3) severe fassting hypoglycemia
4) ketosis, increased plasma lactic acid, marked lipidemia => eruptive xanthomas
5) massive accumulation of glycogen in hepatocytes & renal tubular epithelial cells
6) hepatic adenomas may develop |
|
|
Term
| What is an example of a myopathic GSD? |
|
Definition
|
|
Term
| What is glycogen used for in sk. muscle? |
|
Definition
| source of energy cia glycolysis => lactate release |
|
|
Term
| What happens when ezymes needed for glycolysis are deficient? |
|
Definition
|
|
Term
| What happens after exercise when glycolysis enzymes are deficient? |
|
Definition
| muscle cramps w/o a rise in blood lactate after exercise |
|
|
Term
| What ezyme is deficient in McArdle's disease? |
|
Definition
| myophosphorylase (muscle phosphorylase) |
|
|
Term
|
Definition
| convert glycogen to glucose-1-P & eventually lactate |
|
|
Term
|
Definition
1) Onset: 20s-30s
2) if childhood onset: manifested by easy fatigability & muscle cramps => marked decline in muscle function/wasting with age
3) exercise intolerance => muscle cramps, rhabdomyolysis, myoglobinuria, renal failure
4) sk. muscle biopsy shows absent of low myophosphorylase, sarcolemmal accumulation of glycogen |
|
|
Term
| How is McArdle's disease Dx? |
|
Definition
ischemic exercise test with lactic acid measurement
(note: may be normal in patients with partial deficiency) |
|
|
Term
| What are 2 examples of somatic GSD? |
|
Definition
1) Pompe's disease
2) Anderson's disease (brancher glycogenosis) |
|
|
Term
| What enzyme is deficient in Pompe's disease? |
|
Definition
| α-1,4-glucosidase (acid maltase) |
|
|
Term
|
Definition
1) generalized functional disturbance
2) cardiomegaly (dominates clinical picture)
3) hepatomegaly
4) muscle hypotonia & wasting
5) death from cardiac failure by 2 yrs |
|
|
Term
| Where does glycogen accumulate in Pompe's disease? |
|
Definition
| lysosomes of liver, myocardiu,, sk. muscle, s. muscle of vessels, neurons of CNS |
|
|
Term
| What enzyme is deficient in Anderson's disease (brancher glycogenosis)? |
|
Definition
| amylo-1,4 to 1,6-transglucosidase |
|
|
Term
Sx
Anderson's disease (brancher glycogenosis) |
|
Definition
1) hepatosplenomegaly
2) progressive cirrhosis & ascites
3) death within 2 yrs (due to cirrhosis) |
|
|
Term
| Where is glycogen deposited in Anderson's disease? |
|
Definition
| abnormal glycogen in brain, heart, sk. muscle, liver |
|
|
Term
| What is the only disorder of amino acid metabolism that we discussed? |
|
Definition
|
|
Term
| What enzyme is deficient in classic PKU (type 1)? |
|
Definition
| phenylalanine hydroxylase (PAH) |
|
|
Term
|
Definition
| metabolism of dietary aa phenylalanine to tyrosine |
|
|
Term
| How do the differences of the mutant alleles in PKU affect phenotype? |
|
Definition
| some mutations lead to modest elevation of phenylalanine ∴ no neurologic damage |
|
|
Term
| What enzyme is deficient in type 2 PKU? |
|
Definition
| phenylalanine hydroxylase cofactor tertahydrobiopterin |
|
|
Term
| What enzyme is deficient in type 3 PKU? |
|
Definition
dihyfropteridine reductase
(also unable to metabolize tyrosine & tryptophan ∴ dietary restriction does NOT prevent neurologic impairment) |
|
|
Term
|
Definition
1) MR (w/o dietary restriction)
2) fair hair/blue eyes
3) musty body odor
4) eczema
5) urinary excretion of phenylalanine & biproducts
6) gray & white matter demyelination
7) gliosis in white matter |
|
|
Term
|
Definition
newborn screening
detection of excess phenylalanine |
|
|
Term
|
Definition
infant: strict dietary restriction oh phenylalanine
chile: by 10y, may be able to tolerate normal diet, but need checks in tyrosine levels (usually diet for life)
pregnancy: needs dietary restriction |
|
|
Term
| What's an example of a defect in membrane receptors? |
|
Definition
| familial hypercholesterolemia |
|
|
Term
| What is defective in familial hypercholesterolemia? |
|
Definition
| LDLR transporting cholesterol |
|
|
Term
Sx
familial hypercholesterolemia |
|
Definition
| hypercholesterolemia, accelerated atherosclerosis, skin xanthomas |
|
|
Term
| What's an example of a defect in transport proteins? |
|
Definition
|
|
Term
|
Definition
| membrane transport of Cl (& water) decreased via mutation in CFTR gene |
|
|
Term
Effect
abnormal Cl membrane transport in CF |
|
Definition
| abnormal water content of secretions => thick secretions |
|
|
Term
| With which ancestry is CF more common? |
|
Definition
|
|
Term
| What is the inheritance pattern of CF? |
|
Definition
|
|
Term
| Where are CFTR transport proteins found? |
|
Definition
| lungs, intestines, pancreas, sweat glands, reproductive tract |
|
|
Term
| How are the mutations of CFTR classified? |
|
Definition
as mild or severe
severe: no synthesis or clocked processing
mild: altered conductance or reduced synthesis |
|
|
Term
| What is the most common mutation in CF? |
|
Definition
deletion of F508
(if homozygous => pulmonary & pancreatic disease) |
|
|
Term
|
Definition
Lungs: thick secretions => breeding ground for organisms
Pancreas: thick secretions => block ducks => backup pancreatic enzymes & subsequent autodigestion => fibrosis, reduction of ezyme productio => malnutrition & DM
3) intestines: secretions => blockage & subsequent atresia in utero
5) vas deferens: secretions => blockage => sterility |
|
|
Term
| What's an example of defects in structural proteins? |
|
Definition
|
|
Term
| What enzyme is defective in Marfan syndrome? |
|
Definition
| ECM microfibril protein, fibrillin |
|
|
Term
|
Definition
| hyperextensible joints, sk. deformities, dislocation of lens, mitral valve prolapse, aortic dilation |
|
|
Term
| What is an example of defects in proteins involved in regulation of cell growth & differentiation? |
|
Definition
|
|
Term
| What is the inheritance pattern of NF1 (neurofibromatosis type 1)? |
|
Definition
|
|
Term
| Where is the defect in NF1? |
|
Definition
| 17q11 gene encoding for neurofibromin |
|
|
Term
|
Definition
| formation of multiple tumors involving the peripheral nerves (neurofibromas, plexiform neurofibromas) & CNS (optic gliomas), skin leisons (cafe au lait spots, axillary or inguinal freckling, neurofibromas), scoliosis, vertebral dysplasia, osseous & soft tissue overgrowth, & other developmental abnormalities |
|
|
Term
| How complete is the penetrance of NF1? |
|
Definition
almost complete, tho with variation in clinical manifestations
cafe au lait spots & intertriginour freckling in almost 90% |
|
|
Term
| Are NF1 patients at an increased for malignant tumors, tho neurofibromas are benign? |
|
Definition
| yes due to malignant transformations |
|
|
Term
| What do the optic gliomas in NF1 lead to? |
|
Definition
| blindness & Lisch nodules |
|
|
Term
| What is the Dx criteria for NF1? |
|
Definition
2+ of the following:
1) 6+ cafe au lait sports
2) freckling in axillary or inguinal regions
3) 2+ pigmented hamartomas of iris (Lisch nodules)
4) 2+ neurofibromas or 1 plexiform neurofibroma
5) optic glioma
6) osseous leisons s.a. sphenoid dysplasia or thinning of the long bone cortex w/ or w/o pseudoarthrosis
7) 1st degree relative with NF1 |
|
|
Term
| What is the inheritance pattern of NF2? |
|
Definition
|
|
Term
|
Definition
wide range of tumors s.a. bilateral acoustic schwannomas, multiple meningiomas, ependymomas of SC
Cafe au lait spots can be present |
|
|
Term
| How complete is penetrance of NF2? |
|
Definition
| 100% by age 60 - most have onset in 20s & 30s |
|
|
Term
| What is the mutation in NF2? |
|
Definition
| 22q12 that encodes merlin protein |
|
|
Term
|
Definition
| mediate communication b/w extracellular milieu & the cytoskeleton |
|
|
Term
| What do multifactoral diseases result from? |
|
Definition
| interaction of 2+ mutant genes & environmental influences |
|
|
Term
| What are the general characteristics of multifactorial disorders? |
|
Definition
1) increased occurance in families
2) aggregation shown to be more genetic than environmental
3) familial pattern does not fit Mendelian patterns
4) risk is related to number of deleterious genes inherited
5) environmental factors modify risk of disease expression
6) rate of recurrance is same for all 1st degree relatives (2-7%)
7) risk of recurrence depends on outcome of previous pregnancies (1 child affected = 7% for next, 2 children affected = 9% for next) |
|
|
Term
| What is the most common multifactorial disease? |
|
Definition
|
|
Term
| What are the 2 major classifications of mutlifactorial diseases? |
|
Definition
1) chromosomal disorders
2) single gene disorders with nonclassic inheritance |
|
|
Term
| Are chromosomal disorders constitutional (congenital) or acquired? |
|
Definition
|
|
Term
| Which chromosomes are involved in chromosomal (cytogenetic) disorders? |
|
Definition
| autosomes &/or sex chromosomes |
|
|
Term
| What are the 4 major cytogenetic diseases involving autosomes? |
|
Definition
1) trisomy 21 (down syndrome)
2) trisomy 18 (edward's syndrome)
3) trisomy 13 (patau's syndrome)
4) chromosome 22q11 deletion (DiGeorge syndrome or VCF syndrome) |
|
|
Term
|
Definition
95% nondysjunction
4% translocation
1% chromosomal mosaicism |
|
|
Term
|
Definition
1) IUGR (intra uterine growth retardation)
2) oblique palpebral fissures,
3) hyperextensibility of joints
4) abnormal dermatoglyphic pattern
5) MR
6) hypotonia at birth
7) AD
8) congenital heart disease
9) GI (duodenal obstruction, Hirschsprung disease)
10) Hematologic (leukemia, transient myeloproliferative disorder)
11) immunologic defects => infections
12) reduced growth rate & stature |
|
|
Term
|
Definition
1) prominent occiput
2) microcephaly
3) micrognathia
4) low set ears
5) clenched fist w/ overlapping digits
6) MR
7) congenital heart defects
8) renal malformations
9) rocker bottom feet
10) tracheoesophageal fistulas
11) esophageal atresia |
|
|
Term
|
Definition
1) microcephaly
2) microopthalmia
3) midline facial defects (bilateral cleft lip, proboscis)
4) umbilical hernia
5) MR
6) polydactyly
7) congenital heart defects
8) renal malformations
9) rocker bottom feet |
|
|
Term
| What are 2 22q11 deletion diseases? |
|
Definition
1) DiGeorge syndrome
2) VCF (velocardiofacial) syndrome |
|
|
Term
Sx
22q11 deletion syndrome |
|
Definition
1) congenital heart defects
2) cleft palate (NOT lip)
3) facial dysmorphism
4) developmental delay
5) variable degrees of T cell immunodeficiency
6) hypocalcemia |
|
|
Term
Dx
22q11 deletion syndrome |
|
Definition
FISH
prenatal testing possible |
|
|
Term
| What are 2 cytogenetic disorders involving sex chromosomes? |
|
Definition
1) Klinefelter syndrome
2) Turner's syndrome |
|
|
Term
| What is one of the most common causes of hypogonadism in males? |
|
Definition
|
|
Term
| What are the common karyotypes of Klinefelter Syndrome? |
|
Definition
XXY 82%
XY/XXY, XXY/XXXY & XXYY are the remainder |
|
|
Term
|
Definition
1) elongated body (due to increased length b/w sole & pubic bone)
2) small atrophic testes & sm. penis
3) lack of secondary male sex characteristics
4) 50% have gynecomastia after puberty
5)kidney cyts, hydronephrosis, hydroureters, ureteroceles
6) elevated plasma gonadotropin
7) reduced testosterone
8) increased estradiol
(ratio of estrogen:testosterone determines degree of feminization) |
|
|
Term
| What are the common causes of Turner's syndrome? |
|
Definition
57% monosomy X
29% mosaics
14% structural abnormalities of X chromosome |
|
|
Term
| What is the fetal mortality rate of Turner's syndrome? |
|
Definition
|
|
Term
|
Definition
1) short stature
2) broad chest, wide spaced nipples
3) neck webbing
4) ovarian dysgenesis
5) excessive number of pigmented nevi
6) cardiac defects
7) congenital lymphedema with residual puffiness of dorsum of hands & feet |
|
|
Term
| What are the 3 types of single gene disorders with nonclassic inheritance? |
|
Definition
1) Triple Repeat Mutations
2) Mitochondrial Diseases
3) Genomic Imprinting |
|
|
Term
| What are 4 examples of a triple repeat mutation? |
|
Definition
1) Fragile X
2) Huntington Disease
3) myotonic dystrophy
4) Friedreich ataxia |
|
|
Term
|
Definition
1) moderate MR in affected males, mild MR in affected females
2) abnormal faces (long face, prominent forehead, large ears, prominent jaw)
3) macro-orchidism
4) hyperextensible joints
5) mitral valve prolapse |
|
|
Term
| What is the only genetic cause of MR more common than Fragile X? |
|
Definition
|
|
Term
| Where are the genetic repeats seen in Fragile X? |
|
Definition
|
|
Term
| What if a person has an intermediate number of mutations of FMR1 gene (i.e. not a full mutation, but not normal either)? |
|
Definition
phenotypically normal female carrier
transmitting males
considered pre-mutations |
|
|
Term
| Are patients with a premutation at risk for anything related to Fragile X besides transmission? |
|
Definition
yes
mild cognitive/behavioral deficits
premature ovarian failure
neurodegenerative disorder (fragil X associated tremor/ataxia syndrome) |
|
|
Term
| Do carrier/transmitting males or females have a more significant amplification of the repeats? |
|
Definition
|
|
Term
| Are mitochondrial diseases more or less common? |
|
Definition
|
|
Term
| What can cause mitochrondiral diseases? |
|
Definition
1) genetic defect in mictochondrial DNA (mtDNA)
2) genetic defect in nuclear genes (nDNA) encoding proteins that function in mitochondria |
|
|
Term
| Which cells have no mitochondria? |
|
Definition
|
|
Term
| What is special about mitochondria? |
|
Definition
| only known organelles to have their own DNA |
|
|
Term
|
Definition
| numerous infoldings of the inner mitochondrial membrane |
|
|
Term
| Which mitochondrial membrane is permeable to small molecules & contains receptors for transporting macromolecules? |
|
Definition
|
|
Term
| Which mitochondrial membrane is impermeable & contians transporters for small molecules? |
|
Definition
|
|
Term
| How many genes are encoded by mtDNA? |
|
Definition
| ~37 (13 are for ETC, 2 for ribosomal DNA, 22 for tranlational DNA) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| when wild type (normal) & mutant mtDNA reside in the same cell |
|
|
Term
| What does heteroplasmy cause in the daughter mtDNA? |
|
Definition
| different proportions of normal & mutant DNA |
|
|
Term
| What is affect by the proportion of mutated & normal mtDNA? |
|
Definition
| severity of biochemical defect |
|
|
Term
|
Definition
| creating most of the energy needed for the body to sustain life & support growth |
|
|
Term
| What effect is seen when there's mitochondrial failure? |
|
Definition
| less & less energy is generated => cell injury/death => if repeated thruout body, whole systems can fail |
|
|
Term
| What cells have higher mitochondria content? |
|
Definition
| cells with high energy requirements (CNS, eye, cardiac conduction system, oxidative sk. muscle, kidneys, liver) |
|
|
Term
| What is the inheritance pattern of mitochondiral defects? |
|
Definition
|
|
Term
| What are the 2 categories of mitochondiral dysfunction? |
|
Definition
1) abnormalities with altered number & structure of mitochondria
2) secondary degenerative & destructive changes due to impaired function of mitochondria |
|
|
Term
| What are 3 mitochondrial disorders associated with muscular disease? |
|
Definition
1) Kearns-Sayre syndrome
2) MERRF (myoclonic epilepsy with ragged red fibers)
3) MELAS (lactic acidosis with stroke-like signs) |
|
|
Term
| What disease is a mitochondrial encephalopathy of infancy? |
|
Definition
|
|
Term
|
Definition
| focal, symmetric necrosis in thalamus, brainstem, & posterior columns of the SC |
|
|
Term
|
Definition
| selective inactivation of either the maternal or the paternal allele |
|
|
Term
|
Definition
| inactivation of the maternal allele |
|
|
Term
|
Definition
| inactivation of the paternal allele |
|
|
Term
| Where does imprinting occur? |
|
Definition
| in ovum or sperm (transmitted to all somatic cells) |
|
|
Term
| What are 2 examples of genomic imprinting? |
|
Definition
1) Prader-Willi syndrome
2) Angelman syndrome |
|
|
Term
| What causes Prader-Willi syndrome? |
|
Definition
part of maternal chromosome 15 is normally inactivated, and the functional alleles are provided by the paternal chromosome.
