Oligodengroglia: myelinate multiple axons predominantely glial in white matter CNS

Schwann Cells: each one myelinates only one PNS axon/ multiple schwann cells atteched to one axon.

[image]

What are the primary lymphoid organs?

secondary lymphoid organs?

Primary: bone marrow & thymus

Secondary: Lymph nodes,

spleen, MALT (mucosa associated lymphoid tissue)

Cutaneous associated lymphoid tissue

[image]

scattered throughout the body

Tonsils

Adenoids

Appendix

M cells

Gut

Bronchus

Nose

Genitourinary tract

[image]

[image]

Flattened epithelial cells in the gut that lack microvilli

they pull antigen from the lumen of the gut and present it to cells on the basilar side where antigen presenting cells are hanging out right above the Peyer's patches. The APCs take antigen to PPs to stimulate T and B cells

[image]

[image]

What are the darker staining strutures?

[image]

Peyer's Patches

aggregated lymphoid nodules in the ileum below M cells they contain lymphocytes to protect gut from bacteria

B cells are stimulated in the germinal center of Peyer's Patches

Filter blood (contain macrophages)

Store B cells and T cells

Activation of B cells and

Ab production by plasma cells

[image]

Where are B cells found in the lymph node?

T cells?

Where do B and T cells enter the lymph node from the blood?

Where are macrophages found?

Plasma cells?

B Cells: Follicles (yellow spheres in image)

           T cells: Paracortex

B and T cells enter from the high endothelial venules through the paracortex

Macrophages are in the medulla sinus

plasma cells are in the medullary cords

[image]

Which region specifially of the lymph node becomes enlarged during a viral infection?

Why?

Paracortex because this is the site of T cell immune response would occur

[image]

In which immune disorder would you see an underdeveloped Paracortex

The image below is of a lymph node.

In what immune disorder would you see an underdevelopment of the region outlined in dotted lines?

[image]

DiGeorge syndrome

CATCH22

Thymic aplasia-->no T cell development

Axillary

[image]

What is the lymph drainage for the

stomach

duodenum and jejunum

sigmoid colon

rectum

anal canal above pectinate line

anus below pectinate line

testes

scrotum

thigh

lateral dorsum of foot

stomach: celiac

duodenum and jejunum: superior mesentaric

sigmoid colon: colic-->inferior mesenteric

rectum: internal illiac

anus above the pectinate line: internal iliac

below pectinate line: superficial inguinal nodes

testes: paraaortic

scrotum: superficial inguinal nodes

thigh: superficial inguinal node

lateral dorsum of foot: popliteal

Left internal and left subclavian veins

[image]

Why does lymph fluid have a milky white appearance?

[image]

Helper T cells (CD4) recognize MHC II

(Rule of 8 : 2*4=8)

[image]

Cytotoxic T cells (CD8) recognize MHC I

(rule of 8: 8*1=8)

What do Th1 cells do?

Th 2?

Th1:activate macrophages and cytotoxic T cells

Th2:stimulate plasma cells to make Antibody

[image]

Which Interleukin is a very potent stimulator of T cells?

Which genes encode for MHC molecules?

What are MHC molecules?

MHCs are Major Histocompatability Complexes, located on the cell surface. They present antigen fragments to T Cells and bind TCR

They are encoded by HLA genes (Human Leukocyte Antigen)

[image]

All nucleated cells express MHC I

HLA-A, HLA-B and HLA-C encode them

[image]

Where are MHC II molecules expressed?

What genes encode them?

Antigen presenting cells

(binds to CD4-to make Ab)

HLA-DR, HLA-DP, HLA-DQ genes encode them

[image]

What are the HLA subtypes assocaied with the following diseases:

hemochromatosis

Psoriasis

Graves

Hashimoo's

Rheumatoid Arthritis

Diabetes type I

Celiac disease

Ankylosing Spondylitis

Reiter's syndrome

IBD

Pernicious Anemia

MS

Goodpasture's

SLE

Hay fever

hemochromatosis : A3

Psoriasis Arthritis, Ankylosing Spondylitis, IBD Arthritis, Reiter's Arthritis: B27

Celiac disease: DQ (they love ice cream)

Reiter's syndrome, SLE, hay fever, MS: DR2

Diabetes type I, Grave's: DR3

Rheumatoid Arthritis, Diabetes type I: DR4

Pernicious Anemia, Hashimoto's :DR5

M cells

Dendritic cells

Macrophages

B cells

Birbeck granules

tennis racket look

[image]

Target cells

Thrombocytosis

Howell-Jolly bodies

[image]

[image]

What are the actions of:

IL-2

IL-4

IL-5

IL-10

IFN-gamma

IL-2 :stimulates T cells

IL-4 and IL-5: stimulate B cells

IL-10: inhibits T cells and macrophages

Interferon-gamma: stimulates macrophages

cortico-medullary junction of the Thymus

[image]

IL-12

viral infections induce cells to secrete IL-12

because Th 1 cells secrete IL-2 and Interferon gamma which boost the immune response greatly

IL-10

made by Th2 cells. You don't really need to make both at the same time.

