Term
| what does nitric oxide do? |
|
Definition
| Kills microbes in activated macrophages |
|
|
Term
| what how do lysosomal components specifically mediate cell reactions? |
|
Definition
Leak from PMNs and macrophages after demise, attempts at
phagocytosis, etc.
Acid proteases (only active within lysosomes).
Neutral proteases such as elastaseand collagenase are destructive
in ECM |
|
|
Term
| why does the inflammation response also damage other healthy tissues? |
|
Definition
In addition to initial pathogen or
trauma, tissue injury also
accompanies inflammation
Secretion/degranulation of
lysosomes into healthy tissue
Release of oxidative specieswith
AA formation
Increased edema– tissue
compression |
|
|
Term
| how does inflammation ultimately resolve itself? |
|
Definition
return to Normal vascular
permeability
2. Removal of edema and
proteins by lymphatics. . .
3. . .. or macrophage
pinocytosis
4. Phagocytosis of apoptotic
neutrophils
5. Phagocytosis of cellular
debris
6. Exodus of macrophage |
|
|
Term
| what are some possible outcomes of acute inflammation? |
|
Definition
Complete resolution
Little tissue damage
Capable of regeneration
Scarring (fibrosis)
In tissues unable to regenerate
Excessive fibrin deposition organized into fibrous tissue
Abscess formationoccurs with some bacterial or
fungal infections (results in scarring)
Progression to chronic inflammation |
|
|
Term
| what is the duration of chronic inflammation? when does it happen? |
|
Definition
weeks to years, where inflammation, tissue
injury and healing proceed simultaneously
Lymphocyte, macrophage, plasma cell (mononuclear cell)
infiltration
Tissue destruction by inflammatory cells
Attempts at repair with fibrosis and angiogenesis
When?? When acute phase cannot be resolved
Persistent injury or infection (ulcer, tuberculosis)
Prolonged toxic agent exposure (silica, hepatitis)
Autoimmune disease states (rheumatoid arthritis, multiple
sclerosis) |
|
|
Term
| what are some cell mediators of chronic inflammation? what does each do? |
|
Definition
macrophages -
T and B cells
Eosinophils
Neutrophils |
|
|
Term
| describe granulomatous inflammation |
|
Definition
Clusters of activated
macrophages
engulf and surround
indigestible foreign
bodies
mycobacteria, silica,
suture material, TB
Resemble squamous
cells - called
“epithelioid”
granulomas |
|
|
Term
| what happens in the lymph nodes when you have a lot of inflammation? |
|
Definition
| flow is increased, they become engorged. APC's present in the lymph nodes. maybe some toxins and infectious agents also enter the node and cause some reaction. |
|
|
Term
|
Definition
| when a bacterial infection is widespread and gets into the blood |
|
|
Term
| Describe the 4 patterns of acute and chronic inflammation - Serous, suppurative, fibrinous, and ulceration |
|
Definition
Serous -Watery, proteinpoor effusion (e.g., blister)
Fibrinous -Fibrin
accumulation, Either entirely
removed or becomes fibrotic
Suppurative -Presence of
pus, often walled-off if
persistent
Ulceration -Necrotic and
eroded epithelial surface
(e.g. trauma, toxins,
vascular insufficiency |
|
|
Term
| What are some requirements and factors of tissue repair? |
|
Definition
must have a basement membrane,
nerve cells cannot,
it must be able to induce the cell back into the cell cycle
decreases rate of cell loss
increase in growth factors and proto oncogenes |
|
|
Term
| what happens if you can't regenerate the tissue? |
|
Definition
| it is replaced by fibrous tissue. |
|
|
Term
| what are the differences between the three varietes of proliferative potential: labile, stable, and permanent cells |