When the functional alleles on the paternal chromosome are deleted => Prader-Willi syndrome
(may also result from maternal disomy) |
|
|
Term
|
Definition
| both chromosomes derived from a single parent |
|
|
Term
|
Definition
1) MR (moderate)
2) short stature
3) hypotonia, esp. at birth
4) obesity that progresses with age
5) small hands & feet
6) hypogonadism |
|
|
Term
| What causes Angelman syndrome? |
|
Definition
A group of genes is also paternally imprinted on chromosome 15 normally (~ to Prader-Willi) & the maternal alleles are normally active/
If a deletion of the maternal gene occurs => Angelman Syndrome
(can also be causes by paternal uniparental disomy) |
|
|
Term
|
Definition
1) severe developmental delay or MR
2) severe speech impairment
3) gait ataxia
4) seizures
5) inappropriate laughter (happy puppets) |
|
|
Term
| In normal genomic imprinting, how are the normally inactivated genes inactivated? |
|
Definition
|
|
Term
| What is the pathogenesis of carcinogenesis? |
|
Definition
| accumulation of non-lelthal germ-line &/or acquired abnormalities of protooncogenes, tumor suppressor gene, &/or apoptosis => sequential clonal exansions (tumor growth) => eventual malignant transformation & increasing virulence |
|
|
Term
|
Definition
| NORMAL cellular genes that promote & regulate cell proliferation |
|
|
Term
| *What happens to protooncogenes => malignant transformation? |
|
Definition
| become oncogenes with production of oncoproteins |
|
|
Term
|
Definition
| altered proteins that are integral to cell proliferation & cell cycle regulation that function in an autonomous manner, independent from normal cell mitogenic signaling |
|
|
Term
| *Generally, how many abnormal alleles are needed to increase proliferation of tumors? |
|
Definition
|
|
Term
| *What normally occurs in cell replication? |
|
Definition
| GF binds to & transiently activated its receptor => activation of signal-transducing proteins => mitogenic signal transmission to the nucleus => activation of nuclear regulatory proteins => DNA transcription promoting entrance into the cell cycle |
|
|
Term
| What happens if GF protooncogenes are overexpressed or amplified? |
|
Definition
| increased GF production => increased cell proliferation => consequent risk of mutations |
|
|
Term
| What happens if there is overexpression or amplification of GFR protooncogenes (i.e. ERB-BR [HER2/Neu])? |
|
Definition
| increased GFR expression => increased sensitivity & responsiveness to GFs (even activation w/o GFs) |
|
|
Term
| What happens if there are point mutations or rearrangements of GFR protooncogenes? |
|
Definition
| constitutively active GFRs |
|
|
Term
| *What happens if there is a point mutation of RAS protooncogene? |
|
Definition
| abnormal RAS proteins resistant to augmentation by GAPs (GTPase-activating proteins) => greatly diminished GTP hydrolysis => mutant RAS proteins remain in their GTP-bound, active state => continuous mitogenic signaling |
|
|
Term
| What happens if there's a translocation of ABL from chromosome 9 to chromosome 22 (Philadelphia chromosome)? |
|
Definition
| fusion BCR-ABL gene => hybrid BCR-ABL protein w/ increased tyrosine kinase activity |
|
|
Term
| What happens if there's a translocation or amplification of MYC protooncogene? |
|
Definition
| overproduction of MYC protein => increased gene transcription promoting cell replication |
|
|
Term
| What happens if there's overexpression of cyclin D genes or amplification of the CDK4 gene? |
|
Definition
| increased cell proliferation |
|
|
Term
*def
tumor suppressor genes |
|
Definition
| normal cellular genes that inhibit & regulate cell proliferation |
|
|
Term
| How many tumor suppressor gene alleles must be inactivated for cellular proliferation to go unchecked? |
|
Definition
|
|
Term
| What are the 2 ways tumors can develop due to loss of tumor suppressor genes according to the 2 hit hypothesis? |
|
Definition
1) loss of heterozygosity (LOH) - most frequentlydue to DNA methylation
2) tumor suppressor genes - recessive cancer genes |
|
|
Term
| What are the 2 alternative pathways to lose normal growth inhibition? |
|
Definition
1) inherited predisposition to malignancies
2) development of sporadic malignancies |
|
|
Term
| How do inherited predispositions to malignancies work? |
|
Definition
| germ-line defect of one allele of a tumor suppressor gene + acquired defect of the other allele => loss of normal growth inhibition |
|
|
Term
| How does development of sporadic malignancies lead to loss of normal cell growth inhibition? |
|
Definition
| defects have to be acquired in both alleles of a tumor suppressor gene within a somatic cell |
|
|
Term
| What are the 4 key tumor suppressor genes? |
|
Definition
1) RB gene (retinoblastoma)
2) p53 gene
3) NF-1 (neurofibromatosis)
4) CDKI genes |
|
|
Term
| *What is the most commonly altered tumor suppressor gene in malignancies? |
|
Definition
|
|
Term
| What happens if the RB gene loses it's normal protein function? |
|
Definition
| failure to bind & inactivate E2F transcriptional factor complex => uninhibited E2F-mediated transcription & consequent cell cycle progression |
|
|
Term
| What happens when there is loss of normal p53 protein function? |
|
Definition
| propagation of progressively more genetically damaged cells |
|
|
Term
| What happens where there's loss of normal neurofibromin function? |
|
Definition
| persistence of active, GTP-bound RAS protein => increased mitogenic signaling |
|
|
Term
| What are the 2 ways mutagenic cells can evade apoptosis? |
|
Definition
1) increased expression of anti-apoptotic genes
2) decreased expression of pro-apoptotic genes |
|
|
Term
| What happens when there's DNA damage (external or internal) + cellular inability to repair DNA alterations? |
|
Definition
| propagation of progressively more genetically abnormal cells & increased likelihood of mutations affecting protooncogenes, tumor suppressor genes &/or apoptosis regulatory genes => predisposition to malignant tumors |
|
|
Term
| How many alleles of a DNA repair gene must be inactivated in order for genomic instability to result? |
|
Definition
|
|
Term
| What are the 3 types of defects in DNA repair? |
|
Definition
1) defective mismatch repair
2) defective nucleotide excision repair
3) defective homologous recombination repair |
|
|
Term
| What happens where there's a defective mismatch repair (nucleotide proofreading & error correction during DNA replication)? |
|
Definition
| cellular "replication error" phenotype |
|
|
Term
| What is the prototype of defective mismatch repair? |
|
Definition
| hereditary nonpolyposis colon carcinoma syndrome (HNPCC) |
|
|
Term
| What is the prototype of defective nucleotide excision repair (correction of DNA cross-linking causes by UV radiation)? |
|
Definition
|
|
Term
| What is the prototype of defective homologous recombination repair (detection of DNA damage => induction of cell cycle arrest => error-free recombination DNA repair)? |
|
Definition
| hereditary form of breast & ovarian carcinoma associated iwth BRCA-1 & BRCA-2 gene mutations |
|
|
Term
| What can lead to limitless replicative potential? |
|
Definition
| retention or reactivation of telomerase activity |
|
|
Term
| What happens when there is retention of reactivation of telomerase activity? |
|
Definition
| prevention of chromosomal telomere shortening with sequential cell division & loss of normal cell cycle checkpoint function => maintenance of cellular proliferative capacity |
|
|
Term
| What causes sustained angiogenesis in tumor growth? |
|
Definition
| genetic alterations promoting cellular proliferation &/or survival => development & early growth of a malignancy => additional mutagenic events in the malignant cells => angiogenic switch - production of increased angiogenic factors => neovascularization & vessel growth |
|
|
Term
| What does sustained angiogenesis cause in malignancy? |
|
Definition
| increased size of malignancy & metastatic potential |
|
|
Term
| *What influences a tumor's ability to invade & metastasize? |
|
Definition
| BOTH malignant cells & inducible characteristics of the surrounding stroma |
|
|
Term
| What are the 4 steps of malignant cell invasion of the ECM? |
|
Definition
1) detachment of the malignant cells
2) tumor cell attachment to ECM
3) enzymatic degradation of ECM
4) migration of the malignant cells into ECM |
|
|
Term
| What causes detachment of the malignant cells? |
|
Definition
| loss of cellular homotypic adhesions |
|
|
Term
| How are tumor cells attached to the ECM? |
|
Definition
| increased expression of cell membrane receptors for carious components of the ECM |
|
|
Term
| What causes enzymatic degradation of the ECM? |
|
Definition
| secretion of a variety of proteases by the malignant cells, as well as by the surrounding reactive stromal & inflammatory cells |
|
|
Term
| What mediates the migration of the malignant cells into the ECM? |
|
Definition
| chemotactic ECM degradation products (other ECM breakdown products regulate tumor growth & angiogenesis) |
|
|
Term
| What are the 4 steps of vascular dissemination & homing of the malignant cells? |
|
Definition
1) formation of circulating tumor emboli
2) malignant cell adhesion to the endothelium at distant sites
3) extravasation of the malignant cells
4) induction of angiogenesis & growth of the metastatic deposit |
|
|
Term
| How does the circulating tumor emboli form? |
|
Definition
| tumor cell-tumor cell homotypic adhesions & tumor cell-platelet heterotypic adhesions |
|
|
Term
| How do malignant cells adhere to the endothelium at distant sites? |
|
Definition
| tissue tropism at least partially determined by complementary ligand-receptor expression b/w target organ endothelium & the tumor cells |
|
|
Term
| What occurs in extravasation of the malignant cells? |
|
Definition
| ECM proteolysis & tumor cell migration |
|
|
Term
| What natural body defenses do tumor cells escape from? |
|
Definition
|
|
Term
| *Do functional & epigenetic changes changes play a role in malignant transformation? |
|
Definition
|
|
Term
| What are the 4 mechanisms of carcinogenic gene alterations (structural & functional)? |
|
Definition
1) point mutations
2) deletions
3) chromosomal rearrangements
4) gene amplification |
|
|
Term
| What is the most commonly altered protooncogene in malignancies, esp. adenocarcinomas? |
|
Definition
|
|
Term
| Which carcinogenic gene alterations are caused by deletions? |
|
Definition
| tumor suppressor & DNA repair genes |
|
|
Term
| What are the 2 types of chromosomal rearrangements? |
|
Definition
1) *translocations
2) inversions |
|
|
Term
| What are the 2 effects of chromosomal translocations? |
|
Definition
1) overexpression of carcinogenic genes
2) abnormal gene fusion |
|
|
Term
| What are examples of overexpression of carcinogenic genes due to chromosomal translocation? |
|
Definition
1) protooncogene translocations => overexpression of MYC
2) Cyclin D1 gene translocation => increased expression of Cyclin D1
3) BCL-2 gene translocation => increased transcription of BCL-2 |
|
|
Term
| What's an example of abnormal gene fusion due to chromosomal translocation? |
|
Definition
| fusion of ABL & BCR genes => hybrid BCR-ABL proteins w/ increased TK activity in chronic myelogenous leukemia & some cases of acute lymphoblastic leukemia |
|
|
Term
| Are chromosomal translocations or inversions more common? |
|
Definition
|
|
Term
| How does gene amplification occur? |
|
Definition
| reduplication of protooncogenes => overexpression of their protein products |
|
|
Term
*def
multi-step molecular model |
|
Definition
| multiple, sequential, incremental alterations of cellular oncogenes, tumor suppressor gene &/or apoptotsis regulatory genes are necessary for the progression to a malignancy |
|
|
Term
|
Definition
| genes, such as those with DNA repair, that help protect the stability of the genome |
|
|
Term
| Do alterations in caretaker genes directly or indirectly predispose the development of malignancies? |
|
Definition
|
|
Term
|
Definition
| genes, such as oncogenes & tumor suppressor genes, that directly control cellular proliferation |
|
|
Term
| *Do alterations in caretaker or gatekeeper genes predispose malignancy to a greater degree of risk? |
|
Definition
|
|
Term
| How does the tumor progress thru out development & growth of a malignancy? |
|
Definition
| sequential, clonal expansions of cells with each cellular expansion characterized by additional genetic alterations that confer growth advantages => high degree of tumor cell heterogeneity |
|
|
Term
| *How do carcinogenic chemical compounds become malignant in the body? |
|
Definition
| initial by irreversible DNA injury => promotion via temp. induction of cell proliferation => selective clonal expansion of mutated cell pop. => increased likelihood of additional mutagenic events => eventual development of a malignancy w/ subsequent tumor progression |
|
|
Term
| Does promotion come before or after initiation? |
|
Definition
|
|
Term
| Is initiation & promotion alone sufficient to induce carcinogenesis? |
|
Definition
|
|
Term
| What are the 2 typesof initiators? |
|
Definition
1) direct-acting carcinogens
2) *indirect-acting compounds (procarcinogens) => metabolic transformation => ultimate carcinogens |
|
|
Term
| *What are some examples of procarcinogens? |
|
Definition
1) *polycyclic aromatic hydrocarbons (in cigarette smoke)
2) aromatic amines
3) aflatoxin B1
4) nitrosamines |
|
|
Term
| What must happen for a procarcinogen to become an ultimate carcinogen? |
|
Definition
| balance b/w metabolic activation & inactivation of procarcinogens (partially genetically determined) |
|
|
Term
| What is the pathogenesis of initiation? |
|
Definition
| cellular exposure to a carcinogenic initiating agent => formation of covalent adducts (primarily with DNA bases) => characteristic mutational effects that must be followed by DNA replication |
|
|
Term
|
Definition
| process whereby the mutated (initiated) cells ungdergo increased proliferation => further mutations => subsequent malignant transformations by tumor progression |
|
|
Term
| Are promoters endogenous or exogenous? |
|
Definition
can be either
endogenous: hormones
exogenous: viral inf. |
|
|
Term
| What are the 2 types of radiation carcinogenesis? |
|
Definition
1) UV radiation
2) ionizing radiation |
|
|
Term
| How is UV radiation carcinogenic? |
|
Definition
| induces mutation by formation of DNA pyrimidine dimers => most common skin malignancies |
|
|
Term
| How is ionizing radiation carcinogenic? |
|
Definition
| DNA damage => cumulative mutagenic events => eventual malignant transformation (often after a long latent period) => leukemias, thyroid breast & lung carcinomas |
|
|
Term
| What is in an example of a a viral cancinogenic compound? |
|
Definition
| HPV (human papillomavirus) |
|
|
Term
| How is HPV (the high risk strains) carcinogenic? |
|
Definition
| integration of viral DNA into host genome => increased production of viral E6 & E7 proteins => cellular effects s.a. binding to & increasing degradation of p53 & RB proteins => increased cellular proliferation with decreased ability to repair DNA errors & eliminate cells with damage => mutagenic events => eventual malignant transformation |
|
|
Term
| *What type of conditions are frequently acquired & predispose to malignancy? |
|
Definition
| hyperproliferative conditions => dysplasia => carcinoma |
|
|
Term
| *What can amplify the predisposition to malignancy of acquired disorders? |
|
Definition
| coexistant chronic inflammation (due to DNA damage by ROS) |
|
|
Term
| What are 4 examples of acquired disorders with predisposition to malignancy? |
|
Definition
1) endometrial hyperplasia
2) ulcerative colitis
3) chronic gastritis
4) hepatic cirrhosis |
|
|
Term
| How does endometrial hyperplasia predispose malignancy? |
|
Definition
| => atypical endometrial hyperplasia => endometrial andenocarcinoma |
|
|
Term
| How does ulcerative colitis predispose malignancy? |
|
Definition
| => recurrent mucosal regeneration => glandular dysplasia => adenocarcinoma of the colon |
|
|
Term
| How does ulcerative colitis predispose malignancy? |
|
Definition
| => long-standing glandular epithelial proliferation => gastric adenocarcinoma |
|
|
Term
| How does hepatic cirrhosis predispose malignancy? |
|
Definition
| => regenerative hepatic nodules => dysplastic nodules => hepatocellular carcinoma |
|
|
Term
| What are the major causes of death for infants? |
|
Definition
congenital anomalies
prematurity
low birth weight
SIDS |
|
|
Term
| What are the major causes of death for children 1-4y? |
|
Definition
accidents
congenital anomalies
malignant neoplasms |
|
|
Term
| What are the major causes of death in children 5-14y? |
|
Definition
accidents
malignant neoplasms
homicide |
|
|
Term
| What are the major causes of death in young adults 15-24y? |
|
Definition
|
|
Term
|
Definition
| formation of viable fertilized ovum & determination of genetic sex |
|
|
Term
def
early cell divisions & implantation |
|
Definition
| establisment of pregnancy |
|
|
Term
def
prenatal development
embryo |
|
Definition
1st 8 weeks
establishment of body plan & organ systems |
|
|
Term
def
early cell divisions & implantation |
|
Definition
| establisment of pregnancy |
|
|
Term
def
prenatal development
embryo |
|
Definition
1st 8 weeks
establishment of body plan & organ systems |
|
|
Term
def
prenatal development
fetus |
|
Definition
9 weeks-birth
differentiation & maturation of organ systems
20-38wk: viable period
38-42wk: birth |
|
|
Term
|
Definition
birth til 4 weeks
adjustment to extra-uterine existance |
|
|
Term
|
Definition
1st year of life
early growth & development |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What occurs in the previable period of the fetus - weeks 9-12? |
|
Definition
acceleration of body growth relative to head size
onset of primary ossification
intestines return to abdomen
genitalia become distinguishable
onset of renal function |
|
|
Term
| What occurs in the previable period of the fetus - weeks 13-16? |
|
Definition
onset of reflexes
cerebral cortex begins forming |
|
|
Term
| What occurs in the previable period of the fetus - weeks 17-20? |
|
Definition
appearance of vernix caseosa & lanugo
completion of cerebral cortex formation
movements detected by mother |
|
|
Term
| What occurs in the viable period of the fetus - weeks 21-25? |
|
Definition
maturing of body proportions & weight
cerebral gyration
fingernail appear |
|
|
Term
| What occurs in the viable period of the fetus - weeks 26-29? |
|
Definition
maturation of lungs
CNS becomes adequate for maintaining respiration & exchange (not fully developed)
eyes open
toenails appear |
|
|
Term
| What occurs in the viable period of the fetus - weeks 30-38? |
|
Definition
continued maturation & growth
lung maturation
lanugo disappears
testes descend
grasp & orientation to light |
|
|
Term
| How much weight is gained by the fetus from conception to birth? |
|
Definition
| 8g-3300g (with the weight quadrupling in the 3rd trimester) |
|
|
Term
| What is done to assess stage development prenatally? |
|
Definition
1) dated from LMP
2) imaging studies (ultrasound, xray)
3) amniocentesis |
|
|
Term
| What is done to assess stage development postnatally? |
|
Definition
|
|
Term
def
IUGR
(intra uterine growth retardation) |
|
Definition
| deviation from expected pattern of growth |
|
|
Term
|
Definition
| spontaneous or therapeutic termination of pregnancy prior to viability |
|
|
Term
|
Definition
| intrauterine or intrapartum death of potentially viable fetus |
|
|
Term
|
Definition
birth prior to 37 weeks gestation
usually weigh <2500g
associated with higher morbidity & mortality |
|
|
Term
|
Definition
| birth >42 weeks gestation |
|
|
Term
| How can normal/abnormal fetal growth assessment be measured? |
|
Definition
1) linear measurements (body length, foot length, head circumference)
2) weights (body, organ)
3) developmental status (anatomic, physiologic maturation) |
|
|
Term
|
Definition
appropriate for gestational age
within 10-90%ile |
|
|
Term
|
Definition
small for gestational age
<10%ile
increased morbidity & mortality |
|
|
Term
|
Definition
large for gestational age
>90%ile
increased morbidity & mortality (usually associated with maternal DM or postmaturity syndrome) |
|
|
Term
|
Definition
|
|
Term
| What can cause low birth weight? |
|
Definition
1) prematurity (AGA)
2) normal small fetus (SGA)
3) pathologically small fetus (SGA)
4) very low birth weight infants (<1500g), usually due to extreme prematurity (accounts for half of all neonatal deaths) |
|
|
Term
| What are the 2 types of IUGR? |
|
Definition
1) Symmetric GR
2) Asymmetric GR |
|
|
Term
|
Definition
| body & organ (inc. brain) are proportionate |
|
|
Term
| What causes symmetric GR? |
|
Definition
1) chromosomal disorders
2) congenital anomalies/malformation syndromes
3) early intrauterine infections |
|
|
Term
|
Definition
| body & organ are disproportionate with relative sparing of brain |
|
|
Term
| What causes asymmetric GR? |
|
Definition
| maternal conditions s.a. vascular insufficiency, nutrition, toxin/drug, inf. |
|
|
Term
| What fetal conditions influence fetal growth? |
|
Definition
| intrinsic fetal conditions (chromosomal abnormalities, inherited genetic abnormalities, malformation, inf) |
|
|
Term
| What maternal conditions influence fetal growth? |
|
Definition
most common cause of SGA
decreased placental blood flow s.a. preeclampsia, renal disease, coagulopathy, inf., narcotic abuse, EtOH intake, cigarette smoking |
|
|
Term
| Besides maternal & fetal factors, what other factor's function is important for appropriate fetal growth? |
|
Definition
|
|
Term
| What can cause uteroplacental insufficency? |
|
Definition
1) umbilical-placental vascular anomalies
2) placental abruption
3) placental previa
4) placental thrombosis
5) infarction
6) infection
7) multiple gestations
8) confined placental mosaicism |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| bloody discharge w/o cervical dilation |
|
|
Term
|
Definition
| prolonged bleeding w/ cervical dilation |
|
|
Term
|
Definition
| retention in uterus of portions of conceptus (fetus or placenta) |
|
|
Term
|
Definition
| retention of dead fetus in uterus for >4 weeks |
|
|
Term
|
Definition
| 3+ consecutive spontaneous abortions |
|
|
Term
| Why is spontaneous abortion hard to quantify? |
|
Definition
| many occur <12 weeks and are unrecognized pregnancy |
|
|
Term
|
Definition
| death prior to delivery in potentially viable fetuses (>22 weeks gestation) |
|
|
Term
| What are the 2 ways a child can be stillborn? |
|
Definition
1) intrauterine death (prior to delivery)
2) intrapartum death |
|
|
Term
|
Definition
| autolysis in fetus when death >24hrs prior to delivery |
|
|
Term
|
Definition
| death occuring within 24 hrs of delivery |
|
|
Term
| What usually preceeds death of a fresh stillborn? |
|
Definition
| signs of fetal distress (decreased HR, *meconium passage, acidosis, cessation of movement) |
|
|
Term
|
Definition
dark, greenish material that accumulated in the bowel during fetal life & discharged shortly after birth
(stress may induce fetus to defecate prior to delivery) |
|
|
Term
| What do the causes of spontaneous abortion & stillbirth overlap with? |
|
Definition
|
|
Term
| What are the 4 fetal/placental causes of spontaneous abortion/stillbirth? |
|
Definition
1) chromosomal abnormalities
2) malformations not associated with specific chomosomal disorders
3) other underlying genetic diseases
4) placental factors (multiple births, placental abruption, umbilical cord accidents, etc.)