IL-4

IL-4 and IL-5: stimulate B cells

IL-10: inhibits Th1 and macrophages

TCR (with CD4) recognizes MHC II

CD28 recognizes B7

TCR (with CD8 )binds to MHC I

IL-2 (secreted by Th1 cells)

IL-4 IL,5 IL-6 from Th2 cells

CD40 receptor on B cells binding to CD40 ligand on APCs

release granules filled with perforin (dissolves membrane) and granzyme (signals apoptosis)

NO INFLAMMATION

APOPTOSIS IS CLEAN AND ORGANIZED

inhibit some autoimmune disease formation

suppress graft rejection

IL-12

IFN-beta

IFN-alpha

Which surface markers are associated with NK cells?

What do NK cells secrete?

CD16, CD56

Secretes IFN-gamma to activate macrophages

IL-10 inhibits Th1

IFN-gamma inhibits Th2

substances that coat cells signaling macrophages to eat them

IgG and C3b are strong opsonins

                    CD40

                    CD16

CD14 (unique to macrophages)

-binds LPS endotoxin on gram- bacteria

CRP

Complement

Coagulation factors

                            Ferritin (binds Fe so bacteria can't use it)

Where are T cells found in the spleen?

In the lymph nodes?

PALS of the spleen

Paracortex of lymph nodes

Where are B cells found in the spleen?

In the lymph nodes?

Follicles of white pulp of the spleen

Follicles of the lymph nodes

encapsulated bacteria:

"Even Some Sexy Killers Have Pretty Nice Capsules"

E.Coli

Strep. Pneumoniae

Salmonella

Klebsiella

H.Influenzae

Psuedomonas aeruginosa

Neisseria meningitidis

Cryptococcus neoformans

UGA

UAA

UAG

U Go Away

U Are Away

U Are Gone

structural genes tht are transcribed + promoter region +all regulatory regions

[image]

Helix-loop-helix

Helix-turn-helix

Zinc finger

Leucine zipper

[image]

Transcription factors bind to the _____ region on DNA

Repressors and Inducers bind to the _____ region on DNA

Promotor

Operator

What is the characteristic sequence of the promoter region?

What does a muation on the sequence cause?

25 TATA Box

75 CAAT Box

mutation: less transcription

Methionine

(start codon)

RNA polymerase II

can cause liver failure

[image]

RNA polymerase I

Revs cytochome p450

Red secretions (urine)

[image]

rRNA: nucleolus

mRNA and tRNA: nucleoplasm

5' cap

Poly A tail

splicing out of introns

RNA Polymerase I

encodes for rRNA

RNA Polymerase II

encodes for mRNA

RNA Polymerase III

encodes for tRNA

rna makes things

introns are noncoding segments

exons are coding sequences for specific proteins

Tetracyclines

[image]

Aminoglycosides: bind 30s and inhibit formation of the initiation complex causing misreading of mRNA

Tetracyclines: bind 30s and block Aminoacyl tRNA

_________________________________

Choramphenicol, Linezolid, Streptogramins, Clindamycin: bind 50s and inhibit peptidyl transferase

Macrolides: bind 50s and prevent release of uncharged tRNA afer its donated its amino acid

[image]

Gentamicin

Tobramycin

Streptomycin

Neomycin

Amikacin

Kanamicin

[image]

[image]

Fibroblasts: all that stuff

Hepatocytes: binding proteins, coaulation factors, complement

Plasma cells: Ab

blue sclera

multiple fractures

dental problems

hearing loss

Alpha-1 antitrypsin deficiency

emphysema in a young person/nonsmoker

liver problems

CD 19

CD20

CD21

                       CD40 (all APCs have)

IgM

IgD

At 19,20,21 , I wanted to B the best MD at 40

What happens to memory B cells as you age?

What is the clinical significance?

What is multiple myeloma?

What do you see histologically?

A neoplasm of plasma cells in the bone(plasma cytoma)

where the plasma cells make one type of antibody in excess, resulting in a monoclonal Antibody Spike.

Histologically you see Russell Bodies

[image]

disulfide bonds

connecting the heavy chains and the heavy chains to the light chains

[image]

The Fc region binds complement which is a constant region and consists of heavy chains joined by disulfide bonds

[image]

Fab fragment binds antigen and consists of heavy chains and light chains

[image]

What are the five different heavy chain types?

