CN V1,V2: 1st branchoal arch

CN VII: 2nd branchial arch

CNIX: 3rd branchial arch

CN X: 4th and 6th branchial arch

5,7,9,10

What is the result of a glycolytic enzyme deficiency?

Hep A and Hep E

naked viruses (no envelope)

NO HCC risk

Hep B (integrates into host genome and acts as an oncogene)

Hep C (from chronic inflammation)

Hep D

 IFN-alpha

Ribavirin

What type of viruses are

Hep A

Hep B

Hep C

Hep D

Hep E

Hep A: Picornavirus RNA

Hep B: Hepadnavirus DNA

Hep C: Flavivirus RNA

Hep D: Delta virus RNA

Hep E: Hepevirus RNA

HBsAg : (surface antigen) indicates ACTIVE infection

Anti-HBs: (Antibody to the surface antigen)indicates recovered status

HBcAg:new disease

Anti-HBc: history of disease

HBeAg:(envelope antigen) ACTIVE VIRAL replication and HIGH TRANSMISSABILITY

ANA(+)

ANti-smooth muscle(+)

Anti-liver-kidney microsomal (+)

Anti-mitochondrial (-)

Virologic markers (-)

How do you treat an infection with Entamoeba histolytica?

What would you see serologically and in the stool?

Tx: Metronidazole

[image]

Histologogy:trophozoites

Stool: Cysts

also can cause liver abscesses and bloody diarrhea

[image][image]

What is the vector for Leishmania?

How do you treat it?

Sand fly

Tx: sodium stibogluconae

[image]

can cause visceral and cutaneous infections

hepatosplenomegaly

macrophages containing amastagotes

[image]

hereditary hemochromatosis

iron deposition in pancreas: diabetes

iron deposition in skin: hyperpigmentation

[image][image]

Iron Man has a Bronze chrome Face but deep down he is soft and sweet.

AR disease causing an inability to get copper into bile for excretion so it builds up in liver, brain, cornea, kidney and joints

Tx: Penicillamine

low ceruloplasmin is diagnostic

Cirrhosis of liver

Golden rings aroound the eye

Basal ganglia degeneration with parkinsonian symptoms

hemolytic anemia

HCC

Fanconi Syndrome

Asterexis

Dementia

Dysarthria

Dyskinesia

[image]

What is hemochromatosis?

What are the diagnostic markers?

What is the treatment?

excess Iron deposition

Cirrhosis

Diabetes

Skin pigmentation

elevated ferritin

elevated total iron (decreased total iron binding capacity)

increased transferrin saturation

decreased

increased risk of HCC

secondary(multiple transfusions) or primary (AR)

Tx: phlebotomy and deferoxamine

alpha1-antitrypsin deficiency

Panacinar Emphysema specifically

codominant disease

[image]

Hepatic adenoma

[image][image]

Hepatic Angiosarcoma

[image]

[image]

Hepatocellular Carcinoma

serum marker: alpha fetoprotein

 rsik factor for Bud-Chiari Syndrome

Penacillamine

He has Wilson's disease

Gilbert syndrome

stress caused jaundice

Lactulose (for hepatic encephalopathy)

Vitamin K (to maximize clotting potential)

Diuretics (for ascites and edema)

Beta-blocker  (to preent bleeding of esophageal varices)

IgE (E for Eosinophils)

IL-5

Unconjugated billirubin: Blood, Bugs/Drugs/ Enzyme

Increased bilirubin production

hemolytic anemia

sickle cell

Hematoma breakdown

[image]

Increased bilirubin uptake and storage

Post viral hepatitis

Rifampin

[image]

Decreased UDP-GT activity

Gilbert's Syndrome

Crigler Najjar Syndrome

Neonatal physiologic jaundice

[image]

__________________________________________

Conjugated: Transport, Damage,  Intra/Extra Obstruction

Impaired transport:

-Dubin-Johnson Syndrome

-Rotor Syndrome

[image]

Biliary epithelial damage

-hepatitis

-cirrhosis

-liver failure

[image]

Intrahepatic Biliary Obstruction

-primary biliary sclerosis

-Sclerosing cholangitis

-Chlorpromazine and arsenic

[image]

Extrahepatic biliary obstruction

-pancreatic neoplasms

-choledocholithiasis

-pancreatitis

-cholangiocarcinoma

[image]

acted upon by gut bacteria to form urobilinogen

some is excreted

some is reabsorbed

Concentric onion skin fibrosis of the bile duct

is associated with what disease?

Primary Sclerosing Cholangitis

men around 40yo

60% p-ANCA

ulcerative colitis

cholangiocarcinoma

beads on a string with ERCP

[image]

[image]

Anti-mitochondria

middle aged females

Pruritis without Jaundice

What is the dieases and treatment?

