8: Iron in health and disease Flashcards
What process is iron essential for?
Oxygen transport by RBCs
What part of respiration is iron essential for?
Cytochrome system (electron transport)
What are the two forms of iron found in the body?
Ferrous iron (Fe2+)
Ferric iron (Fe3+)
Iron is ___ in high concentrations - why?
toxic
produces free radicals - oxidative stress
Where is most iron found in the body?
Within RBCs as haemoglobin
Which cells, found in the bone marrow, contain a lot of iron?
Bone marrow macrophages
Where is haem produced?
Cytosol of RBC precursors
Which organ stores iron as ferritin?
Liver
Where in the GI tract is iron absorbed?
Duodenum
Which protein converts Fe3+ to Fe2+ in the duodenum?
Cytochrome B
Which transport protein moves iron from the lumen of the duodenum into the enterocytes?
DMT-1
Which proteins transport iron
a) into duodenal enterocytes
b) from the enterocytes to the circulation
c) through the circulation to the bone marrow?
a) DMT-1
b) Ferroportin
c) Transferrin
Where does iron go to be stored if it isn’t transported directly to the bone marrow?
Liver
Which organ detects iron levels and acts to decrease absorption if there is iron overload?
Liver
Which protein, produced by the liver, decreases iron absorption?
Hepcidin
In what forms is iron
a) found in red blood cells
b) transported in the circulation
c) stored in the liver?
a) Haemoglobin
b) Transferrin
c) Ferritin
Does hepcidin’s effect on ferroportin cause an iron deficiency?
No
The iron is there but it can’t reach the circulation
Lack of iron availability
How many iron ions can transferrin carry at once?
2
How does transferrin know where to deliver iron ions?
Cells express transferrin receptors
Which tissue is rich in transferrin receptors?
Bone marrow
Which cells express transferrin receptors?
Bone marrow macrophages (bone marrow)
Hepatocytes (liver)
What happens to transferrin saturation in
a) iron overload
b) iron deficiency?
a) Increases
b) Decreases
Which measurement is mainly used to diagnose iron deficiency?
Serum ferritin
What does serum ferritin increase in response to?
Iron overload
But also infection, malignancy etc. because it’s an acute phase protein
What happens to serum ferritin in patients with inadequate iron intake?
Decreases
Reflecting exhaustion of iron stores
What type of anaemia is caused by iron deficiency?
Microcytic hypochromic anaemia
Low Hb
Low serum ferritin
What are three clinical signs of iron deficiency anaemia?
Pallor - skin, conjunctiva
Koilonychia - spoon nails
Angular stomatitis
Why might a patient be iron deficient?
Inadequate iron intake
Bleeding
Malabsorption
What is occult blood loss?
Bleeding which isn’t detected by the patient or the doctor
e.g GI bleeds - peptic ulcers, tumours
What causes anaemia of chronic disease?
Inflammatory cytokines associated with chronic disease
What is the mechanism of iron unavailability in anaemia of chronic disease?
Inflammation causes increased storage of iron as ferritin
So hepcidin inhibits transport of iron as transferrin
So loads of iron is stuck in enterocytes and can’t reach the circulation
What is the most common cause of iron overload?
Haemochromatosis
A mutation in which gene causes haemochromatosis?
HFE gene
What causes
a) primary
b) secondary
haemochromatosis?
a) Inherited gene mutation
b) Iron overload due to repeated blood transfusion
Which liver protein is deficient in haemochromatosis?
Hepcidin
So no negative feedback of iron absorption > iron overload
Which organs are affected by iron deposition in haemochromatosis?
Liver - cirrhosis
Skin - bronze
Heart - cardiomyopathy –> arrhythmias
Joints - arthritis
Pancreas - “bronze diabetic”
Pit. gland –> amenorrhoea, testicular atrophy
Why does iron deposition cause disease in haemochromatosis?
High levels of iron ions produce high volumes of toxic free radicals
How is haemochromatosis treated?
Weekly phlebotomy
just take blood to drive more Hb production and exhaust iron stores
What is a common complication of untreated haemochromatosis?
Cirrhosis
Which may cause hepatocellular carcinoma
What is offered to the families of patients with haemochromatosis?
Screening for HFE gene mutations
Why is haemochromatosis screening important?
Liver damage is often clinically silent
What is an iatrogenic cause of iron overload?
Repeated blood transfusions
___ erythropoiesis can cause iron overload.
Ineffective erythropoiesis
Which conditions, requiring regular blood transfusions, may result in secondary iron overload?
Thalassaemia
Myelodysplasia
How is iron overload secondary to blood transfusions avoided?
Iron chelating drugs
How do iron chelating drugs work?
Bind to Fe, form solution and are excreted by kidneys
How are iron chelators administed?
IM
