Flashcards in Week 3. Iron, vitamin b12, folate and anaemias Deck (40):
Where is iron found in the body?
Mostly in haemoprotein e.g. haem in haemoglobin and myoglobin (muscles).
Bound to a protein e.g. transferring or the normal storage proteins- ferreting and haemosiderin.
(hardly any in blood plasma)
2 main forms of iron?
Ferric= Fe3+ (virtually insoluble)
Ferrous= Fe2+ (soluble, most usable form)
The difference of the irons is important in how we take them up
What is total body iron content of healthy adult?
What are the 2 main forms of iron in diet?
Haem and non-haem. Haem is the most usable for humans and is found in meat and fish. Non-haem is found in cereals, vegetables, eggs nuts etc.
In average western diet how much iron do we intake and how much is absorbed?
INtake 10-15mg daily.
5-10% is absorbed through the upper small intestin (duodenum). So 0.5-2mg,
How is iron converted?
As Fe2+ is the most usable form, Fe3+ is converted to Fe2+ be duodenal cytochrome b
How is iron excreted?
There's no mechanism to excrete iron, daily loss is the only way e.g, sweating, faeces, shedding skin cells of git
What inhibits iron absoprrtion?
Phytates- phytic acid found in spinach
Tannins- found in red wines. Best to drink after meal.
Tetracycline- an antibiotic.
What adances iron absoprtion?
How does iron continuously circulate in plasma?
Bound to transferrin.
Transferrin- delivers iron to tissues that have transferrin receptors- e.g. RBCs in bone marrow incorporate it into Haemoglobin
What is molecular mechanism of iron absorption?
Low gastric pH helps to reduce the ferric iron.
Ferrous iron is transported into the enterocyte by the divalent metal transporter (DMT).
Then either stored as ferritin or transported across basal membrane into blood plasma: by ferroportin.
What does transferrin do?
Transports iron to any cell that expresses a transferrin receptor on its surface.
Single membrane spanning receptor.
2 subunits, each able to bind a transferrin molecule.
4 atoms of iron can be absorbed each time the receptor binds and internalises transferrin.
After transferrin binds its receptor- the complex is internalisedm iron is released and the complex goes back to cell surface and recycled. Transferrin released to plasma.
What are the 2 forms of storage iron?
Ferretin (65%) and Haemosiderin (35%).
Ferretin= water soluble. Protein shell enclosing iron core. Serum ferritin levels most valuable diagnostic indicator of iron status. Measured by ELISA.
Haemosiderin= Water insoluble. Derived from lysosomal digestion of ferritin aggregates. Found in macrophages. Increased in iron overload. Pappenheimer bodies (removed by spleen).
What is the WHO definition of anaemia?
Low level of Hb in the blood.
Men less than 13g/dL
Women less than 12g/dL
In anaemia what are the body's physiological responses?
To retain maintain oxygen- 2,3 DPG levels rise- ensure oxygen is uploaded at tissues.
Cardiac output increases and circulation becomes hyperdynamic- rapid pulse and heart murmurs.
What is the most common cause of anaemia worldwide? What are the signs and symptoms of this type of anaemia?
Koilonychias-> flattening or spooning of the nails.
Angular stomatitis-> lesions at corner of mouth.
Glossitis-> Inflammation and depapillation of the tongue.
Reduction in haemoglobin leads to pale skin and fatigue.
On blood film:
Anisocytosis- unequal size RBCs
Poikilocytosis- abnormal shaped RBCs
Hypochromic- pale colour
Microcytic RBCs- small
Iron deficiency anaemia lab findings?
Hb concentration decreased
Mean cell volume
What is the treatment for Iron deficiency anaemia?
Replace the iron lost. By iron sulphate. It's cheap and contains 67mg of iron per 200mg tablet. Treatment for atleast 6 months.
Why is iron overload bad?
What are the main mechanisms of iron overload?
Can't actively excrete iron. Accumulation can result in organ damage, especially the heart, liver and endocrine organs.
Main mechanisms- Increased iron absorption: hereditary haemochromatosis, chronic liver disease, ineffective erythropoiesis. Repeated blood transfusion- in thalassemia and aplastic anaemia.
What is a disorder that's characterised by excessive iron storage?
Hereditary (primary) haemochromatosis.
-excessive absorption of iron from GIT
-Northern European descent:high incidence
( also blood transfusion related diseases e.g. myelofibrosis who need lots of transfusions)
What is cobalamin?
Commonly known as vitamin B12.
Where is cobalamin made?
Made exclusively in microorganisms. Found in the liver of animals bound to protein as methycobalamin or 5'-deoxyadenosylcobalamin.
What are sources of cobalamin?
