B2 - RBC: production and function Flashcards
large early cells of RBC lineage
erythroblast/ pro-normoblast
in the bone marrow macrophages feed the RBCs with
iron
stimulus of EPO production
○ Stimulus to EPO production is renal O2 tension (low oxygen tension)
§ Caused by anaemia, major bleed, giving blood, low atmospheric O2 (high altitudes), defective cardiac or pulmonary function
RBC membrane
phospholipid bilayer membrane with proteins
○ Proteins are inside to give structural integrity
○ Proteins that come out through the membrane that provide blood groups (ABO, Rhesus)
red cell cytoplasm
red cells contain haemoglobin
○ Transports O2 from lungs to tissues
○ Returns CO2 to lungs
iron is absorbed in
upper small bowel (acidic environment)
○ Will increase in times of iron deficiency
percentage of iron ingested that is absorbed
5-10%
iron delivery to normoblast
- Transported to bone marrow - bound to transferrin transport molecule
- Delivers to transferrin receptor on developing normoblast
- Taken up by developing normoblast to make haem
excess iron stored in
macrophages as ferritin - some in liver some in bone marrow
iron daily requirement
1-2mg per day
○ up to 3mg during pregnancy
○ 2mg for menstruating females
when red blood cells die
they go to the spleen and the components are broken down and the iron is released and recycled by going back into ferritin storage form
○ Recycled
- Deficiency of folate or Vit B12
○ Inhibits purine and thymidylate synthesis
○ Impairs DNA synthesis
○ Bone marrow is the most actively replicating organ in the body, and is therefore the first to be compromised by a vit B12 or folate deficiency
○ Deficiency in either of these creates a problem in the manufacture of any cell that is actively being produced in the body - major site is the bone marrow
○ Cause erythroblast apoptosis - erythroid cells being made in the bone marrow are going to die in the bone marrow because the nucleus isn’t being made properly
○ Results in anaemia from ineffective erythropoiesis
B12 body stores
years
folate body stores
3 months
B12 also called
cobalamin because of cobalt ion
B12 absorbed in
terminal ileum
folate absorbed in
upper small bowel
B12 comes from
animal products in diet
folate comes from
vegetables in diet
B12 deficiency blood film
- Hypersegmented neutrophil - too many nucleus fractions (more than 3 or 4)
- Large red blood cells (macrocytic)
- Ovoid shaped macrocytes
alpha global chains on chromosome
16
beta chains on chromosome
11
delta and gamma genes
○ B gene part of a complex containing delta and gamma genes
§ Adult haemoglobin is 2 alpha and 2 beta
§ At birth, some are made of 2 alpha and 2 gamma
sickle cell disease
- Point mutation in the gene that encodes the B globin chain
- Results in abnormal B chain which is sticky and tactile
- Sickle shaped elongated red blood cells
- Stick together and stick across the microvascular tube and block the blood supply
- Child with sickle cell anaemia will have killed most of their spleen through obstruction of blood by age 3 - autosplenectomy - infarcted spleen
○ Through obstruction of blood vessels - Can cause strokes if they get stuck in the brain
- Present with pain at the time when tissue in being infarcted
- Shortened life expectancy
autosplenectomy in sickle cell anaemia
infarcted spleen through obstruction of blood vessels
hereditary spherocytosis
- effects proteins of RBC membrane
- Proteins in the membrane make it too rigid
- RBC cant get through the spleen because it is not deformable
- Spleen will either remove red blood cells completely or remove some of it’s membrane
- When some membrane is lot, the red blood cell has to become tighter around the haemoglobin - causing a rounder shape
- Spherical shaped red blood cells
- Rigid round balls with firm membranes, no biconcave shape
- Causes perpetual anaemia in chronic/severe cases
- Sometimes will only be symptomatic during an infection where preferential destruction of red blood cells occur
- RBC are removed by spleen
red blood cell metabolism occurs through
- Embden-Meyerhof pathway
- Embden-Meyerhof pathway
○ Generates energy for red blood cells
○ One molecule of glucose yields 2 ATP
○ ATP maintains RBC shape and energy for deformity
○ 2 molecules of lactate produced
○ Lactate is transported to blood and in the liver is converted into glucose
○ Uses pyruvate kinase
RBCs metabolise glucose by
anaerobic glycolysis (requires no mitochondria or O2)
pyruvate kinase deficiency
- Prickle shaped RBC
- Acanthocytes - points/prickles on red blood cells
- Don’t have any energy - cant undergo metabolism
Spleen must be removed - to prevent red cells from being removed
pyruvate kinase deficiency red blood film
acanthocytes