What are the two different light chain types?

heavy types:

Mu

Delta

Gamma

Alpha

Epsilon

light types:

Lambda

Kappa

(more kappa than lambda in humans 1:2-in multiple myeloma the ratio will be different)

RAG 1 and RAG 2

[image]

B and T cell arrest

[image]

IgG

IgM

"General Manager can fix it for your complement"

IgG

provides passive immunity

most abundant antibody

distributed evenly bewtween intra- and extravascular pools

fixes complement

Type II and III HSRs

IgA

A mother's milk coats baby's intestinal mucosa and provides protection

monomer in circulation, dimer when secreted

IgE

Allergies and Eosinophils

[image]

IgM

can be a pentamer

[image]

What are live vaccines?

Name them

aka attenuated

A vaccine where the microbe loses it pathogenicity but retains capacity for transient groeth within inoculated host to induce a cellular response

Can induce, strong, life long immunity, but may rever to virulent form (shingles ex.)

Measles, Mumps, Rubella, Polio, Varicella, Yellow Fever, Small Pox

What are inactivated vaccines?

Name them?

aka killed

Pathogen is inactivated by heat or chemicals, maintaining the antigen structure for immune response to induce humoral immunity

stable and safer than live, but weaker and may need boooster shot

Cholera, Hepatitis A, Polio (salk), Rabies

Flu and Yellow Fever

(MMR is too but very small amt-so does not induce allergy)

Match the Autoantibody with the disease.

Anti-IgG

ANA

Anti-dsDNA

Anti-sm (Smith)

Anti-smooth muscle

Anti-histone

Anti-centromere

Anti-Scl-70 (topoisomerase I)

Anti-mitochondrial

Anti-microsomal

Anti-thyoglobulin

Anti-basement membrane

Anti-epithelial (desmoglein)

Anti-SS-A (Anti-Ro)

Anti-SS-B (Anti-La)

Anti-U1RNP

Anti-glutamate decarboxylase

c-ANCA

p-ANCA

excess protein that deposits in tissues in beta pleated sheets

What are the main actions of

IL-1

IL-2

IL-3

IL-4

IL-5

IL-6

and where do they come from?

(Macrophages) IL-1: Fever acute phase reactant

( Th1 cells)IL-2: stimulates Tcells, powerful chemotactant

(all T cells) IL-3: stimulates Bone Marrow

(Th2 cells) IL-4: Stimulates IgE and IgG production

(Th2 cells)IL-5: stimulates IgA production and Eosinophils

(Macrophages) IL-6:Fever acute phase reactant

(Macrophages) IL-8: major neutrophil chemotactant

(Macrophages) TNF-alpha: septic shock

IL-8

C5a

LTB4

C 8 Little Turtles B4 Newts

[image]

recombinant cytokine made by the kidney to stimulate RBC growth

given during anemia, renal failure

epoetin alpha

[image]

What diseases are IFN-alpha, IFN-beta, IFN-gamma used to treat?

IFN-alpha: Hep B, C, Kaposi, leukemia, malignant melanoma

IFN-beta: MS

IFN-gamma: CGD

Hyperacute: minutes

Acute: weeks later

Chronic: months to years (T cell and antibody mediated)

Graft vs. Host: Varies

recombinant cytokines that are used recover bone marrow

filgastrim is a granulocyte CSF

Saragamostim is a granulocyte-macrophage CSF

recombinant cytokine that is like IL-2

used in renal cell carcinoma and metastatic melanoma

A recombinant cytokine that acts like IL-11

used for thrombocytopenia

also can use thrombopoietin

An immunosuppressant that blocks the maturation of T cells by inhibiting calcineurin and thus blocks  the production of IL-2

used to prevent organ rejection, selected autoimmune diseases

side effects: nephrotoxicity

Immunosuppressant that binds to FK binding protein, inhibits calineurin and IL-2

used to prevent organ rejection, topically for eczema

side effects: nephrotoxicity and peripheral neuropathy

Muromonab-CD3

used after kidney transplant

Siromilus *(rapamycin)

inhibits T cell repsonse to IL-2

Immunosuppressant that interferes with the metabolism and synthesis of nucleic acids

side effect is bone marrow suppression

active metabolite mercaptopurine is metabolized by xanthine oxidase---toxic effects can be enhanced by allopurinol

used for hemolytic anemia, glomerulonephritis, kidney transplant

Mycophenolate

[image]

What are these Antibodies used to treat?

Digoxin Immune Fab

Infliximab

Adalimumab

Abciximan

Trastuzumab

Rituximab

Omalizumab

Digoxin Immune Fab: Digoxin intoxication

Infliximab: targets TNF-alpha in Crohn's, RA, Psoriatic Arthritis, Ankylosing spondylitis

Adalimumab: targets TNF-alpha in Crohn's, RA, Psoriatic Arthritis

Abciximab: targets Glycoprotein IIb/IIIa to prevent cardiac ischemia in unstable angina and pts treated wih precutaneous coronoary interventions (stents)

Trastuzumab: HER2 overexpression in breast cancer

Rituximab: B cell non-Hodgkin's lymphona (CD20)

