Erythropoiesis and anaemia Flashcards
What transports iron into enterocytes?
Ferroportin
In what form is dietary iron absorbed?
Fe2+ or as part of a protein, e.g. heme
In what form is free iron?
Ferrous Fe2+
What enzyme on the enterocyte brush border reduces Fe3+ to Fe2+?
ferric reductase enzyme
How many atoms of iron can each transferrin molecule carry? What form is the iron in?
Carry 2 ferric (Fe3+) iron ions
What is transferrin?
Iron-binding blood plasma glycoprotein that regulates the level of free iron in plasma and other extracellular fluids
Takes iron from the enterocytes –> blood –> bone marrow
What occurs when transferrin binds to transferrin receptors?
- iron is taken into the cell by endocytosis
- Once in the cell, the transferrin releases its iron ions
- taken up by Hb or ferritin molecules –> stores iron
When is serum transferrin measured?
in cases of suspected iron deficiency and in iron overload disorders
What are the different stages of RBC formation in a foetus?
- Mesoblastic stage:
- 3rd week: nucleated RBC forms in yolk sac and mesothelial layer of placenta - Hepatic stage:
- 6th week: erythropoiesis mainly in liver and spleen - Myeloid stage:
- 3rd month: bone marrow becomes primary source of RBCs
- exclusively the source of RBCs in last month of gestation
How does the formation of RBC change after birth?
Up to 5 years: RBCs formed in bone marrow of all bones
5-20/25 years: RBCs formed in the bone marrow of long bones (tibia + femur)
25+ years: RBCs formed in the bone marrow of membranous bones (rib, sternum, vertebrae)
What cytokine controls erythropoiesis?
EPO (erythropoietin)
mainly increase the speed of maturation of proerythroblasts
Where is EPO produced?
Fibroblast interstitial cells in the kidney (PCT)
What stimulates EPO release?
EPO secreting cells are sensitive to hypoxia
Hypoxia stimulates EPO release
This increases RBC production
What hormone increases EPO production?
Testosterone
- this is why males have slightly higher Hb levels than women
What does ESR actually measure? Why is it measured?
erythrocytes have a negative surface charge meaning that they repel each other
this means that erythrocytes do not stick together
HOWEVER inflammatory reaction or bacteria in the blood will increase the amount of fibrinogen in the plasma
fibrinogen reduces the -ve charge on the erythrocytes meaning that they clump together
Red cells clump to form stacks = ROULEAUX
these stacks settle faster
a raised ESR is a non-specific marker for infection
How long is the lifespan of a RBC? How are RBCs removed from the blood?
Lifespan: ~120 days
removed from the blood by macrophages as the pass through the spleen
How is bilirubin formed from RBCs?
RBC: broken down into haem protein and globin proteins
Haem – haem oxygenase –> biliverdin – biliverdin reductase –> bilirubin
How is bilirubin released into the blood?
Bilirubin = not very soluble
Binds to albumin in the splenic macrophages and the complex is released into the blood as unconjugated bilirubin
What happens when unconjugated bilirubin reaches the liver?
It is attached to glucuronic acid by the hepatocytes to make it more soluble
when bound to glucuronic acid = conjugated bilirubin
What happens when bilirubin becomes conjugated?
Passes in the bile to the small intestine
bacteria convert it into urobilinogen
most urobilinogen passes out of the body via the faeces
Define anaemia in a female adult.
Hb level <11.5 g/dL
Define anaemia in a male adult.
Hb level <13.5 g/dL
Define anaemia in a child 6 months - 6 years.
Hb <11g/dL
Define anaemia in a child/adolescent 6-14 years.
Hb <12 g/dL
What are the symptoms of anaemia?
- tiredness
- fainting
- SOB
- worsening angina/claudication
- palpitations
What are the signs of anaemia?
- pallor
- tachycardia
- bounding pulse
- systolic flow murmur
- cardiac failure
- retinal haemorrhage
What are the potential causes of anaemia?
- Reduced production of RBCs
- iron deficiency
- B12/folate deficiency
- marrow infiltrate (cancer)
- chronic disease (rheumatoid, cancer)
- infections (HIV, parvovirus) - Increased destruction of RBCs
- haemolytic anaemia –> immune destruction or membrane/enzyme/Hb disorder - Increased loss of RBCs
- bleeding
What is microcytic, normocytic and macrocytic anaemia?
Micro: <76 fl
Normo: 76-96 fl
Macro: >96 fl
Iron deficiency leads to what type of anaemia?
Microcytic hypochromic anaemia
What are causes of microcytic hypochromic anaemia?
Hookworm (most common)
diet
reduced RBC synthesis
increased iron loss
What are the risk factors for iron deficiency anaemia?
- gastric/bowel surgery
- rectal bleeding
- menorrhagia
- change in bowel habit
- appetite/weight changes
- pregnancy/breastfeeding
- unsupplemented vegan diets
- female
- aspirin/NSAIDs
- age (premature or elderly)
- hookworm**
How is iron deficiency anaemia confirmed?
FBC - Low RBC count
Blood film - microcytic, hypochromic
Serum ferritin - is it low?
Serum iron binding capacity - is it low?
How is iron deficiency anaemia treated?
Haem containing proteins Iron tablets (ferrous sulphate)
What might cause normocytic anaemia?
- Anaemia from acute blood loss
- shock syndrome
- treat with blood transfusion and EPO treatment - Anaemia from chronic disease
- chronic inflammation, infection , cancer
- reduced RBC lifespan
- depressed erythropoiesis
- poor marrow response to EPO - Anaemia from abnormal haemolysis
