Haem - Anaemia and Polycythaemia Flashcards
What is the name of the starting point for all cell lines in the bone marrow
Pluripotent haemopoeitic stem cell
Describe erythropoeisis
Pluripotent stem cell –> Myeloid progenitor cell –> BFU-erythroblast –> CFU-erythroblast –> mutiple erythroblast stages –> Reticulocyte –> Mature red blood cell.
What do erythroblasts require for DNA synthesis
B12 and Folate
In erythroblast Hb synthesis, where does the synthesis of Haem and Globin occur
Haem –> requires iron –> in mitochondria
Globin –> in cytoplasm
What is the difference between a reticulocyte and a mature RBC?
Reticulocyte
- penultimate cell type in erythropoiesis
- Contains no nucleus but does contain residual ribosomal RNA for ongoing Hb synthesis.
- 1-2 days after release into circulation residual RNA is lost (and therefore their ability to synthesize Hb) and the cell becomes a mature RBC
How is erythropoiesis controlled?
Hypoxaemia –> sensed by kidney –> EPO released –> Stimulates differentiation of BFU - E and CFU - E progenitor cells –> increasing O2 carrying capacity
This is a negative feedback system
What is the WHO definition and classification of severity of anaemia in men and woman?
Men < 13 g/dL
Mild: 11 - 13
Mod: 8 - 11
Severe: 6.5 - 8
Life-threat: < 6.5
Woman < 12 g/dL
Mild: 10 - 12
Mod: 8 - 10
Severe: 6.5 - 8
Life threat: < 6.5
List the causes of insufficient RBC production
- Iron deficiency anaemia
- Folic acid / B12 deficiency anaemia
- ESRD (No EPO)
- Chronic disease: IL-6 –> hepatic synthesis hepcidin –> blunts response to EPO and reduces Iron absorption GIT
- Bone marrow depression (Cancer/Infection)
List the causes of RBC haemolysis (intravascular and extravascular)
CELL ABNORMALITY (Removed by spleen)
- Inherited abnormalities RBCs (e.g. Hereditary Spherocytosis)
- Inherited abnormalities of Hb (e.g. Sickle cell)
- RBC enzyme deficiencies (G6PD def.: Fe2 –> Fe3)
EXTERNAL ABNORMALITY
- Transfusion reactions (ABO –> intravascular haemolysis)
- Autoimmune haemolytic reactions
- Mechanical trauma to RBCs (e.g. Cardiopulmonary bypass)
Summarise and classify the causes of anaemia
DECREASED PRODUCTION
- Iron deficiency
- B12 / Folate deficiency
- ESRD (EPO deficiency)
- Chronic disease (IL6 -> liver -> hepcidin-> EPO doesn’t work + GIT doesn’t absorb Fe)
INCREASED REMOVAL
Internal (cell) abnormality
1. Inherited Hb abnormality (Heriditary Spherocytosis)
2. Inherited RBC abnormality (Sickle cell)
3. Inherited enzyme abnormality (G6PD deficiency)
External (system) abnormality
- Transfusion reaction (e.g. ABO)
- Autoimmune haemolysis (e.g. SLE)
- Mechanical trauma with haemolysis (e.g. CP-Bypass)
INCREASED LOSS
1. Bleeding (acute or chronic)
DILUTION
- Iatrogenic crystalloid administration
- Pregnancy
What is the role of iron in the body
- O2 transport and storage (Hb and myoglobin)
- Cytochrome c oxidase (ETC)
- Biological reactions (catalysis) - cytochrome enzymes
(e. g. peroxidase and catalase have iron at their active site)
What is total body iron and what proportion is found where in the body
3 - 5 grams
Hb –> 60 %
Liver (Ferritin) –> 30%
Myoglobin + enzymes –> 10 %
How much iron does a typical Western diet contain and how much of this is absorbed daily. By what extent can iron absorption increase?