Primary Biliary Cirrhosis

TX: Ursodiol

Positive Murphy's Sign

pain upon deep palpation and deep breathing

[image]

PBC: middle aged females, positive Anit-mitochondria Ab, Autoimmune diseases *like CREST scleroderma*

PSC:unknown etiology, p-ANCA, middle aged males, ERCP of beading and stricturing, associated with ulcerative colitis and cholangiocarcinoma

Fever

Jaundice

Right Upper Quadrant Pain

Hypotension

Altered Mental Status

Four Fs

Female

Fat

Fertile

Forty

AR disorder lacking ApoB48 ApoB100

Tx: Vitamin E helps

Sx:

failure to thrive

steatorrhea

Acanthocytosis

[image]

retinitis pigmenosa

ataxia

enterocytes swollen with TGs

[image]

Deficiency of LDL receptors

[image]

Apo A-1

A-1 steak sauce on a cat

Apo B-100

Apo B100

[image]

HMG-CoA reductase

Acetyl CoA Carboxylase

[image]

Where do you make fatty acids?

Where do you degrade them?

synthesis: cytoplasm

degradation: mitochondria

What Amino acid is a precursor to the following molecules:

Histamine

Porphyrin, heme

Nitric Oxide

GABA

Creatine

SAM

Histamine: Hisitidine

Porphyrin, heme: Glycine

Nitric Oxide: Arginine

GABA: Glutamate

Creatine: Arginine

SAM: Methionine

Carbamoyl Phosphate Synthetase 1

[image]

gets nitrogen from ammonium

Ornithine Trancabamoylase Deficiency

BUN is low

hyperammonemia: hepatoencephalopathy

Tx: Phenylbutyrate

Lactulose

Carbomoyl Phosphate Synthetase II

gets nitrogen from glutamine

cytosol

Phenylalanine hydroxylase

Tyrosine hydroxylase

Dihydropterin reductase

Dopamine--> HVA

Norepinephrine-->VMA

Epinephrine-->Metanephrine

deficiency in enzyme phenylalanine hydroxylase or the cofactor Tetrahydropbioterin (BH4)

phenylketones build up

can cause mental retardation

growth retardation

fair skin and hair

mousy body odor

If mom has poorly managed PKU, the fetus will suffer-mental retardation, microcephaly and congenital heart defects

screen infants 2-3 days after birth bc mom can give tyrosine to baby but after delivery, you can check for phenylketones if they have PKU

[image]

Dark urine, dark connective tissues and these findings in the eyes

[image]

Alkaptonuria

deficiency of homogentisic acid oxidase

benign, but can cause arthralgias

What is Maple Syrup Urine Disease?

deficiency of the enzyme alpha ketoacid dehydrogenase

leading to a buildup of the branched amino acids Isoleucine, Leucine and Valine

causes mental retardation and death

[image]

Phenytoin

Ethanol

Aspirin

PEA

Acid disassociation constant

the pH where the amount of which the protonated form is equal to the nonprotonated form

If pH is lower than pKa, there is more protonated form

If pH is higher than pKa, there is more nonprotonated form

Sodium bicarbonate

bicarbonate becomes concentrated in the urine which becomes basic and weak acids will be trapped in the urine and excreted

Hydrolysis Oxidation Reduction

results in a slightly polar, water soluble (usually) active metabolite

cytochrome p450 rxns are Phase I rxns

Elderly people lose these rxns first

[image] King Hor 1st active king in 450BC, lost throne when got old

Conjugation reactions

Acetylation

Glucoronidation

Sulfation

Methylation

very polar, inactive metabolites that can be excreted

CYP3A4

If you give two drugs that are both metabolized by the same enzyme, you can have drug-drug interactions

either inducing or inhibiting effect

PICK EGS

Protease Inhibitors

Isonazid

Cimetidine

Ketoconazole

Erythromycin

Grapefruit Juice

Sulfonamides

BCG PQRS

Barbituates

Carbamazepine

Griseofulvin

Phenytoin

Quinidine

Rifampin

St. Johns Wart

Fomepizole

inhibits Alcohol dehydrogenase

Fomepizole prevents formation of Formaldehyde

[image]

Disulfuram inhibits acetaldehyde dehydrogenase, the second step in alcohol metabolism.

Acetaldehydes build up in the blood and cause very untoward symptoms like nausea, vomiting, headache and hypotension

used to discourage alcohol consumption in addicts

Other drugs that have a disulfuram-like reaction:

metronidazole

certain cephalosporins

procarbazine

1st gen. sulfonylureas

Know your drug suffixes

very high yield!

write down as many as you can or have someone quiz you

What is the rate limiting enzyme for the following metabolic pathways?