NOTE: malformations of heart, lungs, kidneys, etc may not become apparent until after birth when placental function ceases. |
|
|
Term
| What are the maternal causes of spontaneous aborption/stillbirth? |
|
Definition
1) maternal age (young or old)
2) infections
3) uterine abnormalities
4) concomitant maternal diseases (HTN, DM, CHF, lupus, shock/trauma, fever, etc)
6) maternal nutritional status
7) exposure to drugs/toxins |
|
|
Term
| How can obstetrical difficulties cause spontaneous abortion or stillbirth? |
|
Definition
|
|
Term
| What is useful to help establis the cause of the fetal death? |
|
Definition
pathological examination of the aborted/stillborn fetus & placenta (esp. by IDing malformations, genetic abnormalities, etc)
also helps establish time of death |
|
|
Term
Sx
maceration
(increase with lapse of time b/w death & delivery) |
|
Definition
1) skin slippage & bulla formation (begins 12-24 hr)
2) hemolysis (color evolves from normal to purple to yellow brown to gray 1-2weeks)
3) fluid collection in body cavities
4) progressive organ softening & loss of histologic function
5) dessication of tissue (after 1 week)
6) fibrin deposition, fibrosis, & calcification in placenta |
|
|
Term
| What does the presence of established non-autolytic tissue changes (necrosis, inflammation, etc) indicate in a stillborn fetus? |
|
Definition
| presence of pathologic processes before death |
|
|
Term
|
Definition
| a condition of generalized edema of fetus |
|
|
Term
| What are the potential causes of hydrops fetalis? |
|
Definition
1) immunologic (Rh, or other blood group incompatability)
2) non-immulnologic |
|
|
Term
def
erythroblastosis fetalis |
|
Definition
immune hydrops
hemolytic disease of fetus or newborn cause by transplacental passage of maternal Abs against fetal erythrocytes |
|
|
Term
| What are the 3 basic mechanisms of non-immune hydrops fetalis? |
|
Definition
1) increased cap/venous pressure
2) decreased oncotic pressure
3) damages cap integrity |
|
|
Term
| What can cause increased cap/venous pressure? |
|
Definition
1) high CO state
2) vascular obstruction
3) cardiac failure |
|
|
Term
| What can cause decreased oncotic pressure? |
|
Definition
1) decreased albumin synthesis (liver)
2) increased loss og albumin (kidney) |
|
|
Term
| What can cause damages cap integrity? |
|
Definition
1) sepsis
2) drugs/toxins
3) hypoxia |
|
|
Term
| What is the result of hydrops fetalis? |
|
Definition
increased extracellular fluid in interstital tissues & body cavities => fetal death & increased peripartum risk of death/injury
(some may recover) |
|
|
Term
|
Definition
1) generalized edema, ascites, pleural effusions, pale fetus & placenta, hepatosplenomegaly, hyperplasia of RBC precursors in bone marrow, increased extramedullary hemtatopoiesis
2) most serious: CNS damage due to hyperbilirubinemia (jaundice and kernicterus) |
|
|
Term
|
Definition
| bright yellow pigmentation in the BG, thalamus, cerebellum, cerebral gray matter & SC |
|
|
Term
| What are the effects of intrapartum birth injuries? |
|
Definition
| intrapartum death or long-term morbidity in surviving patients |
|
|
Term
| What are the 2 categories of intrapartum birth injuries? |
|
Definition
1) traumatic birth injury
2) perinatal asphyxia |
|
|
Term
| What are the important risk factors of intrapartum birth injury? |
|
Definition
1) maternal diseases (DM, HTN, etc)
2) placental abnormalities
3) fetal conditions (immaturity, size [esp. LGA], unusual presentation, etc)
4) other obstetrical problems |
|
|
Term
| What are the 3 important patterns of traumatic birth jury? |
|
Definition
1) Cranial trauma
2) other soft tissue & bone fractures/dislocations, peripheral nerve injuries, & spinal injuries
3) organ injuries |
|
|
Term
| What are the 7 types of cranial traume endoured as a result of traumatic birth? |
|
Definition
1) caput succedaneum
2) caphalhematoma
3) intracranial hemorrhage
4) skull fracture
5) occipital osteodiastasis
6) laceration of falx or tentorium
7) brain parenchymal laceration |
|
|
Term
| What is the most common important birth injury? |
|
Definition
|
|
Term
|
Definition
| interstitial fluid in soft tissues of scalp |
|
|
Term
|
Definition
|
|
Term
| What is intracranial hemorrhage related to? |
|
Definition
| excessive molding of the head & sudden pressure changes effect |
|
|
Term
| What ususally causes skull fractures? |
|
Definition
| inappropriate use of forceps or prolonged labor with disproportion b/w sixe of fetal head & birth canal |
|
|
Term
def
occipital osteodiastasis |
|
Definition
| separation of bone sutures |
|
|
Term
| What are the 3 important pathological patterns of injury due to birth asphyxia? |
|
Definition
1) non-specific evidence of fetal distress
2) hemorrhages on organ surfaces (thymus, lungs)
3) specific pattern of acute organ injury |
|
|
Term
| What are non-specific evidence of patterns of fetal distress? |
|
Definition
| skin staining with meconium, aspirated meconium in lungs, vascular congestion |
|
|
Term
| What are specific patterns of acute organ injury? |
|
Definition
1) hypoxic-ischemic brain damage in vulnerable areas of brain in term infants
2) neonatal resp. distress syndrome
3) renal failure with acute tubular necrosis & infarcts
4) lymphocyte depletion in thymus
5) adrenal hemorrhage |
|
|
Term
| What is important for identification of potential or actual clinical problems, s.a. evidence of malformation, inf., asphyxia, etc? |
|
Definition
| rapid assessment of liveborn neonate |
|
|
Term
|
Definition
a rapid general clinical assessment of living neonate (0-10) usually assessed at 1, 5, & 10 min after delivery.
It reflects the physiologic condition, responsiveness of newborns & their chances of survival |
|
|
Term
| What does the clinical manifestation of perinatal asphyxia reflect? |
|
Definition
| severity & location of damage & ranges from death to complete recovery |
|
|
Term
| What is a bad outcome of survivors of perinatal asphyxia? |
|
Definition
| premanent deficits s.a. static encephalopathy |
|
|
Term
|
Definition
| non-specific term for non-progressive syndrome of brain dysfunction due to intrauterine or perinatal brain damage |
|
|
Term
| What is the relation of birth weight & prematurity? |
|
Definition
1) <500g ususally do not survive
2) 500-1000g may survive with intensive care, but with high risk of complications & mortality
3) 1000-2500g usually survive, but may have complications & mortality |
|
|
Term
| What organ's development is critical to the neonate's ability to survive in extrauterine environment? |
|
Definition
|
|
Term
| What are the anatomical stages of lung development? |
|
Definition
Lug Bud: 4-6 weeks
Pseudoglandular: 6-16 weeks
Canalicular: 16-26 weeks
Saccular (alveolar): 26 weeks - term |
|
|
Term
| When is the development of alveoli complete? |
|
Definition
|
|
Term
| What are the psysiological stages of lung development? |
|
Definition
Episodic breathing movements: after 10 weeks
Type I & II alveolar cells: 26-32 weeks
Synthesis of surfactant: with appearance of type II alveolar cells, but most abundant after 35-36 weeks |
|
|
Term
| How can maturity of lungs be measured in utero? |
|
Definition
| measuing the lecithin:sphingomyelin ratio in amniotic fluid (>2:1 => low risk of neonatas RDS) |
|
|
Term
| What 5 other organ system immaturities have significant manifestations? |
|
Definition
1) Nervous system
2) BBB
3) Germinal matrix
4) Liver
5) Immune system |
|
|
Term
| What manifestations are seen due to immaturity of the nervous system? |
|
Definition
| homeostatic mechanisms for regulartion of temp, vasomotor control, resp., feeding are poor |
|
|
Term
| What manifestations are seen due to immaturity of the BBB? |
|
Definition
| may permit ingress of unconjugated bilirubin => risk of producing damage to basal ganglia (kernicterus) |
|
|
Term
| What manifestations are seen due to immaturity of the germinal matrix? |
|
Definition
| residual embryonic brain structure susceptible to spontaneous homorrhage |
|
|
Term
| What manifestations are seen due to immaturity of the liver? |
|
Definition
| physiologic immaturity w/ inability to conjugate bilirubin => hyperbilirubinemia |
|
|
Term
| What manifestations are seen due to immaturity of the immune system? |
|
Definition
| predispostion to inf. & sepsis |
|
|
Term
| What are 3 particular patterns of disease related to prematurity? |
|
Definition
1) RDS (respiratory distress syndrome)
2) intracerebral hemorrhage
3) NEC (necrotizing enterocolitis) |
|
|
Term
| What is the leading cause of morbidity & mortality among premature infants? |
|
Definition
RDS
(50% of infants born before 30 weeks gestation die of this disorder) |
|
|
Term
|
Definition
|
|
Term
|
Definition
premature infant, resuscitation may be necessary at birth (usually breathing & color normalize later). Within 30 min, resp. difficulty w/ retraction & grunting appear.
Chest xray show opacification of lungs & infants require intubation & mechanical ventilation |
|
|
Term
| What do the lungs look like grossly in RDS? |
|
Definition
airless, red, & firm
(sink in water) |
|
|
Term
| What do the lungs look like microscopically in RDS? |
|
Definition
| dilated alveolar ducts & hyaline membrane formation with paucity of neutrophilic reaction if early death occurs. |
|
|
Term
| What reparative changes are seen in infants who survive over 48 hrs of RDS? |
|
Definition
| proliferation of alveolar epithelium, desquamation of membranes into the airspace, followed by digestion & phagocytosis of macs. |
|
|
Term
| What type of dysplasia may form if an infant survives RDS? |
|
Definition
| bronchopulmonary dysplasia |
|
|
Term
| How is bronchopulmonary dysplasia (BPD) diagnosed? |
|
Definition
| in a neonate under 32 weeks gestational age who requires at least 28 days of oxygen therapy |
|
|
Term
| What do lungs look like grossly of BPD? |
|
Definition
| bulky, firm with cobblestone surface |
|
|
Term
| What do lungs look like microscopically with BPD? |
|
Definition
1) alveolar wall, peribronchial & interstitial fibrosis
2) obliteration of airspace
3) hyperplasia & squamous cell metaplasia in bronchi & bronchioles |
|
|
Term
| What is the major abnormality in new BPD? |
|
Definition
| decreased alveolar number (alveolar hypolasia) |
|
|
Term
| What causes alveolar hypoplasia? |
|
Definition
| arrested development of alveolar setation in the saccular stage |
|
|
Term
| What is the pathogenesis of hyaline membrane formation in RDS? |
|
Definition
| deficient pulmonary surfactant => increased alveolar surface tension => hypoxemia & CO2 retention => acidosis => pulmonary vasoconstriction & hypoperfusion => pulmonary endothelial/epithelial damage => leakage of plasma into alveoli => hyaline membrane formation |
|
|
Term
| What 3 other factors contricute to the pathogenesis of hyaline membrane formation in the lungs? |
|
Definition
| 1) fetal (damage to resp. centers, meconium aspiration, intrapartum asphyxia)
2) maternal (sedative drugs, DM)
3) therapeutic interventions (high O2, high ventilatory pressure) |
|
|
Term
| Where do most intracerebral hemorrhages occur? |
|
Definition
| in ganglionic eminence (germinal matrix) with secondary bleeding into the ventricles |
|
|
Term
|
Definition
| embryonic structure in wall of lateral ventricle in bran (normally persists until 30 weeks gestation) |
|
|
Term
| What is the microcirculation of the germinal matrix susceptible to damage from? |
|
Definition
| hypoxia & changes in perfusion pressure |
|
|
Term
| Who is usually affected by intracerebral hemorrhage? |
|
Definition
| premature infants <30 weeks gestation |
|
|
Term
| What do the manifestations & prognosis of intracerebral hemorrhage depend on? |
|
Definition
size:
small = asymptomatic
large = seizures, coma, quadriparesis, resp. arrest, & drops in hematocrit => death |
|
|
Term
| What is used to assess the size & extension into adjacent brain parenchyma of the intracranial hemorrhage? |
|
Definition
|
|
Term
| What are the 4 grades of intracranial hemorrhage? |
|
Definition
I: confined to germinal matrix
II: extension into ventricle w/o dilation
III: intraventricular hematoma w/ dilation
IV: extension back into brain parenchyma |
|
|
Term
| What sequelae can survivors of intracranial hemorrhage have? |
|
Definition
| long-term hydrocephalus & neurological deficits |
|
|
Term
| What is the most common GI emergency of newborns? |
|
Definition
|
|
Term
|
Definition
premature infant recovering from RDS & other complications of prematurity following introduction to oral feedings.
andominal distention, bloody stool, features of abdominal obstruction => metabolic acidosis & shock
radiographs show pneumatosis intestinalis |
|
|
Term
def
pneumatosis intestinalis |
|
Definition
| air within intestinal wall |
|
|
Term
| What does the prognosis of NEC depend on? |
|
Definition
| length of involved segment & associated pathologies |
|
|
Term
|
Definition
| if caught early, may be managed conservatively, but many cases require resection of the necrotic segment |
|
|
Term
| What secondary complication can arise due to the resection of the necrotic section in NEC? |
|
Definition
"short gut syndrome" if sifnificant length of sm. intestine was removed.
secondary strictures & chronic obstruction can result from fibrosis |
|
|
Term
| What is the pathogenesis of NEC? |
|
Definition
| generalized hypoperfusion or selective reduction of blood flow to the intestine in order to divert oxygen to vital organs => intestinal ischemia => transluminal migration of gut bacteria => inflammation, further necrosis => perforation, peritonitis, sepsis, shock |
|
|
Term
| What part of the bowel is usually affected by NEC? |
|
Definition
| any part can be, but usually terminal ileum, cecum, & righ colon |
|
|
Term
| What do the intestines look like grossly with NEC? |
|
Definition
| dilation, segmental necrosis, air bubbles in the wall, sometimes perforation |
|
|
Term
| What do NEC intestines look like microscopically? |
|
Definition
| mucosal or transmural coagulative necrosis, ulceration, bacterial colonization with minimal inflammation & sometimes filled with air spaces |
|
|
Term
| What is the leading cause of death in infants 1 mo - 1 yr? |
|
Definition
|
|
Term
|
Definition
| subset of infants dying unexpectedly during the 1st year of life with apparent onset during sleep that remains unexplained after the performance of a complete postmortem investigation, including autopsy, exam of death scene, & review of case Hx showing no signs of Sx of lethal disease |
|
|
Term
| When do most cases of SIDS occur? |
|
Definition
| b/w 2-4 mo & before 6 mo. |
|
|
Term
| What are ths risk factors for SIDS? |
|
Definition
1) low socioeconomic status
2) young maternal age
3) maternal smoking during pregnancy
4) drug abuse in either parent
5) high marity for maternal age
6) Hx of deficient prenatal care
7) short interval b/w pregnancies
8) Hx of prior SIDS in siblings
9) low maternal education
10) low birth weight, IUGR
11) prone sleep position |
|
|
Term
| What are the external findings in an infant with SIDS? |
|
Definition
well developed & nourished
cyanosis of lips & nailbeds
postmortem lividity |
|
|
Term
| What are the internal findings of infants with SIDS? |
|
Definition
congested lungs
prominent petechiae on pleura, thymus, & epicardium
involution of thymus
histological evidence of URTI (not severe enough to account for death)
gliosis of brain stem & cerebellum |
|
|
Term
|
Definition
|
|
Term
| What can change the pathological Dx of SIDS? |
|
Definition
| findings of a specific disease |
|
|
Term
| What conditions mimic SIDS? |
|
Definition
1) sepsis & inf.: myocarditis, bronchopneumonia
2) intoxication: drugs, toxins
3) congenital heart disease: arotic stenosis, anomalous origin of LCA from pulmonary a.
4) Metabolic & genetic diseases: long QT syndrome, fatty acid oxidation disorders, histiocytoid cardiomyopathy
5) trauma/abuse/infanticide |
|
|
Term
| What is the pathogenesis of SIDS? |
|
Definition
unknown, but likely multifactorial
(possible a delayed development of brain arousal & cardiorespiratory control centers, or altered chemoreceptor function)
(NOT a reaction to DPT immunization & effects of previous placental dysfunction) |
|
|
Term
| What accounts for 20% of all fetal/neonatal diseases? |
|
Definition
|
|
Term
| Why is the fetus protected from infection in the womb? |
|
Definition
| sterile environment & natural barriers |
|
|
Term
| What normal barriers protect the fetus from infection? |
|
Definition
1) maternal: mucous membranes of cervix & vagina, intact maternal immune system & maternal IgG
2) placental: amnion provides physical barrier & amniotic fluid is bacteriostatic
3) fetal/infant: skin, mucous membrane, immune system (starts to mature) |
|
|
Term
| What determines the fetal/neonatal response to infection? |
|
Definition
| maturity (immaturity) of developing immune system |
|
|
Term
| When do monocytes/macs first appear? |
|
Definition
|
|
Term
| When do granulocytes first appear? |
|
Definition
|
|
Term
| When do T & B cells first appear? |
|
Definition
|
|
Term
| When does immune function being? |
|
Definition
after 12 weeks gestation
(tho doesnt reach adult efficiency until after 1 year) |
|
|
Term
| What does the immature hemodynamic & thermal control lead to if stressed (i.e. inadequate production of RBCs, WBCs, platelets, & coag. factors when infection present)? |
|
Definition
|
|
Term
| What are the 2 reasons patterns of infection early in life may differ from adults? |
|
Definition
1) damage to developing fetal cells/tissues or placenta => subsequent hypoplasia, malformations, & disruptions
2) inflam. or reparative reactions may be minimal |
|
|
Term
| What are the 2 routes infections can reach the fetus? |
|
Definition
1) transplacental (hematogenous)
2) transcervical (ascending, amniotic) |
|
|
Term
| When can transplacental infections occur? |
|
Definition
| any time during gestation or occationally at time of delivery via maternal to fetal transfusion |
|
|
Term
| Where do organisms that infect fetuses via transplacental route originate? |
|
Definition
| from mother, usually viral, & invade fetal bloodstream from chorionic villi & become widely disseminated |
|
|
Term
| What are the 7 common transplacental infections? |
|
Definition
1) TORCH (toxoplasma, other, rubella, CMV, HSV)
2) listeria
3) HIV |
|
|
Term
|
Definition
1) premature, IUGR
2) CNS damage (microcephaly, calcification, hydrocephalus, psychomoto retardation, eye & ear damage)
3) liver (hepatomegaly, jaundice)
4) cardiopulmonary (congenital heart disease, pneumonitis, myocarditis)
5) musculoskeletal deformities
6) skin & mucossal vesicular & hemorrhagic leisons |
|
|
Term
| What are the effects of a parvovirus B19 fetal infection? |
|
Definition
| "fifth disease" (erythema infectiosum) => spontaneous abortion, stillbirth, hydrops fetalis, congenital angina |
|
|
Term
| Where does parvovirus B19 replication occur? |
|
Definition
|
|
Term
| Where do diagnostic cytopathic changes occur in parvovirus B19? |
|
Definition
|
|
Term
| Where do organisms that infect fetuses via transcervical route originate? |
|
Definition
| maternal genital tract ascend thru tract or ruptured membranes & can invade amniotic fluid => fetus inhales before birth/during delivery |
|
|
Term
| Can the placenta get infected transcervically? |
|
Definition
| yes (chorioamnionitis & funisitis) ∴ postnatal exam of placenta may help to recognize presence of infection |
|
|
Term
| What agents tend to infect fetuses transcervically? |
|
Definition
| variety of bacteria, Candida, & HSV |
|
|
Term
| Can intrauterine/fetal instruments provide access for organisms? |
|
Definition
| yes, esp. bacteria (but's rare) |
|
|
Term
| What infective organisms are neonates exposed to in the intrapartum route? |
|
Definition
| verious orgs. s.a. staph, PSA, non-group B step |
|
|
Term
| Why is the diagnosis of infection in neonates complex? |
|
Definition
| includes the ability to recognize evidence of previous intrauterine inf., presence of active inf, & neonate's risk of developing an inf. in early postnatal period |
|
|
Term
| What are some potentially important clues in the Dx of infection in the neonate? |
|
Definition
1) chorioamnionitis
2) IUGR
3) hydrops fetalis
4) hydrocephalus or microcephaly
5) eye leisons
6) failure to thrive
7) jaundice/hepatosplenomegaly
8) skin rashes
9) RDS |
|
|
Term
| What is the most common cause of early onset sepsis & bacterial meningitis of neonates? |
|
Definition
|
|
Term
def
early perinatal infection |
|
Definition
| within first 7 days of life |
|
|
Term
def
late perinatal infection |
|
Definition
| b/w 7 days & 3 months postnatal |
|
|
Term
| What is the leading cause of death in children (after trauma)? |
|
Definition
|
|
Term
| What are the most common adult neoplasms? |
|
Definition
|
|
Term
| What are the most common neoplasms in children? |
|
Definition
| hematopoietic neoplasms, CNS neoplasms, embryonic neoplasms, & sarcomas |
|
|
Term
| What are the common neoplasms in children <3 months (congenital)? |
|
Definition
1) hemangiomas
2) lymphangiomas
3) nevi
4) leukemia
5) neuroblastoma
6) sacrococcygeal teratoma
7) tissue sarcomas |
|
|
Term
| What neoplasms are common in infancy & early childhood (<5y)? |
|
Definition
1) leukemia
2) CNS tumors
3) lymphoma
4) Wilms tumor
5) neuroblastoma
6) retinoblastoma
7) tissue sarcomas |
|
|
Term
| What neoplasms are common in late childroom (5-14y)? |
|
Definition
1) leukemia
2) CNS tumors
3) lymphoma
4) soft tissue sarcomas |
|
|
Term
| What are the common neoplasms in adolescence (14-19y)? |
|
Definition
1) lymphoma
2) CNS tumors
3) leukemia
4) bone tumors |
|
|
Term
| Are benign or malignant tumors more common in the pediatric population? |
|
Definition
|
|
Term
| What can cause non-neoplastic masses due to errors in development in the pediatric population? |
|
Definition
1) heterotopias/choristomas
2) hamatomas |
|
|
Term
def
heterotopias/christomas |
|
Definition
| masses of microscopically normal cells or tissues in abnormal locations (i.e. sctopic pancreatic tissue in jejunum) |
|
|
Term
|
Definition
| excessive focal overgrowth of cells & tissue native to organ of origin (i.e. pulmonary hamartoma) |
|
|
Term
| What 5 benign neoplasms commonly present as congenital leisons? |
|
Definition
1) hemangiomas
2) lymphangiomas
3) congenital melanocytic nevi
4) fibromatoses
5) teratomas |
|
|
Term
| What's the most common type of congenital tumor? |
|
Definition
|
|
Term
|
Definition
| tumors of mature blood vessels |
|
|
Term
| What happens to juvenile hemagiomas over time? |
|
Definition
| may initally enlarge with the growth of the child, but usually spontaneously regress |
|
|
Term
| What can large hemangiomas lead to? |
|
Definition
| coagulopathies or high output cardiac failure |
|
|
Term
| Do hemangiomas just occur alone, or as part of a synfrome? |
|
Definition
|
|
Term
|
Definition
| tumor of lymphatic vessels |
|
|
Term
| Where do lymphangiomas usually arise? |
|
Definition
| on neck or axillary region, and can be superficial or involve deeper structures |
|
|
Term
| How do neck/axillary lymphangiomas cause problems? |
|
Definition
| compression of neck structures/resp. system |
|
|
Term
| Which lymphangiomas tend to compromise vital structures, tho benign? |
|
Definition
|
|
Term
def
congenital melanocytic nevi |
|
Definition
| benign proliferation of melanocytes |
|
|
Term
| Which congenital melanocytic nevi have an increased risk of malignant transformation to melanoma? |
|
Definition
|
|
Term
|
Definition
proliferation of fibroblastic cells in soft tissues
(vary cellularly & may mimic sarcomas in adults, but don't metastasize) |
|
|
Term
| Where are fibromatoses often found? |
|
Definition
| subq or intramuscular in skin, head & neck (esp. SCM), fingers |
|
|
Term
| When can fibromatoses cause more morbidity & mortality? |
|
Definition
multifocal (vs. solitary)
vital organs s.a. lung & heart |
|
|
Term
| What happens to fibromatoses if left untreated? |
|
Definition
| generally enlarge, but some spontaneously regress |
|
|
Term
| What are the most frequent malignant tumors? |
|
Definition
1) leukemia
2) CNS tumors
3) lymphoma
4) Wilms' tumor
5) neuroblastoma
6) soft tissue sarcomas |
|
|
Term
| What are the 3 types of malignant hematopoietic neoplasms? |
|
Definition
1) leukemias
2) lymphomas
3) histocytoses |
|
|
Term
| What is the most common malignant neoplasm of children? |
|
Definition
|
|
Term
| Wht are predisposing conditions for leukemia? |
|
Definition
1) leukemic twin/sibling
2) chromosomal abnormalities
3) inherited primary immunodeficiency diseases
4) some genetic syndromes |
|
|
Term
| What is the most common leukemia in children? |
|
Definition
| ALL (acute lymphoblastic leukemia) |
|
|
Term
def
Langerhans cell histocytosis (LHC)
(histocytosis X) |
|
Definition
tumor-like proliferation of Langerhans cells
(Note: there is controversy if this is true clonal neoplastic proliferation or a reactive process) |
|
|
Term
| What are the 3 clinical forms Langerhans cell histocytosis presents as? |
|
Definition
1) acute disseminated (Letterer-Siwe)
2) multifocal leisons (Hand-Schuller-Christian)
3) solitary leisons (eosinophilic granuloma) |
|
|
Term
|
Definition
onset: infancy
skin & systemic involvement |
|
|
Term
|
Definition
Onset: childhood
usually within bones or organs
50% develop DI (due to involvement of hypothalamus & post. pituitary) |
|
|
Term
|
Definition
Onset: late childhood/easrly adult
usually within bones |
|
|
Term
| Which of the LHC forms is associated with poor outcome? |
|
Definition
|
|
Term
| Which of the LHC forms is associated with excellent prognosis (either by spontaneous healing or local excision)? |
|
Definition
|
|
Term
| What is the prognosis of multifocal leisons LHC? |
|
Definition
| depends on sites of involvement, but in most patients can be controlled by chemo |
|
|
Term
| What is the histology of all clinical forms of LHC? |
|
Definition
leison is made of sheets of large "histiocytoid" Langerhans cells with grooved irregular nuclei ("X" cells) with variable numbers of eosinophils, plasma cells, & lymphocytes.
