Notes on Red Blood Cell Disorders

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• RBC production.

• Stimulated with EPO from kidneys.

• Stimulated by testosterone.

Increased during:

• Hypoxemia, anemia, left-shifted OBC, high altitude.

• Polycythemia vera (increased O2) suppresses EPO release.

• EPO may also be produced ectopically.

Extramedullary hematopoiesis:

• RBC production outside bone marrow; liver, spleen.

• This is a disease and produces hepatosplenomegaly.

Hb, Hct, RBC count:


• Physiologic anemia 3 days after birth.

• HbF replaced by mostly HbA.


• Increased plasma volume; normal RBC count causes dilutional effect.


• Decreased Hb, Hct, RBC concentration.


• Iron deficiency, thalassemia.


• Folate, B12/cobalamine deficiency.


• Release lactic acid as end-product of metabolism.

• Synthesize antioxidant glutathione via pentose phosphate pathway; used to oxidize H2O2.

• Luebering-Rapaport pathway: BPG synthesis.

• Older RBCs disposed by spleen; end product is bilirubin.



• Used to store iron; correlates with serum iron.


• Iron deficiency.


• Anemia of chronic disease, iron overload disease.

TIBC ~ concentration of transferrin.

Percentage of Hemoglobin:


• 97%


• 2%


• 1%

Microcytic anemias:

• Defective Hb, heme, globin chain synthesis.

Iron deficiency:

• Decreased heme synthesis.

• Plummer-Vinson syndrome: dysphagia, achlorhydria, glossitis.

• Causes: blood loss, decreased intake, increased utilization.

• Decreased iron, MCV, ferritin; increased TIBC, RDW.

Anemia of chronic disease:

• Common in hospitalized patients.

• Decreased heme synthesis.

• Causes: alcoholism, inflammation, malignancy.

• Liver synthesis of hepcidin: prevents macrophages from releasing iron to transferrin.

• Decreased MCV, iron, TIBC; increased ferritin.


AD disorder:

• Alpha = SE Asia, blacks.

• Beta = blacks, Greeks, Italians.

Alpha Thalassemia:

• Gene deletions on same chromosome.

• Decreased MCV, Hb, Hct; increased RBC count.

Beta Thalassemia:


• Defective DNA splicing mechanism.

• Mild.

• Protection against falciparum malaria.

• Decreased MCV; Hb; Hct.

• Increased RBC count.

• Decreased HbA; increased HbA2 and HbF.


• Formation of stop codon - causes severe anemia.

• Severe.

• Increased RDW.

• No HbA; increased HbA2 and HbF.

Sideroblastic anemia:

• Caused by alcoholism (mitochondrial toxin), pyridoxine / B6 deficiency (ALA synthase; plays role in rate-limiting step in heme synthesis), lead poisoning (causes denaturation of ferrochelatase / heme synthase).

• Defective heme synthesis.

• Abdominal colic with diarrhea.

• Encephalopathy and growth retardation in children.

• Pb deposits in bone.

• Foot drop; damage to renal tubules.

• Increased ferritin, iron; decreased MCV and TIBC.

Macrocytic anemias:

Folate or B12 deficiency:

• Impaired DNA synthesis.

• Ineffective erythropoiesis.

• Increased plasma homocysteine.

• Thymidylate synthase inhibited by 5-flurouracil.

• Dihydrofolate reductase inhibited by methotrexate, trimethoprim.

• Achlorhydria, antibodies of pernicious anemia, antibodies of destruction of gastric parietal cells, smooth sore tongue, neurologic disease.

• Pancytopenia, oval macrophages, hyperpigmented neutrophils; Schilling test.

More on folate deficiency:

• Same like B12 deficiency except neurologic disease.

• Neural tube defects.

Aplastic anemia:

• Alteration of multipotent myeloid stem cells.

• Fever, neutropenia, thrombocytopenia, fatigue.

• Caused due to drugs, infection, idiopathic, chemicals, etc.

Chronic renal failure:

• Decreased EPO synthesis.


• Anemia, burr cells, platelet dysfunction, thrombocytopenia.

Hereditary spherocytosis:

• AD disorder.

• Extravascular hemolysis.

• Jaundice, gallstones, splenomegaly, aplastic crisis.

• Anemia, MCHC, RBC fragility.


• Splenectomy.

Hereditary elliptocytosis:

• AD disorder.

• No or mild anemia.

• Splenomegaly.

• RBC is elliptical; RBC fragility.


• Splenectomy.

Paroxysmal nocturnal hemoglobinuria:

• Defective multipotent myeloid stem cells.

• Intravascular RBC lysis.

• Occurs at night.

• Sucrose hemolysis test (sugar water test).

• Acidified serum test (Ham test).

• Pancytopenia.

Sickle cell anemia:

• AR disorder.

• Expressed only in homozygotes.

• Extravalscular hemolysis of sickle cells.

• Protection against malaria.

• Missense point mutation.

• HbS causes RBCs to assume sickle shape.

• HbF prevents sickling.

• Dactylitis in infants, acute chest syndrome, necrosis of femoral head, autosplenectomy, infections (S. pneumoniae, S. paratyphi), aplastic crisis.

Glucose-6-phosphate dehydrogenase deficiency:

• XR disorder.

• Protective against malaria.

• Intravascular hemolysis caused by Heinz bodies.

• Decreased NADPH and glutathione/GSH synthesis in pentose phosphate pathway.

• Heinz bodies.

• Instigated by drugs such as primaquine, chloroquine, etc.; fava beans.

• Back pain with hemoglobinuria.

• Bite cells (macrophage removal of membrane); anemia.

Pyruvate kinase deficiency:

• AR disorder.

• Defective Embden-Meyerhof pathway.

• Extravascular hemolysis.

• Dehydration of RBCs.

• Anemia and jaundice at birth; increased 2,3 BPG.

• RBCs with thorny projections; echinocytes.

• RBC enzyme assay test.

Immune hemolytic anemias:

• Caused by drugs, SLE, IgG/IgM, etc.

• RBCs coated with IgG or C3b or C5-C9.

• Jaundice, hepatosplenomegaly.

• DAT (detects RBCs coated with IgG/C3B); direct/indirect Coombs' test.

Micro- and macroangiopathic hemolytic anemias:

• Intravascular hemolysis.

• Anemia, hemoglobinuria.

• Schistocytes in peripheral blood.


• Female Anopheles mosquito transmits Plasmodia to humans.

• Fever, splenomegaly.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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