Omalizumab: Targets IgE in sever asthma

tRNA charging: Aminoacyl-tRNA synthetase

Peptide bond formation: Peptidyltransferase

classic: IgG or IgM mediates

alternative: microbe surface molecules

C3a

C5a

cause

anaphylaxis

Tx for anaphylactic shock: epinephrine

[image]

C1 esterase normally inhibits the classic complement pathway

causes episodic attacks of swelling that may affect the face, extremities, genitals, gastrointestinal tract and upper airways

A deficiency will cause an increase in bradykinin and hereditary angioedema

[image]

[image]

angioedema is th rapid swelling of the dermis, subcutaneous tissue mucosa and mucosal tissues

severe recurrent pyogenic respiratory tract infections

especially strep. pneumonia

haemophilus influenzae

Type III- HSR-glomerulonephritis

Gonoccocal

Neisseria bacteremia and recurrent neisseria infections

An acquired, chronic intravascular hemolytic anemia

A complement mediated lysis of red blood cells due to a deficiency of DAF (Decay Activating Factor (CD55, CD59)

Iron spills into blood and urine resultiing in hemosidinuria and  iron deficiency anemia,

thrombosis

Dx: Ham's test: POSITVE if RBCs lye at low pH, and flow cytometry

[image]

Rx: Iron replacement, Anticoagulant (warfarin), Bone marrow transplant

[image]

What is Paroxysmal Nocturnal Hemoglobinuria?

Clinical signs?

Dx?

Tx?

An acquired, chronic intravascular hemolytic anemia A complement mediated lysis of red blood cells due to a deficiency of DAF (Decay Activating Factor (CD55, CD59)

[image]

Iron spills into blood and urine resulting

ing in hemosidinuria and  iron deficiency anemia,

thrombosis

Dx: Ham's test: POSITVE if RBCs lye at low pH, and flow cytometry

[image]

Rx: Iron replacement, Anticoagulant (warfarin), Bone marrow transplant

[image][image][image]

Explain Type I Hypersensitivity

provide examples.

Free Antigen cross links IgE on pre-sensitized mast cells and basophils. Increased vascular permeability

rapid wheal and flare reaction

[image]

 Types: Allergy, Asthma, Anaphylaxis, Atopic disorders: eczema, Allergic rhinits, Atopic dermatitis

[image]

Explain Type II Hypersensitivity

name examples.

Dx.

Antibodies (IgG or IgM) to self creating an inflammatory cascade and tissue damage

-activate complement

-recruit phagocytes--> tissue damage

Dx. Coombs Test

[image]

Examples: Autoimmune hemolytic anemia, pernicious anemia, idiopathic thrombocytopenic purpura , acute transfusion reactions, Erythroblastosis fetalis, Rheumatic Fever, Good Pasture's, Bullous Pemphigoid, Pemphigous Vulgaris, Grave's disease, Myasthenia Gravis

Explain Type III Hypersensitivity

give examples

Antibodies-antigens complexes depositing into tissues

Examples: serum sickness, Arthus skin reaction (5-12 hours), SLE, Rheumatoid Arthritis, Polyarteritis Nodosa, PSGN, Hypersensitivity Pneumonitis

[image]

What is Erythroblastosis Fetalis?

Maternal Antibodies (IgG) against Fetal RBCs

resulting in anemia due to hemolysis of RBC by maternal AB, Jaundice and possible kernicterus, hydops fetalis and possible IU death

Prevention:

dose any Rh- mom with Rh-D immunoglobulin at 28 wks, any traumatic event, and within 3 days of delivery

[image]

Explian Type IV Hypersensitivity

give examples

T-cell mediated : bind to antigen and induce macrophage which in turn causes damage.

Delayed reaction (28-48hours)

Examples: PPD, Poison Ivy, contact dermatitis (poison ive, nickel, poison oak), MS, Hashimoto's, Guillan Barre, GvH

[image][image][image]

[image]

What causes eosiniphilia?

Which Interleukin stimulates Eosinophils?

DNAAACP

Drugs

Neoplasm

Atopy, Allergy, Asthma: Churg's Strauss

Addison's Disease

Acute Interstitial Nephritis

Collagen Vascular Disease

Parasites (Helminths especially)

IL-5

What drug prevents degranulation in this cell?

[image]

This is a mast cell which is basically a basophils found in tissues

Cromolyn is a mast cell stabalizer that can be used to treat food allergy or prevent inflammatory bowel disorders

What is this? What do they release?

