Step 1 Heme/onc

Front 1

What substance inhibits thrombin from activating fibrinogen?

Back 1

Antithrombin

Front 2

How does Heparin work?

Back 2

It inhibits thrombin by activating antithrombin.

Front 3

What role would a Ca2+ binder (EDTA, trisodium citrate)

Back 3

Essential for coagulation cascade to be effective. Decreases clotting.

Front 4

What is the role of plasmin?

Back 4

1. Clot buster!
2. Activates complement cascade

Front 5

TPA, streptokinase function?

Back 5

Facilitates plasminogen conversion to plasmin (bust clots!)

Front 6

Bradykinin function:

Back 6

1. increases vasodilation
2. increasdes permeability
3. increases pain

Front 7

Which type of membrane transporter is contained in the erythrocyte membrane?

Back 7

Cl-HCO3- antiporter.

Function: allows RBC to sequester HCO3- and transport CO2 to lungs for elimination

Front 8

What is contained in the platelet 1) dense granules and 2) alpha granules, and what is their function?

Back 8

Dense granules: ADP, Calcium, histamine, 5-HT (thrombogenic)
- deficiency: Hermansy-Pudlak syndrome

Alpha granules: vWF, fibrinogen (clotting ptns)
IGF-1, PDGF, TGFβ, platelet factor 4 (which is a heparin-binding chemokine)
- deficiency: Grey platelet syndrome

Front 9

Which is the receptor for vWF?

Back 9

GpIb

Front 10

Which is the recepetor for Fibrinogen?

Back 10

GpIIb/IIIa

Front 11

What is the WBC differential, from highest to lowest % composition?

Back 11

Neutrophils Like Making Everything Better

Neuts - 54-62%
Leuks - 25-33%
Monocytes - 3-7%
Eosinophils - 1-3%
Basophils - 0-0.75%

Front 12

What is contained in neutrophil 1) small, specific granules, and 2) larger azurophilic granules?

Back 12

Small, specific: alkaline phosphatase, collagenase, lysozyme, and lactoferrin

Large, azurophilic: acid phosphatase, peroxidase, ß-glucuronidase

Front 13

How do neutrophils appear in a Vitamin B12/folate deficiency?

Back 13

Hypersegmented (5 or more loibes)

Front 14

How do neutrophils appear in either a bacterial infection or CML?

Back 14

Increased band cells (immature cells)

Front 15

What are the different names for monocytes in the following tissues:

1. blood, alveoli, intestines
2. connective tissue
3. liver
4. kidney
5. brain
6. bone

Back 15

1. macrophage
2. histiocytes
3. kupffer cells
4. mesangial cells
5. microglia
6. osteoclasts

Front 16

What is the cell surface marker for macrophages, and what are they activated by?

Back 16

surface marker: CD14

activated by: IFN-gamma

Front 17

What are the causes of eosinophilia?

Back 17

NAACP:
Neoplastic
Asthma
Allergic processes
Collagen vascular diseases
Parasites (invasive)

OR DNAAACP
Drugs
Neoplasm
Atopic disease (eczema, asthma)
Addison's disease (primary adrenal insufficiency)
AIN (acuite interstitial nephritis)
Collagen vascular disease (SLE, Churg-strauss)
Parasites (Ascaris, Loeffler eosinophilia pneumonities)

Front 18

What are contained in eosinophils' granules?

Back 18

Histaminase and arylsulfatase - limits reaction following mast cell degranulation.

Front 19

What is contained in the basophilic granules of basophils?

Back 19

Heparin (anticoagulant)
Histamine (vasodilation)
Leukotrienes (LTD4)

Front 20

What drug is used to prevent mast cell degranulation?

Back 20

Cromolyn sodium- inhaled (asthma) or intranasal (allergy) - for prophylaxis

Use 3-4x/day

Front 21

How does degranulation take place?

Back 21

Mast cells bind Fc portion of IgE to membrane.
IgE cross links upon Ag binding, causing degranulation, which releases histamine, heparin, and eosinphil chemotactic factors.

Type 1 hypersensitivity.

Front 22

Which cell surface markers do dendritic cells have?

Back 22

MHC II and Fc receptor.

Front 23

What is the signal needed to differentiate B lymphocytes to plasma cells/memory cells?

Back 23

Ag

Also stimulated by Th2 cells (which produce IL-4 and IL-5).

Front 24

Clock-faced chromatin distribution, off center nucleus, abundant rER.

Back 24

Plasma cells - produce large amts of Ab specific to a particular Ag.

Front 25

What are the three cell types that the general T lymphocyte can differentiate into?

Back 25

1. Tc cells (express CD4, recognize MHCII)
2. Th cells (express CD8, recognize MHC I)
3. Treg cells

CD28 is required for T cell activation.

Front 26

What is the MOA of Warfarin?

Back 26

Inhibits epoxide reductase.

Epoxide reductase reduces Vitamin K, which is required s a cofactor for factors 2, 7, 9,10 and ptns C and S.

Front 27

Function of vWF?

Back 27

Carries/protects factor 8, preventing coagulation???

