iron metabolsim

total body content of iron

4g

bone marrow and RBC content in the body

3g

RES content in the body

200-500g

myoglobin content in the body

200-300mg

enzyme content in the body

100g

what enzymes are found within iron

• Cytochromes

 

• Peroxidases

 

• Xanthine oxidase

 

• Catalases

 

• RNA reductase

what two ways is iron stored in cells

ferritin and haemosiderin

properties of ferritin

soluable, iron safe and readily available from RES

properties of haemosiderin

insoluable conglomerates of ferritin, iron only slowly available

what is serum ferritin in iron deficiency anaemia

decrease

what is the serum ferritin in iron overload

increased

what is transferritin

glycoprotein

where is transferrin synthesised

hepatocytes

correlation between transferring and iron

low iron → increased transferrin

increased iron → low transferrin

how many iron domains is there in transferrin

two

daily iron need

1-2mg/d

what is the correlation between menstrual loss and Iron

Pre menopausal women are more at risk of IDA, regular menstrual loss accounts for an average additional daily loss of 1-2mg/day over the month

how are minimal daily losses of iron balanced

the duodenum absorbs approximately 1-2mg/day of dietary iron to replenish the circulating transferrin pool

what is the role of RES

will phagocytose RBC using macrophages, located in the spleen liver and bone marrow and will extract the haem from RBC

what does RES do to the recycled iron

will released back into the blood stream via the ferroportin exporter and binding it to transferrin for transport

what happens when RBCs grow old

they will return to the RES to complete the cycle

how does RES release recycled iron into the blood stream

using ferroportin exporter

where is iron predominantly absorbed

duodenum

how us non haem iron released from foodstuff

by acid digestion and proteolytic enzyme in the stomach

what must non haem iron be reduced to, from what

must be reduced from the ferric to the ferrous form by duodenal cytochrome b1

what influences the reduction of non haem iron from ferric to ferrous

vitamin C

how is iron taken into the enterocytes

divalent metal transporter 1

when might divelant metal transporter 1 be upregulated

in iron deficiency

where does iron in enterocytes move to

plasma ferritin

how is iron exported from the enterocytes into plasma transferrin

through the transmembrane protein ferroportin and the circulating hormone hepcidin

what is the interaction between ferroportin and hepcidin

single most important regulator of GI iron absorption and RES iron release

how do RES macrophages acquire iron

from effete RBCs - haem is broken down to iron and bilirubin; globin to amino acid pool

what is haem broken down into

iron and bilirubin

where is globin taken to

amino acid pool

how is RES iron stored

as ferritin (or haemosiderin)

how is RES iron release regulated

ferroportin and hepcidin

how is RBC iron recycled

effete RBCs are removed by the macrophages of the RES

how much iron is stored in the RES

500mg

where does RES release iron to in plasma

transferrin

what is transferrin taken up by and where

Tf receptors on erythroblasts and hepatocytes

role of transferrin in the cellular uptake of iron and its intracellular fate

Tf iron will take iron from the plasma ro the erythroblast, the TfR is located on the erythroblast membrane, transferrin will bind to TfR causing endocytosis pf the complex into the endoscope, acidification of the endosome releases the ferric iron which is reduced to ferrous iron and transported into cytoplasm via DMT1

what is the two pathways that iron can take when intracellular in the erythroblast

functional and storage

what is the storage pathway of intracellular iron

Excess iron not immediately needed for heme synthesis is safely sequestered into ferritincomplexes within the cytoplasm to prevent iron-induced oxidative damage (via Fenton reactions).

what is the functional pathway of intracellular iron

the majority of iron in developing erythroblasts is directed straitjacket into the mitochondria via transporter mitoferrin 1. the rate limiting erythropoietin specific enzyme located in the mitochondria that catalyses the first step of haem synthesis. In the final step ferochelatase inserts the imported iron into protoporphyrin IX indies the mitochondria to produce haem

what is iron deficiency anaemia in men and post menopausal women likely due to

GI bleeding

why might there be iron malabsorption

the coeliac mucosa is characterised by villi hypertrophy, enlarged hyperplasticity crypts and increased infiltration of lymphoid cells in lamina propria and epithelium

what is a folate deficiency likely due to

• most likely

        dietary source: green veg, orange fruit, liver

daily requirements and body stores of folate deficiency

daily requirements: high 150mg

        body stores : low 15mg (~3 months)

daily requirements and body stores of iron deficiency

daily requirements: 1mg (20mg in diet)

        body stores : 200-500mg

daily requirements and body stores of vit b12 deficiency

daily requirements: 1-3mg/d

        body stores : 3mg (3-5 years)

 

what are common haematinic deficiencies

folate

ferritin

b12

role of hepcidin

it reduced the levels of iron in plasma

how does hepcidin and ferroportin decrease iron levels

reducing GI iron absorption (enterocyte) and

         reducing macrophage iron release from the RES.

where is hepcidin synthesised

liver

what does hepcidin loss cause

increased GI iron absorption, increased RES iron release, increased TfR saturation & parenchymal iron overload (GH)

what is haemachromatosis

autosomal recessive disorder of iron metabolism causing iron overload.

what is the most common mutation in haemachromatosis

Homozygous C282Y mutation of the HFE gene

what other mutations can occur in haemachromatosis

Compound heterozygotes C282Y/H63D weak GH.

who is haemachromatosis more severe in and why

males, women are protected by menstruation and child birth

how much transferrin is saturated with iron in normal conditions

1/3

what is the difference of transferrin saturation in individuals with IDA

more total transferrin molecules synthesise but very few will carry iron

what is the difference of transferrin saturation in individuals with haemachromatosis

fewer transferrin molecules are present relative to the overwhelming amount of circulating iron causing 100% saturation

transferrin saturation, iron and ferritin levels in normal circumstance

transferrin: normal

iron: normal

ferritin: normal

transferrin saturation, iron and ferritin levels in IDA

transferrin: decreased

iron: decreased

ferritin: decreased

transferrin saturation, iron and ferritin levels in haemachromatosis

ferritin: high

iron: high

transferrin: high

how might haemachromatosis impact the livers pancreas, skin and joints

cirrhosis

diabetes

bronzing

arthritis

what is sideroblastic anaemia

the bone marrow will fail to make haemoglobin from iron, so iron is trapped in RBC and will form a ring like appearance around the nucleus, leading to a shortage of healthy red blood cells and an increased concentration of iron

why is iron deposited to bone marrow via transferrin

the bone marrow will use iron to synthesise haemoglobin for new RBC

what are erythroblasts

developing red blood cells

where are the erythroblasts located

located in bone marrow, intracellular uptake or iron occurs here as iron which has been released by the RES is being used to create haemoglobin for new RBC

what is a valuable measurement for the investigator of anaemia and why

serum transferrin as it is directly correlated with the amount of iron stored in the body

where in an erythroblasts does haem biosynthesis occur

mitochondria

Which of the following patients would not have target cells on their blood film?

1. Irritable bowel disease

2. Obstructive jaundice

3. Abnormal haemoglobin

4. Coeliac disease

1 - irritable bowel syndrome

What is the main cause of tissue damage in patients with haemochromatosis?

1. Increased non-transferrin ferrous iron

2. Decreased hepcidin

3. Decreased transferrin

4. Increased transferrin saturation

1 - increased non - transferrin ferrous iron

what is the most serious complication of haemachromatosis

liver cirrhosis