[image]

MAC proteins:

any of the complements C5b-C9

Baby Boys

B-cell disorder -->low levels of all Ig

def. in tyrosine kinase gene

recurrent bacterial infections after 6 months of age (passive immunity from mom)

CATCH 22 syndrome

22q11 deletion detect with FISH

failure of 3rd and 4th pharyngeal pouches to develop

T-cell disorder

Thymic Aplasia and Parathymic

no thymic shadow

No T cells

Low calcium

Hypocalcemia-->Tetany

Cardiac abnormalities (heart and great vessels)

Abnormal facies

recurrent viral, fungal and protozoal infection

defect in early stem cell differnetiation

-Adenosine deaminase deficiency

NO B CELLS or T CELLS

no thymic shadow

only have NK cells

Presentation triad:

Severe recurrent infections: Candidiasis, RSV, VZV, HSV, measles, flu, parainfluenzae

Chronic Diarrhea

Failure to thrive

 [image]

T cell dysfunction

recurrent C.albicans infection

Rx: Ketoconazole

WAITER

Wiskott

Aldrich

Immunodeficiency-X linked

Thrombocytopenia and purpura

Eczema

Recurrent pyogenic Infections

No -low IgM High IgA

3 types

increased IgM decreased everything other Ig

X-linked resulting in no CD ligand

AR results in no CD40

-NEMO deficiency

IgA deficiency

cerebellar ataxia, poor smooth pursuit of moving target with eyes

Tenegiectasias of face> 5 yo

increased cancer risk of lymphoma and acute leukemias

radiation sensitivity( avoid Xrays in these pts!)

increased AFP in children after 8 months of age

25 yo is average age of death

[image]

IgA deficiency

commonly seen in people with recurrent sinus and lung infections

1/600 europeans

associated with atopy, asthma

are at an increased risk for anyphylaxis during blood transfusions; therefore, ideally should be transfused with blood from someone that also has IgA deficiency

CGD is an immunodeficiency dieases due to a lack of NADPH oxidase activity resulting in

impotent phagocytes

susceptible to organisms with catalase: staph, candida, aspergillus, nocardia

Dx. with NBT (Nitroblue tetrazolium) dye

positive: no yellow to blue black oxidation

(darker cels are normal, notice the pale neutrophils that didn't stain)

[image]

Tx: TMP-SMX, IFN-gamma

Trimethoprim/Sulfamethoxazole aka Bactrim

[image]

What disease is characterized by partial albinism, recurrent respiratory and skin infections and neurologic disorders?

What would you see histologically?

What is the cause?

Chediak-Higashi Syndrome

defective LYST gene (transport gene)

defective phagocyte lysosome resulting in giant cytoplasmic granules in PMNs

[image]

aka Job Syndrome

deficiency of IFN-gamma production

high levels of IgE

Triad:

Eczema

Cold Boils

Coarse Facial Features

have two rows of teeth

[image]

Leukocyte Adhesion Deficiency Syndrome

rare AR disorder where they lack LFA1 integrin (CD18), which allows neutrophils to make their way out of the blood stream by adhering to the Ig family receptor ICAM on the apical surface of endothelial cells in the infected areas of the body

-inability of phagocytes to exit circulation

recurrent soft tissue infections

no pus formation despite high white blood cell counts in peripheral blood

[image]

[image]

T cell

DiGeorge

ELISA because it is very sensitive

after, positve results are confirmed by Western Blot

Flu-like (acute)

Feeling Fine (latent)

Falling count (CD4 counts)

Final Crisis

What are the following clinical presentaions associated wit HIV:

-Systemic

-Dermatologic

-GI

-Neurologic

-Oncologic

-Respiratory

-Systemic  :

Histoplasma Capsulatum : low grade fever, cough, hepatosplenamegaly, tongue ulcer

 ____________________________________________

-Dermatologic :

Candida Albicans : fluffy, white cottage cheese

[image]

CMV, HSV , EBV can cause oral sores as well

Bartonella Henselae: bacillar angiomatosis superficial vascular proliferation

[image]

______________________________________

-GI 

Cryptosporidium : chronic watery diarrhea

 ___________________________________________

-Neurologic

JC Virus: Progressive Multifocal LeukoEncephalopathy

[image]

Toxoplasma gondii: Abscesses (ring enhancing lesions)

[image]

Cryptococcus neoformans: meningitis

[image]

CMV: Retinits (treat with Ganciclovir)

[image]

HIV: Dementia

-Oncologic

HHV8: Kaposi's Sarcoma

[image]

EBV:Hairy Leukoplakia; Primary CNS lymphoma

[image]

HPV: Squamous cell carcinoma

________________________________________

-Respiratory

CMV: Interstitial Pneumonia (owl's eye inclusion bodies)

[image]

Aspergillus fumigatus:Invasive Aspergillosis

[image]

Pneumocystis jirovecii:Pneumonia (<200 CD4 count, interstital infiltrates)

[image]

Mycobcterium avium-intracellulare: Tuberculosis-like disease (<50 CD4 count)

CD4<200

Start on PCP prophylaxis:

TMP-SMX

Dapsone

Aerosolized Pentamidine

[image][image][image]

__________________________________

CD4<100 Toxo Prophylaxis

TMP-SMX

Dapsone+pentamidine+leuvocorin

____________________________________

CD4<50 MAC/MAI Prophlaxis

Azithromycin (once weekly)

pol (reverse transcriptase)

env (gp120 and gp41)

gag (p24)