Glycolysis

Gluconeogenisis

TCA Cycle

Glycogen Synthesis

Glycogenlysis

Glycolysis : Phsophofructokinase

__________________________________

Gluconeogenesis: Fructose-1.6-bisphosphophatase

___________________________________

TCA Cycle: Isocitrate Dehydrogenase

_______________________________________

Glycogen Synthesis: Glycogen Synthase

__________________________________________

Glycogenlysis: Glycogen Phosphorylase

Factor VIII

prolonged PTT

[image]

Factor IX

prolonged PTT

Because warfarin not only inhibits Factors II, VII, IX, X, but it also inhibits Protein C and S more rapidly

Protein C and S normally inhibits Factors V, and VIII (ACCELERATING FACTORS)

so you should give pts heparin for first days they are on warfarin

What mineral is necessary for coagulation?

How can this be used clinically to decrease coagulation?

Calcium

Calcium binders can decrease coagulation (IV citrate)

[image][image]

Factors II, VII, IX, X

10,9,7,2

Protein S

Protein C

SC in 1972 was filled with Koalas

Increase both

(intrinsic PTT

extrinsic PT)

40-50% of hereditary thrmobosis syndromes

mutation of Factor V which is resitant to inhibition by protein C

increased vascular permeability

vasodilation

increased pain

superchargeS antithrombin

short half life

can be used in pregancy bc doesn't cross placenta

used: pulmonary embolism, stroke, DVT, MI

monitor PTT

SE:bleeding, bone loss, osteporosis, HIT (Heparin Induced Thrombocytopenia-->hypercoagulable state so have to treat hese patients with Lepirudin/Bivalrudin

1.stop heparin

2. stop the clotting potential -start them on a direct thrombin inhibitor until platelets rise again  (can't start warfarin right awat for risk of warfarin necrosis in HIT pts) and

3. start warfarin

Explanation:In HIT, the immune system forms Antibodies against heparin when it is bound to a protein, Platelet Factor 4. These antibodies are usually of the IgG class and their development usually takes about five days. However, those who have been exposed to heparin in the last few months may still have circulating IgG, as IgG-type antibodies generally continue to be produced even when their precipitant has been removed.

The IgG antibodies form a complex with heparin and PF4 in the bloodstream causing platelet activation---> formation of blood clots----->platelet count drops---->thrombocytopenia

Protamine Sulfate

[image]

Enoxaparin (Lovenox)

Dalteparin

inactivate Factor Xa

longer half life

can be given subcutaneous instead of IV like heparin

no need to monitor

not interchangeable however

"Low Maintenance"

"Longer Life"

aka Coumadin

inhibits Vitamin K epoxide reductase

inhibits liver from manufacturing clotting factors

effects PT

used for: atrial fibrillation, DVT prophylaxis and treatment, PE treatment

pts on warfarin shouldn;t eat green leafy veggies or food high in Vit.K

TERATOGEN! Do not use in pregnacy. crosses placenta

What are the important differences between heparin and warfarin?

Heparin:

IV

short half life

immediate acting

treatment for overdose:protamine sulfate

[image]

(Hepburn is the Protaganist)

monitor: PTT

safe in pregnant women

_______________________________________

Warfarin:

Oral

long half life

must be started with heparin initially or become hypercoagulable

treatment for overdose: Oral or IV Vit.K or fresh frozen plasma

monitor: PT/INR

TERATOGENIC

[image]

declares WAR on the fetus

activate plasmin to lyse clots

used in early MI, acute stroke

tPA, rPA, TNK-tPA

contraindicated in pts. with active bleeds, hx of intracranial bleeds, recent surgery, bleeding diatheses, severe HTN

Treat toxicity with: Aminocaproic Acid (inhibits fibrinolysis)

Crohn's disease

barium small bowel follow through

looking for string sign

Young Liver Synthesis Blood

Yolk Sac

Liver and Spleen

Bone Marrow

(flat bones especially on young children)

axial skeleton in adults

Associate the pathology to the disease

Acanthocytes

Liver disease

Abetalipoproteinemia

[image]

Associate the pathology to the disease

Basophilic Stippling

TAIL

Thalassemias

Anemia (chronic)

Iron deficiency

Lead Poisoning

inhibiting enzyme that breaks down RNA

[image]

Associate the pathology to the disease

Heinz Bodies and Bite Cells

G6PDeficiency

[image][image]

[image]

Associate the pathology with the disease.

Elliptocytes

Hereditary Elliptocytosis

[image]

Associate the pathology with the disease.

Macroovalocyte

Megaloblastic Anemia

Marrow Failure

[image]

Associate the pathaology with the disease.

Sideroblast

nuclear RBC precursors with granules of iron in cytoplasm

found in bone marrow of healthy people

Too many is called a ringed-sideroblast in the bone marrow and this is not normal

Anemia due to a lot of other things

[image]

Associate the pathology with the disease

Schistocyte

Fragmented RBCs by being forced through areas like fibrin bands in vasculature

DIC

TTPHUS

[image]

Associate the pathology with the disease.