High-> liver and kidneys
Others-> shellfish, meat, dairy products
Why do we need vitamin b12?
Maintains normal function of brain and nervous system and formation of RBCs.
Involved in metabolism of almost all cells.
Role in DNA synthesis and regulation
Describe the steps of the absorption and transport of vitamin b12
1. Intrinsic factor (IF) produced in gastric parietal cells.
2. B12/IF complex moves to ileum from stomach.
3. Binds to receptor on enterocyte, absorbed.
4. B12 released into circulation.
5. IF not recycled.
6. Post-eneterocyte circulation on TC-II or TCI (transcobalamin II or I)
7. Surface of rceiving cell accepts the B12/TC-II and release B12 into cell. TCII degraded inside and release B12
What is pyridoxine?
Essential co-factor: conversion of succinyl coA and glycin into ALA by ALA synthase.
Common in fruit, veg, cereal and meat.
How is pyridoxin absorbed?
Passive absorption in jejenum and ileum.
Recommended daily requirement= 1.5-2.0mg
What metabolic pathway are both B6 and B12 involved in?
In the production of Haem in the mitochondria.
B12 helps L-methylmalonyl-coA ---> succinyl coA
B6 helps succinyl coA---> ALA
How much B12 do we need to absorb daily?
How is it lost?
To maintain body stores-> 1-3ug.
To maintain health ~0.5ug.
Lost in urine and faeces- desquamination of epithelial and bile. Only lose 0.05-1% of body content each day. (body content= 3-5mg)
What are folates?
How are they taken up and where are they found?
Consist of a large number of compounds. Folic acid: also known as vitamin b9. Humans cannot make folate so all of folate intake comes from diet. Folates found in both animal and plants.
What are some sources of folate?
Why do we need folate?
1. leafy green veg, fruit, liver, bakers yeast and fortified breakfast cereals.
2. Synthesis of purine/pyramidine precursors of DNA.
Especially important in periods of rapid growth- infancy/pregnancy
Production of healthy red blood cells.
What happens with folic acid in the body?
Folic acid (folate) is not the active form. It must be reduced to tetrahydrofolate (THF) absorption happens in the duodenum and jejenum.
Absorbed folates converted into 5-methyltetrahydrofolate before entering the portal blood system.
Plasma folate circulated bound or unbound to plasma proteins.
What are causes of vitamin b12 deficiency?
Pernicious anaemia= impairs absorption of vitamin B12 as a consequence of a reduction in intrinsic factor.
Veganism= no B12 in plants.
What causes folate deficiency?
There's usually enough folate in diet. Caused by impaired absorption or increased demand of folate. Usually pregnancy. Oral contraceptives can impair absorption. Anticonvulsants increase rate of folate metabolism.
What are clinical features of folate and b12 deficiency?
1. Neural tube defects-
if not enough folate before and during first month of pregnancy-> spina bifida and anencephaly.
2. Neurological complications-
Progressive demyelination of nerves thought to be caused by B12 deficiency (increase in methylmalonylcoA)
3. Mild jaundice- ineffective erythropoiesis
4. Neuropathy- affects spinal cord and peripheral nerves
5. Tingling feet- hard to walk
6. Glossitis- inflammation/infection of the tongue
What are 2 haematological disorder due to b12 or folate deficiency?
1. Megaloblastic anaemia due to folate deficiency
2.Pernicious anaemia= megaloblastic anaemia due to vit b12 deficiency. Caused by lack of intrinsic factor.
Why is it called megaloblastic anaemia?
What caused it etc..
1. Deficiency of folate reduces conversion of dUMP to dTMP.
2. DNA synthesis is delayed and chromosomes often break.
3. RNA not effected as much so protein synthesis in cytoplasm is much faster than the DNA replication.
4. Delays cell division!
Rapidly dividing cells like RBCs need to replicate DNA before dividing.
5. BUT DNA replication is delayed so the cells get bigger but don't divide yet resulsting in MEGAblasts in the bone marrow and large RBCs in the blood.
What dp we see in periheral blood with megaloblastic anaemis?
-Macrocytosis (increased RBC size) as protein synthesis is still happening but division is slower.
Increased MCV >90fl
Decrease in division of RBC precursors
Oval macrocytes- large RBC are oval shaped.
Increased lobe number >5 in neutrophil nuclei- probably due to structural abnormalities with chromatin.
Describe the aetiology and antibodies in pernicious anaemia?
(megaloblastic anaemia due to lack of IF.)
Autoimmune attack on the gastric mucosa.
Stomach wall becomes thin, reduced gastric secretion of acid and intrinsic factor.
Antibodies against gastric parietal cells are found int he serum in about 85% of patients.