Red Blood Cell Formation

What is the primary function of RBCs?

Transport oxygen via hemoglobin to body tissues.

Where does hematopoiesis occur in early fetal development?

Yolk sac initially, followed by the liver and spleen.

Where does hematopoiesis primarily occur in adults?

Red bone marrow of the axial skeleton, including skull, sternum, vertebrae, and pelvis.

What happens to red bone marrow with aging?

Much converts to yellow marrow, which can resume hematopoiesis when stimulated.

What is the function of the bone marrow microenvironment?

Supports hematopoietic stem cell maintenance, self-renewal, differentiation, and stress responses.

What are the two major hematopoietic progenitor lineages?

Myeloid and lymphoid progenitor cells.

Which progenitor lineage produces erythrocytes?

Myeloid progenitor cells.

What is the sequence of erythropoiesis?

Hematopoietic stem cell → myeloid progenitor → proerythroblast → erythroblast → reticulocyte → erythrocyte.

What essential substances are needed for erythropoiesis?

Erythropoietin, iron, vitamin B12, folate, cytokines, and transcription factors.

What happens to the nucleus and organelles during erythropoiesis?

They are lost as erythroblasts mature into reticulocytes.

What is a reticulocyte?

An immature RBC that enters circulation and matures in approximately 1-2 days.

What does an elevated reticulocyte count indicate?

Increased RBC production, commonly compensating for hemolysis or blood loss.

Where is dietary iron primarily absorbed?

Duodenum.

What protein transports iron in the bloodstream?

Transferrin.

What protein stores iron intracellularly?

Ferritin.

What is hemosiderin?

An intracellular iron storage form.

What transporter exports iron from intestinal cells into blood?

Ferroportin.

What is the role of hepcidin?

Inhibits ferroportin, decreasing intestinal iron absorption and iron release.

Where is hepcidin produced?

Liver.

What is the function of HFE protein?

Promotes regulation of hepcidin production.

What causes increased iron absorption in hereditary hemochromatosis?

Reduced hepcidin activity or impaired regulation of ferroportin.

Where is vitamin B12 absorbed?

Terminal ileum.

What substance is required for vitamin B12 absorption?

Intrinsic factor.

Which cells produce intrinsic factor?

Gastric parietal cells.

What causes pernicious anemia?

Autoimmune destruction of parietal cells or intrinsic factor impairment, causing B12 malabsorption.

Where is folate primarily absorbed?

Proximal small intestine, especially the duodenum.

What is the role of iron in RBC production?

Required for heme synthesis and oxygen binding.

Why are folate and B12 necessary for erythropoiesis?

They support DNA synthesis and maturation of developing RBCs.

Where is erythropoietin primarily produced?

Kidneys.

What stimulates erythropoietin production?

Tissue hypoxia through hypoxia-inducible factor signaling.

What is the primary function of EPO?

Stimulates erythroid progenitor survival and RBC production in bone marrow.

Why does chronic kidney disease cause anemia?

Reduced kidney production of erythropoietin.

What cytokines regulate erythropoiesis?

EPO, IL-3, stem cell factor, and IGF-1.

What transcription factors regulate erythroid differentiation?

GATA1, TAL1, NFE2, EKLF, FOXO, STATs, GFI-1B, and NF-kB.

What is the normal shape of an RBC?

Biconcave disc.

What proteins maintain RBC shape and deformability?

Spectrin and ankyrin.

What is the normal lifespan of an RBC?

Approximately 120 days.

Why do mature RBCs lack mitochondria?

They rely on anaerobic glycolysis and do not consume the oxygen they transport.

What is the primary function of hemoglobin?

Bind and transport oxygen.

What is the structure of hemoglobin A?

Two alpha chains and two beta chains (α2β2).

What is the structure of hemoglobin A2?

Two alpha chains and two delta chains (α2δ2).

What is the structure of fetal hemoglobin?

Two alpha chains and two gamma chains (α2γ2).

Why does fetal hemoglobin have higher oxygen affinity?

It binds oxygen more strongly, facilitating oxygen transfer from maternal blood.

How many oxygen molecules can one hemoglobin molecule bind?

Four oxygen molecules.

What component of hemoglobin binds oxygen?

Iron within the heme group.

Why is carbon monoxide poisoning dangerous?

CO binds hemoglobin with greater affinity than oxygen, reducing oxygen transport.

What are poikilocytes?

Abnormally shaped RBCs.

What are echinocytes or burr cells?

RBCs with multiple spiked projections, associated with altered plasma environments.

What are schistocytes?

Fragmented RBCs caused by mechanical damage in the circulation.

What are spherocytes?

Round RBCs that have lost their normal biconcave shape.

What are target cells?

RBCs with a densely stained center surrounded by a pale ring.

What conditions are associated with target cells in the lecture?

Liver disease and prior splenectomy.

What does hypochromia indicate?

RBCs with decreased staining and increased central pallor.

What causes normal RBC senescence?