Spherocytes

Hereditary Spherocytosis

[image]

Myelofibrosis

[image]

Thalassemia

Hemoglobin C

Asplenia

Liver disease

[image]

ALA Synthase

require B6

[image]= [image] +[image]

Abdominal pain, port wine urine, polyneuropathy, psychological disturbances

What's the disease and cause?

Acute Intermittent Porphyria

uroporphyrinogen I synthase

Blistering, photosensitivity, tea colored urine, facial hyperpigmentation, excessive hair growth, elevated ALT and AST

What's the disease and cause?

Porphyria Cutanea Tarda

 deficiency in Uroporphoryinogen decarboxylase

[image][image]

GI disturbances, basophilic stippling, microcytic anemia, wrist drop and foot drop, darkened gingiva

What disease?

Lead poisoning

Burton's lines

[image]

elevated erythropoietin

renal cell carcinoma

HCC

Pheochromocytoma

Hemangioblastoma

Chronic Hypoxia (COPD , OSA)

Polycythemia Vera

Down Syndrome

4 Beta globins

seen in:

alpha thalassemia

Hemoglobin H disease

A House of 4 Beta fish will be bad because they each have to be the alpha

[image]

[image]

[image]

[image]

What charge is on histones?

What gives them this charge?

Positive

Lysine and Arginine

LA makes you positive bc its always sunny

[image]

Nucleotides:

Purines: Adenine and Guanine

Pyrimidine: Cytosine,Uracil (deaminated Cytosine) and Thiamine

CUT the Pyrimadine

[image]

C-G has 3 H bonds (more C-G, Higher melting temp,stronger bond)

A-T has 2 H bonds

Glycine, Aspartate, Glutamine

CO2, Tetrahydrofolate

[image][image][image]

Carbon sources: CO2, Tetrahydrofolate and Glycine

Aspartate, Glutamine, Tetrahydrofolate, CO2

[image][image][image]

Carbomyl phosphate-->Orotic acid (Base) +sugar

 [image]  [image][image]

For an erotic night for 2, make a Py (Pie), but you will need to start with your 2 Carb base and add sugar and take a dip in the pool

Carbomyl phosphate Synthetase II- rate limiting step (found in the cytosol)[image]

Two causes:

1: disruption in urea cycle Ornithine TransCarbamylase Deficiency (OTCD)

2: The inability to convert Orotic acid to UMP, ends up in the urine

due to enzyme defects

AR disorder

failure to thrive

Megaloblastic anemia that does not improve with folate or B12 supplementation

Normal Ammonia levels

 [image]

[image]

Elevated Orotic Acid

Hyperammonemia

Ornithine Transcarbamylase Deficiency

OTCD

disruption of Urea Cycle

What drug inhibits Ribonucleotide reductase?

Why?

UMP--->UDP

Hydroxyurea inhibits this enzyme

used to treat sickle cell

[image]

and drugs to treat cancer

[image]

Pyrimidine Analog that irreversibly Inhibits Thymydilate Synthase

dUMP--(x)--->dTMP

[image][image]

[image]

5-flouwers and a Py were seen at the dUMP to show cancer can't stop thy beauty

Anticancer/immunosuppressant drug that inhibits enzyme Dihydrofolate reductase from making folate in eukaryotes

The Method is Reducing the Trees

[image] [image]

bacteriostatic agent that inhibits Dihydroreductase in Prokaryotes inhibiting folate production

Tri reducing the trees

[image]

drug that inhibits PRPP Synthetase and thus inhibits purine synthesis

Mycophenolate Mofetil is an Immunosuppressant that inhibits Inosine Monophosphate Dehydrogenase in the de novo pathway of purine synthesis (guanine)

which is needed for creation of B and T cells

drug used for autoimmune disorders and organ transplant to prevent rejection

Myco Ino Mono

Xanthine----(xanthine oxidase)--->Uric acid

6-Mercaptopurine and Azathioprine are metabolized by Xanthine oxidase.

Allopurinol inhibits xanthine oxidase

So if these drugs are taken with Allopurinol, their toxicity is increased

HGPRT deficiency

Lesch-Nhyan Syndrome

deficiency of HGPRT----> build up of uric acid

gout, self mutilation(lip biting), writhing chorea, mental retardation

Tx: Allopurinol (only for hyperuricemia)

[image]

_______________________________________

Adenosine Deaminase deficiency

SCID

AMP--->Adenosine--(X)-->Inosine

chronic diarrhea, severe, recurrent infections, failure to thrive, absen thymic shadow

[image][image][image][image]

Tx: Enzyme replacement, Gene therapy, bone marrow transplant

___________________________________________

similarities: both are Dihydrofolate reductase inhibitors

differences:

TMP:bacteriostatic, works in prokaryotes : treats UTIs, used in combo with Sulfamehoxazole

Methotrexate: anti-cancer and immunosupressant: used in eukaryotes

Xeroderma Pigmentosa: hypersensitivity to UV light-->1000x increased risk of skin cancer