|
Definition
labile is always dividing, ex: pithelia: skin, oral cavity,
exocrine ducts, GI tract, GU
tract, hematopoietic
Stable - quiescent cells, usually in G0, but can be driven into G1. ex:Liver, kidney, pancreas,
endothelium, fibroblasts
Permanent - non dividing cells. permanently removed from the cell cycle. ex: nerve cells and myocardium |
|
|
Term
| what are two things you really need in the ECM to help regeneration? |
|
Definition
| interstitial matrix and the basement membrane should be collagen type IV |
|
|
Term
| what are the components of the ECM? |
|
Definition
ollagen, elastin, proteoglycans,
glycoproteins
Fibronection, laminin, integrins |
|
|
Term
| what are some functions of the ECM? |
|
Definition
Mechanical support (laminin,
fibronectin)
Determination of cell orientation
and differentiation (remember
epithelial linings)
Control of cell growth (Integrins)
Scaffolding for tissue
removal/renewal |
|
|
Term
| what are the steps in the repair by fibrosis? |
|
Definition
Angiogenesis
2. Fibroblast
migration/proliferation (24
hrs)
3. ECM deposition – collagen
(granulation tissue in 3-5
days)
4. Maturation and
reorganization |
|
|
Term
| what is granulation tissue? when does this tissue appear after the start of fibrosis? |
|
Definition
pink, soft, granular appearance underneath
wounds (fibroblasts and angiogenic tissues)
Large # fibroblasts, angiogenic tissue in ECM
3-5 days |
|
|
Term
| angiogensis, step 1 in repair by fibrosis, how does it work? |
|
Definition
Preexisting vessels send out capillary-like sprouts
Different from vasculogenesis – organization of primitive
vascular network (use of angioblasts)
Granulation tissue –
edematous with leaky
capillaries
Regulatory factors – basic
fibroblast GF and vascular
endothelial GF (VEGF |
|
|
Term
| Describe fibroplasia, and give its place in the tissue repair. |
|
Definition
Occurs within the granulation
tissue framework
Proliferation of fibroblasts at site
of injury regulation by growth
factors and cytokines
Deposition of ECM (collagen)
starts days 3-5 post-injury
Continues for weeks-months
Net collagen = synthesis -degradatio |
|
|
Term
|
Definition
Remodeling to strengthen repair
Continued deposition, degradation
as necessary by
metalloproteinases
interstitial collagenases,
gelatinases
Produced by macrophages,
neutrophils, fibroblasts as
inactive precursors
(suppressed by steroids)
Debris carried away by
phagocytes (debridement) |
|
|
Term
| what is the general process of wound healing (with time frames!) |
|
Definition
1.Acute inflammatory responses
2. Parenchymal cell regeneration if
possible
3. Migration/proliferation of
parenchymal and CT cells
4. ECM protein synthesis
5. Parenchymal cell remodeling
6. CT remodeling to increase wound
strength |
|
|
Term
| what is a primary union? what do we learn from this? |
|
Definition
| we get regeneration in this instance, but not a lot of scar formation. |
|
|
Term
| what is the time course of healing by pprimary intention? |
|
Definition
< 24 hrs – neutrophils at
incision, basal skin cells increase
division
24-48 hrs – skin cell migration,
proliferate along dermis with
deposition of collagen IV (BM
formation
days
neutrophils gone,
macrophages enter
granulation tissue forms
5 days
Neovascularization peaks
collagen fibrils bridge line
of closure
epidermis at pre-incision
thickness
Weeks 1-2
Continued collagen
accumulation from FBs
“Blanching” -decreased edema,
inflammatory cells
End of month
Cellular CT without
inflammatory cells
Fibrous union of CT
(70-80% at 3 mo.)
