Haematopoiesis Erythropoiesis & Iron

Question 1

What is the function of bone marrow?

Answer 1

RBCs, WBCs, platelets prod here

Question 2

What hormones control haematopoiesis?

Answer 2

Lymphocytes = ILs, TNFα. 
Granulocytes = G-CSF. 
Megakaryocytes = TPO. 
Erythroid = EPO.

Question 3

What is the reticuloendothelial system?

Answer 3

Network in blood/tissues that is part of the immune system that consists of phagocytic cells = in the spleen can dispose of damaged RBCs

Question 4

What is the role of a RBC?

Answer 4

Carry Hb, maintain iron in ferrous state, generate ATP, maintain osmotic equilibrium, flexible/large surface area means good gas exchange

Question 5

Describe Hb

Answer 5

Tetramer of 2 pairs of globin chains,
gene on chromosome 11 + 16,
carry O2/CO2,
protects haem from oxidation

Question 6

What are the stages of Hb breakdown?

Answer 6

Hb = bilirubin = conjugated with glucuronic acid in liver = enter bile = small intestine = bacterial proteases break off urobilinogen = portal vein to liver = blood to kidney = excreted in urine

Question 7

What controls erythropoiesis?

Answer 7

Reduced pO2 detected by interstitial peritubular cells in kidney = increased prod of EPO = stim RBC release from bone marrow

Question 8

What 2 metabolic pathways do RBCs use?

Answer 8

Glycolysis,

pentose phosphate pathway

Question 9

Discuss the role of iron in the blood?

Answer 9

Transport/stores oxygen,
integral part of many enzymes,

body has no mechanism of excreting iron,
~80% from recycling

Question 10

Outline the difference between available iron and stored iron

Answer 10

Stored = ferritin, haemosiderin.

Available = Hb, Mb, tissue iron, transported iron (on transferrin)

Question 11

Where is the majority of stored iron found?

Answer 11

95% found in hepatocytes as ferritin

Question 12

Why is a haem source of iron better than a non-haem source?

Answer 12

Haem source = in ferrous form.

Non-haem source = has to go through additional step to become ferrous

Question 13

What vitamin increases the absorption of iron?

Answer 13

Vit c = ascorbic acid

Question 14

How is iron absorption regulated?

Answer 14

Iron levels sensed by villi of enterocytes.

Control mechanism = reg of transporters, expression of HFE/transferrin receptors, hepcidin and cytokines

Question 15

What is the central regulator of iron met and how does it function?

Answer 15

Hepcidin = secreted by liver/kidneys - increased in iron overload

degrades ferroportin (protein involved in moving iron out of cells) = prevents iron release from macrophage + iron absorb from gut

Question 16

How does iron def present on a blood film and in blood parameters?

Answer 16

Hypochromic, microcytic, anisopoikilocytosis, low serum ferritin, low reticulocyte Hb content (CHR)

Question 17

What tests should be ordered when testing for iron def?

Answer 17

1) ferritin (do bear in mind it’s an acute phase protein),

2) CHR: reticulocyte Hb content (remains low during inflam)

Question 18

How is iron def treated?

Answer 18

Diet, oral iron, IM iron, IV,

transfusion (only in severe anaemia)

Question 19

Why is excess iron dangerous?

Answer 19

Haemochromatosis = autosomal recessive, excess iron deposited in tissues = end organ damage.

Reduced Fe (Fe2+) can prod highly reactive hydroxyl and lipid radicals = damage lipid membrane, nucleic acid, protein

Question 20

What is the pathophysiology of haemochromatosis?

Answer 20

autosomal recessive,

mutated HFE = believes transferrin is high (iron carrier) = increased intestinal release of iron as if there is iron def = excess deposition in tissues = first stored as ferritin then haemosiderin (toxic) = end organ damage.

Question 21

What is ferritin?

Answer 21

Intracellular protein that stores iron

Question 22

What is transferrin?

Answer 22

Iron-binding blood plasma glycoprotein that controls the level of free iron in fluids

Question 23

What is pO2?

Answer 23

(partial pressure of oxygen) reflects the amount of oxygen gas dissolved in the blood

Question 24

What is the primary source of ATP prod in RBCs?

Answer 24

Glycolysis

Question 25

Defect in genes coding for which protein cause hereditary spherocytosis?

Answer 25

Spectrin, ankyrin, band 3 protein, protein 4.2

Question 26

Roughly when does the switch from fetal to adult Hb occur?

Answer 26

3-6 months of age

Question 27

Iron is absorbed in which part of the GI tract?

Answer 27

Duodenum and jejunum

Question 28

Which transporter facilitates the uptake of ferrous iron from the intestinal lumen into enterocytes?

Answer 28

DMT1 = divalent metal transporter

Question 29

What food product has adverse affects on iron availability?

Answer 29

Tea = tannins

Question 30

How is iron excretion controlled?

Answer 30

There is no pathway for iron excretion, only absorbtion and mobilisation