__________________________________________

Ataxia Telengiectasia: sensitivity to ionizing radiation, immunodeficeincy, ataxia beginning 1-2 years

_________________________________________

Bloom Syndrome: hypersensitivity to sunlight, leukemias and lymphomas are common, avg. age of cancer onset is 25

______________________________________

Hereditary Nonpolyposis Colorectal Cancer

_______________________________________

BRCA1 and BRCA2

• Inhibits ribonucleotide reductase : HYDROXYUREA

• Inhibits dihydrofolate reductase: TRIMETHOPRIM (prok) and METHOTREXATE (euk)

• Inhibits thymidylate synthase : 5-FLOUROURACIL

• Inhibits inosine monophosphate dehydrogenase: MYCOPHENOLATE

• Inhibits PRPP synthetase: 6-MERCAPTOPURINE

What eukaryotic DNA polymerase matches the following description?

• Replicates lagging strand, synthesizes RNA primer

• Repairs DNA

• Replicates mitochondrial DNA

• Replicates leading strand DNA

• Replicates lagging strand, synthesizes RNA primer: DNA Polymerase alpha

• Repairs DNA: DNA polymerase beta, and epsilon

• Replicates mitochondrial DNA : DNA polymerase gamma

Replicates leading strand DNA: DNA Polymerase delta

CPS I:

rate limiting enzyme in urea cycle

loaction : mitochondria

nitrogen source: ammonia

_____________________________________________

CPS II:

rate limiting enzyme in pyrmidine synthesis

location:cytosol

nitrogen source: glutamine

bound to ferritin in the liver

Ferritin is released from the liver during times of inflammation or infection bc it can bind teh iron that the bacteria want and need to replicate

So increased levels of ferrtitin in serum could be indicative of inflammation/infection

Zinc is essential for what?

What does Zinc deficiency cause?

Carbonic Anhydrase

Wound Healing

Lactate Dehydrogenase

Zinc Deficiency :

decreased wound healing

rash around eyes, mouth, nose, anus

*acrodermatitis enteropathica*

[image]

anorexia

diarrhea

growth retardation

impaired night vision

infertility

depressed mental function

Transferrin binds Iron in the blood and transports it from one location to the next

half life of 8 days

increased in times of Iron Deficiency

(think of lots of cabs waiting by the curb when peak times are low-- less customers, more cabs available)

Tetany and neuromuscular irritability

Chvostek's sign

Trousseau's sign

[image]

ALA dehydrogenase

Ferrochelatase

resulting in microcytic anemia

ringed sideroblasts (RBC precursors with mitochondira and lost of IRON)

[image]

ADULTS:

EDTA

Succimer

______________________________________

CHILDREN:

EDTA

Dimercaprol

Succimer (3rd line)

kidney and brain

[image][image]

some areas of Bangladesh have arsenic in ground water

causes:

increase of cancer in every tissue, especially:

in lungs, skin

basal cell and squamous cell

[image]

some areas of Bangladesh have arsenic in ground water

causes:

increase of cancer in every tissue, especially:

in lungs, skin

basal cell and squamous cell

look for key clinical finding : garlic odor breath

[image]

Tx: Dimercaprol

[image]

Lung, Kidney, Bone

[image][image][image]

Obstructive lung disease

increased risk of lung cancer

Kidney injury

Osteoperosis/Osteomalacia

Calcium loss

Which antibiotic matches the following description?

• Inhibits 50S peptidyltransferase
• Binds 50S, blocking translocation
• Bind 30S, preventing attachment of tRNA
• Inhibits prokaryotic RNA polymerase
• Inhibits prokaryotic topoisomerase
• Inhibits prokaryotic dihydrofolate reductase

• Inhibits 50S peptidyltransferase: Streptogramins, Chlormaphenicol

_________________________________________

• Binds 50S, blocking translocation: Linezolid, Macrolides

________________________________________

• Bind 30S, preventing attachment of tRNA:Tetracyclines

________________________________________

• Inhibits prokaryotic RNA polymerase:Rifampin

___________________________________________

• Inhibits prokaryotic topoisomerase: Flouroquinolones

___________________________________________

• Inhibits prokaryotic dihydrofolate reductase: Trimethoprime

What are the microcytic anemias?

How do you tell?