[image]

Standard regimen for HIV therapy

stands for Highly Active AntiRetroviral Therapy

combo of 3 drugs:

-2 Nucleoside reverse transcriptase inhibitors (NRTI)

-third drug from a different class

indicated for all HIV patients, especially with CD4<350

"Navir tease a protease"

-Saquinavir

-Indinavir

Ritonavir

and others that end in -navir

prevents development of new viruses

Side effects: GI Intolerance (nausea and diarrhea), hyperglycemia, hyperlipidemia, lipodystrophy, nephrolithiasis (kidney stones) jaundice-Atazanavir

[image]

metabolized by cyt p450

aka AZT

HAART

HIV pregnant women to reduce transmission

newborns

Occupational prophylaxis (plus Lamivudine)

What are the side effects of NRTIs?

What are they used for?

HAART

 competitively binds viral reverse transcriptase and requires phosphorylation

side effects:

Didanosine, Zalcitabine, Stavudine:

Pancreatitis, Peripheral neuropathy

[image][image]

Didanosine, Stavudine:

Hepatic Steatosis

[image]

Abacavir:

Hypersensitivity Reactions (life threatening)

[image]

What are NNRTIs?

HAART

noncompetitively binds viral reverse transcriptase

DO NOT REQUIRE PHOSPHORYLATION

side effects: RASH

Efavirenz:

Skin rashes, Teratogenic, neuro-psychiatric issues, false positve to marijuana

Maraviroc

only used in people with R5 virus becuase it inhibits this receptor

Raltegravir

Elvitegravir

side effects: hyperglycemia, hyperlipidemia, pancreatitis, hepaotoxicity

Match the HAART to the side effect

Lactic acidosis

GI Intolerance

Pancreatitis

Peripheral Neuropathy

Megaloblastic Anemia

Rash

Hyperglycemia, DM and Lipd abnormalities

Bone Marrow Suppression

Lactic acidosis: NRTIs

GI Intolerance: Protease Inhibitors

Pancreatitis: Ritonavir, Didanosine, Zalcitabine, Stavudine

Peripheral Neuropathy: Didanosine, Zalcitabine, Stavudine

Megaloblastic Anemia: Zidovudine

Rash: NNRTIs

Hyperglycemia, DM & Lipid abn: Protease Inhibtors

Bone Marrow Suppression: Zidovudine

gp120: Maraviroc

CCR5 antagonist and entry inhibitor

gp41: Enfuvirtide

entry inhibitor

             Ritonavir(protease inhibitor)

Didanosine (NRTI)

Stavudine (NRTI)

Zalcitabine (NRTI)

foregut: pharynx to duodenum

celiac artery

midgut: duodenum to transver colon

SMA

hindgut: distal transverse colon to rectum

IMA

[image]

What is wrong with this baby?

[image]

Omphalocele:

type of abdominal wall defect  of lateral folding in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall

Tx: close up

different than a gastroschisis:

[image]

gastroschisis lacks a sac

however, omphalocele is associated with other abnormalities and gastroschisis usually is not.

Child presents with poor feeding and vomitting. Xray looks like this. Most likely diagnosis?

[image]

Duodenal Atresia

blind pouch

often assoc. with Trisomy 21

Chaga's disease

Trypanosoma cruzi

A newborn is having trouble feeding. He vomits milk when fed and has a gastric air bubble on X-ray.  What is the problem?

TE Fistula

[image]

Zenker's diverticulum: immediately above UES

[image]

_______________________________

Traction diverticulum: near the midpoint

_________________________________

Epiphrenic diverticulum: right above the LES

[image]

upper 1/3

: usually caused by toxins (alcohol and smoking)

_________________________________________

Adenocarcinoma: usually occures in lower 1/3 bc associated with GERD and Barret's esophaus

A patient that struggles with EtOH abuse comes in becuase he's been coughing up blood and noticed some in his vomit. An endoscopy is performed and looks like this. What does h most likely have?

[image]

Mallory Weiss Syndrome

common in alcoholics and bullemics

tears at the mucosal layer

[image]

This is an image of an endoscopy of a patient with chronic liver disease. What does this show?

[image]

Esophageal varices

Esophageal varices are abnormal, enlarged veins in the lower part of the esophagus. --occur most often in people with serious liver diseases.

Esophageal varices develop when normal blood flow to the liver is obstructed by scar tissue in the liver or a clot. Seeking a way around the blockages, blood flows into smaller blood vessels that are not designed to carry large volumes of blood. The vessels may leak blood or even rupture, causing life-threatening bleeding

Herpes Simplex of the esophagus

[image]

Achalasia

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Warthin's Tumor

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Leucovorin is used as an antidote for cells that have decreased levels of folic acid.

