Hematology/Coagulation Flashcards
How is iron absorbed in the duodenum?
DMT1 transporter on duodenal enterocytes
What form is iron stored as in the cell?
Ferritin
What transports iron across the basement membrane?
Ferroportin
What is iron bound to in the plasma?
Tranferrin
How is transferrin measured?
- Indirectly
2. Reported as total iron binding capacity
What transports iron into the target cell?
- Transferrin receptor 1
What is the major form of stored iron in the body?
- Ferritin
* >95% of iron in the body
* Mostly in cytoplasm of hepatocytes
How is iron uptake systemically regulated?
- “Dietary regulator” - uptake by duodenal enterocytes is affected by amount of iron recently consumed.
- “Stores regulator” - uptake by duodenal enterocytes is affected by body iron in circulation.
- “Erythropoietic regulator” - uptake by duodenal enterocytes is increased according to erythropoietic demands.
- “Inflammatory regulator” - iron is sequestered in cells in response to systemic inflammation.
What is the most important regulator of iron homeostasis? What does it do?
- Hepcidin
- Binds to FERROPORTIN and triggers internalization of ferroportin → inhibits export from duodenal enterocytes
- Also inhibits DMT1 expression
How long do RBCs circulate?
100 days
How is hemoglobin broken down?
- Hemoglobin → iron and biliverdin
2. Biliverdin → reduced to bilirubin → binds to albumin in plasma for transport to liver → excreted in bile
Serum ferritin (does/does not) correlate well with tissue iron stores
Does
How long does the regenerative response take from onset of bone marrow response?
3 days
Why does anemia of inflammatory disease occur?
Cytokine derangements decrease EPO production, alter iron metabolism, and shorten RBC lifespan
How does inflammatory disease cause a relative iron deficiency?
L-6 and LPS → increased hepcidin → increased degradation of ferroportin → iron sequestered in enterocytes, macrophages, and hepatocytes → iron not available for systemic use → cant be used for erythropoiesis
Why does iron deficiency anemia occur?
- There is an absolute iron deficiency → either from chronic external blood loss, decreased iron dietary uptake, or decreased iron uptake
- Metarubricytes stay in bone marrow and divide continually, waiting for completion of Hb synthesis which is dependent on iron
- Results in a microcytosis
What are the common lab findings for an iron deficiency anemia?
- Microcytic, hypochromic anemia
2. Low ferritin with high-normal to high transferrin
Why does anemia of chronic disease occur?
- Decreased renal mass → decreased EPO production → decreased RBC production in the bone marrow
What is the most common syndrome associated with FeLV infection?
- Anemia
What is the most common type of FeLV associated anemia?
- Pure red cell aplasia
How does immune mediated hemolytic anemia occur?
Antibody mediated destruction of RBCs
- Antibody binds to RBC → Fc fragment of antibody binds to receptors on splenic macrophages
- Either complete phagocytosis occurs or partial phagocytosis of the RBC membrane, leading to formation of spherocytes
How does oxidant-mediated hemolytic anemia occur?
Oxidation exceeds reductive capacity of RBC
1. Hemoglobin precipitates as Heinz bodies in erythrocyte membrane
Why is polycythemia a problem?
- Increased blood viscosity
- Decreased venous return
- Sludging of blood in capillaries - Increased blood volume
- Increased venous return
What is the most common cause for a relative polycythemia?
- Dehydration
* EPO production is not altered
What does it mean if there is an appropriate secondary polycythemia?
Hypoxemia is present
- Congenital heart defects with right to left shunting of blood
- Chronic pulmonary disease due to V/Q mismatch
- Chronic upper airway obstruction
- High altitude
- Defective O2 carrying capacity of Hb
What does it mean if there is an inappropriate secondary polycythemia?
Hypoxemia is NOT present
- Usually due to renal neoplasia
What is primary polycythemia?
- Acquired myeloproliferative disorder leading to clonal expansion of sing hematopoietic stem cell
- RBC production proceeds without regard for EPO level
- Expected to have low plasma EPO due to negative feedback mechanism
How does primary hemostasis occur?
- Platelets adhere to damaged vessel wall (vWF is important here)
- Platelets are activated and release granules
- Platelets aggregate
Which clotting factors are vitamin K dependent? Why are they dependent on vitamin K?
- Factors II, VI, IX, and X
2. Must be carboxylated to become active → requires vitamin K
What is the most important initiator of coagulation?
Tissue factor
What occurs in the initiation phase of coagulation?
- Flowing blood contacts exposed TF on damaged cell → generates factor IX and thrombin on the surface of the damaged cell
- Thrombin and factor IXa diffuse from cell surface
What occurs in the amplification phase of coagulation?
- Thrombin that was generated during initiation phase
- Activates platelets
- Releases vWF
- Generates active factors V, VIII, and XI - Calcium may induce clustering of phosphitidylserine on platelet surface and facilitate binding of coagulation factors → promotes clotting formation