Epithelialization at
surface |
|
|
Term
| what are some differences with healing by secondary intention vs primary intention? |
|
Definition
Large tissue defect – greater
volume of necrotic debris,
exudate, fibrin
More granulation tissue –
increase scar tissue
Wound contraction –
myofibroblasts
Wound strength (primary or
secondary) |
|
|
Term
| what is pharmacokinetics? |
|
Definition
what you do to the drug. rug action requires
presence of a certain
concentration in the fluid
bathing the target tissue
magnitude of response
depends on concentration
of the drug at the site of
action
balance between
absorption and elimination |
|
|
Term
| what are the processes determining drug concentrations? |
|
Definition
administration/absorption
distribution
metabolism
excretion
fifth process - liberation (release of drug from the formulation) |
|
|
Term
| what are the routes for drug administration |
|
Definition
oral
mucousal
parenternal (outside the mouth)
inhalation
percutaneous (transdermal) |
|
|
Term
| what are some properties of oral adminstered drugs? |
|
Definition
Most common but most variable route
Absorption from duodenum primarily, some in stomach
gradual increase in concentration
Agents typically lipophillic; or requires transporter across
microvilli
Resistant to low pH as passes through stomach
First pass metabolism limits total concentration
Portal circulation to liver,small intestine conversion
sublingual is passing through the oral mucosa
rectal? |
|
|
Term
| multicompartment drug administration |
|
Definition
| i pill with several compartments and drugs with different effects/time frames/ etc... |
|
|
Term
| what are some advantages and disadvantages of intravenous administration? |
|
Definition
Advantages
Avoids first-pass inactivation by liver
Rapid onset of plasma concentration/distribution to
various compartments
Disadvantages
Cannot be recalled rapidly
Potential introduction of bacteria into bloodstream
Potential for hemolysis |
|
|
Term
| describe intramuscular and subcutaneous injections. |
|
Definition
| pretty obvious. one is in the muscle, one is under the skin |
|
|
Term
| describe intrathecal drug administration |
|
Definition
|
|
Term
| iontophoresis vs phonophoresis |
|
Definition
| ionto is using electricity to drive the drug through the skin and dermis, phonophoresis is using ultrasound to drive it through |
|
|
Term
| what are some barriers to drug absorption? |
|
Definition
Phospholipid bilayer – hydrophobic vs. –phillic
Passive diffusion
Weak acids – neutral in
stomach, diffuse easily
Weak bases – neutral in
intestine
Leaky endothelium
Charged particles require
facilitated transport |
|
|
Term
| What is volume of distribution, Vd? |
|
Definition
| Vd= amount of drug administered / plasma concentration |
|
|
Term
| how is the durg eventually finally removed? |
|
Definition
| by excretion either through urine or bile |
|
|
Term
| what does cytochrome p450 do in biotransformation? |
|
Definition
chanisms
Oxidation – cytochrome P450 monooxygenases (aka drug
microsomal metabolizing system – DMMS)
Reduction
Remove oxygen, add hydrogen
Cell cytoplasm
Hydrolysis and Conjugation – with AA, acetylCoA
IN THE LIVER! |
|
|
Term
| for elimination rates of drugs, what are clearance and half life? |
|
Definition
clearance = total blood flow to organ x extraction ratio
Half life - time for plasma concentration to reduce by 50% |
|
|
Term
| what is zero order vs first order kinetics? |
|
Definition
| zero order = constant amount of drug metabolized over time, 1st order is a constant FRACTION of the drug is metabolized over time. |
|
|
Term
| what are some factors which effect elimination? |
|
Definition
| genetics, disease and age, and drug interactions, diet, and gender differences |
|
|
Term
|
Definition
| occupies and activates a receptor →cellular response |
|
|
Term
|
Definition
| occupies and activates a receptor →WITHOUT cellular response |
|
|
Term
| what is the difference between a competitive and non competitive antagonist? |
|
Definition
| competitive binds to the receptor site directly and blocks the primary ligand. a noncompetitive antagonist binds to a different site on the receptor and modulates the receptor's affinity for the primary ligand |
|
|
Term
| what is an inverse agonist? |
|
Definition
| it is a drug that binds to a receptor (maybe like a g-protein) and turns on the receptor (illicits a cellular response) WITHOUT primary ligand binding! |
|
|
Term
| know how to draw a dos response curve for a competetive antagonist |
|
Definition
| shifts curve to the right, but we still eventually can reach maximum response with high enough dose |
|
|
Term