Leucovorin can be converted to THF by normal cells by bypassing the block caused by methotrexate. Therefore, the normal cells can synthesize deoxthymidine and carry out DNA Synthesis

AML, CML and Papillary carcinoma of thyroid

by generation of OH- free radicals which damage DNA

BCC, SCC and melanoma of the skin

UVB light results in formation of pyrimidine dimers in DNA which are normal excised by restriction endonuclease

(remember Xeroderma pigmentosum- these ppl lack or have mutation of the endonuclase)

Astrocytoma

example of a growth factor proto-oncogene→oncogene

HER2/neu (ERBB2/amplification)→Breast cancer

drug:Trastuzamab is against this receptor

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RET (point mutation)→MEN2A, MEN2B and sporadic medullary carcinoma of the thyroid

 RET studies allows us ti prophylactically remove the thyroid before cancer occurs

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KIT (point mutation)→  GI stromal tumor

RAS gene family (GTP binding protein) point mutation→

Carcinomas, melanoma and lymphoma

GAP is missing in many cases so RAS isn't shut off

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ABL (tyrosin kinase) t(9,22) with BCR→ CML and some types of ALL

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c-MYC (transcription factor) t(8;14) involving IgH(14)→ Burkitt Lymphoma

"starry sky" Immunoglogublin heavy chain locus and myc translocation

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N-MYC (transcription factor)Amplification→Neuroblastoma

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L-MYC (transcription factor)Amplification→ Lung Carcinoma (small cell)

Cyclin D1 (CCND1) t(11;14) involving IgH(14)→ Mantle Cell lymphoma

B cell lymphoma of the mantle region in the lymph node

allowing cell to go from G1→S phase

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CDK4 amplification→melanoma

slow growing, well circumscribed, distinct and mobile

organized growth, uniform nuclei, more cytoplasm than nuclei, minimal mitotic activity, lack of invasion,no metatastic potential

rapid growing, poorly circumscribed, infiltrative, fixed to surrounding tissues

disorganized growth, nuclear pleomorphism with hyperchromasia, large nucleus compared to cytoplasm, high mitotic activity, invasion

neuroendocrine cells

small cell carcinoma and carcinoid tumors

(ex. PSA)

screening-->(must get a tissue biopsy for dx)

monitoring response to treatment

monitoring recurrence

downregulation of E-cadherin (move away from neighbors)

binding laminin (start diggin )

destroy basement membrane using collagenase type 4 (make a tunnel though the basement)

attach to fibronectin in ECM and spread locally

(find the pipe)

enter vascular or lymph for metastasis

(go through the pipe)

via regional lymph nodes

exceptions:

Renal cell carcinoma: renal vein

HCC: hepatic vein

Follicular carcinoma of the thyroid

Choriocarcinoma

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Ovarian carcinoma likes to seed in in body cavities (omentum)

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(mesenchymal tissues) sarcomas like to spread in the blood

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Think :"Mine Ears" disease

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I think of a U shaped crypt in the Rectory (rectum)

Associated with

p-ANCA and

primary sclerosing cholangitis

starts at rectum and moves up

smoking is protective against UC

pseudopolyps with loss of haustra (lead pipe appearance)

crypt abscess with neutrophils

left lower quadrant pain

increased risk for toxic megacolon and carcinoma if colonic disease is present

I like to think of a creepy Crohn grandma(granuloma) skipping with a knife on the right side of a cobblestone road

[image][image][image]

knife like fissures

right lower quadrant pain

skip lesions (can be all over the colon)

cobblestone mucosa, creeping fat and strictures

lymphoid aggregates with granulomas

smoking increases risk for Crohns

increased risk for fistulas, and cholelithiasis and carcinoma if colonic disease is present

associated with ankylosing spondylitis, sacroiliitis, migratory polyarthritis, erythema nodosum, and uveitis

How would you test for Hirschsprungs?

rectal suction biopsy

(need to get enough tissue from submucosa to indentify if ganglion is missing)

rectal bleeding

diverticulitis (left sided appendicitus like sx)

fistula  (air or stool in the urine if fistula is with the bladder)

depends on the side..

left colon: diverticula

right colon: angiodysplasia

both result in hematochezia

APC on chromosome 5 (increased risk)

↓

KRAS (polyp formation)

↓

p53 and ↑COX  (Adenocarcinoma)

Aspirin is protective against this last step

1st) adenocarcinoma sequence

(left sided carcinoma usually: iron deficiency anemia and vague pain)

2nd)microsatellite instability pathway (HNPCC) due to mutation in mismatch repair enzyme

(right sided carcinoma usually:pencil poops)

(increased risk for colorectal, ovarian and endometrial carcinoma)

Alkaptonuria

"Our homo captain Al with dark eyes and urine"

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the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidated form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over thirty years old, although the dark discoloration of the urine is present from birth.

Purkinje

↓

Atrial

↓

Ventricular

↓

AV node

"Park At Ventura AVenue"

How do you teat people with IL-12 receptor deficiency?

