Anaemia Flashcards
Basic development of erythrocyte?
- Stem cell - B12 and folate
- Pro-erythroblast - EPO and ferritin
- Erythroblast - EPO and ferritin
- Normoblast
- Reticulocyte - 48hr, anucleus, RNA fragments, some in circulation
- Erythrocyte (RBC) - Hb to carry O2
Normal cycle of RBCs?
- Red bone marrow
- Circulation
- 10% haemolysis: kidney excretion or macrophage recycle (spleen, liver, marrow)
- 90% ~120 day life -> macrophage recycle
- Haem -> bilirubin (liver -> kidney or gut)
Erythrocyte STIMULATION?
- EPO
- Growth factors (eg. G-CSF)
- Stem cell factor
- Regulating factors
Erythrocyte PRODUCTION (haemopoiesis)?
Early embryo - yolk sac
Foetus - liver, spleen
Child - red marrow in almost all bones
Adult - red marrow in axial skeleton
Red marrow -> RBCs, leukocytes, platelets
Erythrocyte MATURATION?
Reticulocytes -> have no nucleus, some RNA fragments, enter circulation via capillaries as RBCs or erythrocytes (in times of stress)
~2 days to from stem cell to reticulocyte
~2 days to mature to RBC
Erythrocyte DESTRUCTION (apoptosis)?
100-120 day lifespan
Phagocytosis by spleen + liver
Haem -> bilirubin
Globin -> amino acids, Fe+ recyled
Erythropoietin (EPO) production?
Peritubular interstitial cells of KIDNEY - 90%
Perisinusoidal cells of LIVER - 10%
Detection by peritubular capillaries @ JGA
Erythropoietin (EPO) release factors?
In response to Low: Hb, O2, RBC
Rapidly produced/released (MINUTES) of stimulus. Max output @ 24hours (continues until stimulus removed.
Testosterone = increased EPO
Erythropoietin (EPO) effect?
Increases pro-erythrocyte production (from stem cells) @ bone marrow.
Accelerates differentiation of progenitor cells and maturation time.
EPO SPEEDS SYNTHESIS OF RBCs!
Gastroferrin?
Transports Fe2+ in the GIT.
Serum iron?
Iron (Fe2+)
TIBC (total iron binding capacity)
How much iron is in the blood!
Transferrin?
Plasma protein that binds and transports Fe2+ in circulating blood.
“Trucks that carry the iron”
Transferrin saturation?
Fe2+ / TIBC
Ferrritin?
Stores of Fe2+.
Mostly in cells (entercytes, macrophages).
Small amount blood.
Ferroportin?
Transporter of iron out of cell.
Hepcidin?
Regulator of ferroportin by (increased hepcidin = decreased ferroportin transport).
Chronic disease / cytokines stimulate increased release of hepcidin (not good).
Ferritin trapped in cells!
3 classifications of anaemia?
- Microcytic hypochromic (MCV<80fL)
- Normocytic normochromic (MCV 80-94fL)
- Macrocytic (MCV>94fL)
B12 / Folate deficiency?
Macrocytic anaemia.
Inhibits DNA synthesis and cell division - cells keep growing!
Cells: large, immature, Hb-poor.
Reduced activity of METHIONINE SYNTHASE (vit B12) inhibits the regeneration of TETRAHYDROFOLATE (folate) in DNA synthesis.
Compensatory mechanisms of chronic anaemia?
- Increased 2,3 DPG…
- Increased EPO…
- Increased cardiovascular…(HR, RR, shunting to vital organs)
MCV?
Mean cell volume (fL)
(measures cell size)
80-100fL: normocytic
<80fL: microcytic
>100fL: macrocytic
MCH?
Mean cell haemoglobin (pg)
(Average mass of Hb per RBC)
(Responsible for colour)
30-34pg: normochromic
<30pg: hypochromic
MCHC?
Mean cell haemoglobin concentration
Gives bigger picture
Reticulocyte count?
Measure of erythrocyte production.
Decreased = problem @ marrow.
Increased = response to problem with RBCs (eg haemolysis) in circulation
Reasons for MICROCYTIC hypochromic anaemia?
Low Fe2+
- ACD
- Fe2+ deficiency
Normal Fe2+
- Siderblastic (problem haem synthesis)
- Thalassaemia (problem Globin synthesis)
- Lead poisoning
Reasons for NORMOCYTIC normochromic anaemia?
Low/normal reticulocytes:
- Renal disease
- Bone marrow problem (eg stem cell defect)
HIGH reticulocytes:
- Haemolysis
- Haemorrhage
- Splenomegally = increased phagocytosis
Haemolysis causes?
Hereditary / Intracorpuscular:
- G6PD deficiency
- Sickle cell
Acquired / Extracorpuscular:
- Auto-immune (pregnancy)
- Allo-immune (transfusion)
- Medications (eg Methyldopa)
Reasons for MACROCYTIC anaemia?
Megloblastic:
1. Vitamin B12 and Folate deficiency!
Non-megloblastic:
- Liver disease
- Alcoholism
- Hypothyroidism (endocrine problem)
- Aplastic / hypoplastic
Thalassaemia (alpha)?
Chromosome 16 - deletion
Loss of 4 alpha-globin genes = not compatible with life (HYDROPS FETALIS)
Loss of 3 alpha-globin genes = Hb H disease; mod-severe anaemia; slpenomegally
Loss 1 or 2 alpha-globin genes = silent carrier; usually asymptomatic / no anaemia
Beta-Thalassaemia?
Chromosome 11 - mutation
Beta-Thalassaemia MINOR:
Single gene defect, mild anaemia, symptomless
Beta-Thalassaemia MAJOR:
- Severe anaemia @ 3-6 mo post birth
- hepatomegaly
- splenomegaly
- facies (bone expansion, marrow hyperplasia)
- regular blood transfusions: Fe2+ overload, chelation
RCDW?
Red cell distribution width.
Normal: 11.5 - 14.5%
Indicates reason for anaemia - low or high variation.