ultrastructural exam shows classic cytoplasmic inclusions (Birbeck granules) |
|
|
Term
|
Definition
| tumors whose cell components recapitulate components of the gonadal cell, embryo, or placenta |
|
|
Term
|
Definition
| oogonia/oocytes & spermatogonia |
|
|
Term
| What are the most common location of germ cell tumors? |
|
Definition
| gonadal tumors (ovary & testis) |
|
|
Term
| Where do extragonadal germ cell tumors arise? |
|
Definition
| in midline structures s.a. sacrococcygeal region, pineal gland, mediastinum, & retroperitoneum |
|
|
Term
| What is the most common type of germ cell tumors in children? |
|
Definition
|
|
Term
| What is the most common childhood teratoma? |
|
Definition
|
|
Term
| Are sacrococcygeal teratomas more common in girls or boys? |
|
Definition
| girls (often associated with congenital anomalies, esp. midline defects like spina bifida & meningocele) |
|
|
Term
| What is the most common type of malignant germ cell tumor in children? |
|
Definition
|
|
Term
| What helps Dx of germ cell tumors? |
|
Definition
| hormone secretion in blood s.a. α-fetoprotein (AFP) in YST, HCG in choriocarcinoma |
|
|
Term
|
Definition
| highly malignant neoplasms compsed of primitive appearing cells resembling embryonic or fetal somatic cells |
|
|
Term
| When do embryomas become apparent? |
|
Definition
usually at birth (congenital) or during childhood
(incidence decreases with age, and are very rare in adults) |
|
|
Term
| Where do embryomas usually occur? |
|
Definition
| in particular organs as mass leisons, with characteristic features |
|
|
Term
| What is the most common extracranial solid tumor in children? |
|
Definition
|
|
Term
| Where does neuroblastoma dervive from? |
|
Definition
| neural crest cells of the sympathetic ganglia or adrenal medulla |
|
|
Term
| What familial gene mutation is neuroblastoma associated with? |
|
Definition
|
|
Term
| How does neuroblastoma usually present? |
|
Definition
large abdominal mass
often wide metastasis
may secrete catecholamines |
|
|
Term
| What is the prognosis of neuroblastoma? |
|
Definition
depends on age, stage, & various histologic and molecular genetic parameters
tumors classified into high risk & low risk |
|
|
Term
| What is the behavior of embryonic tumors? |
|
Definition
| destructive local behavior & metastasis |
|
|
Term
| What is the prognosis of embryonic tumors? |
|
Definition
depends on type & clinical stage at Dx
some may spontaneously mature or regress |
|
|
Term
| What are pediatric tumors frequently associated with? |
|
Definition
developmental/genetic diseases s.a.
1) syndromes (tumors + malformations)
2) chromosomal & genetic disorders
3) malformed organs (i.e. germ cell tumors in gonadal dysgenesis) |
|
|
Term
| Are all congenital anomalies/malformations present at birth? |
|
Definition
| yes, but may not become clinically apparent until later in life |
|
|
Term
| Are single defects specific or non-specific (i.e. associated with any one syndrome or etiology)? |
|
Definition
|
|
Term
| Do congenital malformation expression/severity vary or remain static among individuals with the same syndrome? |
|
Definition
| varies, can even vary within the same individual with one anomaly predominating over others |
|
|
Term
| Do the same phenotypes arise from the same congenital anomalies/malformations? |
|
Definition
| not necessarily, ~ phenotypes may result from different etiologies |
|
|
Term
|
Definition
| morphologic defect resulting from an intrinsically abnormal developmental process that may involve a single body system of multiple systems |
|
|
Term
|
Definition
| adverse effect on organ function/social function or acceptability |
|
|
Term
|
Definition
| may be configurational or cosmetic |
|
|
Term
|
Definition
| frequent, usually w/o effect on function |
|
|
Term
|
Definition
| abnormal form, shape, position caused by extrinsic mechanical force |
|
|
Term
|
Definition
| most commonly uterine restraint, but also uterine anomalies/tumors, multiple fetuses, oligohydraminos, CNS abnormalities, & musculoskeletal dysplasia in the fetus - appear later in fetal life |
|
|
Term
| Are deformations of next child at an increased risk if the first child has a deformation? |
|
Definition
| less risk of recurrance (but still risk) |
|
|
Term
|
Definition
| abnormal form due to breakdown or destruction of originally normal structures during development, not heritable. |
|
|
Term
|
Definition
| environmental factos s.a. radiation & inf. or uteroplacental factors s.a. amniotic deformity & adhesions and uterine leiomyomas |
|
|
Term
|
Definition
Amniotic Deformities
Adhesion
Mutilation
(or amniotic band syndrome) |
|
|
Term
| What is the cascade of events in the ADAM complex? |
|
Definition
| single known primary malformation, disruption, or deformation => early rupture of amnion => formation of adhesions (amniotic bands) => constriction/distortion of fetus |
|
|
Term
| Is the ADAM complex thought to be related to any particular syndrome? |
|
Definition
| multiple anomalies are thought to be related, but can't be explained on the basis of a single initiating defect |
|
|
Term
| What is the most common cause of amniotic band syndrome? |
|
Definition
| single etiologic agent s.a. viral inf. or chromosomal abnormality, which simultaneously affects several tissues |
|
|
Term
| What do the multiple anomalies associated with the ADAM complez result from? |
|
Definition
| disturbed development of a morphogenic region of embryo |
|
|
Term
|
Definition
| complete absence of an organ & its associated primordium |
|
|
Term
|
Definition
| absence of an organ due to failure of development of the primordium |
|
|
Term
|
Definition
| absence of an opening, usually of a hollow visceral organ |
|
|
Term
|
Definition
| incomplete development or underdevelopment of an organ with decreased number of cells |
|
|
Term
|
Definition
| overdeveopment of an organ associated with increased numbers of cells |
|
|
Term
|
Definition
| overdevelopment of an organ associated with increased in size of individual cells |
|
|
Term
|
Definition
| underdevelopment due to decrease in size of individual cells, known as atrophy |
|
|
Term
|
Definition
abnormal organization of cells
(in the context of malformation vs. neoplasia) |
|
|
Term
| What are the causes of congenital anomalies? |
|
Definition
1) genetic
2) environmental
3) multifactorial
4) unknown (40-60%) |
|
|
Term
| Are all chromosomal syndromes congenital anomalies? |
|
Definition
|
|
Term
| How many neonates with congenital anomalies are due to karyotypic abnormalities? |
|
Definition
|
|
Term
| What is the most common chromosomal anomaly? |
|
Definition
Down Syndrome
(followed by Klinefelter, Turner, and Trisomy 13) |
|
|
Term
| How do the majority of chromosomal anomalies arise? |
|
Definition
| de novo as defects in gametogenesis & ∴ are not transmissible |
|
|
Term
| Can any chromosomal anomalies be transmitted? |
|
Definition
| yes (i.e. translocation form of trisomy 21) |
|
|
Term
| What pattern of inheritance do single gene mutations follow? |
|
Definition
| Mendelian pattern of inheritance |
|
|
Term
| What % of single gene mutations are X-linked? |
|
Definition
|
|
Term
| Can mutations in more than one gene produce similar phenotypes? |
|
Definition
| yes (but they may vary in severity) |
|
|
Term
| What environmental factors are fetuses subject to? |
|
Definition
| maternal exposureduring pregnancy to carinogens that are teratogenic |
|
|
Term
| What are 3 environmental factors the fetus may be exposed to? |
|
Definition
1) viruses
2) drugs/chemicals
3) radiation |
|
|
Term
| What viruses can infect the fetus? |
|
Definition
| many s.a. rubella, CMV, HSV, VZV, influenza, mumps, HIV, & enterovirus |
|
|
Term
| What is important in determining the extent of viral damage to the fetus? |
|
Definition
| gestational age at time of maternal exposure |
|
|
Term
|
Definition
| major tetrad: cataracts, heart defects, MR, & deafness |
|
|
Term
| When are fetuses more at risk for rubella syndrome? |
|
Definition
| shortly before conception to 16 weeks gestation (with the first 8 weeks posing the greatest hazard) |
|
|
Term
| What is the most common fetal viral inf.? |
|
Definition
|
|
Term
|
Definition
most commonly asymptomatic
can be:
CNS - MR, microcephaly
deafness
hepatosplenomegaly |
|
|
Term
| What commonly used drugs/chemicals are teratogenic? |
|
Definition
| variety inc. thalidomide, folate antagonists, androgenic hormones, EtOH, anticonvulsants, warfarin, 13-cis retinoic acid (acne med) |
|
|
Term
Sx
thalidomide use during pregnancy |
|
Definition
(used as a tranquilizer in the past)
limb abnormalities in 50-80% exposed fetuses |
|
|
Term
Sx
FAS (fetal EtOH syndrome) |
|
Definition
growth retardation
microcephaly
atrial septal defect
short palpebral fissures
maxillary hypoplasia
other minor abnormalities |
|
|
Term
|
Definition
mutagenic
carcinogenic
teratogenic |
|
|
Term
| What can exposure to heavy doses of radtion during organogenesis lead to? |
|
Definition
| malformations s.a. microcephaly, blindness, skull defects, spina bifida, & other deformities |
|
|
Term
| When was radiation exposure prominent? |
|
Definition
| in past when used to treat cervical cancer |
|
|
Term
| What is in example of multifactoral causes of congenital anomalies? |
|
Definition
congenital dislocation of the hip:
depth of socket & laxity of ligaments = genetic
infants in breech position more likely to have a dislocation of the hip |
|
|
Term
| What decreased incidence of neural tube defects? |
|
Definition
| supplementary intake of folic acid in prenatal care |
|
|
Term
| What 3 things are important in the pathogenesis of congenital anomalies? |
|
Definition
1) timing of prenatal teratogenic insult
2) teratogenic agent
3) duration of exposure |
|
|
Term
| What are the 2 phases of intrauterine development? |
|
Definition
1) embryonic period (first 9 weeks of gestation)
2) fetal period (9 weeks to birth) |
|
|
Term
|
Definition
| characterized by creation of organs out of the germ cell layers |
|
|
Term
| What happens if an embryo is exposed to a teratogen in the first 3 weeks? |
|
Definition
1) damage enough cells to cause abortion
2) damage only a few cells & the embryo recovers w/o developing defects |
|
|
Term
| When is the embryo extremely susceptible to teratogenesis? |
|
Definition
| b/e 3 & 9 weeks gestation (peak sensitivity b/w 4 & 5 weeks) |
|
|
Term
|
Definition
| characterized by growth & maturation of the organs |
|
|
Term
| Is the fetus more of less susceptible to teratogens in the fetal period than the embryonic period? |
|
Definition
|
|
Term
| What is the fetus more susceptible to in the fetal period via teratogens(vs. the embryonic period)? |
|
Definition
| growth retardation & injury to already formed organs |
|
|
Term
| How many defects do each teratogen cause? |
|
Definition
| 1+ (some only 1, some multiple) |
|
|
Term
| What determines an individual's susceptibility to a particular teratogen? |
|
Definition
| variable & involez complex interactions among genetic, maternal, placental, & other factors (s.a. time of exposure to agen & dose) |
|
|
Term
| Does each teratogen have a specific site of action? |
|
Definition
| yes (tho mechanism may be unknown) |
|
|
Term
| What are possible effects/outcomes following exposure to a teratogen? |
|
Definition
1) death of embryo/fetus in utero
2) malformation
3) functional impairment w/o recognizable malformation
4) growth retardation
5) no effect |
|
|
Term
Do teratogens & genetic defects act only in one step involved in normal morphogenesis?
What are the possible steps? |
|
Definition
no, can act at one of more than one step s.a.
1) cell migration
2) cell proliferation
3) cellular interactions
4) cell-matrix associations
5) apoptosis
6) hormonal influences & mechanical forces |
|
|
Term
|
Definition
| cells move to predetermined locations that influence the development of other structures |
|
|
Term
| What determines the size & form of embryonic organs? |
|
Definition
|
|
Term
| What effect do cellular interactions among tissues derived from different structures have on morphogenesis? |
|
Definition
| affect differentiation of one or both structure |
|
|
Term
| What affects growth & differentiation? |
|
Definition
|
|
Term
Function
apoptosis in embryogenesis |
|
Definition
| orderly organization of tissues & organs |
|
|
Term
Function
hormonal influences & mechanical forces in morphogenesis |
|
Definition
| affect morphogenesis at many levels |
|
|
Term
| When do CNS malformations occur? |
|
Definition
|
|
Term
| When do heart malformations occur? |
|
Definition
|
|
Term
| When do GI/lung malformations occur? |
|
Definition
|
|
Term
| When do GU malformations occur? |
|
Definition
| as early as 12 gestational week, or as late as 7-9 months |
|
|
Term
| When do face malformations occur? |
|
Definition
| 6-10th week gestational age |
|
|
Term
| When do limb malformations occur? |
|
Definition
| 4-6th week gestational age |
|
|
Term
|
Definition
| structural & functional changes that occur in a cell or organism over time => impairment of performance, increased susceptibility to disease, & ultimately, death.WE |
|
|
Term
| What is the general view of aging? |
|
Definition
| it's the sum of all changes occuring with time |
|
|
Term
| What is the specific view of againg? |
|
Definition
| it's a particular post-maturational period of decline in health and physiological vigor (i.e. senescence, culminating in death) |
|
|
Term
| What are the 7 stages of life? |
|
Definition
1) conception
2) development
3) reproduction
4) sageing
5) senescence
6) dying
7) death |
|
|
Term
|
Definition
|
|
Term
|
Definition
| medical specialty dealing with diseases affecting the elderly |
|
|
Term
| How long do bacertia live? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| How long do animals live? |
|
Definition
| some (insects) < 1 day to > 150 years (tortoise, giant clam) |
|
|
Term
|
Definition
| plot of percent surviving individuals of a population cohort over time until the last remaining individual dies |
|
|
Term
def
maximum lide span potential |
|
Definition
| time at which the last individual in the population dies |
|
|
Term
def
50% (or median) survival |
|
Definition
| time at which 50% of the population/cohort has died |
|
|
Term
|
Definition
| observed length of life for an individual |
|
|
Term
| What are the 2 possible forms a survival curve may possess? |
|
Definition
1) exponential decline
2) sigmoid ("rectangularized") decline |
|
|
Term
| What is implied when an exponential decline is seen in a survival curve? |
|
Definition
1) fraction of dying remains constant over time
2) reflects constant intensity of exogenous hazards (accidents, preditors, inadequate nutrition, etc) |
|
|
Term
| What type of populations tend to have an exponential decline in their survival curve? |
|
Definition
| populations "in the wild" |
|
|
Term
| What is implied when an sigmoid decline is seen in a survival curve? |
|
Definition
1) fraction of dying changes over time
2) reflects diminished exogenous hazards throughout life
3) exhibits the phenomenon of "aging" |
|
|
Term
| What type of populations tend to have an sigmoid decline in their survival curve? |
|
Definition
| non-wild conditions (civilization, domestication) |
|
|
Term
| Why has there been a shift from exponential to sigmoid survival curves over time? |
|
Definition
reduced birth & infant mortality
improved hygiene & nutrition
reduced mortality from inf. & other medical conditions |
|
|
Term
| What has happened to life expectancy & maximum life span potential over time? |
|
Definition
LE: increased
MLSP: no change |
|
|
Term
| What life phase do most individuals NOT reach if the survival curve is more exponential? |
|
Definition
|
|
Term
| What is life expectancy related to? |
|
Definition
| intensity of environmental hazards & can be prolonged by reducing them |
|
|
Term
| Does maximum lide span potential depend on life expectancy? |
|
Definition
|
|
Term
| What determines the maximum life span potential? |
|
Definition
| varies among species (usually limited) |
|
|
Term
| What 4 things must the theories of aging account for? |
|
Definition
1) individuals within a species have similar MLSP
2) individuals from different species have diffeernt MLSP
3) aging changes are similar among individuals of one species & share similarities among species & even among widely different groups
4) there is a trend for increased survival to later years |
|
|
Term
| What contributes to aging? |
|
Definition
| genetic & environmental factors |
|
|
Term
| How do we know aging has a genetic comonent? |
|
Definition
1) longevity runs in familys
2) differents in longevity vary more in fraternal vs identical twins
3) genetic syndromes can mimic aging
4) normal molecular processes
5) experimental observations |
|
|
Term
| What 2 genetic syndromes mimic aging? |
|
Definition
1) infantile progeria syndrome
2) adult progeria syndrome |
|
|
Term
| How is infantile progeria syndrome inherited? |
|
Definition
| sporadic or autosomal recessive |
|
|
Term
| What is the life expectancy in infantile progeria syndrome? |
|
Definition
|
|
Term
| What is the genetic defect in infantile progeria syndrome? |
|
Definition
| single gene defect in lamin A gene (nuclear membrane protein) |
|
|
Term
| How is adult progeria syndrome inherited? |
|
Definition
|
|
Term
| What is the life expectancy of adult progeria syndrome? |
|
Definition
|
|
Term
| What gene is defective in adult progeria syndrome? |
|
Definition
| single gene defect in DNA helicase gene (DNA repair & recombination) |
|
|
Term
Sx
infantile/adult progeria syndrome |
|
Definition
(NOT identical to normal aging)
hair loss
loss of subq fat
accelerated atherosclerosis
osteoporosis
cataracts
etc |
|
|
Term
| What controls the programmed sequences of events in populations of normal cells s.a. cell production, maturation, senecence & death? |
|
Definition
|
|
Term
| What was observed in the Hayflick & Moorhead experiments? |
|
Definition
1) number of doublings of non-transformed fibroblast-like cells in cell culture is finite, followed by deterioration (senescence)
2) number of doublings is related to MLSP of the species |
|
|
Term
| What is the average number of doublings of non-transformed fibroblast-like cells in cell culture for humans? |
|
Definition
|
|
Term
| When does apoptosis occur? |
|
Definition
| during normal development & throughout life |
|
|
Term
|
Definition
| specific genes & proteins |
|
|
Term
|
Definition
| repetitive short DNA sequences (TTAGGG) at the ends of each chromosome |
|
|
Term
|
Definition
plays a role in the regulation of the number of cell divisions since they shorten with each division
They are lost after ~50 divisions, after which, division can no longer occur => cell cycle arrest & cell senescence |
|
|
Term
|
Definition
1) lengthen DNA sequence during development, but activity is progressively lost later & is absent from somatic cells
2) has a role in carcinogenesis
3) telomere-telomerase interaction may play a role in aging & progerias |
|
|
Term
|
Definition
| NAD dependent protein deacetylases |
|
|
Term
|
Definition
variety of cell functions s.a. DNA recombination, repair, gene expression
They protect against acetylation of molecules |
|
|
Term
| What effect does acetylation have on most molecules? |
|
Definition
| progressive interference with normal function |
|
|
Term
| How does caloric restiction increase longevity? |
|
Definition
oxidative/free radical damage
(tho role in human biology is uncertain) |
|
|
Term
What effect does controlling genetic/environmental hazards have on LE?