Front 28

Function of antithrombin on clotting cascade?

Back 28

inhibits activated forms of factors 2,7,9,10,11,12

Front 29

What is the result of Factor 5 leiden mutation?

Back 29

It produces a factor 5 that is resistant to inhibitor by Ptn C.

Therefore, more clotting occurs.

40-50% of all hypercoagulable states.

Front 30

Describe the 4 steps of 1) injury 2) adhesion 3) activation and 4) aggregation in platelet plug formation:

Back 30

1. Injury: vWF binds to exposed collagen on damaged endothelium

2. Adhesion: Platelets bind vWF via GpIb receptor @ site of injury (specific). Platelets release ADP and Ca2+ from dense granules (necessary for coagulation cascade). ADP helps platelets adhere to endothelium.

3. Activation: ADP binding to receptor induces GpIIb/IIIa expression @ platelet surface.

4. Aggregation: Fibrinogen binds GpIIb/IIIa and links platelets. Balance is struck between pro-aggregation (TXA2 released by platelets decreases blood flow; platelets aggregate) and anti-aggregation (PGI2 and NO released by endothelial cells increase blood flow, platelet collection breaking).

--> Temporary plug that stops bleeding

Front 31

What is the deficiency in Bernard-Soulier syndrome?

Back 31

Deficiency of Gp1b --> thus platelets cannot bind to vWF, and clotting cannot take place.

Front 32

What is the deficiency in von Willebrands' disease?

Back 32

No vWF. Thus, cannot recognize exposed endothelial collagen in an injury, and cannot initiate the platelet plug.

Front 33

What is blocked by clopidogrel and ticlopidine?

Back 33

The ADP receptor, preventing the ADP released by platelets (dense granules) from binding to platelets and aiding in platelet binding.

Front 34

MOA of clopidogrel?

Back 34

Irreversible inhibition of the ADP receptor. Prevents platelet activation.

Front 35

MOA of ticlopidine?

Back 35

Irreversible inhibition of the platelet receptor ADP receptor. Prevents platelet activation after the platelet has bound the GpIb on vWF.

Front 36

MOA of ASA related to clotting?

Back 36

Irreversibly inhibits COX, which inhibits TXA2 synthesis. TXA2 decreases blood flow in vessels where injury has taken place, and is thus thrombogenic.

Thus, ASA is anti-thrombotic.

Front 37

MOA of Abciximab related to clotting?

Back 37

Inhibits GpIIb/IIIa direcdtly, thus preventing fibrinogen from binding to it and lkinking platelets together in clot formation.

Front 38

ID this RBC path:

Back 38

Acanthocyte (spure cell)

A/W liver disease
Abetalipoproteinemia (cholesterol dysregulation)

Front 39

ID this RBC path:

Back 39

Basophilic stippling

A/W: Thalassemias, Anemia of chronic disease, Lead poisoning.

Baste the ox TAiL (wow, that's a terrible pnemonic).

Front 40

ID this RBC path:

Back 40

Bite cell

A/W G6PD deficiency.
- This is an ENZ of the PPP (HMP Shunt), which is the only source of reduced glutathione in the RBC. When RBC undego oxidative stress (e.g. fava beans --> favism) and ENZ and other ptns cross link damage membrane. These cells are removed by the spleen, and this digestion is manifested as bite cells.

Front 41

ID this RBC path:

Back 41

Elliptocyte

Hereditary elliptocytosis.

Front 42

ID this RBC path

Back 42

Macro-ovalocyte

Megaloblastic anemia (also a/w hypersegmented PMNs), and marrow failure.

Front 43

ID this RBC path:

Back 43

Ringed sideroblasts

Sideroblastic anemia. XS iron in mitochondria = pathologic.

Front 44

ID this RBC path:

Back 44

Schistocyte, helmet cell

A/W: DIC, TTP/HUS, traumatic hemolysis (metal heart valve prosthesis)

Front 45

ID this RBC path:

Back 45

Sickle cell

Sickle cell anemia

Front 46

ID this RBC path:

Back 46

Spherocyte

Hereditary spherocytosis

Autoimmune hemolysis

Front 47

ID this RBC path:

Back 47

Teardrop cell

A/W BM infiltration (e.g. myelofibrosis)

RBC "sheds a tear" because it's been forced out of its home in the bone marrow.

Front 48

ID this RBC path:

Back 48

Target cell:

a/w: HALT said the hunter to her target!

HbC disease
Asplenia
Liver disease
Thalassemia

Front 49

ID this RBC path:

Back 49

Heinz bodies

Oxidation of Iron from Ferrous to Ferric leads to denatured Hgb precipitation and damage to RBC membrane --> formation of bite cells

Seen in G6PD deficiency. Heinz body-like inclusions are seen in alpha-thalassemia.

Front 50

ID this RBC path:

Back 50

Howell-Jolly bodies

Basophilic nuclear remnants found in RBCs.

Howe'll Jolly bodies are normally removed from RBCs by splenic macrophages.

Seen in pts with functional hyposplenia or asplenia, or after mothball ingestion (naphthalene).