Look for MCV first <80 fL

HYPOchromic cells= low MCHC

MC: Iron Deficiency Anemia[image]

-due to blood loss,increased demand, colon cancer

hypochromic, assoc. with Plummer Vinson and glossitis

ferritin is low

transferrin is high

%transferrin saturation<12%

_________________________________________

Thalassemias: AR disorder of hemoglobin synthesis

Alpha Thalassemia[image]

defect in alpha globin synthesis

Alpha Thalassemia (African and Asians)

(2 or more alpha globins-mild)

HgH disease (4 beta globins)

[image]

Hydrops Fetalis (no alpha globin production)

_____________________________________________

Beta Thalassemia (mediterranean populations) [image]

Beta Thal minor

Beta Thal Major (no beta globins,severe anemia--> requires a lot of blood transfusions-->hemochromatosis (treat with deroxamine to chelate iron)

Histology:

-Target cells, marrow expansion and -hyperplasia (crew cut in skull imaging),

-increase in HgF (two alpha and two gamma)

____________________________________________

Lead poisoning  [image]

ferrochetalase and ALA dehydrogenase are inhibited

sideroblastic anemia

(ringed sideroblasts in bone marrow: mitochondria in RBC precursors with granules filled with lead)

__________________________________________

Anemia of Chronic Inflammation

Iron is trapped in Macrophages

ferritin is normal or high

serum iron is low

transferrin is low

% transferrin saturation: normal or elevated

TIBC is decreased

Decreased cell production

(hematopoietic cell damage from infection, drugs, radiation etccc oR deficiency of factors required for heme or DNA synthesis like Iron, B12, folate)

Increased RBC loss

(hemorrhage, destruction)

Chronic Blood Loss

-menorrhagia

-bleeding GI lesion (like carcinoma of colon) (USA)

-hookworm disease (outside USA)

[image]

Iron Deficiency:

Decreased serum Iron

Decreased Ferritin

Increased TIBC

_________________________________

Thalassemia

Normal Iron

Normal Ferritin

Normal TIBC

Target Cells

Colon Cancer

(blood loss from lesion)

HMCV> 100 in adults

Megaloblastic (impaired DNA synthesis)

B12 deficiency Anemai: neurologic deficits

[image]

Folate deficiency Anemia

In both look for hypersegmented neutrophils, glossitis, elevated homocysteine

causes: malnutrition, malabsorption (disease, drugs, alcohol), increased requirement (pregnancy)

__________________________________________

Orotic Aciduria

*doesn't respond to B12 or folate replacement

________________________________________

____________________________________

Non-Megaloblastic

Liver disease

Alcoholism (can cause both megaloblastic and nonmegaloblastic macrocytic anemia)

Drugs:

AZT, 5-Flourouracil, Hydroxyurea ----->myelosuppression----> anemia

Hemolytic vs. Nonhemolytic Anemias

Nonhemolytic

Anemia of Chronic disease

-inflammatry mediator IL-6 causes liver to trap Iron

low iron

low TIBC

normal-high ferritin

_____________________________

Aplastic Anemia

-pancytopenia

caused by infections, drugs, radiation, Fancon's anemia, idiopathic

-hypocellular bone marrow with fatty infiltration

[image]

-fatigue, malaise, pallor, petechia, purpura, mucosal bleeding, infections

Chronic Kidney Disease

kidneys stop making Erythropoietin

______________________________________

Hemolytic

What is the cause of anemia given the following statement?

• Microcytic anemia + swallowing difficulty + glossitis

• Microcytic anemia + > 3.5% HbA2

• Megaloblastic anemia not correctable by BI2 or folate

• Megaloblastic anemia along with peripheral neuropathy

• Microcytic anemia + basophilic stippling

• Microcytic anemia reversible with B6

• HIV positive patient with macrocytic anemia

• Normocytic anemia + red urine in the morning
• Normocytic anemia and elevated creatinine

• Microcytic anemia + swallowing difficulty + glossitis:

Plummer-Vinson Syndrome

• Microcytic anemia + > 3.5% HbA2:

Beta Thalassemia

• Megaloblastic anemia not correctable by BI2 or folate:

Orotic Aciduria

• Megaloblastic anemia along with peripheral neuropathy

B12 Deficiency

• Microcytic anemia + basophilic stippling

Lead Poisoning

• Microcytic anemia reversible with B6

Sideroblastic Anemia

• HIV positive patient with macrocytic anemia

Zidovudine (possibly)

• Normocytic anemia + red urine in the morning

Paroxysmal Nocturnal Hemoglobinuria

• Normocytic anemia and elevated creatinine

Chronic Kidney disease

Calcium dependent enzymes

Ubiquitin protein ligase

lysosomes

Succimer and EDTA in Adults

Dimercaprol, EDTA and Succimer (3RD line) in Kids

normocytic, normochromic anemia

Intravascular or Extravascular

Intravascular:

decreases haptoglobin

increase in unconjugated bilirubin

types:

Paroxsymal Nocturnal Hemoglobinuria

Autoimmune Hemolytic Anemia

Mechanical Destruction (Aortic stenosis, prosthetic valves)

____________________________________________

Extravascular

something wrong with RBCs and cells are actively destroyed by macrophages in spleen

 G6PD

Sickle Cell

HgC disease

Pyruvate Kinase deficiency

Hereditary Spherocytosis

Babesiosis

Malaria

different kinds of autoimmune hemolytic anemias

Warm: IgG chronic anemia, or with certain drugs seen in SLE, CLL, alpha-methyldopa