on MLSP? |
|
Definition
LE: increases
MLSP: may also increase |
|
|
Term
| What organ size shares a direct correlation to longevity? |
|
Definition
|
|
Term
| What are the 4 possible mechanisms of aging? |
|
Definition
1) changes in properties of replicating cells
2) loss or injury in replicating or postmitotic cells
3) primary changes in intracellular or extracellular materials
4) alteration of regulatory systems |
|
|
Term
| What are the 3 mechanisms by which aging theories are grouped? |
|
Definition
1) genomic mechanisms
2) "wear & tear" mechanisms
3) regulatory system mechanisms |
|
|
Term
def
genomic mechanisms of aging |
|
Definition
| aging is affected thru the function of specific genes (gerontogenes), inc. genes important in cell doubling limitations (telomerases), apoptosis, & gene regulation (sirtuins) |
|
|
Term
| What's an example of a genomic mechanism theory? |
|
Definition
|
|
Term
def
somatic mutations theory |
|
Definition
errors in somatic or mitochondrial DNA replication accumulate & ultimately impair capacity of cells/organism to survive
(may be important in pathogenesis of increased cancer rate in elderly) |
|
|
Term
def
"wear & tear" mechanisms of aging |
|
Definition
| aging occur thru accumulation of damage due to random events (i.e.e free radical damage, glycosylation, trauma, etc) |
|
|
Term
| What's an example of a "wear & tear" mechanism theory? |
|
Definition
|
|
Term
|
Definition
endogenously generated free radicals causing damage to nucleic acids, proteins, & membrane lipids by free radicals ultimately lead to cell dysfunction/death
(may contribute to the pathogenesis of some diseases s.a. cataracts, CAD, cancers, etc) |
|
|
Term
| Similar arguments of the free radical theory can be applied to what other cellular damage that occurs with age? |
|
Definition
| glycosylation of proteins & nucleic acids |
|
|
Term
def
regulatory system mechanisms |
|
Definition
| aging occurs thru read-out of physiologic programs involving specific body systems |
|
|
Term
| What are the 3 main regulatory system mechanism theories? |
|
Definition
1) immunologic theory
2) neuroendocrine theory
3) metabolic energy (rate of living) theory |
|
|
Term
|
Definition
changes in immune system lead to abnormal immune function, ultimately causing aging & death
(may be related to increased incidence of autoimmune disease & neoplasms in the elderly) |
|
|
Term
|
Definition
impairment or loss of function in hypothalamic-pituitary-adrenal axis, ultimately impairs the homeostasis for the whole organism
includes the concept of the brain "pacemaker" or "master timekeeper" |
|
|
Term
| What is the evidence for the neuroendocrine theory? |
|
Definition
| observations of normal control of reproductive function, but site has not been localized |
|
|
Term
def
metabolic energy (rate of living) theory |
|
Definition
| MLSP is proportional to the amount of energy consumed by the organism during it's lifetime |
|
|
Term
def
lifespan energy potential |
|
Definition
| a fixed average energy consumed over a lifetime per unit of body weight |
|
|
Term
| What are the 3 criticisms of the aging hypotheses? |
|
Definition
1) hypotheses dependent on random events are difficult to reconcile with the relative uniformity of the aging process
2) many mechanisms imply death of individual cells as the end point, so how does damage to individual cells translate into aging & death of the whole organism?
3) no single mechanism explains all phenomenon - ∴ aging is likely a combination of genetic & regulatory factors interacting with environmental factors |
|
|
Term
| What is the overall number one cause of death? |
|
Definition
|
|
Term
| What is the major cause of death in children 1-14y? |
|
Definition
|
|
Term
| What is the major cause of death of the elderly (>85y)? |
|
Definition
|
|
Term
|
Definition
| diseases increasing in frequency with aging, but not caused directly by aging |
|
|
Term
| What are some examples of age-related diseases? |
|
Definition
1) atherosclerosis
2) atherosclerotic cardiac/cerebrovascular disease
3) septicemia
4) pneumonia
5) emphysema
6) cancer
7) AD
8) PD |
|
|
Term
def
age-dependent diseases |
|
Definition
| diseases largely limited to aging populations & directly related to effects of age or chronic exposure |
|
|
Term
| What are some examples of age-dependent diseases? |
|
Definition
1) osteoporosis
2) osteoarthritis
3) cataracts
4) prostatic hyperplasia
5) prostatic carcinoma
6) temporal arteritis
7) otosclerosis |
|
|
Term
def
aging changes (primary) |
|
Definition
| non-disease conditions present in virtually every elderly individual |
|
|
Term
| What are examples of aging changes? |
|
Definition
1) menopause
2) gonadal atrophy
3) wrinkles
4) graying/loss of hair
5) intracellular accumulation of lipofuscin
6)arcus senilis |
|
|
Term
|
Definition
| occuring in all members of a species |
|
|
Term
|
Definition
| not related to environmental factors |
|
|
Term
|
Definition
| continuous & gradual over time |
|
|
Term
def
deleterious (to organism) |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why is normal aging difficult to assess? |
|
Definition
1) manifestations of aging can vary in severity & time of onset among racial & ethnic groups, families, and individuals
2) aging changes may be obscured by concomitant occurance of diseases (primary aging vs. secondary aging)
3) some aging changes may actually be due to environmental or other causes (i.e. wrinkling due to sun exposure) |
|
|
Term
| What changes of body composition occur with aging? |
|
Definition
1) increased propotion of body fat
2) decreased bone & muscle mass (lean mass)
3) decreased tissue water |
|
|
Term
| What alterations in cardiovascular function occur with age? |
|
Definition
1) decreased compliance of lg. arteries
2) decreased β-adrenergic responsiveness of myocardium
3) decreased baroreflex sensitivity
4) increased end-diastolic volume
5) increased systolic BP
6) thickening & calcification of cardiac vavle leaflets |
|
|
Term
| What alterations in resp. function occur with age? |
|
Definition
| decreased lung compliance w/ hyperinflations ("senile emphysema") |
|
|
Term
| What alterations in renal function occur with age? |
|
Definition
1) decreased renal BF
2) decreased GFR
3) decreased creatinine clearance |
|
|
Term
| What alterations in immune function occur with age? |
|
Definition
1) postpubertal involution of thymus
2) decreased proliferative response of lymphocytes to mitogens
3) decreased T cell function (helper & killer cells)
4) diminution in capacity of B cells to produces Abs
5) increase in generation of autoantibodies
6) increased incidence of autoimmune diseases, cancer |
|
|
Term
| What neuroendocrine & metabolic changes occur with age? |
|
Definition
1) involution of gonads (decreased E2/T4)
2) atrophy of adrenal cortex, thyroid
3) impaired glucose tolerance (insulin resistance)
4) reduced capacity to handle stress
5) cell loss in some brain areas (catecholaminergic brainstem nuclei, cholinergic neurons)
6) alteration of neuronal dendritic trees
7) changes in sleep/wake cycles & EEG rhythms |
|
|
Term
| How much does each physiologic system decline per decade after age 30? |
|
Definition
|
|
Term
| What happens to proteins in aging? |
|
Definition
1) cross-linking
2) glycosylation
3) loss of amide groups
etc. |
|
|
Term
| What happens to nucleic acids in aging? |
|
Definition
1) oxidation
2) base pair substitutions
3) insertions
4) deletions
5) mitochondrial DNA damage
6) shortening of telomeres
etc |
|
|
Term
| What happens to lipids in aging? |
|
Definition
|
|
Term
| The changes in aging provide clues to possible aging interventions. Are there any aging interventions that work? |
|
Definition
| no, most have little effect on the inevitable |
|
|
Term
| What is the relationship b/w aging changes & diseases in the elderly? |
|
Definition
| the concurrence of aging changes & 1+ underlying disease may affect the presentation, natural history, & therapeutic response of diseases occuring elderly (vs. younger individuals) |
|
|
Term
| What is common among Sx of diseases in the elderly? |
|
Definition
| vague, atypical, unreported |
|
|
Term
| What is common among presentation & course of diseases in the elderly? |
|
Definition
more subacute/chronic rather than acute
multisystem involvement is common |
|
|
Term
| Is risk of iatrogenic morbidity/mortality increased or decreased in the elderly? |
|
Definition
|
|
Term
| What is the effect of impairment of immune & vascular systems, poor nutrition, etc. in the elderly? |
|
Definition
|
|
Term
| What is the effect of impaired cardiovascular & renal handling of fluid & electrolyte increases in the elderly? |
|
Definition
| increased susceptibility to dehydration or volume overload |
|
|
Term
| What effect does diminished hepatic & renal function have in the elderly? |
|
Definition
| may affect the ability to metabolize drugs & contribute to the increased incidence of adverse drug reactions |
|
|
Term
| What effect does reduced DA production by substantia nigra have in the elderly? |
|
Definition
| increases suscceptibility to extrapyramidal SE of neuroleptic drugs |
|
|
Term
| What effect do changes in body composition & serum protein binding capacity have in the elderly? |
|
Definition
|
|
Term
| What 3 things must geriatric clinicians be aware of? |
|
Definition
1) differenced in normative lab values
2) normal physiologic responses
3) possible presence of other underlying diseases |
|
|
Term
| Why should physicians be aware of aging? |
|
Definition
| the % of elderly individuals in our society is increasing => need to face the challenge of increasing numbers of individuals siffering from diseases & debilitations associated with aging |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What 5 areas need to be addressed by the physician to help an individual grow old while staying healthy & active? |
|
Definition
1) appraise age differences among older people (young-old, vs. old-old)
2) establish an agenda for "successful aging"
3) fostering good health early in life to promote good health later
4) continuing advances in Tx of disease w/ awareness of role of aging in disease
5) coordinating socioeconomic & biomedical arena to ensure high QOL in old age. |
|
|
Term
|
Definition
derived from the parents & transmitted in the germline ∴ familial
may be congenital or present later in life |
|
|
Term
|
Definition
| born with (tho not necissarily genetic) |
|
|
Term
A 7 year old girl has a disfiguring soft tissue mass on her eyelid. When resected, it's gross appearance is similar to a "bag of worms." Unpon microscopic view of the mass, the leison is composed of tortuous mass of exampnded nerve branches with hypocellular peripheral nerve fibers explanded by pale-staining matrix with spindle shaped cells (plexiform neurofibroma)
She has had mutliple skin leisons (cafe au lait spots) since bith, and they have increased with age. She also has Lisch nodules in her irises.
What is the likely diagnosis? |
|
Definition
|
|
Term
|
Definition
| LOH of NF1 gene => inactivated neurofibromin protein => decreased GTP hydrolysis => RAS remains bound to GTP => uninhibited RAS |
|
|
Term
|
Definition
2+ of the following:
1) 6+ cafe au lait spots
2) freckling in axillary/inguinal regions
3) pigmented hamartoma
4) 2+ neurofibromas of any type or 1 plexiform neurofibroma
5) optic glioma
6) 2+ lisch nodules
7) 1st degree relative affected |
|
|
Term
| What is the probability that a person with neurofibromatosis 1 has a younger sibling with the same disease? |
|
Definition
|
|
Term
| What are clues to a malignant neoplasm? |
|
Definition
no defined borders, basement membrane infiltrated
mitotic figures (lots & in abnormal places)
pleomorphic cells/nuclei
disorganization
nuclear hyperchromasia
high N:C ratio
etc |
|
|
Term
26 y/o patient, diagnosed with neurofibromitosis 1 at age 7 comes in with back pain.
MRI reveals a retroperitoneal mass that is malignant.
What complication has she developed? |
|
Definition
| MPNST (malignant peripheral nerve sheath tumor) |
|
|
Term
A 19 y/o male of Eastern European ancestry presents with easy bruisability.
PE reveals multiple subq bruises as well as conjuntival petechiae, hepatospenomegaly & several enlarged lymph nodes.
Lab shows thrombocytopenia.
What Dx is suspected? |
|
Definition
|
|
Term
| What is seen via microscopy to confirm Gaucher Disease, type 1? |
|
Definition
Gaucher cells (macs)
cytoplasm with crumpled paper appearance |
|
|
Term
| In addition to liver, spleen & lumph nodes, what other organ is frequently affected in patients with Gaucher type 1? |
|
Definition
|
|
Term
| What enzyme is deficient in Gaucher type 1? |
|
Definition
|
|
Term
| What is the inheritance pattern of Gaucher type 1? |
|
Definition
|
|
Term
| How common is Gaucher type 1 compared to other lysosomal storage disoders? |
|
Definition
|
|
Term
| Why is there thrombocytopenia & bleeding complications seen with Gaucher type 1? |
|
Definition
1) increased splenic sequestering of platelets
2) possible replacement of bone marrow?
=> decreased platelet production |
|
|
Term
|
Definition
| non-neoplastic mass composed of disorganized tissue elements normally found at the site |
|
|
Term
def
heterotopia (choristoma) |
|
Definition
| developmental anomaly of normal tissue in an abnormal location |
|
|
Term
|
Definition
| mass leison resulting from uncontrolled proliferation of cells |
|
|
Term
| What are the more frequent benign tumors & tumor-like leisons in children? |
|
Definition
1) hemangiomas
2) lymphangiomas
3) melanocytic nevi
4) fibromatoses
5) teratomas
6) non-neoplastic/developmental errors (choristoma, hamartoma) |
|
|
Term
| What are the more common malignancies in children? |
|
Definition
1) hematopoietic neoplasms (leukemia, lymphoma)
2) germ cell tumors (yolk sac tumor)
3) embryomas/blastomas (neuroblastoma, Wilms tumor, retinoblastoma) |
|
|
Term
| What should be seen microscopically with a hemangioma? |
|
Definition
| multiple, enlarged, thin-walled blood vessels lined by normal appearing endothelial cells |
|
|
Term
|
Definition
| regression is common, so Tx not usually necessary (but depends on subtype) |
|
|
Term
| What is expected to be seen upon autopsy of an infant born with hyaline membrane disease? |
|
Definition
gross: "solid looking"
microscopically: alternating areas of atelectasis (complete/partial collapse of lung) & dilation w/ eosinophilic, hyaline membranes lining the open alveoli & scattered areas of hemorrhage |
|
|
Term
| What is the pathogenesis of hyaline membrane disease? |
|
Definition
| prematurity => deficiency of pulmonary surfactant => increased alveolar surface tension => atelectasis => hypoventilation/perfusion mismatch => hypoxemia & CO2 retention => acidosis => pulmonary VC => hypoperfusion => pulmonary endothelial & epithelial damage => leakage of plasma into alveoli with hyaline membrane formation |
|
|
Term
An infant's hospital course is complicated by mechanical ventilation for 6 weeks, sepsis & recurrent seizures. Eventually she's stabilized & weaned off the ventilator.
Oral feeding was initiated at week 7 of life. 2 days later, she develops abdominal distention. X ray reveals abnormal lung opacities.
What complication has she probably developed? |
|
Definition
| bronchopulmonary dysplasia |
|
|
Term
| What should be seen in an infant's lungs with bronchopulmonary dysplasia? |
|
Definition
gross: cobblestone appearance
microscopically: fibroblasts & mononuclear inflammatory cells, enlarged type II pneumocytes |
|
|
Term
An infant has oral feeding initiated at week 7 of life. 2 days later, she develops abdominal distention.
Grossly, her bowel is dusky & hemorrhagic.
Microscopically her bowel has massive areas of hemorrhage with early signs of coagulative necrosis. Also noted are large, clear, air filled spaces within the submucosa (pneumatosis intestinalis).