Front 51

Antidote for heparin OD:

Back 51

protamine sulfate (positively charged molecule that binds negatively charged heparin).

Front 52

Reversal agent for the thrombolytics (streptokinase, tPA, rPA, TNK-tPA)?

Back 52

Aminocaproic acid - inhibits fibrinolysis.

Thrombolytics directly or indirectly aid coversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increases PT and PTT, no change in platelet count.

Front 53

Which enzymes are affected in lead poisoning?
What are the clinical manifestations?

Back 53

Ferrochetolase, ALA dehydratase --> decreased heme synthesis.

Inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA --> basophilic stippling.

Clinical sx: LEAD
Lead Lines on gingivae (Burton's lines) and on metaphyses of long bones on Xray (esp in young kids)
Encephalopathy and Erythrocyte basophilic stippling.
Abdominal colic and sideroblastic Anemia.
Drops - wrist and foot. Rx = Dimercaprol and EDTA.

Succimer used for chelation in kids - It "sucks" to be a kid who eats lead.

Front 54

Which enzymes are affected in acute intermittent porphyria?

Hint: ACUTE sx
Hint: 5P's

Back 54

Trick question! It's just one: porphobilinogen deaminase (aka uroporphyrinogen-1 synthase)

This is the step that converts porphobilinogen to hydroxymethylbilane.

Sx: 5 P's:
Painful abdomen (neuropathic pain)
Port-wine colored urine (uroporphyrin)
Polyneuropathy (neurotoxic precursors buildup)
Psychological disturbances (neurotoxic precursors)
Precipitated by drugs (Metoclopramide, barbituates, seizure meds, rifampin, alcohol (p450 inducers))

Front 55

Which Enzymes are affected in porphyria cutanea tarda? What are the clinical sx?

Hint: Think of the typical homeless man

Back 55

Enz: Uroporphyrinogen decarboxylase

Sx: Hypertrichosis
Facial hyerpigmentation
Hepatitis C
Alcoholism
Elevated LFTs (AST, ALT, GGT)
Blistering photosensitivity
Tea-colored urine (uroporphyrin)

Front 56

Which is the RLS in heme synthesis?

Back 56

ALA synthase

(glycine+succinyl-coA --> delta aminolevulinic acid)

Front 57

Which cofactor is required for the RLS of heme synthesis?

Back 57

B6 (required for ALA synthase)

glycine+succinyl coA --> delta aminolevulinic acid)

Front 58

What is HbA made of?

Back 58

alpha2ß2

97% of normal hgb

Front 59

What is HbA2 made of?

Back 59

alpha2∂2

2% normal hgb

Front 60

What is HbA1c made of?

Back 60

alpha2ß2-glucose

poorly-controlled diabetes

Front 61

What is HbF made of?

Back 61

alpha2gamma2

Fetal hgb

Front 62

What is Hb Gower made of?

Back 62

zeta2epsilon2

Embryonic hgb

Front 63

What is HbS made of?

Back 63

alpha2betaS2 (glutamine-->valine mutation in beta chain)

sickle cells hgb

Front 64

What is HbC made of?

Back 64

alpha2betaC2 (glutamine-->lysine mutation in beta chain)

HgbC dz and sickle cell dz

Front 65

What is Hb Bart's made of?

Back 65

gamma4 (no alpha)

severe alpha thalassemia

Front 66

What is HbH made of?

Back 66

beta4 (no alpha)

severe alpha thalassemia

Front 67

What is the deficiency in Hemophilia A?

Back 67

Deficiency of factor 8.

Elevated PTT (intrinsic pathway)

Macrohemorrhage in hemophilia - hemarthroses, easy bruising.

Front 68

What is the deficiency in Hemophilia B?

Back 68

Deficiency of factor 9

Elevated PTT (intrinsic pathway)

Macrohemorrhage in hemophilia - hemarthroses, easy bruising.

Front 69

What is the deficiency seen in Vitamin K deficiency - who gets it?

Hint: "DiSCo started in 1972."

Back 69

General coagulation defect - bc reduced vitamin K is required for factors 2, 7, 9, 10 and ptns C and S synthesis.

Newborns (give injections)
Pts on Warfarin (inhibits epoxide reductase, which reduces vitamin K)
End stage liver disease - can't make any coagulation factors.

Front 70

Name some relative causes of polycythemia?

Back 70

This is a relative increase in the number of RBC for the plamsa available. Plasma volume is decreased, normal numbers of RBC and normal O2 sat.

Dehydration, diuretics.

Front 71

Name some causes of appropriate absolute polycythemia?

Back 71

This is an increased RBC mass relative to the amt of plasma (normal plasma, increased RBC, but decreased O2 sat).

D/t lung disease, congenital heart disease, high altitude, obstructive sleep apnea.

Front 72

Name some causes of inappropriate absolute polycythemia?

Back 72

This is an increased RBC mass rel to the normal plasma volume. O2 sat is normal.

D/t renal cell carcinoma, Wilm' tumor, cyst, hepatocellular carcinoma, hydronephrosis, pheochromocytoma, hemangioblastoma.

D/t elevated EPO.