______________________________________________

Cold: IgM, acute anemia triggered by cold, seen in CLL, Mycoplasma Pneumonia infections, EBV

HALT said the huntress to her target

HbC disease

Asplenia

Liver Disease

Thalassemia

[image]

BIG T

Bernard-Soulier Syndrome:

  hereditary defect: platelet plug formation,

decreased GpIb-->defect in platelet to vWF adhesion

increased BT, decreased PC

enlarged platelet that are taken out of circulation by the spleen

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Glanzmann's Thrombasthenia

hereditary defect: platelet plug formation

decreased GpIIb/IIIa-->defect in platele to platelet aggregation

normal platelet count, increased BT

No platelet clumping on lab smears

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Idiopathic Thrombocytopenic Purpura (ITP)

[image]

acquired defect: anti GpIIb/IIIa antibodies

causing splenic macrophages to chew up platelt/antibody complexes and decrease platelt life span

increased megakaryotes, decreased PC, increased BT

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Thrombotic Thrombocytopenic Purpura (TTP)

defect: ADAMTS 13 (vWF metalloprotease)

causes a decrease in degradation of vWF multimers

increased vWF multimers-->increased platelet agg & thrombosis-->decreased platelet survival

Labs show schistocytes, increased LDH, decreased PC, increased BT

Sx: pentad:

Neuro

Renal (Uremia)

Fever

Thrombocytopenia

Microangiopathic Hemolytic Anemia

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TTP-HUS

milder form of TTP

Triad: Hemolysis, Uremia, Thrombocytopenia

assoc. with E.Coli 0157:H7 infection

[image]

von Willebrand's disease

mixed platelet and coagulation disorder

Tx: DDAVP(Desmopressin) releases vWF stored in endothelium

increased BT, normal or increased PTT

mild disease, AD

Dx: Ristocetin cofactor assay

von Willebrand's disease

&

DIC

A mixed platelet and coagulation disorder characterized by widespread clotting that leads to a deficieincy in clotting factors, creating a bleeding state

Causes: Stop Making New Thrombi

Sepsis (gram-)

Trauma

Obstetric complications

Pancreatitis

Malignancy

Nephrotic Syndrome

Transfusion

Labs: schistocytes, increased fibrin split products (D-dimers), decreased fibinogen, decreased coag factors V and VIII

Increased PT, PTT, and BT

Decreased PC

Ribonucleotide reductase inhibitor resulting in decreased DNA Synthesis (S phase specific)

treats: Melanoma, Sickle Cell(increases HbF), and CML

Toxicity: Bone marrow suppression, GI upset

[image][image]

Platelet inhibitors

ADP receptor blockers

reducing expression of GpIIb/IIIa-->no platelet aggregation

used for: acute MI, prevent strokes, 6-12 months after stenting following, aspirin alternative

monoclonal antibody

block GpIIb/IIIa

USED FOR: acute coronary syndromes, especially non-ST elevation MI, and angioplasty

can cause bleeding and thrombocytopenia

What is the mechanism of action of the following drugs?

• Streptokinase

• Aspirin
• Clopidogrel
• Abciximab
• Tirofiban
• Ticlopidine
• Enoxaparin
• Eptifibatide

• Streptokinase (tPA): converts plasminogen to plasmin which cleaves fibrin and breaks clots *thrombolytic*

• Aspirin: irreversibly inhibits COX-1

• Clopidogrel: blocks ADP receptors

• Abciximab: binds to GpIIb/IIIa

• Tirofiban: binds to GpIIb/IIIa

• Ticlopidine: blocks ADP receptor

• Enoxaparin:LMW heparin: catalyzes activation of anithrombin III

• Eptifibatide: binds to Gp IIb/IIIa

Kaposi Sarcoma

Invasive SCC

CNS lymphoma

Non-Hodgkin lymphoma

Leukemia is lymphoid or myeloid neoplasms with widespread involvement of bone marrow. Tumor cells found in peripheral blood

Lymphoma is discrete tumor masses arising from the lymph nodes

localized single group of nodes with contiguous spread, rubbery feel, can be seen mediatinally sometimes

Characterized by Reed-Sternberg cells

CD30+ and CD15+B cell origin

more of these cells, the worse the prognosis

[image]

Bimodal distribution=young adults &>55yo.

more common in men except for nodular sclerosing type

1/2 associated with EBV

low grade fever, night sweats, weight loss, painless lymphadenopathy

[image]

Types:

MC: Nodular Sclersosing (good px --only one more common in women than men)

2nd MC: Mixed Cellularity (poor px :()

Lymphocyte predominant (good px)

Lymphocyte depleted (poor px :( )

more extranodular involvement

peak incidence 20-40 years

assoc. with HIV and Immunosuppression

Fever, constitutional sx

majority of B cell lineage (except, of course, lymphoblastic T cell lymphomas)

