Lecture 8 – RBC production and survival Flashcards
RBC production - ON DIAGRAM
ON DIAGRAM
Hormonal Control of Erythropoiesis (5)
Hypoxia caused by decresed RBC/O2/Hb. Increases of EPO in kidney. EPO to red bone marrow. Increases RBC. Increases O2 carried in blood.
What is required for erythropoiesis? (4)
Vitamin B12/Folic acid.
Fe2+.
Amino acids.
EPO.
Iron (5)
- Sources Meat, eggs, vegetables, dairy foods.
- Absorption
- Normal Western diet provides 15mg daily.
- 5-10% absorbed (1mg) principally in duodenum and jejunum.
- Gastric secretion (HCl) and ascorbic acid help absorption.
Vitamin B12 and Folic Acid (4)
• Both essential for RBC maturation DNA synthesis.
o Both needed for formation of THYMIDINE TRIPHOSPHATE.
o B12 is coenzyme for methionine synthase in methylation of homocysteine to methionine.
• Deficiency in either of them causes abnormal, diminished DNA, leading to failure of nuclear maturation.
What happens in folate and B12 deficiencies? (4)
• Megaloblastic anemia, with macroovalocytes and hypersegmented neutrophil.
Megaloblastic anemia - A condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts).
• Treatment
B12 - Hydroxycobalamin: 1mg im
Folate: -Folic acid: 5mg/day oral
Causes of Vitamin B12 deficiency (10)
ON DIAGRAM
Causes of Folate deficiency (12)
ON DIAGRAM
Other causes of failure of RBC production (4)
• Renal dx - ineffective erythropoiesis.
• Reduced BM erythroid cells.
o Aplastic anaemia.
o Marrow infiltration by leukaemia or other malignancies.
RBC Survival and Destruction (1)
Stress placed on RBC (4)
Longevity and survival (3)
• Energy supply in cells but RBC unable to carry out oxidative phosphorylation and protein synthesis. • Stress placed on RBC • Life span 120 days. • 300 miles travelled through microcirculation. • 8μm diameter. • Capillaries as small as 3μm. • Longevity and survival depends on o Membrane integrity. o Hb structure. o Presence of red cell enzymes.
Classification of Haemolytic Anaemia (6) - ON DIAGRAM
ON DIAGRAM
Classification of Haemolytic Anaemia - Acquired
ON DIAGRAM
Classification of Haemolytic Anaemia - Hereditary
ON DIAGRAM
Classification of Haemolytic Anaemia - Intra/Extravascular Haemolysis
ON DIAGRAM
Globin disorders (5)
• Globin genes cluster on chromosomes.
• Expression of alpha and beta globin closely balanced.
• Mutations or deletions may lead to;
o Abnormal synthesis of globin chain as in Sickle Cell Diseases.
o Reduced rate of synthesis of normal α- or -globin chains as in Thalassaemias.
Sickle cell disease (3)
ON DIAGRAM
Thalassemia (5)
- Beta-thalassaemia
- Loss of 1 -chain causes mild microcytic anaemia (thalassaemia trait)
- Loss of both (0) causes thalassaemia major
- Excess α-chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis.
- Alpha-thalassaemia
- There can be loss of 1, 2, 3 or 4 alpha chains.
Red Cell Enzymes (4)
• Two main enzymes
o Glucose-6-Phosphate Dehydrogenase (G-6-PD)
o Pyruvate Kinase (PK)
• Support 2 main Metabolic Pathways o Pentose Phosphate pathway Using G6PD o Glycolytic pathway Using PK
What happens in G6PD deficiency? (4)
- NADPH and GSH generation impaired.
- Acute haemolysis on exposure to oxidant stress: oxidative drugs, fava beans (broad beans) or infections.
- Hb precipitation – Heinz bodies.
- G6PD deficiency most common known enzymopathy, estimated to affect 400 million people worldwide but evolutionary beneficial.
What happens in PK (Pyruvate Kinase) deficiency? (4)
What happens in PK deficiency?
ATP-depleted cells lose large amount of potassium & water, becoming dehydrated & rigid.
Because cation pumps fail to function.
Causes chronic non-spherocytic haemolytic anaemia.
Excess haemolysis leads to jaundice, gallstones.