What is likely the complication seen? |
|
Definition
| NEC (necrotizing enterocolitis) |
|
|
Term
|
Definition
| ischemic injury => migration of bacteria => inflammation & necrosis => loss of integrity of intestinal wall => air accessing the portal-hepatic venous system |
|
|
Term
| Do you think introduction of oral feeding can lead to NEC? |
|
Definition
| yes (increases bacteria exposure) |
|
|
Term
| What possible sequelae are seen with survivors of NEC? |
|
Definition
1) strictures & chronic obstruction due to fibrosis
2) "short gut syndrome" if part of the bowel had to be resected
3) malabsorption |
|
|
Term
| What complication would be manifested in an infant with germinal matrix hemorrhage with intraventricular rupture? |
|
Definition
|
|
Term
| What sequelae are seen if an infant survives germinal matrix hemorrhage with intraventricular rupture? |
|
Definition
1) hydrocephalus
2) permanent neurological deficits |
|
|
Term
*def
Creutzfeldt-Jakob Disease (CJD) |
|
Definition
| rare transmissible (infectious) spongiform encephalopathy characterized by abnormal forms of prion protein (PrP) & usually resulting in rapidly progressive dementia |
|
|
Term
| What is the pathogenesis of CJD? |
|
Definition
| conformational change of PrP from normal α heliz containing isoform (PrPC) to an abnormal β pleated sheet isoform (PrPSC or PrPres) => development of a relative resistance to proteolysis & the ability to transform other normal PrPC molecules |
|
|
Term
|
Definition
| 1) *usually occurs spontaneously at a slow rate => sporadic cases
2) mutations in PRNP gene, ecodes for PrPC protein => rare familial cases
3) direct, infectious transmission of abnormal prion protein |
|
|
Term
| *When are brain function abnormalities seen with CJD? |
|
Definition
| Secondary to accumulation of PrPC within the CNS |
|
|
Term
| What is seen microscopically in CJD? |
|
Definition
| spongiform change within the cerebral cortex & basal ganglia w/ eventual nuronal loss & secondary reactive gliosis |
|
|
Term
| How is presence of cerebral PrPSC demonstrated? |
|
Definition
|
|
Term
|
Definition
middle-aged to older adults
rapid progressive dementia
frequently prominent startle myoclonus
survival: several months |
|
|
Term
| What characteristic inflammatory response is seen with viral infection? |
|
Definition
|
|
Term
| What type of virus is the mumps virus? |
|
Definition
paramyxovirus
(enveloped, -RNA) |
|
|
Term
| How is mumps transmitted? |
|
Definition
|
|
Term
|
Definition
usually relatively mild, self-limited disease
*lymphocytic infiltration
3-5 days of fever, malaise, myalgia, headache, anorexia, sore throat
1) parotisis (=> increased amylase)
2) CNS (common w/ no Sx)
3) orchitis (rarely leads to sterility)
4) pancreatitis (uncommon => hyperglycemia)
5) oophoritis (rare) |
|
|
Term
| What is the incubation period of mumps? |
|
Definition
|
|
Term
| What type of virus is herpesvirus? |
|
Definition
|
|
Term
| What are the 8 human herpesviruses? |
|
Definition
HSV (1 & 2)
VZV
EBV
CMV
HHV6
HHV7
Kaposi's Sarcoma |
|
|
Term
|
Definition
resp. droplets
direct contact
aerosolization of fluid from infective skin leisons |
|
|
Term
| What does VZV look like microscopically? |
|
Definition
intraepithelial vessels (epidermal/mucosal) with characteristic viral cytopathic effects inc.:
1) MULTINUCLEATED epithelial cells with ground-glass chromatin
2) nuclear molding
3) large, eosinophilic, intranuclear inclusions (IDed by Tzanck smear) |
|
|
Term
| What are the 2 clinical manifestations of VZV? |
|
Definition
1) chickenpox (primary inf.)
2) shingles (reactivation) |
|
|
Term
|
Definition
usually fairly mild, self-limited disease of children
low grade fever, maliase, wide-spread pruitic rash of successive crops of sm. vesicles, pustules, & crusted papules |
|
|
Term
|
Definition
reactivation of VZV in adults
painful, erythmatous, vesicular rash in a dermatomal distribution |
|
|
Term
| What are the complications of shingles? |
|
Definition
| ocular involvement & postherpetic neuralgia |
|
|
Term
|
Definition
| 50-80% of middle-aged adults have been inf. |
|
|
Term
|
Definition
| contact with infected bodily fluids (saliva, breast milk, urine, semen, blood, etc) |
|
|
Term
| What does CMV look like microscopically? |
|
Definition
1) enlarged cells
2) large, basophilic, intranuclear inclusion
3) surrounded by a halo & multiple, sm. basophilic, INTRACYTOPLASMIC inclusions
(NOT multinucleated) |
|
|
Term
| Who are considered high risk for severe, life-threatening disease with CMV inf? |
|
Definition
| fetus & immunocompromised adults |
|
|
Term
|
Definition
typically asymptomatic
mild, mononucleosis-type illness (fever, sore throat, fatigue, lymphadenopathy) |
|
|
Term
|
Definition
(maternal primary inf)
multiple fetal CNA abnormalities
IUGR
hepatosplenomegaly
thrombocytopenia |
|
|
Term
|
Definition
(newly acquired or reactivated)
multiple organ Sx inc. lung, GI, liver, retina |
|
|
Term
|
Definition
Taxoplasmosis
Other (s.a. syphillis)
Rubella
CMV
HSV |
|
|
Term
| What is the most common TORCH inf? |
|
Definition
|
|
Term
| What type of virus is HBV? |
|
Definition
| small, enveloped, circular ±DNA |
|
|
Term
|
Definition
|
|
Term
| What does HBV look like microscopically? |
|
Definition
| "ground-glass" hepatocytes with high viral loads |
|
|
Term
| What are the 3 clinical manifestations of HBV inf? |
|
Definition
1) acute hepatitis
2) chronic carrier state ± chronic hepatitis
3) hepatocellular carcinoma |
|
|
Term
| How often is acute hepatitis from an HBV inf. cleared? |
|
Definition
| most do within weeks & develop immunity (HBsAb) |
|
|
Term
| What pathological features are seen with acute HBV hepatitis? |
|
Definition
random hepatocyte injury & regeneration
mononuclear inflammatory cell infiltrates
± bile stasis
elevated ALT & AST |
|
|
Term
|
Definition
malaise
anorexia
N/V
low-grade fever
right upper quadrant pain
jaundice/icterus |
|
|
Term
| When is chronic HBV inf. more likely to occur? |
|
Definition
if acquired early in life
individuals with impaired immunity |
|
|
Term
Sx
chronic HBV inf (carrier ± chronic hepatitis) |
|
Definition
range from
no Sx w/ minimal hepatocyte injury
to
severe, progressive disease with gradual development of cirrhosis |
|
|
Term
|
Definition
| diffuse hepatic fibrosis with regenerative nodules |
|
|
Term
| Does HBV induced hepatocellular carcinoma always occur after cirrhosis? |
|
Definition
| no, and it doesn't need cirrhosis to proceed it, either |
|
|
Term
| What ype sof virus is HPV? |
|
Definition
| nonenveloped, circular ±DNA |
|
|
Term
|
Definition
|
|
Term
| What tissue cells does HPV like to infect? |
|
Definition
| mucosal & cutaneous epithelial cells (usually squamous) |
|
|
Term
| How does viral replication of HPV occur? |
|
Definition
1) basal epithelial cells - ONLY replication of viral genome
2) superficial, mature keratinocytes - production of virus particles |
|
|
Term
| What are the high-risk HPV serotypes? |
|
Definition
|
|
Term
| What makes HPV serotypes 16 & 18 high-risk? |
|
Definition
genome in INEGRATED into the host DNA
(as opposed to low-risk where genome replicated as an extrachromosomal episome) |
|
|
Term
| What does HPV look like microscopically? |
|
Definition
| kilocytes, esp. within superficial epi (squamous epi with hyperchromatic, wringles nuclei with perinuclear clearing) |
|
|
Term
| What is changes to the epithelium is seen with HPV? |
|
Definition
| epithelial thickening & abnormal keratinization |
|
|
Term
|
Definition
children - cutaneous warts
adults - genital warts
frequently latent/subclinical
warts can be:
1) cutaneous
2) mucocutaneous anogenital
3) epidermodysplasia verruciformis |
|
|
Term
| *What is the name of the common wart? |
|
Definition
|
|
Term
Sx
cutaneous
verruca vulgaris |
|
Definition
usually self-limited
small, pale papules with roughened surface
often on the dorsum of hands |
|
|
Term
*Sx
mucocutaneous anogenital leisons |
|
Definition
very coomon & affect a wide variety of sites
1) condyloma acuminatum (venereal wart)
2) dysplasia/invasive carcinoma |
|
|
Term
*Dx
mucocutaneous anogenital leisons |
|
Definition
cytological screening, biopsy & HPV DNA typing
(Pap smear) |
|
|
Term
| Which HPV serotypes are common with condyloma acuminatum? |
|
Definition
|
|
Term
|
Definition
| slow growing, fleshy, exophytic, cauliflower-like, perineal mass (frequently multiple leisons) |
|
|
Term
| What type of invasive carcinoma is frequently seen with mucocutaneous anogenital leisons of HPV? |
|
Definition
|
|
Term
| When will dysplasia/invasive carcinoma be seen due to an HPV infection? |
|
Definition
| a number of years after initial HPV inf. |
|
|
Term
| What is the pathogenesis of dysplasia/invasive carcinoma due to HPV inf? |
|
Definition
| inf. with high risk HPV serotypes (16 & 18) => production of viral proteins E6 & E7 => inactivation/degradation of p53 & RB => increased proliferation of genetically altered cells => intraepithelial neoplasia => carcinoma (potentially) |
|
|
Term
| What is seen grossly in dysplasia due to HPV |
|
Definition
|
|
Term
| What is seen grossly in invasive carcinoma due to HPV? |
|
Definition
| poorly demarcated ulcerating leison |
|
|
Term
| What is seen microscopically in dysplasia due to HPV? |
|
Definition
| atypical cells confined to epithelium often accompanied by superficial koilocytosis |
|
|
Term
| What is seen microscopically in invasive carcinoma due to HPV? |
|
Definition
| infiltrative nests of malignant cells with surrounding desmoplasia |
|
|
Term
| When are leisons with epidermodysplasia verruciformis seen? |
|
Definition
| with a rare genetic disorder associated with increased susceptibility to HPV skin inf. |
|
|
Term
What type of bacteria is step pneumo?
Gram?
catalase?
shape?
hemolysis? |
|
Definition
pyogenic
encapsulated
G+
cat -
lancet shaped diplococci
α hemolysis |
|
|
Term
| Where does strep pneumo normally colonize? |
|
Definition
|
|
Term
| What are the 2 major virulence factors of strep pneumo? |
|
Definition
| polysaccharide capsule & pneumolysin |
|
|
Term
| Who are at high risk for strep pneumo inf? |
|
Definition
young children
older adults
immunodeficient
defective pulmonary
defective blood clearance (i.e. decreased splenic function) |
|
|
Term
| Who is recommended to recieve the strep pneumo vaccine? |
|
Definition
|
|
Term
|
Definition
typical acute inflam. response presented as:
1) acute bacterial pneumonia (often lobar) - most common CAP
2) otitis media
3) bacteremia
4) meningitis
5) acute sinusitis
6) exacerbations of chronic bronchitis |
|
|
Term
What type of bacteria is clostridium perfringens?
Gram?
shape?
ana/aerobic?
hemolysis? |
|
Definition
exotoxin producing
large
G+
boxcar-shaped bacilli
spore forming
anaerobic
double zone of hemolysis |
|
|
Term
| Where is clostridium perfringens found? |
|
Definition
| ubiquitous in the environment (usually soil) |
|
|
Term
| What are the major virulence factors of clostridium perfringens? |
|
Definition
exotoxinss s.a.:
lectinases (α toxin)
collagenases
hemolysins
hyaluronidases |
|
|
Term
| What are the 2 possible clinical manifestations of clostridium perfringens inf? |
|
Definition
1) food poisoning (more common)
2) gas gangrene |
|
|
Term
| How does clostridium perfringens cause food poisoning? |
|
Definition
| ingestion (usually in undercooked/improperly prepared meat) => production of bacterial enterotoxin |
|
|
Term
Sx
clostridium perfringens
food poisoning |
|
Definition
self-limited abdominal cramps & diarrhea
(begins 6-24 hrs after contaminated food) |
|
|
Term
| How does clostridium perfringens cause gas gangrene? |
|
Definition
| inoculation of orgs into poorly oxygenated tissue => org proliferation & production of exotoxins (w/ associated metabolic gas formation) |
|
|
Term
Sx
clostridium perfringens
gas gangrene |
|
Definition
| necrosis of soft tissue & skeletal muscle (acute inflam. response) => life-threatening dissemination & sepsis |
|
|
Term
What type of bacteria is treponema pallidum?
shape?
motility? |
|
Definition
spirochete
small
motile
fragile |
|
|
Term
| How is treponema pallidum detected? |
|
Definition
| special stains by dark field microscopy w/ serologic tests |
|
|
Term
| How is t. pallidum transmitted? |
|
Definition
sexual contact (more common)
parenteral
vertical |
|
|
Term
| What does t. pallidum look like microscopically? |
|
Definition
| dense, mononuclear inflam. cell infiltrate with NUMEROUS PLASMA CELLS => obliterative endarteritis |
|
|
Term
|
Definition
primary: deep, painless, genital papule that ulcerates
secondary:
1) multiple, symmetric, reddish-brown macules, papules & pustules, often affecting palms & soles
2) genital condylomata lata (plaques)
associated with constitutional Sx, lymphadenopathy, & occasionally patchy alopecia
tertiary:
1) aortitis w/ aneurysm formation
2) neurosyphillis (chronic memingitis, tabes dorsalis, general peresis)
3) gumma formation (destructive granulomatous leisons at multiple sites) |
|
|
Term
Sx
t. pallidum
congenital syphillis |
|
Definition
1) rash similar to that of secondary syphillis
2) rhinitis
3) periostits (saber shins)
4) Hutchinson teeth
5) destruction of the nasal bridge
6) hepatosplenomegaly
7) lymphadenopathy
8) thrombocytopenia
9) neurologic & ocular abnormalities |
|
|
Term
| What type of bacteria is chlamydia trachomatis? |
|
Definition
|
|
Term
| What is the life cycle of chlamydia? |
|
Definition
| infectious elementary body (EB) binds to target cell (usually columnar epi cells) => induction of own endocytosis => inhibits phagolysosomal fusion => transforms to reticulate body (RB) => RB divides to produces lage, intracellular inclusion => RB transforms back to EB => EB released via exocytosis |
|
|
Term
| How is chlamydia transmitted? |
|
Definition
| person-person via infected secretions => mucosal membrane infections |
|
|
Term
| What determinec the clinical manifestations of chlamydia? |
|
Definition
| org serotype & site of inf |
|
|
Term
| What are the 4 clinical manifestations of chlamydia? |
|
Definition
1) sexual transmitted inf.
2) ocular inf.
3) reactive arthritis (Reiter syndrome)
4) perinatal inf. |
|
|
Term
| Who have the highest STI infection rates of chlamydia? |
|
Definition
|
|
Term
| What are the 3 clinical manifestations of chlamydia? |
|
Definition
1) sexual transmitted inf.
2) ocular inf.
3) reactive arthritis (Reiter syndrome) |
|
|
Term
| *Who is most commonly infected via STI chlamydia? |
|
Definition
|
|
Term
| *How is diagnosis of chlamydia made? |
|
Definition
nucleic acid amplification
isolated in cell culture
Ag detection |
|
|
Term
|
Definition
often asymptomatic, esp. in women
1) cervicitis => PID (abnormal cervical discharge/bleeding, pelvic pain, fever)
2) urethritis - esp. in men (urethral irritation/discharge, dysuria, fever)
3) protitis (rectal pain, dicharge, bleeding)
4) pharyngitis
5) lymohogranuloma venereum - esp. in men, more often in Africa/Asia/S. America (initially sm., painless ulcers/vesicles => painful, suppurative inguinal lymphadenopathy w/ constitutional Sx) |
|
|
Term
| What are the 2 types of ocular infections seen due to chlamydia? |
|
Definition
1) trachoma - esp. in developing countries
2) inclusion body conjunctivitis - perinatal transmission |
|
|
Term
Sx
trachoma due to chlamydia |
|
Definition
1) inflam. & scarring of conjunctiva & cornea => blindness
2) superimposed seondary bacterial inf. |
|
|
Term
Sx
inclusion body conjunctivitis due to chlamydia |
|
Definition
| mucopurulent discharge & corneal infiltrates |
|
|
Term
| What causes reactive arthritis due to chlamydia? |
|
Definition
| immune-related response to a chlamydial inf (more common in men) |
|
|
Term
Sx
reactive arthritis due to chlamydia |
|
Definition
triad: polyarthritis, urethritis, conjuntivitis
often associated with mucocutaneous leisons |
|
|
Term
Sx
perinatal chalmydial inf. |
|
Definition
| conjunctivitis in newborns &/or infant pneumonia |
|
|
Term
What type of bacteria is rickettsia rickettsii?
Gram?
shape? |
|
Definition
obligate intracellular
small
G-
pleomorphic
coccobacilli |
|
|
Term
| Where is R. Rickettsii found? |
|
Definition
|
|
Term
| How is r. rickettsii transmitted? |
|
Definition
|
|
Term
| What cells in humans tend to be infected by r. rickettsii? |
|
Definition
| vascular endothelial cells |
|
|
Term
| What should the physician do once r. rickettsii is suspected? |
|
Definition
| Tx right away and THEN confirm via serological tests/immunostaining |
|
|
Term
|
Definition
initially:
non-specific - fever, headache, myalgias, N/V
later:
1) maculopapular rash with centripetal spread (extremeties first then trunk) - esp. plams & soles => petechial leisons with thrombocytopenia
2) systemic organ involvement
(potentially life-threatening) |
|
|
Term
What type of bacteria is mycobacterium leprae?
Gram?
shape?
slow/fast growing? |
|
Definition
facultative intracellular
G+
acid-fast
bacillus
show-growing |
|
|
Term
| What species can be infected by mycobacterium leprae? |
|
Definition
humans
armadillos
non-human parasites |
|
|
Term
| Where is leprosy still prevalent? |
|
Definition
SE Asia (esp. India)
S. America
Africa |
|
|
Term
| What part of the body is affected by leprosy (Hansen disease)? |
|
Definition
skin
perioheral nerves
URT
eyes |
|
|
Term
| Does m. leprae have a long or short incubation period? |
|
Definition
|
|
Term
|
Definition
| curable with multidrug therapy - taken for months |
|
|
Term
| What are the 3 subtypes of leprosy? |
|
Definition
1) *tuberculoid (paucibacillary) leprosy
2) borderline forms of leprosy
3) lepromatous (multibacillary) leprosy |
|
|
Term
| *Who are affected by tuberculoid (paucibacillary) leprosy? |
|
Definition
| patients with effected cell-mediated immunity |
|
|
Term
*Sx
tuberculoid (paucibacillary) leprosy |
|
Definition
| hypopigmented anesthetic skin macules w/ thickening of peripheral nerves |
|
|
Term
| *What is seen microscopically in tuberculoid (paucibacillary) leprosy? |
|
Definition
| many well-formed granulomas w/ few bacilli |
|
|
Term
|
Definition
| development of multiple cutaneous papules, plaques, & nodules |
|
|
Term
| Who are affected with lepromatous (multibacillary) leprosy? |
|
Definition
| patients with poor cell-mediated immunity |
|
|
Term
Sx
lepromatous (multibacillary) leprosy |
|
Definition
1) progressive formation of larger, deeper, more destrictive skin leisons & involvement of the nose
2) trauma & secondary inf (due to lack of sensation) => many deformities & disfiguring manifestations |
|
|
Term
| What is seen microscopically in lepromatous (multibacillary) leprosy? |
|
Definition
| sheets of foamy macs containing numerous acid-fast orgs (also present in endothelial & Schwann cells) |
|
|
Term
|
Definition
morphological ID
Ag detection
nucleic acid detection
culture |
|
|
Term
| *What special stains are often helpful in IDing fungi? |
|
Definition
|
|
Term
| What is the most common fungal inf (esp. in the immunocompromised)? |
|
Definition
|
|
Term
| Where is candida albicans found? |
|
Definition
| ubiquitous (even normal flora of mucosal surfaces) |
|
|
Term
| What forms are there of candida albicans? |
|
Definition
budding yeast
pseudohyphae |
|
|
Term
|
Definition
range from:
common superficial mucocutaneous candidiasis to less common nosocomial candidemia & life-threatening disseminated candidiasis |
|
|
Term
| What does c. albicans look like microscopically? |
|
Definition
| hyphae-life, that "pinch off" at new buds |
|
|
Term
| What type of fungi is blastomyces dermatitidis? |
|
Definition
|
|
Term
| What form of blastomyces is found in the soil? |
|
Definition
|
|
Term
| Where is blastomyces dermatitidis endemic to? |
|
Definition
|
|
Term
| How is blastomyces dermatitidis transmitted? |
|
Definition
| inhalation of aerosolized conidia => transformation to yeast at body temp. |
|
|
Term
| What does blastomyces dermatitidis look like microscopically? |
|
Definition
large, broad-based budding, thick walled YEAST (circles)
*inital neutrophilic infiltration => chronic granulomatous inflammation |
|
|
Term
Sx
blastomyces dermatitidis |
|
Definition
1) pulmonary disease: range from asymptomatic to subclinical flu-like illness to acute/chronic penumonia
2) occasional extrapulmonary dissemination (esp. to skin then bones) - leisons begin as sm. papules & pustules => ulcerated plaques with central scarring |
|
|
Term
| What type of fungi is coccidioides immitis? |
|
Definition
|
|
Term
| What form of coccidioides immitis is found in the soil? |
|
Definition
|
|
Term
| Where is coccidioides immitis endemic to? |
|
Definition
SW US (esp. Cali)
Central America
S. America |
|
|
Term
| How is coccidioides immitis transmitted? |
|
Definition
| inhalation of airborne arthroconidia (occupational hazard) => tranformation to large, thick walled spherules at body temp |
|
|
Term
| How does coccidioides reporduce? |
|
Definition
|
|
Term
Sx
coccidioides immitis
(i.e. Valley Fever) |
|
Definition
can be subclinical
pulmonary findings are most common
headache
arthralgia
skin manifestations
~ to TB: variants inc. cavitary, progressive pulmonary & disseminated coccidioidomycosis |
|
|
Term
| *What is seen microscopically with coccidioides immitis? |
|
Definition
initial acute inflam.
if not cleared => chronic granulomatous inflam.
large round endospores (bubbles in a large circle) |
|
|
Term
| What type of fungi is histoplasma capsulatum? |
|
Definition
|
|
Term
| What form of histoplasma capsulatum is found in the environment? |
|
Definition
|
|
Term
| When does histoplasma capsulatum become a small, intracellular yeast? |
|
Definition
|
|
Term
| Where is histoplasma capsulatum endemic to? |
|
Definition
soil of Ohio, Missouri, & Mississippi river valleys
(esp near bat/birds) |
|
|
Term
| How is histoplasma capsulatum transmitted? |
|
Definition
| aerosolization & inhilation of mycelial fragments |
|
|
Term
|
Definition
immunocompetent: asymptomatic
immunocompromised or lg. innoculum: pulmonary inf. => latent inf. or progessive disease => dissemination to extrapulmonary sites |
|
|
Term
| What does histoplasma capsulatum look like microscopically? |
|
Definition
small yeast, huddled together to form oval structure
killed by macs & walled off in granuloma => calcification |
|
|
Term
*With which fungi is inflammatory response often minimal?