And how much iron is used every day for erythropoeisis
15 mg
1 - 2 mg is absorbed
(Can double absorption during pregnancy and iron deficiency)
Erythropoeisis requires 20mg/day.
BUT iron absorption is 1 mg/day!
This means that conservation of iron within the body is very important. At the end of the erythrocyte life span, iron is liberated from Hb and carried by transferrin to the bone marrow where it is recycled
What are the two form of dietary iron. Describe how their absorption differs
Haem groups
- Directly absorbed via a haem transfer protein
- Once inside enterocytes, iron released
Dietary iron salts (Ferrous Fe2+ and Ferric Fe3+))
- Only Ferrous Fe2+ can be absorbed
- Gastric pH < 3.0 facilitates conversion Fe3+ –> Fe2+
- Fe2+ can then be absorbed in duodenum
- PPI increases pH > 3.0 –> reduced absorption of iron salts
Where is iron absorbed in the GIT
In the duodenum in the Ferrous form Fe2+. Low gastric pH converts Fe3+ to Fe 2+
What are the two possible fates of Fe2+ once absorbed into enterocyte
- Remain in enterocyte –> sloughed off and excreted in feces
- Transport across basolateral membrane
- Via ferroportin channel
- In plasma converted to Fe3+ and bound to transferrin
- Transferrin transfers Iron to liver and bone marrow
How is excess iron stored
As Ferritin = intracellular protein Liver and other cells
why is it important that Iron is recycled at the end of the erythrocyte life span
Erythropoeisis daily iron requirement is 20 mg/day
Iron absorption from GIT is 1 mg/day
Iron conservation is vital
How does the body control iron homeostasis?
Absorption:
- Low iron levels –> reduced hepcidin synthesis liver –> reduced hepcidin binding to ferroportin –> more functional ferroportin iron channels –> increased iron transfer into blood from enterocytes.
- High iron levels –> increased hepcidin synthesis in the liver –> increased hepcidin binding to ferroportin –> reduced functional ferroportin available –> less iron absorption.
What is the suggested mechansim for iron accumulation in hereditary haemachromocytosis
Hepcidin deficiency –> excess total body iron
How do hepatocytes regulate hepcidin production and what goes wrong in haemachromotosis
Unknown
Define polycythaemia
Persistently increased RBC to plasma ratio (haematocrit) of 0.51 in males and 0.48 in females.
Classify polycythaemia
PRIMARY POLYCYTHAEMIA
- AbN in bone marrow –> excessive RBC production
- E.g. Polycythema Rubra Vera (myeloproliferative condition defined by excessive erythropoeisis)
SECONDARY POLYCYTHAEMIA
- Increased erythropoeisis due to increased EPO
- E.g. Chronic hypoxia (altitude, chronic pulm disease, CHD, Obesity Hypoventilation Syndrome)
Are patients with primary and secondary polycythaemia at increased risk for venous thromboembolic disease.
No. Only primary polycythaemia.
Why are patients with primary polycythaemia at increased risked of venous thrombosis? (i.e. in polycythemia rubra vera)
Why is this increased risk of VTE not present in patients with secondary polycythemia?
- Hyperviscosity (Hagen-Poiseulle: increased resistance to flow)
- Hypercoagulability
- Abnormal coagulation cascade in PRV despite venesection to normal Hct. - Thrombocytosis
- Some patients also have excessive platelet production
Secondary polycythemia does not increase VTE risk as points 2 and 3 are not applicable to acquired polycythema
How does anaesthetic management of a patient with polycythaemia rubra vera differ
- Increase risk perioperative venous + arterial thrombosis (MI/CVA/DVT/PE/Hepatic/Portal vein thrombosis)
ELECTIVE
- Phlebotomy/Hydroxyurea –> normalize Hct
EMERGENCY
- Venepuncture + crystalloid
Neuraxial anaesthesia relatively contraindicated for both (as they are also at risk for coagulopathy and platelet dysfunction)