Subtypes:

 Burkitt's Lymphoma: t8;14 translocation of c-myc(8) and heavy chain Ig(14)

adolescents and young adults

Starry sky appearance

[image]

sheets of lymphocytes with interspersed macrophages

assoc. with EBV

Jaw lesion in endemic form (Africa)

Pelvic or Abdomen in sporadic

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Diffuse Large B cell Lymphoma:

older adults but 20% are children, most common adult NHL and in the USA in general!, may be mature T cell in origin 20%

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Mantle Cell Lymphoma:

older males

t(11;14) translocation of cyclin D1 and heavy chain Ig

poor prognosis

CD5+

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Follicular Lymphoma:

Adults

t(14;18) translocation of heavy chain Ig (14 and bcl-2(18)

difficult to cure; indolent course

bcl-2 inhibits apopotosis

most common malignancy in children

males>females

whites>blacks

predominance of lymphoblasts in the circulating blood and bone marrow

bone pain is common

most have TdT

PAS+

 very good prognosis-->very responsive to therapy

best prognosis is CD10+ type, hyperdiploidy and t(12;21)/TEL-AML1 rearrangement

assoc. with Down's Syndrome

difficult to dx on blood smear

poor prognosis: Philadephia Chr. t(9;22)

Acute Myeloid(myeloblastic) Leukemia

most often in adults

chracteristic Auer Rods

[image]

predominance of myeloblasts

most CD 13/33+

nonspecific esterase+ myeloid cells

PAS-

worse prognosis than ALL

associated with numerous risk factors (including Down's Syndrome)

classification into subgroups based on a variety of factors

Chronic Lymphocytic Leukemia

(same as small lymphocytic lymphoma)

<5% blasts (more mature cells)

characterized by proliferation of neoplastic lymphoid cells (usually B cells) with widespread infiltration of the bone marrow, peripheral blood, lymph nodes, spleen, liver and other organs

older than 60 yo, mostly men

express surface Ig and pan-B cell markers like CD19, CD20 and CD5+ also

often appear as smudge cells

[image]

peripheral WBC count can vary normal to high

hepatosplenomegaly,lymphadenopathy

Complications: Warm antibody hemolytic anemia

Hypoagammaglobulinema

Survival 5-10 years

a chromic form of AML

Philadelphia chromosome always present

t(9;22) bcr-abl

fatigue, abdominal pain and splenomegaly

monoclonal proliferation of mature myeloid cells

Polycythemia Vera

Essential Thrombocytosis

Myelofibrosis

CML

malignancy of plasma cells

large production of antibodies

most common tumor of the bone in ppl over 50

hypercalcemia, renal insufficiency, anemia, back pain

plasma cells make local osteolytic cytokines that stimulate osteoclasts and inhibit osteoblasts

susceptible to infection, amyloidosis (deposition of monoclonal IgG light chains (usually)), punched out lytic bone lesions, excessive monoclonal antibodies in serum and urine *not measured on ordinary urinalysis*

M protein, proliferation of plasma cells in the bone marrow

[image]

Krukenberg tumor

signet ring cells

RBCs=malaria

ovary=krukenberg tumor (metastasis from stomach)

stomach= gastric adenocarcinoma

Quelling test

"Quelling for a shelling"

Epiglottitis

Haemophilus influenza type B (uncommon bc of vaccine)

scarlet fever

kawasakis disease

*do not give to pts with delerium, dementia, BPH, ileus*

Atropine

TCAs

H1 blockers (Diohenhydramine)

LOW potency Neuroleptics (Thioridazine, Chlorpromazine)

Digoxin

Amantadine

Promethazine

*don't give to ppl at risk for MI, CAD, prinzmetal angina*

Cocaine

Amphetamines

Methamphetamines

Triptans (migraines and cluster headaches)

Ergotamines

Vancomycin (RED man syndrome)

Niacin

Adenosine

Dihydripyridine CCBs (-dipines)

Doxorubicin

Daunorubicin

What drugs cause torsades de pointes?

What is treatment for torsades?

Class IA Na channel blockers

Class III K channel blockers

Macrolides

Haloperidol

Chloroquine

Protease inhibitors (-navir)

tx: IV magnesium

Clozapine

Carbamazepine

Colchicine

PTU

Methimazole

Dapsone

Chloramphenicol (grey baby syndrome)

Benzene

NSAIDs

PTU

Methimazole

Isoniazid

Sulfonamides

Primaquine

High dose aspirin

Ibuprofen

Nitrofurantoin

Dapsone

Fava beans

Napthalene

Phenytoin

Methotrexate

Sulfa drugs

Zidovudine

Heparin (HIT)

H2 blockers

Bleomycin

Busulfan

Amiodarone (anti-arrhythmic)

Halothane

Acetaminophen

Valproate

Amanita phalloides (mushroom toxin)