Erythropoiesis + Iron deficiency anaemia Flashcards
Total body iron
3-5g
Majority of iron absorption
Duodenal lining
Ferroproteins
Transporter proteins in Enterocytes
Allow iron into body
Free iron form
Ferrous Fe2+ form
Fe3+ –> Fe2+
Ferric reductase enzyme
Enterocyte brush border
Transferrin
Iron-binding blood plasma glycoproteins
Regulate level of free iron in plasma + other ECFs
1 molecule can carry 2 Fe3+
low pH transferrins
Low pH makes transferrin release its iron ions
Ferritin
Polyprotein
24 Apoferritin subunits
Stores many iron atoms inside it in the inactive Fe3+ form
Ferritin MOA
Releases iron into cell in controlled fashion when needed
Buffer against iron deficiency and overload
Plasma ferritin
Diagnostic test for iron deficiency anaemia
Yellow marrow
Fat droplets and cells
Red marrow
Where most erythropoiesis occurs in adults
RBC formation in foetus
Mesoblastic Stage
Hepatic Stage
Myeloid Stage
Mesoblastic stage
3rd week
Nucleated RBCs form in Yolk sac + mesothelial layers of placenta
Hepatic stage
6 week
Erythropoiesis in liver and spleen
Myeloid stage
3 months +
Bone marrow principle source RBCs
Erythropoiesis exclusively in bone marrow last month
RBC formation up to 5 yrs
Bone marrow in all bones
RBC formation 5-25
Marrow of long bones
RBC formation 25+
Marrow of membranous bones e.g. vertebrae, sternum, ribs, cranial bones + ileum
Erythropoiesis sequence
Hemocytoblast Proerythroblast Erythroblast Normoblast Reticulocyte Erythrocyte
Diapedesis
Mature reticulocyte expels nucleus + newly formed erythrocyte squeezes through pores in marrow capillary membrane into blood
EPO
Protein
Produced in fibroblast interstitial cells in kidney
Around proximal tubule
Testosterone
Increases EPO production
RBC energy source
ATP via anaerobic glycolysis
Powers GLUT1 transporters
Lactate from erythrocyte
Exported from erythrocyte
Taken up by liver or muscle cells
Converted back to glucose
–> re-exported back into blood
Erythrocyte surface charge
Negative surface charge
Membrane glycoproteins contain sialic acid
Fibrinogen
Binds to RBC membrane
Reduces negative charge–> adhere
Rouleaux
RBC clump
Increases ESR
Raised ESR
Non-specific marker of infection
Normal ESR
(age + 10(if female))/2
RBC recycling
120 days
Lack of deformability- old cells are more rigid
RBC breakdown
Broken up by osmotic lysis
Haem prosthetic groups removed from globin proteins
Haem broken down by haemoxygenase enzyme
Iron atoms in Haem carried away by transferrin
Biliverdin
Opened porphyrin ring minus its iron atom
Greenish colour
Antioxidant
Biliverdin –> Bilirubin
In macrophage
By biliverdin reductase
Bilirubin
Yellowish colour
Not v soluble
Antioxidant
Unconjugated bilirubin
Bilirubin bound to albumin in splenic macrophages
Released into blood
Conjugated bilirubin
When unconjugated bilirubin binds to glucuronic acid
Conjugated bilirubin normal level
0.1-0.3mg/dL
Urobilinogen
Conjugated bilirubin passes in the bile in SI where bacteria convert it
Passes out of body in faeces (most)
10% passes back in the portal vein in liver
–> leaves liver in venous blood, passes through kidney, urine
Anaemia
Hb below the reference range for that age and gender
Adult Anaemia
<13.5g/dL Hb (male)
<11.5 g/dL Hb (female)
6months - 6years anaemia
<11g/dL Hb
6-14 years anaemia
<12 g/dL Hb
Anaemia signs
Pallor
Rapid HR
Systolic flow murmur
Microcytic anaemia
<76 fl
Normocytic anaemia
76-96fl
Macrocytic anaemia
> 96 fl
Femtolitre
1 cubic micrometre
Iron deficiency anaemia
Microcytic
Hypochromic (low Hb)
Blood loss iron deficiency
10ml/day
Developing countries IDA
Hookworm
Nutrition
Developing societies IDA
GIT bleeding
malabsorption
Chelators
chemicals which hold iron + prevent absorption
Sources of iron
Plants have a lot but have chelators so not absorbed
Calf liver
Steak
Enhance iron absorption
Ferrous salts (fe2+) Acid stomach pH pregnancy hypoxia iron deficiency haem iron (meat)
Impair absorption
Non-haem iron (veg) Ferric salts (Fe3+) Alkaline stomach pH iron overload PPIs
Causes IDA
Menorrhagia Varices, Ulcer, Cancer Coeliac Pregnancy, Growth spurt Hookworm
Hookworm
Parasitic Nematode worm
Punctures gut blood vessels and drinks erythrocytes
Confirming IDA
FBC
Blood film
Serum ferritin
Serum iron total iron binding capacity