haematology 3

Question 1

what is the function of iron in haemoglobin

Answer 1

• Fe2+ and Fe3+
• participates in redox reactions by switching reversibly between states
• Fe2+ can bind to molecular oxygen haem group
• excess Fe is toxic as it forms free radicals so is stored and transported in ferric Fe3+ state

Question 2

how is iron transported

Answer 2

1) Fe3+ in diet
2) ferric reductase converts it into Fe2+
3) transported into cell via haem transporter, endosomes or divalent metal transporter 1
4) Fe2+ can be converted back to Fe3+ and bound to transferrin within the intestinal cell or can be transported into the blood by ferroportin (FP) and hephaestin (HP).
5) in the blood Fe2+ is oxidised by HP to form Fe3+ which is used to form plasma transferrin made in the bone marrow

Question 3

what causes a reduction in ferric iron

Answer 3

• high pH
• lack of gastric acid - impairs absorption
• inorganic anions - form insoluble complex with iron
• ascorbic acid (vitamin c) enhances absorption

Question 4

what is hepcidin

Answer 4

• regulator of iron absorption, produced by the liver upon availability of iron from transferrin

Question 5

what occurs in ribosomes when iron stores are low

Answer 5

• ribosomes produce more DMT1
• DMT1 mRNA has iron response element in 3’ untranslated region
• low iron causes iron regulatory proteins to bind to these iron response elements and protect mRNA from nuclease attack

Question 6

when is hypoxia-inducible factor 2a activated and what does it do

Answer 6

• decreased O2 supply activates it
• transcription factor that binds to promotor region of DMT1 and FP stimulating transcription
• mechanism which chronic anaemia increases iron absorption

Question 7

what are the causes, symptoms and treatment of iron deficiency

Answer 7

• chronic blood loss, growth spurts, late stage of pregnancy, lactation, acute massive haemorrhage
• pallor, weakness, fatigue
• ferrous sulphate combined with ascorbic acid

Question 8

what is the haem structure

Answer 8

• a porphyrin containing iron and 4 pyrrole rings connected by methylene bridges

Question 9

where does haem synthesis occur

Answer 9

• 85% in the bone marrow

Question 10

where is porphobillinogen (PBG) present and what does it do

Answer 10

• mitochondrial membrane
• removes 2 H20 from the 2 x gamma-ALA to form 1 x PBG released into the cytosol

Question 11

what is linear tetapyrrole made of and what does it form

Answer 11

4 PBG molecules
- looses 4 x CO2 and re entreres mitochondria as protoporphyrinogen IX

Question 12

what does ferrochelatase do

Answer 12

• adds Fe2+ to protoporhyrin IX to form haem

Question 13

what regulates game-ALA synthase

Answer 13

• haem
• degades after 1-3 hours

Question 14

what inhibits PBG synthase and ferrochelatase

Answer 14

• heavy metals eg. Pb

Question 15

what is haem production required for in the liver and erythroid cells

Answer 15

• liver - formation of haemoproteins for detoxification
• erythroid cells - synthesis of Hb

Question 16

what role does macrophages play in degradation

Answer 16

• engulf senescent erythrocytes
• oxide haem to ferric (3+) state to produce hemin
• haem oxygenate catalyses hemin to billiverdin

Question 17

what do splenic macrophages do in haem degradation

Answer 17

• catalyse the production of bilirubin from biliverdin by biliverdin reductase

Question 18

how is bilirubin transported and converted

Answer 18

• from the spleen to the liver by tight, non-covalent forces to serum albumin
• in hepatocyte ER it is conjugated with glucuronic acid to form bilirubin diglucuronide by uridine diphosphate
• intestinal bacteria de-conjugate to form uncoloured urobilinogen

Question 19

what is the pathway of urobilinogen

Answer 19

1) some absorbed by ileum
- reduced to stercobilin by intestinal bacteria - brown
- small amount excreted by kidneys which is oxidised to urobilin
2) most is cleared by the liver and re-secreted in bile

Question 20

what is the causes of jaundice

Answer 20

• hyperbilirubinemia by conjugated and unconjugated bilirubin

Question 21

what is conjugated bilirubin

Answer 21

• water soluble
• causes yellow-brown colouration of urine
• causes of choleric jaundice

Question 22

what is unconjugated bilirubin

Answer 22

• tightly bound to albumin
• lipid soluble
• can enter brain causing bilirubin encephalopathy/ kerniecterus infants

Question 23

what happens in pre-hepatic jaundice

Answer 23

• increased production or impaired hepatic uptake of bilirubin
• haemolysis increases total plasma due to excess unconjugated fraction
• increase in urine bilirubin because unconjugated bilirubin is insoluble

Question 24

what happens in intra hepatic jaundice

Answer 24

• caused by parenchymal liver disease
• causes bilirubin conjugation and impairments of energy dependent secretion of conjugated bilirubin into bile

Question 25

what is post hepatic jaundice

Answer 25

• obstruction or reduction of bile flow
• impacted gallstone, pancreatic cancer, liver diseases that prevent bile formation
• cannot reach intestine so overflows into blood

Question 26

what is Gilbert syndrome

Answer 26

• compensatory haemolysis
• impaired uptake and conjugation of bilirubin

Question 27

what is rotors syndrome

Answer 27

• conjugated hyperbilirubinameia
• caused by intermittent jaundice

Question 28

what is cringer nejjar syndrome

Answer 28

• servere unconjugated hyper-bilirubinaemia
• deficiency in enzyme needed for bilirubin conjugation

Question 29

what is Dublin-johnson syndrome

Answer 29

• retention of conjugated bilirubin
• turns the liver black with intermittent jaundice

Question 30

what are the treatments for jaundice

Answer 30

• phototherapy - adds oxygen to bilirubin to increase solubility
• phenobarbital - induction of enzyme synthesis
• breastfed babies - higher risk of jaundice