Why? |
|
Definition
opportunistic fungi
host is usually immunocompromised => less effective inflam. response |
|
|
Term
| What type of fungi is cryptococcus neoformans? |
|
Definition
opportunistic
narrow-based budding yeast (always yeast)
prominent capsule |
|
|
Term
| Where is cryptococcus neoformans found? |
|
Definition
|
|
Term
| How is cryptococcus neoforman transmitted? |
|
Definition
|
|
Term
| *What determines the severity of Sx seen with cryptococcus neoformans inf? |
|
Definition
| adequacy of host's cell-mediated immune response |
|
|
Term
Sx
cryptococcus neoformans |
|
Definition
1) pulmonary disease (varied in severity, but often only mild Sx)
2) CNS involvement => most common clinical presentation: headache, altered mental status, N/V, focal neurological deficits
3) less frewuently - skin, bone, eyes, prostate |
|
|
Term
| What does cryptococcus neoformans look like microscopically? |
|
Definition
| dark, budding yeast surrpounded by a hugh halo/capsule |
|
|
Term
| What type of fungi is aspergillus fumigatus? |
|
Definition
opportunistic
always hypheal |
|
|
Term
| Where is aspergillus found? |
|
Definition
| ubiquitous mold in the environment |
|
|
Term
| How is aspergillus transmitted? |
|
Definition
| fungal spored via inhalation |
|
|
Term
| How do you tell the difference b/w aspergillus & candida albicans microscopically? |
|
Definition
| aspergillus is ladder-like. No "pinching off" at each new bud like in candida albicans |
|
|
Term
| *What are the 4 typical patterns of clinical disease of aspergillus? |
|
Definition
1) allergic bronchopulmonary aspergillosis
2) aspergilloma
3) chronic necrotizing Aspergillus pneumonia
4) invasice aspergillosis |
|
|
Term
def
allergic bronchpulmonary aspergillosis |
|
Definition
| hypersensitivity rxn to aspergillus colonization of airways (associated with asthma & CF) |
|
|
Term
|
Definition
"fungus ball"
localized collection of aspergillus orgs growing w/in a pre-existing pulmonary cavity |
|
|
Term
def
chronic necrotizing aspergillus pneumonia |
|
Definition
| disease associated with some degree of immunosuppression |
|
|
Term
def
invasive aspergillosis |
|
Definition
readily progressive, life-threatening inf. that occurs in severely immunocompromised patients
(commonly causess angioinvasion => hemorrhagic & thrombotic complications & dissemination) |
|
|
Term
| What type of fungus is zygomycetes (Mucor & Rhizopus sp.)? |
|
Definition
opportunistic
always hypheal |
|
|
Term
| Where is zygomycetes found? |
|
Definition
| ubiquitous mold found in soil & decaying organic matter |
|
|
Term
| How is zygomycetes transmitted? |
|
Definition
|
|
Term
| *Who is usually affected by zygomycetes inf? |
|
Definition
| immunosuppressed, most frequently with neutrophil dysfunction or neutropenia |
|
|
Term
| *What does zygomycetes look like microscopically? |
|
Definition
irregular, wide, ribbon like, nonseptae hyphae that branch at right angles
often seen with hemorrhage, thrombosis & infarction |
|
|
Term
|
Definition
1) rhinocerebral disease (=> orbital, face, CNS extention)
2) pulmonary, cutaneous, GI, disseminated forms
3) usually severe, life-threatening w/ high morbidity/mortality |
|
|
Term
| What is the most common intestinal parasite? |
|
Definition
|
|
Term
| What type of protozoa is giardia lamblia? |
|
Definition
|
|
Term
| How is giardia transmitted? |
|
Definition
ingestion of giardia cysts (contaminated water, fecal-oral)
low inoculum => disease |
|
|
Term
| What is the life cycle of giardia lamblia? |
|
Definition
| cyst ingestion => excustation => release of flagellate trophozoites => multiplication & colonization of upper sm. intestine => encystation => exit via feces |
|
|
Term
|
Definition
(can be asymptomatic)
persistent/recurrent watery/fatty diarrhea
abdominal cramping
bloating
constitution Sx (anorexia, malaise, wt. loss) |
|
|
Term
| How is giardiasis diagnosed? |
|
Definition
examination of stook for cysts/trophozoites
detection of Ag in stool
string test
duodinal aspirate
biopsy |
|
|
Term
|
Definition
|
|
Term
| What type of protozoa in trypanosoma cruzi? |
|
Definition
|
|
Term
| How is trypanosoma cruzi transmitted to the mammalian host? |
|
Definition
triatomine bug (kissing bug) via infected feces
blood transfusions
perinatal
ingestion of contaminated food |
|
|
Term
| What are the 3 developmental stages of the t. cruzi life cycle? |
|
Definition
1) replicative epimastigote (insects)
2) infectious, nondividing, flagellate trypomastigote (enters mammalian host & circulates blood)
3) replicative amastigote (mammals) - intracellular esp. in cardiac & smooth muscle |
|
|
Term
| What disease is seen with t. cruzi inf? |
|
Definition
|
|
Term
| Where is Chagas disease endemic to? |
|
Definition
|
|
Term
| How is Chagas disease Dx? |
|
Definition
ID of parasite in blood/tissue
xenodiagnosis
seologic
PCR |
|
|
Term
| What is the current management protocol for Chagas disease? |
|
Definition
| vector & transfusional control |
|
|
Term
|
Definition
acute phase: asymptomatic or localized swelling at site of entry (chagoma) w/ mild constitutional Sx (subclinical)
indeterminate phase: prolonged asymptomatic period w/ few circulating parasites
chronic phase (decades later, 20-30% infected individuals):
1) myocaditis (most lethal consequence)
2) GI (megaesophagus & megacolon)
3) nervous system |
|
|
Term
| What type of helminth is wuchereria banchrofti? |
|
Definition
|
|
Term
| *What disease manifests with a wuchereria banchrofti inf? |
|
Definition
| lymohatic filariasis (elephantiasis) |
|
|
Term
| Where is wuchereria bancrofti found? |
|
Definition
|
|
Term
| When does lymphatic filariasis develop? |
|
Definition
| after years of repeated exposure to infected vector (usually mosquitos) |
|
|
Term
| What type of parasites causes lymphatic filariasis? |
|
Definition
| nematode filarial parasites |
|
|
Term
| How is elephantitis (a major cause of long-term disability worldwide) prevented? |
|
Definition
| mosquito control & mass Tx with anti-filariasis drugs |
|
|
Term
| *What are the five developmental stated b/w the vertebral & arthropod hosts of nematode filarial parasites s.a. wuchereria bancrofti? |
|
Definition
1) adult worms
2) microfilariae (first stage larvae)
3) second stage larvae
4) third stage larvae
5) nymph |
|
|
Term
| What is the filarial life cycle? |
|
Definition
| adult female worms (in vertebrate) produce microfilariae => insect vector ingests microfilariae => microfilariae undergo 2 larval changes in the insect => inoculation into vertebral host => final stage of development |
|
|
Term
|
Definition
fever
lymphadenopathy
chronic limb/genital swelling
skin thickening
(caused by adult worms in lymph nodes & lymphatic vessels) |
|
|
Term
| How is wuchereria bancrofti diagnosed? |
|
Definition
| detection of microfilariae or filarial Ag in peripheral blood |
|
|
Term
| What does wuchereria bancrofti look like microscopically? |
|
Definition
|
|
Term
| What type of helminth in schistosoma? |
|
Definition
| extracellular trematode (fluke/flatworm) |
|
|
Term
| Where is schistoma endemic? |
|
Definition
|
|
Term
| What is schistosomiasis second to as a tropical public health problem? |
|
Definition
|
|
Term
| What species of schistosoma are common? |
|
Definition
1) mansoni & japonicum (hepatic/intestinal)
2) haematobium (urinary) |
|
|
Term
| What is the vector for schistosoma? |
|
Definition
|
|
Term
| What is the life cycle of schistosomal cercaria? |
|
Definition
| snails serve as intermediate host for asexual reproduction => release of swimming cercariae into water => penetration of intact human skin & disseminate => maturation to adult worms in portal circulation =? mesenteric (hepatic) or vesicular (bladder) veins => eggs released => shed via stool/urine |
|
|
Term
| What do schistosomal cercaria look like? |
|
Definition
seamen with a V for a tail:
>--o> |
|
|
Term
| What do schistosoma eggs look like microscopically? |
|
Definition
| oval with circles forming microtubule like shapes inside |
|
|
Term
|
Definition
pruritic, papular rash, fever/chills, cough, headache, myalgia, lymphadenopathy, hepatosplenomegaly, EOSINOPHILIA
=> later complications or additional organ involvement |
|
|
Term
| What later complications (months-years) can occur after schistosoma inf? |
|
Definition
1) hepatic/intestinal schistosomiasis
2) urinary schistomiasis |
|
|
Term
Sx
hepatic/intestinal schistomiasis |
|
Definition
| intially colicky abdominal pain & bloody diarrhear => development of intestinal obstruction, hepatic periportal pipestem fibrosis, signs/Sx of portal HTN (ascites, hematemsis, splenomegaly) |
|
|
Term
Sx
urinary schistosomiasis |
|
Definition
| initially dysuria, hematuria & urinary frequency => development of urinarty tract obstruction, secondary chronic bacterial UTI, chronic kidney disease, *carcinoma of urinary bladder |
|
|
Term
*What type of bladder carcinoma is seen due to schistosoma?
Why is this strange? |
|
Definition
| squamous cell carcinoma due to squamous metaplasia (from transitional epi) |
|
|
Term
| What type of helminth is trichinella spiralis? |
|
Definition
| intracellular nematode (intestinal roundworm) |
|
|
Term
| What is the life cycle of trichinella spiralis? |
|
Definition
all stages occur in a single host, but different hosts are required to complete the life cycle
ingestion of improperly processes/undercooked meat (usually pork) containing encysted larvae => cysts digested out of muscle in stomach => larvae penetrate villi of sm. intestine => develop into adult worms => female burrows deep into mucosa to produce new larvae after fertilization => newborn larvae disseminate via lymphatics & blood => formation of cyts in skeletal muscle
(larvae remain viable for months to years) |
|
|
Term
|
Definition
usually asymptomatic/undiagnosed
with heavy infestation:
1) enteral/intestinal phase
2) parenteral/migratory phase
3) encystation phase w/ tissue repair |
|
|
Term
Sx
enteral/intestinal phase
trichinella spiralis |
|
Definition
(in first week)
V/D
abdominal pair
mucosal hyperemia
edema
hemorrhage
inflammation
ulceration |
|
|
Term
Sx
parenteral/migratory phase
trichinella spiralis |
|
Definition
(after 1 week)
early: fever/chills, facial edema, EOSINOPHILIA, petechiae
penetration into sk. muscle: muscle swelling/tenderness/weakness, enlargement of muscle fibers w/ nuclear proliferation (NURSE CELL formation), surrounded by edema & interstitial inflam., elevation of muscle enzymes
potential involvement of other organs |
|
|
Term
Sx
encystation phase w/ tissue repair
trichinella spiralis |
|
Definition
sk. muscle biosy shows encysted spiral-shaped larvae surrounded by fibrosis
eventual cyst wall calcification
gradual resolution of clinical Sx |
|
|
Term
| What does trichinella look like microscopically? |
|
Definition
worm coiled up
in biopsy, looks like coiled worm cut |
|
|
Term
|
Definition
| disease &/or injury which sets in motion the sequence of events that leads to a person's death |
|
|
Term
|
Definition
natural
unnatural (accident, suicide, homicide, undetermined) |
|
|
Term
|
Definition
| physiologic abnormality that occurs due to natural disease or following an injury incompatible with life |
|
|
Term
def
livor mortis (lividity) |
|
Definition
| red-purple discoloration of the skin due to pooling of blood |
|
|
Term
| When does lividity begin? |
|
Definition
| at time circulation stops, but isn't noticable until 30-45 min later |
|
|
Term
| Where is lividity not seen? |
|
Definition
| in areas of body where there's external pressure |
|
|
Term
| When does lividity become permanent (fixed)? |
|
Definition
|
|
Term
| What test can be done to see if lividity is fixed? |
|
Definition
|
|
Term
|
Definition
| small blue-purple hemorrhage in areas of lividity due to increased pressue of small blood vessels => rupture |
|
|
Term
|
Definition
| chrmical process that causes stiffening of the muscles after death |
|
|
Term
| When does rigor mortis occur? |
|
Definition
| soon after death, but peaks 8-12 hours |
|
|
Term
| When does rigor mortis dissappear? |
|
Definition
| progressivly over 24-30 hrs |
|
|
Term
| What muscles are involved in rigor mortis? |
|
Definition
|
|
Term
| ***What is the time frame of decomposition (rigity & lividity inc.) dependent on? |
|
Definition
| environmental conditions s.a. temp. & humidity |
|
|
Term
| What does it mean if rigor mortis is absent, but lividity can blanche? |
|
Definition
| rigor mortis hasn't set in yet |
|
|
Term
| What does it mean if rigor mortis is absent, but lividity can't blanche? |
|
Definition
| rigor mortis has already occured |
|
|
Term
|
Definition
| postmortem cooling of the body |
|
|
Term
What does postmortem fly egg deposition look ike?
When does it occur? |
|
Definition
grated parmesan cheese - often in warm, moist areas s.a. eyes, corners of mouth, nose, etc.
can occur soon or up to several days after death |
|
|
Term
| What do postmortem ant/roach bites look like? |
|
Definition
| superficial skin leisons with irregular boders & must be differentiated from antemortem abrasions |
|
|
Term
| How do you differentiate a postmortem injury from a antemortem injury? |
|
Definition
| no bruises on skin => postmortem mutilation |
|
|
Term
| What happens in putregactive decomposition? |
|
Definition
| gree/red/black skin discoloration => gaseous distention of body => skin marbling => skin slippage => purge fluid from nose/mouth => putrefaction of tissue => maggots => adipocere (takes several months to develop) => skeletonization |
|
|
Term
|
Definition
| linear black discoloration across sclerae from eyes being partially opened allowing sclerae to dry |
|
|
Term
| What are the 3 important types of blunt force injuries? |
|
Definition
1) contusions
2) abrasions
3) lacerations |
|
|
Term
|
Definition
| impact that results in injury to blood vessels with bleeding into surrounding tissue |
|
|
Term
| What color are bruises if injury occured within 24 hours? |
|
Definition
|
|
Term
| Should you be concerned of abuse if an elderly person has bruises? |
|
Definition
| possibly, but generally, the elderly have think skin & fragile blood vessels => brusing due to minimal trauma |
|
|
Term
| When should child abuse be suspected? |
|
Definition
|
|
Term
| When are old & new bruises seen in adults? |
|
Definition
| repeated falls s.a. alcoholics or dementia, arthritis, stroke |
|
|
Term
| What contusion pattern is seen in a fall with impact to the head? |
|
Definition
| coup & countercoup (with countercoup being more extensive) |
|
|
Term
|
Definition
injury to upper layers of skin s.a. brash burns
can be patterned or non-patterned, and not typically associated with bruises |
|
|
Term
|
Definition
| injury where the skin is torn causing separation og the skin edges |
|
|
Term
|
Definition
| edges are abraded (scraped) w/ tissue bridges (thin bands of connective tissue, nerved, and blood vessels stretched b/w the edges of the skin) |
|
|
Term
|
Definition
| sharp force entry with smooth edges & no tissue bridges |
|
|
Term
| Where do abrasions occur? |
|
Definition
|
|
Term
| What is the pattern of injury used to help determine? |
|
Definition
| what kind of weapon and the directionality |
|
|
Term
| What are the 3 types of pedestrian injuries via a motor vehicle? |
|
Definition
1) front impact collision
2) sideswipe
3) run-over |
|
|
Term
def
front impact collision |
|
Definition
|
|
Term
| What are the 3 degrees of injury in front impact collisions? |
|
Definition
primary: usually to legs - due to impact by bumper
secondary: to body if brought up into the hood of car
tertiary: body injuries when thrown back on the road |
|
|
Term
| What injuries are most severe in front impact collisions? |
|
Definition
|
|
Term
| Why when front impact occurs do adults get propelled up onto the hood, while children get propelled forward? |
|
Definition
| children are hit above center of gravity, adults are hit below |
|
|
Term
| When will leg injuried due to a front impact collision be lower on the legs? |
|
Definition
|
|
Term
| How does a sideswipe injury occur (absense of bumper injury)? |
|
Definition
| pedestrian walked into the side os the vehicle or was struck as the car swerved |
|
|
Term
| What are the 2 injury types caused by run-over? |
|
Definition
1) passage of wheel over body
2) from pavement & undercarriage of vehicle |
|
|
Term
| Why do run overs in children not result in fractures? |
|
Definition
| children have elastic, resilient bones, tho crush injuries to organs will occur |
|
|
Term
| What suggests a pedestrian was hit from the rear? |
|
Definition
| traumatic stretch marks in the groins |
|
|
Term
| How are trace evidence preserved when ovserving a hit & run? |
|
Definition
| undressing the body on a clean sheet |
|
|
Term
| What opinions can be formed based on evaluation of injuries of a pedetrian hit? |
|
Definition
| sequence of injuries & speed at time of impact |
|
|
Term
| What is one of the most important things that needs to be determined in a motor vehicle collision? |
|
Definition
|
|
Term
| What can help determine driver vs. passenger? |
|
Definition
1) steering wheel vs. dashboard injuries
2) seat belt injuries
3) tempered glass injuries |
|
|
Term
| What leaves the barrel when a gun is fired along with the slug/pellets? |
|
Definition
unburned, burning, & burned gunpowder
soot
gas |
|
|
Term
| How can firing distance be determined? |
|
Definition
characteristics of wound
amount/distribution of soot/gunpowder on target |
|
|
Term
| What are the 5 distances that can be determined from a gunshot wound? |
|
Definition
contact range
near-contact range (2-3 in)
close range (6-8 in)
intermediate range (2-2.5 ft)
distant range (>2.5 ft) |
|
|
Term
| What is seen of the wound at contact range? |
|
Definition
soot, gunpowder, gasses deposited under the skin
muzzle imprint/searing of skin edges at entrance |
|
|
Term
| What is the difference in close contact wounds to the head/abdomen or chest? |
|
Definition
head: increased subq pressure => stellate-shaped entrance wound
ab/chest: gases have room to dissipate ∴ no stellate wound |
|
|
Term
| What is seen at the wound of a near contact range? |
|
Definition
soot & gunpowder stippling are seen over a small distribution on skin surrounding the wound.
muzzle flame may burn skin edges |
|
|
Term
| What is seen in a wound of close range? |
|
Definition
presence of soot & gunpowder stippling on skin surrounding entrance wound.
