Hematology Flashcards by Paulo Rivera

Erythropoietin is formed by which organs?

90% made by the kidney

10 % Liver

How well did you know this?

Not at all

Perfectly

What stimulates renal production of EPO?

Hypoxia

How well did you know this?

Not at all

Perfectly

How does EPO exert its effects?

Triggers hematopoietic stem cells to produce more proerythroblasts

How well did you know this?

Not at all

Perfectly

What is the result of vitamin B12 or folic acid deficiency?

Maturation failure during the process of erythropoiesis.

How well did you know this?

Not at all

Perfectly

Final maturation of RBCs requires what?

(2 factors)

Vitamin B12

Folic Acid

How well did you know this?

Not at all

Perfectly

What is pernicious anemia?

Atrophic gastric mucosa (GI defect) leads to decreased B12 absorption.

How well did you know this?

Not at all

Perfectly

What is intrinsic factor?

Glycoprotein that binds to Vit B12 and protects B12 from digestion. Then the intrinsic factor-B12 complex is absorbed by pinocitosis in the ileum.

How well did you know this?

Not at all

Perfectly

What cells produce intrinsic factor?

The parietal cells of the gastric glands

How well did you know this?

Not at all

Perfectly

At what RBC cell stage does the process of hemoglobin synthesis start?

A the proerythroblast stage

How well did you know this?

Not at all

Perfectly

What are the components of hemoglobin?

Heme - molecule

Globin - long polypeptide

How well did you know this?

Not at all

Perfectly

What is the total iron distribution in the body?

Hemoglobin - 65%

Ferretin - 15-30%

Myoglobin - 4%

Compounds of intracellular oxidation - 1 %

Transferrin - 0.1%

How well did you know this?

Not at all

Perfectly

How is iron absorbed in the GI?

Iron combines with apotransferrin in the small intestine.

Apotransferrin is converted to transferrin.

Transferrin transports Iron in plasma.

How well did you know this?

Not at all

Perfectly

How is iron (transferrin form) is distributed and stored in the cell?

Transferrin circulates iron and deposits it in:

Liver and reticuloendothelial cells of bone marrow

Once inside the cell - iron combines with apoferritin to form ferritin.

How well did you know this?

Not at all

Perfectly

What happens when iron plasma levels decrease?

Iron dissociates from ferritin in the cells and then it is recirculated to where it is needed (via transferrin)

How well did you know this?

Not at all

Perfectly

How is Iron stored in the cell?

Via ferritin

How well did you know this?

Not at all

Perfectly

How is iron transported in the blood?

Transferrin

How well did you know this?

Not at all

Perfectly

Where does transferrin bind particularly strongly?

Receptors of erythroblasts and bone marrow (cells that need large amounts of iron)

Transferrin is endocytosed and it delivers iron directly to the mitochondria.

How well did you know this?

Not at all

Perfectly

What receptor does transferrin use to bring iron into the cell? How is it brought into the cell?

Transferrin receptor 1 (TFR1) - outside of the cell
Once transferrin is bound to TFR1 - endosome is formed.
DMT1 receptor is within endosome - Is proton pump that brings iron into cytoplasm

How well did you know this?

Not at all

Perfectly

What are the two main receptors involved in cellular uptake of Iron?

Transferrin receptor 1 (TFR1) - Outside cell > stimulates endosome

Divalent metal transporter 1 (DMT1) - Within endosome > brings it into cytoplasm

How well did you know this?

Not at all

Perfectly

What is the primary regulator of iron homeostasis?

Hepcidin

How well did you know this?

Not at all

Perfectly

What organ produces hepcidin?

Liver mainly

Some is produced by monocytes/macrophages

How well did you know this?

Not at all

Perfectly

In what part of the small intestine is iron mostly absorbed?

Duodenum

How well did you know this?

Not at all

Perfectly

What is the major effect of hepcidin?

Inhibits iron export from cells

Causes iron retention in the cells

How well did you know this?

Not at all

Perfectly

What triggers hepcidin expression?

Iron overload

Inflammation

Hypoxia

Anemia

How well did you know this?

Not at all

Perfectly

What is aplastic anemia?

Anemia from nonfunctioning bone marrow (e.g. cancer, radiation, toxicity)

What is megaloblastic anemia?

Results from lack of B12 (e.g. pernicious anemia), folic acid or intrinsic factor. =Slow RBC production = erythrocytes grow into large megaloblasts

What are the types of polycythemia

1. Physiologic polycythemia - High altitude, R-L shunt, chronic hypoxia 2. Polycythemia vera - Genetic defect in RBC line

What is the effect of hepcidin in the GI?

Decreased iron absorption by the duodenum

What are the signs of acute iron toxicity?

Early - GI signs Followed by circulatory collapse Last stage - Pulmonary edema, hepatic failure, cyanosis, coma, death

In which condition would you expect development of microcytosis before hypochromia?

Iron deficiency anemia - RBC progressively get smaller (MVC), then decrease in color (MCHC)

How many subunits does hemoglobin have?

Four - each contain a heme moiety (contains iron)

Oxygen binds to iron in what state?

Ferrous state (Fe²⁺)

What is methemoglobin?

