Red blood cell production and survival Flashcards
(25 cards)
describe the stages of red blood cell production
→HEMOCYTOBLAST (Stem Cell) →PROERYTHROBLAST (Committed Cell) → EARLY ERYTHROBLAST → LATE ERYTHROBLAST → NORMOBLAST →RETICULOCYTE → ERYTHROCYTE
what is required for erythropoiesis?
→Fe2+
→Vitamin B12
→Amino acids (to make globin)
→ Folic Acid
what are the sources of iron and how is it absorbed?
→ meat, eggs, vegetables, dairy foods
→Gastric secretion (HCl) and ascorbic acid help absorption.
what are some causes of iron deficiency?
DECREASED UPTAKE OF IRON:
→inadequate intake
→malnutrition
INCREASED DEMAND:
→pregnancy
→ growth spurt
INCREASED LOSS:
→GI bleed
→ excess loss in menses
how does the kidney control erythropoiesis?
include the 3 stimuli
→Stimulus is hypoxia due to :
→ decreased RBC count
→decreased amount of haemoglobin
→ decreased availability of O2.
→ reduced levels of O2 in the blood
→ The paratubular cells in the kidney and liver,release erythropoietin
→ erythropoietin stimulates redbone marrow.
→ Enhanced erythropoietin increases RBC count.
→ increases the O2-carrying ability of the blood.
→ Homeostasis is restored.
what are vitamin B12 and folic acid needed for and what happens if there is a deficiency of both?
→ essential for RBC maturation and DNA synthesis.
→ they are needed for the formation of thymidine triphosphate.
→ deficiency in either of them causes abnormal and diminished DNA leading to failure of nuclear maturation.
what does B12 do?
→B12 is the coenzyme for methionine synthase in the methylation of homocysteine to methionine A
what happens in Folate and B12 deficiencies?
→Megaloblastic anaemia can occur, with macroovalocytes and hypersegmented neutrophil.
what are some causes of a vitamin B12 deficiency?
INADEQUATE INTAKE:
→vegans
ABSORPTION DEFECT:
→ tropical sprue (malabsorption disease, flat villi, affects the small intestine)
→ coeliac disease
→ blind loop syndromes (small intestine bacterial overgrowth, compete for B12)
IF DEFICIENCY (intrinsic factor deficiency,which is needed for B12 absorption):
→pernicious anaemia
→ Crohn’s disease (GI tract affected)
→gastrectomy and other causes (where parietal stomach cells are affected, so can’t make IF)
what are causes of folate deficiency?
INADEQUATE UPTAKE:
→ poor nutrition
ABSORPTION DEFECT:
→coeliac disease
→Crohn’s disease
→ tropical sprue
INCREASED DEMAND/LOSSES:
→pregnancy
→ haemolysis
→ cancer
DRUGS
→ anticoagulants (inhibit folate absorption)
what other causes prevent RBC formation?
→RENAL DISEASE: ineffective erythropoiesis
→ REDUCED BONE MARROW ERYTHROID CELLS
→ APLASTIC ANAEMIA
→MARROW INFILTRATION BY LEUKAEMIA/OTHER MALIGNANCIES: it infiltrates the bone marrow and inhibits RBC production
what are three ways in which you can classify haemolytic anaemia?
→hereditary/congenital or acquired
→intrinsic factors or extrinsic factors
→intravascular or extravascular
what are the causes of immune haemolytic anaemia?
→Autoimmune (when the body itself fights red cells)
→ Alloimmune (when given blood fights the body)
→Drug-induced (when drugs induce the fighting)
what are the causes of non-immune haemolytic anaemia?
→ Red cell fragmentation (when, for example, a heart valve is replaced, and when red blood cells flow through it, they get fragmented)
→ Infection (eg. malaria)
→Secondary (eg. liver/ kidney diseases)
what are hereditary causes of haemolytic anaemia?
HAEMOGLOBINOPATHIES:
→sickle cell diseases
→thalassaemias
RED CELL ENZYMOPATHIES:
→ G6PD deficiency
→ PK deficiency
RED CELL MEMBRANE DISORDERS:
→ hereditary spherocytosis (RBCs are spherical)
→ hereditary elliptocytosis (RBCs are elliptical, oval-shaped)
how does sickle cell arise?
→The normal β-globin gene has the nucleotides GAG, which codes for glutamic acid.
→ In the sickle β-globin gene, the A is replaced with a T, changing the amino acid to Valine.
what are the other types of sickle cell?
→ HbS/βthal
→HbSC
→ HbSD
→ HbSE
what is sickle cell anaemia?
→There is a group of haemoglobin disorders with an inherited sickle β-globin gene
→Sickle Cell Anaemia is homozygous (Hbss), and it is the most common of all Sickle Cell Diseases.
what are the two types of thalassemia?
→ β thalassaemia
→ α thalassaemia
describe β thalassemia
β THALASSAEMIA:
→ loss of one β-chain causes mild microcytic anaemia (a thalassaemia trait)
→ loss of both β-chains causes thalassaemia major.
→excess of α-chains precipitate into the erythroblasts, causing haemolysis and ineffective erythropoiesis.
describe α thalassemia
α THALASSAEMIA:
there can be a loss of one, two, three or four α-chains. →red blood cells called target cells
→cells that look like teardrops.
what are the main RBC enzymes and what metabolic pathways do they support?
→Glucose-6-Phosphate Dehydrogenase (G6PD)
→ Pyruvate Kinase (PK)
pathways
→Pentose Phosphate Pathway
→Glycolytic Pathway
what happens if G6PD is deficient and where is it prevalent?
→NADPH and GSH generation is impaired.
→Acute haemolysis occurs on exposure to oxidant stress, such as oxidative drugs, fava beans (broad beans) or infections.
→A G6PD deficiency is most commonly known as enzymopathy.
→ prevalent in places with high malaria rates, as the patients infected with malaria then aren’t affected as severely, and are able to survive it. evolutionarily beneficial
what is seen when G6PD is deficient?
→Haemoglobin precipitates, causing Heinz bodies (red blood cells with denatured haemoglobin) to be seen.
→ blister/basket cells are visible which are red blood cells with the haemoglobin on one side.