Aging and loss of membrane flexibility, leading to macrophage recognition.

Where are aging RBCs primarily cleared?

Spleen, liver, and bone marrow macrophages.

What happens to globin after RBC destruction?

It is broken down into reusable amino acids.

What happens to heme after RBC destruction?

Iron is recycled and the remaining heme is converted to biliverdin, then bilirubin.

What transports unconjugated bilirubin in blood?

Albumin.

Where is bilirubin conjugated?

Liver.

What molecule is added during bilirubin conjugation?

Glucuronic acid.

Where does conjugated bilirubin travel after leaving the liver?

Into bile and eventually the small intestine.

What is urobilinogen?

An intestinal product formed from bilirubin metabolism.

What gives stool its brown color?

Stercobilin.

What gives urine its yellow color?

Urobilin, derived from urobilinogen.

Why can hemolysis cause jaundice?

Increased heme breakdown produces excess unconjugated bilirubin.

What metabolic pathway produces ATP in mature RBCs?

Anaerobic glycolysis (Embden-Meyerhof pathway).

What is the net ATP yield of anaerobic glycolysis in RBCs?

Two ATP per glucose.

What happens to pyruvate during RBC anaerobic glycolysis?

It is converted to lactate by lactate dehydrogenase.

What is the function of the Rapoport-Luebering shunt?

Produces 2,3-BPG, which regulates hemoglobin oxygen affinity.

What is the role of 2,3-BPG?

Decreases hemoglobin affinity for oxygen, promoting tissue oxygen delivery.

What activates PFK-1 in RBC glycolysis?

Low ATP and high AMP.

What inhibits PFK-1 in RBC glycolysis?

High ATP, citrate, and low pH.

What is the primary purpose of the pentose phosphate pathway in RBCs?

Generate NADPH to protect against oxidative damage.

What enzyme initiates the pentose phosphate pathway?

Glucose-6-phosphate dehydrogenase (G6PD).

What happens to NADPH production in G6PD deficiency?

It decreases, making RBCs vulnerable to oxidative stress.

Why does G6PD deficiency cause hemolytic anemia?

Insufficient NADPH reduces antioxidant protection and promotes RBC destruction.

What is the Bohr effect?

Decreased hemoglobin oxygen affinity in response to increased CO2 and decreased pH.

What happens to the oxygen-hemoglobin curve during acidosis?

Right shift, indicating decreased oxygen affinity.

What does a right shift of the oxygen dissociation curve mean?

Hemoglobin releases oxygen more readily to tissues.

What factors cause a right shift of the oxygen dissociation curve?

Increased CO2, increased H+, increased temperature, and increased 2,3-BPG.

What factors cause a left shift of the oxygen dissociation curve?

Decreased CO2, decreased H+, decreased temperature, decreased 2,3-BPG, and HbF.

What is hereditary spherocytosis?

An inherited RBC membrane disorder causing reduced deformability and premature splenic destruction.

What is the common inheritance pattern of hereditary spherocytosis?

Autosomal dominant.

Which membrane protein is highlighted in hereditary spherocytosis?

Ankyrin.

Why does hereditary spherocytosis cause splenomegaly?

Rigid RBCs are trapped and destroyed in the spleen.

What laboratory findings are expected in hereditary spherocytosis?

Anemia, reticulocytosis, and increased unconjugated bilirubin.

Why does hereditary spherocytosis cause gallstones?

Chronic hemolysis increases bilirubin production and pigment gallstone risk.

What distinguishes mild from severe hereditary spherocytosis?

Mild disease may have no anemia; severe disease causes marked hemolysis and may require regular transfusions.

What causes beta-thalassemia?

Reduced beta-globin production due to mutations involving chromosome 11.

What is the inheritance pattern of beta-thalassemia?

Autosomal recessive.

Why does beta-thalassemia cause RBC destruction?

Excess unpaired alpha chains damage RBC membranes.

What causes alpha-thalassemia?

Reduced alpha-globin production due to genetic defects involving chromosome 16.

What is the inheritance pattern of alpha-thalassemia?

Autosomal recessive.

What causes hemolysis in alpha-thalassemia?

Globin-chain imbalance damages RBCs and impairs effective erythropoiesis.

Why can thalassemia cause skull enlargement?

Chronic hypoxia stimulates expanded marrow erythropoiesis.

What causes hepatosplenomegaly in severe thalassemia?

Extramedullary hematopoiesis and increased RBC destruction.

What is hydrops fetalis in severe alpha-thalassemia?

Absence of functional alpha chains causes gamma-4 hemoglobin and profound fetal hypoxia.

Why is hemoglobin Bart's ineffective at tissue oxygen delivery?

Gamma-4 tetramers have extremely high oxygen affinity.

What causes sickle cell anemia?

A beta-globin mutation produces HbS, which polymerizes when deoxygenated.

What is the inheritance pattern of sickle cell anemia?

Autosomal recessive.