Iron in the Fe³⁺ state Does not bind oxygen

What are the feline blood types? Which one is more common?

A, B and AB A (≥94% of non-pedigree cats)

Which one is worse in transfusion medicine? Type A cat getting type B blood Type B cat getting type A blood

Type B cat getting type A blood

Regarding feline RBC antigen and genetics: Which allele is dominant? Type A or type B

Type A is dominant over type B

What is the most antigenic blood type in dogs?

DEA 1.1

Why are type B cats so reactive to type A blood?

Type B cats have naturally occurring antibodies against the type A antigen (anti-A antibodies). These antibodies are **strong** hemagglutinins and hemolysins (IgM). (Type A cats have weak anti-B antibodies)

What transports iron across the basement membrane?

Ferroportin

What are acanthocytes?

RBC with excess membrane = finger-like projections. Associated with lipid loading. They have increased cholesterol:phospholipid ratio

What are acanthocytes associated with?

Liver disease Renal disease Splenic disease (e.g. HSA, LSA)

What are target cells?

Increased membrane/cytoplasm ratio. Associated with reticulocytes in circulation. Immature cells. NORMAL cholesterol:phospholipid ratio

What is the progression of erythroblast maturation?

Rubriblast; prorubricyte; rubricyte; metarubricyte (nucleated RBC); Reticulocyte; erythrocyte “Rarely, politicians rub me repeatedly”

What are the 3 broad processes involved in anemia of chronic disease?

1. Altered iron metabolism 2. Decreased red blood cell survival 3. Decreased bone marrow erythropoesis

Erythrocytes do not have mitochondria. How do they derive their energy?

Anaerobic glycolysis

What is phosphofructokinase (PFK) deficiency?

Autosomal Recessive condition in *springer spaniels* and american *cocker spaniels*. Leads to exertional myopathy and episodic hemolysis

What cells in the kidney produce EPO?

Renal tubular epithelial cells

What are the contents of eosinophil granules?

1. Major basic protein - mast cell /basophil degranulation 2. Eosinophilic cationic protein - creates pores 3. Eosinophilic peroxidase 4. Eosinophil derived neurotoxin

What receptor does clopidogrel ([thienopyridine](https://en.wikipedia.org/wiki/Thienopyridine)s) work in?

Block ADP receptors (P2Y12) → prevents a platelet plug from forming because platelets cant be activated

What factors make up the extrinsic pathway of coagulation?

VII Tissue factor

What factors make up the common pathway of coagulation?

I, II, V and X | (Remember - 1 x 2 x 5 = 10)

What factors make up the intrinsic pathway of coagulation?

VIII, IX, XI, XII

What is the only protein that is attached to the membrane surface?

Tissue factor

What factor is deficient in Hemophilia A

Factor VIII

What factor is deficient in Hemophilia B

Factor IX

What is the only coagulation factor that routinely circulates in its active form?

Factor VII (1% is activated at any given time)

What forms the prothrombinase complex?

Factors Xa and VIIa

What does the prothrombinase complex do?

Cleaves prothrombin to thrombin (Factor IIa)

What does factor XIII do?

Modifies the polymerized fibrin to form cross links between fibrin strands

What do D-dimers test for?

Degradation of insoluble cross-linked fibrin

What does an elevated PT and normal PTT indicate?

Factor VII deficiency

What factor deficiency in cats is usually clinically insignificant?

Factor XII

What are acquired anticoagulants?

Antibodies against specific factors to bind and inactivate.

How does hypophosphatemia cause hemolytic anemia?

Decreased ATP stores

How does systemic inflammation lead to anemia?

IL-6 leads to hepcidin production, which results in relative iron deficiency.

What breed is predisposed to leukocyte adhesion deficiency?

Irish Setters - They get severe infections as puppies

Severe combined X-linked immunodeficiency results in the deficit of what cytokine?

IL-2

Mechanism of action of Aspirin

Inhibits COX 1 (also COX 2 but less so) and prostaglandin synthase. Results in decreased prostaglandin and thromboxane A2 Irreversible inhibition of platelet aggregation as they cannot produce new COX

Mechanism of action of aminocaproic acid

Inhibits fibrinolysis - Inhibits plasminogen activator substances

MOA of warfarin

Inhibits vitamin K epoxide reductase - Inhibits the action of vitamin K on coag factors II, VII, IV, X

Clopidogrel MOA

Blocks ADP receptors and Inhibits P2Y12 receptor on platelets

What is copper bound to in the plasma?

Ceruloplasmin

How are Heinz bodies formed?

Oxidation of exposed sulfhydryl groups on hemoglobin causes formation of disulfide bonds and distortion of the tertiary structure of the hemoglobin molecule = Precipitation of hemoglobin

In what species Heinz bodies may be normal?

Cats

Acanthocytes have an (increased/decreased) cholesterol:phospholipid ratio?

Increased

Describe iron absorption in the gut.

Iron is absorbed in the apical membrane of GI epithelium by DMT-1 Moves through ferroportin in basolateral membrane of GI epithelium. Ceruloplasmin converts it from Fe2 to Fe3 Fe3 binds to transferrin in the bloodstrem