Anaemia Flashcards
A red cell that is larger than average with RNA remnants?
Reticulocyte - immature red blood celll
How long does the up regulation of reticulocyte production take in response to anaemia?
1 -2 days (there may also be a transient initial response)
What type of anaemia do you get in iron deficiency?
Microcytic
In what two situations might Haemoglobin/Haematocrit not be good markers of anaemia?
Heavy Bleeding
IV fluids
What two things can cause loss/destruction of red blood cells?
Bleeding
Haemolysis
What two things can cause a decreased production of RBCs?
Reduced amount of erythropoiesis
Maturation abnormality - erythropoises present but ineffective
(Cytoplasmic defects causing impaired haemoglobinisation or nuclear defects causing impaired cell division
What cell parameter is most useful for deciding whether or not your anaemia is caused by increased loss or decreased production of RBCs?
Reticulocyte count
What do cytoplasmic defects of erythropoesis result in?
Impaired haemoglobinisation
What do nuclear defects of erythropoesis result in?
Impaired cell division
If the MCV is low what kind of anaemia is it?
Microcytic
If MCV is high what kind of anaemia is it?
Macrocytic
If there is a problem with haemoglobinisation what kind of anaemia will you have/?
Microcytic
If there is a problem with maturation what kind of anaemia will you have?
Macrocytic
Where is haemoglobin synthesised?
Cytoplasm
What causes hypochromic, microcytic anaemia?
Deficient haemoglobin synthesis = cytoplasmic defect
What is the most common underlying cause of hypochromic microcytic anaemia?
Iron deficiency
Aside from iron deficieny what is the other large cause of hypochromic microcytic anaemia?
Thalassaemia
What is thalassaemia?
Deficiency of globin
What two states can iron exist in?
Fe2+
Fe3+
How many oxygen molecules can bind to a haem group?
1
What molecule is iron stored as?
ferritin
What molecule is iron transferred as?
Transferrin
What is transferrin?
A protein with two binding sites for iron atoms
What does transferrin do?
Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expresssing transferring receptors (especially in erythroid marrow)
What would transferrin levels be reduced?
Iron deficiency
Anaemia of chronic disease
What would transferrin levels be increased?
Haemachromatosis
What do low ferritin levels mean?
Iron deficiency
What is serum ferritin a measure of?
Storage iron
What is a megaloblast?
An abnormally large nucleus cell precursor
What happens in megaloblastic anaemia?
Defects in DNA synthesis and nuclear maturation with relative preservation of RNA and hameoglobin synthesis
What does free B12 bind to first in the stomach?
Haptocorrin
What does B12 bind to after it is released from haptocorrin?
Intrinsic factor
Where is B12 absorbed?
Ileum
Where is folate absorbed?
Duodenum
Jejunum
If you stopped consuming B12 how long would it take for you to become deficient?
2 - 4years
If you stopped consuming folate how long would it take for you to become deficient?
4 months
How much folate do you need a day?
100ugs
How much B12 do you need a day?
1 - 3ug
What problems are particular to Vitamin B12 deficiency?
Neurological deficiency due destruction of the myelin dheath
Why is the cell large in megaloblastic anaemia?
There is failure of the cell to get smaller
What is pernicious anaemia?
Autoimmune condition with resulting destruction of gastric parietal cells
What other conditions is pernicious anaemia particularly associated with?
Hypothyroid
Vitiligo
Addisons
What is the blood film like in patient with B12 or folate deficiency?
Macrocytes - oval
Abnormal nuclear segmentation of the neutrophils (greater than 5 segments?
What auto antibodies are you looking for in pernicious anaemia?
Anti - gastric parietal cell antibodies
Anti intrinsic factor
What signs on examination would be looking for in anaemia?
Koilonychia Conjunctival Pallor Atrophic glossitis Angular stomatitis High flow murmur Tachycardia Dysphagia (very rarely)
Where is the main sight of iron absorption in the the body?
Duodenum
Low Hb
Low MCV
Low ferritin
What is the cause of anaemia?
Iron deficient anaemia
What are the problems with ferritin measurement?
Ferritn is an acute phase protein so will be raised in inflammation and maligancy
What would you be looking for on a blood film on someone with iron deficient anaemia?
Microcytic cells
Hypochromic cells
Variation in cell size and shape
What abnormality would you expect to see in the neutrophils of a patient with macrocytic anaemia due to B12 deficiency?
Hypersegmented nucleus - greater than 6 lobes to the nucleus
leucopenia will be seen in severe cases
What abnormality would you expect to see in the platelets of a patient with macrocytic anaemia due to B12 deficiency?
Thrombocytopenia
Describe the process of absorption of Vitamin B12:
- Vitamin B 12 absorbed in the stomach
- Then they bind to intrinsic factor which is produced by parietal cells.
- This complex then travels through intestine to be absorbed by the terminal ileum.
Where is vitamin B12 absorbed?
Terminal ileum
In what two parts of the digestive system could a problem lead to B12 deficiency?
Ileum
Stomach
A man has crohn’s disease affecting his ileo - caecal junction. Which vitamin is he most likely to be deficient in?
B12
A women has has a gastrectomy due to gastric cancer. What vitamin is she most likely to be deficient in?
B12
What cells are attacked in pernicious anaemia?
Parietal cells
What is the treatment for B12 deficiency?
Hydroxycobalamin IM every three months
At the start of treatments a high dose will be given over three weeks as a loading dose
What is the danger of starting someonw on folate without checking their B12?
If their B12 is low and you give them folate you can precipitate neurological problems and cause demyelination of the spinal cord.
What drugs have anti folate actions?
Methotrexate
Alcohol
Some anti convulsants
What is the diagnostic test for B12 deficiency?
Serum B12
What is the diagnostic test for folate deficiency?
Red cell folate
What is the treatment of folic acid deficiency?
Folic acid oral tablets
What is the mechanism of anaemia of chronic disease?
In response to inflammatory cytokines (mostly IL 6) the liver produces increased amounts of hepcidin.
Hepcidin then causes increased internalisation of ferroportin molecules on cell membranes which prevents release of iron from stores.
This also blunts erythopoiesis by decreasing the ability of the bone marrow to respond to EPO
Why might the ferritin be high in anaemia of chronic disease?
It is an acute phase protein - responds to inflammation.
What is myelodysplasia?
Mild malignancy of early myeloid progenitor cells mostly seen in the elderly.
What is aplastic anaemia?
A deficiency of all types of blood cell caused by failure of bone marrow development.
In what kind of conditions do you get normochromic, normocytic anaemia?
In hypoproliferative anaemic conditions….
Chronic inflammatory, infective and malignant conditions
Renal failure
Hypometabolic states such as hypothyroid
Marrow aplasia
What test on he FBC gives information about whether the anaemia is hypochromic or normochromic?
Mean Cell Haemaglobin (MCH)
Low Hb, Love MCV, Normal ferritin stores
Thalassaemia