Red Blood Cell production and survival Flashcards
What is the origin and control of red blood cell production?
Proerythroblast is the first recognisable RBC precursor in marrow. Maturation to late orthochromatic erythroblast (nomoblast) occurs in bone marrow. Number of RBC is inversely related to ambient O2 pressures. Ie. people living in high altitudes have more RBCs. The key regulator is EPO
The central role of iron in haemoglobin structure, and in erythropoiesis
A normal Western diet provides 15mg a day. Iron is required to create heme in the production of haemoglobin.
Causes of iron deficiency and their clinical effects
Decreased uptake: inadequate intake in meals, malabsorption
Increased demand: Pregnancy, growth spurt
Increased loss: GI bleed, Excess loss in menses
Role of vitamin B12 and folic acid in erythropoiesis
It is essential for RBC maturation and DNA synthesis. Both are needed for formation of thymidine triphosphate. B12 is a coenzyme for methionine synthesis in methylation of homocysteine to methane. Deficiency leads to failure of nuclear maturation.
Other causes of failure of red cell production B12 and folate deficiency disorders
Inadequate intake: poor intake (vegans)
Absorption defect: Coeliac disease, Crohn’s, Tropical sprue
Increase in demand/loss: Pregnancy, haemolysis, cancer, Gastronomy
Drugs: Anticonvulsants
- Renal dx - ineffective erythropoiesis
Reduced BM erythroid cells - Aplastic anaemia, marrow infiltration by leukaemia or other malignates.
B12 and folate deficiency disorders
Megaloblastic anaemia, macroovalocytes, hyperhsegmented neutrophils
B12 - Hydroxycobalamin
Folate: Folic acid
The normal red cell life span and the consequence of red cell destruction
Approximately 120 days without nuclei/ cytoplasmic organelles. Without it, you get haemolytic anaemia.
Factors affecting red cell survival
Components needed for function and survival are present
in matured rbc.
o their functions do not require the consumption of much
energy
RBC therefore are capable of limited metabolic activity.
Metabolic processes, include :
o Embden-Meyerhof pathway - Generates energy in ATP; to maintain red cell shape and deformability regulates intracellular cation conc. via cation pumps (Na/K pump). ATP is depleted: cells lose large amount of potassium & water, becoming dehydrated & rigid. Causes chronic non-spherocytic haemolytic anaemia.
o Hexose monophosphate shunt (or PPP) - 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.
o Luebering Rapaport Shunt - 2,3 DPG binds to deoxyHb to
stabilise at lower O2 affinity state this makes it harder for O2 to bind to Hb; favours O2 release
o Methaemoglobin reductase pathway -The Embden-Meyerhof pathway is a primary source of
NADH; it reduces cytochrome b5(cb5), which in turn reduces oxidized ferric ion of haemoglobin. without this reaction, haem iron would be oxidized to methaemoglobin, which is not a functional oxygen transporter
Classification of haemolytic anaemia.
Split into acquired and hereditary.
Aquired splits into immune ( Autoimmune, Alloimmune, drug induced) and Non-immune (Red cell fragmentation, infection, secondary).
Hereditary splits to:
RBC membrane disorder: Hereditary spherocytosis, Hereditary elliptocytosis
RBC enzymopathies: G6PD deficiency, PK deficiency
Haemoglobinopathies: Sickle Cell, Thallasaemia