| know how to draw a dose response curve for a non-competitive antagonist |
|
Definition
| shifts the curve to the right a bit and depresses it so it can never reach the maximum response. |
|
|
Term
|
Definition
| ability of a drug to elicit a maximal response. |
|
|
Term
|
Definition
| measure of drug amount required to obtain a response |
|
|
Term
|
Definition
median effective dose
dose at which 50% of maximum
biological response occurs
OR
median dose at which 50%
of population demonstrates
desired effects |
|
|
Term
|
Definition
| dose at which 50% of patients demonstrate a negative effect |
|
|
Term
| therapeutic index, what is it? what would the TI of a cancer drug be? |
|
Definition
| TI = TD50/ED50. cancer drugs TI would be close to 1. |
|
|
Term
| for safety factors, what would be a measure of risk to benefit ratio? |
|
Definition
| TD1 to ED99 ratio. gives a therapeutic window where 1% have unwanted effects but 99% have the desired effect. |
|
|
Term
| what are the resident cells of connective tissue? |
|
Definition
| fibroblasts, osteocystes, chondroblasts |
|
|
Term
| what are the circulating cells of connective tissue? |
|
Definition
|
|
Term
| what are the protein fibers of the ECM? |
|
Definition
|
|
Term
| what is the ground substance of the ECM? |
|
Definition
| fluid or gel like substance that binds everything together. |
|
|
Term
| collagen makes up what percentage of all proteins in a mammal? |
|
Definition
|
|
Term
| give examples of type I collagen |
|
Definition
| accoutns for 90% of body collagen, skin, bone ligament, tendon, fascia, joint capsules |
|
|
Term
| give examples of type II collagen |
|
Definition
| hyalin cartilige, nucleus pulposus |
|
|
Term
| give examples of type III collagen |
|
Definition
| skin, blood vessels, tendons, ligaments |
|
|
Term
| give examples of type IV collagen |
|
Definition
|
|
Term
| give examples of type V collagen |
|
Definition
|
|
Term
| What is ehlers danlos syndrome? what is its prevalence? |
|
Definition
autosomal dominant trait – 6-10 different types
Hyperextensible skin, hypermobility of joint
Hypermobility (EDS III) - Recurring joint subluxations, dislocations
Classical type (EDS I/II) – skin extensibility, widened atrophic scars
Vascular (EDS IV) - most serious form, possibility of arterial or
organ rupture
prevalence as 1 in 5,000, affect both males and females of all
racial and ethnic backgrounds |
|
|
Term
| what are some properties of elastin? |
|
Definition
Repeating Gly amino acid, more proline (AA)
Single crosslinked strands (no triple helix)
Elastic fibers = elastin + fibrillin
can undergo 120-160% strain with no resulting
permanent damage |
|
|
Term
| what are some areas where elastin is found in the body? |
|
Definition
| skin, external ear, tracheobronchial tree, arterial walls, ligamentum nuchae and flavum |
|
|
Term
| what is some elastin related pathology? |
|
Definition
emphysema - loss of elastin,
skin - from excessive sunlight
arterial walls - results in stiffness and hypertension |
|
|
Term
|
Definition
utosomal dominant trait - mutations in the fibrillin-1 (FBN1)
gene
impaired structural integrity of the skeletal, ocular, and
cardiovascular systems
1 in 10,000 individuals, and perhaps as many as 1 in 3000-5000
aortic dilatation and dissection is the major cause of morbidity and
mortality
mitral-valve and tricuspid prolapse
average age at death is 30-40 year
CLINICAL SIGNS:
elayed achievement of motor
milestones secondary to
ligamentous laxity
(hypermobility)
Dysrhythmia (a primary feature),
dyspnea
Joint pain in adult patients
Visual problems - lens
dislocation
disproportionately long limb vs.
trunk (arachnodactyly) |
|
|
Term
| what is the groud substance made of? |
|
Definition
| glycoproteins and proteoglycans. proteoglycans are a glycosaminoglycans + a protein core |
|
|
Term
| what do the Proteoglycans do for connective tissue? |
|
Definition
forms reservoir for nutrients and growth factors
Support - Increases rigidity of ECM
Increases ability to resist compressive forces
GAG chains are (-) charged: hydrophilic (H2
O flows into
ECM)
In ECM, water creates tensile stress on collagen network
Collagen resists and contains the swelling, increasing the
rigidity of the ECM |
|
|
Term
| how do gags resist compression? |
|
Definition
| through both electrostatic forces (GAGs are negatively charged and repel each other) and hydrostatic pressure. |
|
|
Term
| GAGs help resist compression, but collagen keeps the whole structure intact to keep your meniscus or other cartilage from blowing out the sides |
|
Definition
|
|
Term
| how do we draw a dose response curve for an agonist? |
|
Definition
| it increasees the start point for the response. |
|
|