(Soot not discernible after 7 inches) |
|
|
Term
| What is seen at an intermediate range gunshot wound? |
|
Definition
gunpowder stippling
absence of soot
(after 18-36 in, no gunpowder is visible) |
|
|
Term
| What is seen at a gunshot wound from distant range? |
|
Definition
chracteristics only of an entrance wound
can't determine exact distance, just that its further than 2.5-3 feet |
|
|
Term
| What happens to pellet spread the greater the firing distance of a shot gun? |
|
Definition
|
|
Term
| When will there be a circular wound be seen with a shot gun? |
|
Definition
|
|
Term
| When will separate pellet wounds be seen with a shotgun? |
|
Definition
|
|
Term
| When can pellets disperse via a billard ball effect, even when fired at a short distance? |
|
Definition
if they hit an intermediary target
or sawed off shotguns |
|
|
Term
| When can a stellate wound appear in the head when fired from a distant range? |
|
Definition
|
|
Term
| What causes the injuries seen in high velocity rifles? |
|
Definition
| velocity of bullet (not size or weight) |
|
|
Term
| Why is there a "lead snowstorm" seen upon x-ray of the high velocity riffles? |
|
Definition
|
|
Term
| What are the clues to differentiate an exit wound from an entrance wound? |
|
Definition
entrance: abrasion rim, eccentric abrasion if enters at an angle, muzzle imprint, soot, gunpowder stipple, searing of skin, beveling of the bone
exit: NO abrasion rim (EXCEPT if there is external pressure against area of exit) |
|
|
Term
| Why does a bullet appear larger than it is on xray, but smaller when looking at entrance site? |
|
Definition
entrance site: skin contracts making hole smaller
xray: shadow occurs |
|
|
Term
| Where do suicidal gunshot wounds tend to occur? |
|
Definition
|
|
Term
| When should homicide be suspected over suicide? |
|
Definition
multiple to head
(multiple self inflicted can occur) |
|
|
Term
| When should a suicide be suspected? |
|
Definition
contact/near contact range
blow back (blood splatter)/soot on victims hand |
|
|
Term
|
Definition
| cuts that are superficial - longer than they are deep |
|
|
Term
|
Definition
| deep, penetratinf wounds, deeper than long |
|
|
Term
| How are chops by machete or hatchet determined from a cut/incision? |
|
Definition
| cuts/incisions are clean, non-abraded & unbruised |
|
|
Term
| Is it possible to determine a serrated blade from a ordinary blade cut? |
|
Definition
| not unless the blade is scraped across the skin |
|
|
Term
| Why can one knife cause variety of appearance? |
|
Definition
| stab, tqist, victim moves, etc. |
|
|
Term
| What is most important when measuring wound size to match with a particular blade? |
|
Definition
|
|
Term
| When will a hilt abrasion/contusion be seen in a stabbing? |
|
Definition
| if there's full length penetration of the blade |
|
|
Term
|
Definition
| stab & incision wounds on arms, forearms & hands of victim |
|
|
Term
|
Definition
| superficial cuts often seen in sucide victims prior to actual attempt |
|
|
Term
| What can cause death by asphyxiation? |
|
Definition
1) hanging
2) strangulation
3) smothering
4) choking
5) traumatic/positional asphyxiation
6) asphyxiating gases
7) drowining |
|
|
Term
| What causes death from asphyxiation? |
|
Definition
| lack of oxygen (anoxia) to the tissues |
|
|
Term
| What evidence of asphyxiation is seen in death? |
|
Definition
| congestion & petechiae (exept in hanging) |
|
|
Term
| What causes death from asphyxiation in hangings? |
|
Definition
primarily: obstruction of cerebral blood flow (carotid a. compressed)
airway obstruction |
|
|
Term
|
Definition
| only in execution where the neck is broken & the odontoid process in pushed against the medulla |
|
|
Term
Where does lividity occur in hangings?
Is there any evidence of tardieu spots? |
|
Definition
lividity independent portions of face & body
tardieu spots in legs |
|
|
Term
| What is the difference in the ligature furrow of a hanging vs. a strangulation? |
|
Definition
hanging: upsidedown V
strangulation: horizontal |
|
|
Term
| Why are fingernail marks often present in strangulation? |
|
Definition
| victim's attempt to remove assailant's hands or noose |
|
|
Term
| Why would petechiae be present in strangulation? |
|
Definition
| the back and forth from struggle from strangulation to not to strangulation => petechiae |
|
|
Term
| Why would the hyoid bone/thyroid cartilage be fractured in the elderly who are strangled? |
|
Definition
| some calcification => reduced elasticity |
|
|
Term
| What additional tests need to be done if the stangled victim is a young woman? |
|
Definition
|
|
Term
| Who are usually killed by smothering? |
|
Definition
|
|
Term
| What is the most common type of accidental smothering? |
|
Definition
| overlay suring co-sleeping (risk increased if parents obese or intoxicated) |
|
|
Term
| Who tends to be affected by choking? |
|
Definition
infants
intoxicated/mentally impaired adults |
|
|
Term
| What are commonly aspirated foods? |
|
Definition
|
|
Term
|
Definition
| breathing is compromised to a crush injury |
|
|
Term
|
Definition
| breathing is compromised b/c of the position of the decedent |
|
|
Term
|
Definition
| death while in the water or within 24 hrs of removal from the water |
|
|
Term
|
Definition
| death from medical complications that develop as a consequence of being submerged in water. occurs >24 hrs after the incident |
|
|
Term
| What is the drowning sequence? |
|
Definition
1) struggle to stay afloat
2) breath holding (1-2 min)
3) involuntary inhalation of water
4) vimiting
5) convulsions
6) continued inspiratory effort
7) cardiorespiratory arrest
8) death from cerebral anoxia
(<5 min) |
|
|
Term
| What factors contribute to drowning? |
|
Definition
human: physical/mental health, intoxication
environmental: current, temp, marine life, electrical hazards, equipment failure |
|
|
Term
| ***What is seen on an autopsy to Dx drowning? |
|
Definition
| there are NOT diagnostic autopsy finding or lab tests |
|
|
Term
| What are common scuba related deaths? |
|
Definition
1) natural (cardiac arrest)
2) equipment failure
3) decompression sickness
4) arterial gas emboli
5) nitrogen narcosis/oxygen toxicity |
|
|
Term
| What are the main issues in a thermal injury? |
|
Definition
1) who is the victim?
2) was the victim alive in the fire?
3) was death caused by the fire? |
|
|
Term
| What provides evidence that the victim in a fire was alive prior to the fire? |
|
Definition
soot in airway (evidence of breathing)
CO in blood (tho 10% is normal in smokers) |
|
|
Term
| How does CO produce tissue hypoxia? |
|
Definition
| competing with oxygen for binding sites on hemoglobin, tho the affinity for CO is much greater |
|
|
Term
| What happens to lividity with CO poisoning? |
|
Definition
|
|
Term
| What is the fatal level of carboxyhemoglobin? |
|
Definition
| 50% (tho lower in patients with COPD or severe anemia) |
|
|
Term
| Why do children & animals build fatal CO levels faster? |
|
Definition
greater metabolic rates
(fetal death can occur even if mother survives) |
|
|
Term
| Why do the body & organ shrint due to thermal injury? |
|
Definition
|
|
Term
| What does a charred body look like? |
|
Definition
| pugilistic appearance secondary to contraction of arms & legs with skin splitting (if occurs in abdomen, loops of sm. intestine can protrude thru) |
|
|
Term
| When can the bones sustain heat-related fracture? |
|
Definition
|
|
Term
| What are epidural hemorrhage as a postmortem artifact often misinterpreted as in thermal injury? |
|
Definition
|
|
Term
| When should hemorrhage be considered a "real injury" as opposed to a postmortem artifact in thermal injury? |
|
Definition
|
|
Term
| What do thermal & electrocution burns look like? |
|
Definition
| surrounded by a pale margin & narrow red zone (due to blood being pushed from the benter of the burned area..NOT an indication the victim was alive) |
|
|
Term
| What is used to determine the % of burned surface area? |
|
Definition
|
|
Term
| What is the leading cause of serious head injury in infants? |
|
Definition
|
|
Term
|
Definition
| injuries ascribed to vigorous manual shaking of an infant |
|
|
Term
| What are the injuries sustained from shaken baby syndrome similar to? |
|
Definition
|
|
Term
|
Definition
| foreign, often lipophilic, potentially injurous chemicals that can be absorbed thru inhalation, ingestion or skin contact |
|
|
Term
| *What is the primary site of xenobiotic metabolism? |
|
Definition
|
|
Term
| *What are xenobiotics metabolized to? |
|
Definition
1) nontoxic, water-soluble metabolites that can be excreted
2) toxic products |
|
|
Term
|
Definition
hydrolysis, oxidation, reduction
(CYP450s) |
|
|
Term
|
Definition
conjugation with hydrophilic groups
(GSH) |
|
|
Term
| *Where is air pollution the greatest? |
|
Definition
densely populated regions
near heavy industry |
|
|
Term
| *Where does air pullition have its most significant effects on the body? |
|
Definition
airways & lungs
(can also affect, eyes, nose, & throat) |
|
|
Term
| *Who is especially susceptible to pulmonary complications of air pollution? |
|
Definition
| asthmatics & those with COPD |
|
|
Term
| What is the problem with ground level ozone (O3)? |
|
Definition
| produces pree radical injury & secondary inflammation |
|
|
Term
| What are the 3 main outdoor air pollutions? |
|
Definition
ground-level ozone
sulfur/nitrogen oxides
particulates (soot) |
|
|
Term
| What are indoor air pollutants? |
|
Definition
1) smoke
2) microbial contaminated aerosols
3) allergens
4) radon
5) formaldehyde |
|
|
Term
| *What increased the mortality associated with tobacco abuse? |
|
Definition
|
|
Term
| *Is smoking synergistic or additive with the carcinogenic effects of other agents? |
|
Definition
|
|
Term
| *What happens when a person quits smoking? |
|
Definition
slows loss of pulmonary function
decreased mortality due to CVD & lung carcinoma |
|
|
Term
| *Who is secondhand smoke particularly deleterious to? |
|
Definition
| children exposed in the home |
|
|
Term
| What are the components of cigarettes? |
|
Definition
1) nicotine
2) mucosal irritants
3) CO
4) chemical carcinogens |
|
|
Term
|
Definition
| stimulated release of catecholamines => CV effects s.a. increased BP & HR |
|
|
Term
| What does CO do in tobacco? |
|
Definition
| decreased oxygen carrying capacity |
|
|
Term
| Are the chemical carcinogens in cigarettes initiators or promotors? |
|
Definition
|
|
Term
| What are examples of chemical carcinogens in cigarettes? |
|
Definition
benzo[a]pyrene
polycyclic aromatic hydrocarbons
tar
phenol
nitrosamines |
|
|
Term
| What are the adverse effects on health seen with smoking? |
|
Definition
1) COPD
2) Carcinomas (lung, bladder, kidney, etc)
3) atherosclerosis
4) MI
5) pregnancy related complications (miscarriage & IUGR)
(atherosclerosis & MI are a bigger problem than the others) |
|
|
Term
| *Where is EtOH abuse prevelent in the US? |
|
Definition
|
|
Term
| *What causes variability in EtOH metabolism (i.e. tolerance)? |
|
Definition
genetic variability
acquired induction of enzymatic activity |
|
|
Term
| *What in EtOH contributes to tissue toxicity inc. liver damage & carcinogenic effects? |
|
Definition
|
|
Term
| What enzymes metabolize EtOH? |
|
Definition
ADH in cytosol
microsomal EtOH oxidizing system (with high levels)
catalase (to a lesser extent) |
|
|
Term
| What is EtOH metabolized to? |
|
Definition
|
|
Term
| What enzyme metabolizes acetaldehyde? |
|
Definition
|
|
Term
| What is acetaldehyde metabolized to? |
|
Definition
|
|
Term
| What acute adverse health effects are seen with EtOH use? |
|
Definition
1) liver (fatty change/steatosis)
2) upper GI
3) CNS (depressant: drowsiness, impaired motor & cognitive function, stupor, coma, resp. arrest) |
|
|
Term
| What chronic adverse health effects are seen with EtOH abuse? |
|
Definition
1) *protein-energy malnutrition
2) *deficiencies in water soluble vitamins
3) liver (hepatocyte injury & necrosis => hepatitis & cirrhosis)
4) GI (gastritis, peptic ulcer disease, esophageal varices => upper GI bleeding)
5) pancreas (acute & chronic pancreatitis)
6) CNS/PNS (cerebral & cerebellar atrophy w/ coexistant thiamine deficency => peripheral neuropathy & Wernicke-Korsakoff)
7) CV (atherosclerosis & HTN)
8) carcinomas
9) FAS |
|
|
Term
*Who is more often affected by Pb toxicity?
Why? |
|
Definition
| children due to increased intestinal absorption & less effective BBB |
|
|
Term
| How to Pb toxicities occur? |
|
Definition
| ingestion (children) or inhalation (adults) |
|
|
Term
| What bone change is seen with Pb toxicity? |
|
Definition
| *matrix of bone (competed with calcium for incorporation in osteoid => increased bone density & decreased bone mineralization => poor bone growth & remodeling |
|
|
Term
| What enzyme is inhibited by Pb in the synthesis of Hb? |
|
Definition
| ALA dehydrogenase & ferrochelatase |
|
|
Term
| How does Pb inhibition of ALA dehydrogenase & ferrochelatase lead to decreased synthesis of heme? |
|
Definition
| decreased incorportion of iron into protoporphyrin => decreased protoporphyrin & decreased synthesis of hemoglobin |
|
|
Term
| What effects are seen in the bone marrow & peripheral blood due to decreased hemoglobin synthesis? |
|
Definition
bone marrow: ringed sideroblasts
peripheral blood: microcytic, hypochromic anermia w/ puntate basophilic stippling of the RBCs |
|
|
Term
| What CNS/PNS Sx are seen in Pb toxicity? |
|
Definition
CNS (children): learning diabilities, ADHDs, behavioral problems, poor motor coordination, impaired hearing, irritability, & decreased intelligence => seizures, dementia, coma, & death w/ associated cerebral edema, neuronal necrosis & demyelination
PNS (adults): demyelinating motor neuropathy => muscle weakness (wristdrop) |
|
|
Term
| What tends to have pain with Pb toxicity? |
|
Definition
severe abdominal pain (colic)
muscle & joint pain |
|
|
Term
| What kidney Sx are seen with Pb toxicity? |
|
Definition
| tubular injury => decreased uric acid excretion & chronic kidney disease |
|
|
Term
| Where might black-blue lines (lead lines) occur with Pb toxicity? |
|
Definition
|
|
Term
| What GU Sx is caused by Pb toxicity? |
|
Definition
|
|
Term
| *How is Hg toxicity acquired? |
|
Definition
| inhaled, ingested, or absorbed |
|
|
Term
| *What are the 3 forms of Hg? |
|
Definition
1) inorganic Hg
2) elemental (metallic) Hg
3) *organic Hg (methylmercury) - most common |
|
|
Term
| Where is inorganic mercury seen? |
|
Definition
mining (Hg as well as gold & silver ores)
manufacturing Hg products
fossil fuel combustion
solid waste incineration
volcanoes
fungicides |
|
|
Term
| What happens to elemental Hg at room temp? |
|
Definition
| liquid metal that vaporizes at room temp |
|
|
Term
| Where does elemental Hg exposure occur? |
|
Definition
| producing, using or breaking products containing Hg |
|
|
Term
| How does organic Hg toxicity occur? |
|
Definition
ingestion of contaminated fish & shellfish
inorganic & elemental Hg from the atm & sooil gets in water => conversion by microorganisms to methylmercury => concentration up the food chain |
|
|
Term
|
Definition
*primarily CNS damage => cognitive abnormalities, impaired hearing/vision, seizures, sensory/motor nerve dysfunction, fine tremor, personality change
occasional injury to other organs s.a. kidneys, GI, lungs, gingiva, skin, & CV |
|
|
Term
| What is the sourse of exposure for Arsenic (As) toxicity? |
|
Definition
*primarily ingested
inhaled
absorbed |
|
|
Term
| Where is naturally occuring, inorganic arsenic compounds found? |
|
Definition
soil, water
increased contamination from industrial processes & agricultural runoff
(groundwater contamination most severe & widespread in Bangladesh) |
|
|
Term
|
Definition
metallic taste in mouth
garlic odor to breath
hypersalivation
vomiting
abdominal pain
bloody diarrhea
hemolytic anemia
hypovolemic shock
seizures
delirium
coma
death |
|
|
Term
Sx
chronic low-level As poisoning |
|
Definition
1) non-malignant disorders:
-pigmentation disorders
-hyperkeratosis (esp. palms & soles)
-sensorimotor peripheral neuropathy
-CV, pulmonary, hepatic, renal, & done marrow disorders
2) malignancies (esp. skin & lung) |
|
|
Term
| How does Cadmium (Cd) toxicity occur? |
|
Definition
1) inhalation of aerosolized particles (industrial workplaces, cigarette smoking, hobbies)
2) ingestion (contaminated food/water) |
|
|
Term
|
Definition
1) *kidney: worsening renal tubular dysfunction => glomerular damage & chronic kidney disease
2) RT: acute - chemical pneumonitis & flu like Sx (lethal); chronic - decreased pulmonary function, lung carcinoma, anosmia
3) bone: osteomalacia & osteoporosis |
|
|
Term
|
Definition
| organic solvent with an aromatic ring |
|
|
Term
| How does benzene toxicity occur? |
|
Definition
| *inhalation, but can be ingested & absorbed |
|
|
Term
| What are the sources of benzene exposure? |
|
Definition
industrial emissions
incomplete combustion of carbon-rick materials |
|
|
Term
|
Definition
| primarily CNS (drowsiness, dizziness, confusion, loss of consciousness, death) |
|
|
Term
Sx
chronic benzene toxicity |
|
Definition
| toxic metabolites primarily affect the bone marrow pluripotent stem cells => various cytopenia & malignancies (esp. AML) |
|
|
Term
|
Definition
| industrial chemical used in the production of polyvinyl chloride (PVC) |
|
|
Term
Sx
chronic vinyl chloride toxicity |
|
Definition
| hepatic angiosarcoma (lining of sinusoids) - a rare liver malignancy that's lethal |
|
|
Term
|
Definition
| an arylamine previously used commercially in the rubber & dye industries |
|
|
Term
Sx
chronic 2-naphthylamine toxicity |
|
Definition
| increased risk of urothelial carcinoma of bladder |
|
|
Term
| *What organs are affected by medication adverse reactions? |
|
Definition
|
|
Term
| *What causes the variability of the risk:benefit ratio of the HRT of estrogen progestin combinations? |
|
Definition
drug preparation
route of administration
patient age
duration of Tx |
|
|
Term
| *Does estrogen-progestin HRT cause ovarian carcinoma or dementia? |
|
Definition
|
|
Term
| What are the benefits of HRT with estrogen/progestin? |
|
Definition
1) decreased menopausal Sx
2) decreaed bone loss & fractures
3) decreased risk of colorectal carcinoma |
|
|
Term
| What are the risks of HRT with estrogen/progestin? |
|
Definition
1) increased thromboembolic complications (esp. in women with additional predisposing conditions)
2) increased breast carcinoma
3) increased breast density (makes it harder to detect breast carcinoma &/or lead to falsse positive mammorgrams)
4) increased CV atherosclerotic disease
5) increased gallbladder disease |
|
|
Term
| *What influences the health risks of oral contraceptives? |
|
Definition
specific formulation
mode of delivery
age
smoking Hx |
|
|
Term
| What are the increased risks associated with oral contraceptives? |
|
Definition
1) thromboembolic risks
2) CVD (esp. in patients who smoke &/or are >35y)
3) endometrial/ovarian carcinoma
4) liver cell adenoma (esp. with prolonged use) |
|
|
Term
| *Why are anabolic steroids (synthetic testosterone forumlations) taken at high doses? |
|
Definition
| to enhance athletic performance |
|
|
Term
| *What are the adverse effects of anabolic steroids? |
|
Definition
men: gynecomastia & testicular atrophy
women: virilization (masculinization)
adolescents: stunted growth
acne, CV complication, psychiatric abnormalities, liver damage |
|
|
Term
|
Definition
detoxification via phase II enzymes
if saturated, alternate pathway that needs GSH to convert to non-toxic product.
If GSH becomes saturated, toxic products are formed => liver failure & hepatocyte necrosis |
|
|
Term
|
Definition
hepatocellular necrosis => acute liver failure
(*the most common cause of acute liver failure) |
|
|
Term
*Sx
aspirin (ASA) toxicity |
|
Definition
1) acid-base disturbances (resp. alkalosis => metabolic acidosis)
2) GI (=> upper GI bleeding)
3) dehydration
4) ototoxicity
5) hemorrhagic diathesis
6) CNS effects
7) CV & liver abnormalities |
|
|