What are they susceptible to?

Mycobacterial infections

Tx: IFN-γ

Fragile X syndrome

silent mutation resulting in CGG repeats on FMR1 gene of the long arm of X chromosome causing a loss in the FMRP

repeats exceeding 200 cause the disease

Shock

pancreatic pseudocyst

pancreatic abscess

DIC and ARDS

tumor in the head: obstructive jaundice with pale stools and palpable gallbladder

epigastric abdominal pain and weight loss

tumor in the body or tail: secondary diabetes mellitus

pancreatitis

migratory thromboplebitis

serum tumor marker CA 19-9

TX: Whipple: removal of head and neck of the pancreas, proximal duodenum and gallbladder

<10% 1 year survival

RUQ pain that radiates to the right scapula

increased ALP

Acute CHOLECYSTITIS

urine urobilinogen 

(NOT UCB bc UCB is not water soluble)

makes  the UCB water soluble

(DO NOT BE CONFUSED: phototherapy does not conjucate the UCB it only makes it water soluble so it can be excreted in the urine and not deposit in the infant's brain)

Dubin-Johnson (def. of transport proteins to put bile in canaliculi→ CB builds up in hepatocytes →black liver)

Rotor's Syndrome: milder form of Dubin-Johnson (no black liver)

Biliary Tract obstruction ↓urobilinogen ↑alk phos

(dark urine, pale stool)

Viral hepatits (both increase in UCB and CB)

increase urine bilirubin, dark urine

Extravascular hemolysis or ineffective erythropoiesis

Physiologic jaundice of the newborn

Gilbert Syndrome (Mild or low UGT Activity, usually asymptomatic but jaundice occurs with stress/sever infections)

Crigler-Najjar Syndrome (absence of UGT-->kernicterus--> fatal)

resolved HBV infection

or

immunization

TGF-beta which mediates fbrosis

lies beneath endothelial cells that line sinusoids

HFE gene

C282Y

Hemachromatosis

iron overload

"bronze diabetes"

What are the layers of the epidermis?

Corny Lucy's Gran is a Spinster basically

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Neurofibromatosis type 1

Albrights syndrome

Axillary nerve

Posterior circumflex artery

Supraspinatus

anterior glenohumeral ligament

glenoid labrum

posterolateral humeral head

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Which fungus matches the following statements

• found in SW U.S. including west Texas and California

• found in the Mississippi and Ohio River basins

• Causes "San Joaquin Valley Fever"

• Found in rural Latin America

• Found east of the Mississippi River

• Associated with plant thorns and cutaneous injury

• found in SW U.S. including west Texas and California:

Coccidioides immitis

• found in the Mississippi and Ohio River basins:

 Histoplasma capsulatam

• Causes "San Joaquin Valley Fever"

Coccidioides immitus

• Found in rural Latin America

Paracoccidioides brasiliensis

• Found east of the Mississippi River

Blastomycoses Dermatitidis

• Associated with plant thorns and cutaneous injuries

Sporothrix Schenkii

Which fungus matches the following statements

• Found in bird and bat droppings

• Mold form contains barrel-shapped arthroconidia

• Associated with dust storms

• Broad based budding of yeast

• Multiple budding of yeast form

• Causes diaper rash

• Histoplasma
• Coccidioides
• Coccidioides
• Blastomyces dermatitidis
• Paracoccidioides
• Candida albicans

Which fungus matches the following statements

Opportunistic mold with septate hyphae that branch at 45 degree angle

Which fungus matches the following statements

opportunistic mold with nonseptate hyphae that branch at wide angles

Which fungus is known for causing pneumonia in AIDS patients?

Histoplasma

Cryptococcus

Chlamydophila psittaci

West Nile virus

HSN1 avian influenza

Permethrin or Pyrethrin

(crabs or pubic lice)

we don't use lidane bc neurotoxicity and resistance

Your patient has facial angiofibroma, ash leaf spots of skin depigmentation, histry of seizures and mental retardation. What condition does this patient have and what neoplasms is he at risk of developing?

[image][image]

Tuberous sclerosis

at risk of developing:

Cardiac Rhabdomyoma

Astrocytoma

Angiomyolipoma

Posterior communicating artery

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Anterior communicating artery

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PFTsL Pulmonary fibrosis

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LFTs: hepatotoxicity

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TFTs: Thyroid dysfunction

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fungal nail infections

Terbinafine and/or Griseofulvin

caused by dermatophytes (tinea infections)

cigar shaped yeast, patient that works with trees and got cut on the bark and his arm looks like this

[image]

Sporothrix Schenckii

lymphocutaneous sporotrichosis

Tx:

Itraconazole

saturated Potassium Iodide (back in the day)

Amphotericin and/or

Capsofungin

debridement and Voriconazole

angiovasive: Amphotericin B

Fluctytosine+

Amphotericine B

followed by fluconazole