L7 - Intro To Anaemia Flashcards
What is anaemia?
Haemoglobin below the reference range for the normal population
CORRECT ANSWER
What are some symptoms of anaemia the patient may recognise
Shortness of breath/fatigue/palpitations/headache/cardiac failure
Upon examination of an anaemia patients what signs may we see suggesting anaemia
Pallor , tachycardia, breathlessness, hypotension
One way in which anaemia can ensure is through reduced erythropoiesis (dyserythropoiesis). eryhtropoiesis (production of RBC’s) is stimulated by what hormone?
Erythropoietin
How is erythropoiesis stimulated in detail?
Reduced pO2 senses by the kidney -> increase in erythropoietin production by kidney -> hormone stimulates red marrow to increase no of red cells -> increases oxygen delivery -> feedback loop causes erythropoietin levels to fall
Name three problems which can cause reduced erythropoiesis
1) Kidney stops making erythropoietin - chronic kidney disease
2) ‘empty bone marrow’ - lack of haemopoietic cells in the marrow to respond to EPO - aplastic anaemia
3) marrow infiltrated by cancer cells or fibrous tissue thus reducing the normal amount of haemopoietic cells - myelofibrosis
What clinical tests point to dyserythropoiesis (defective development of RBC’s)?
Increased CRP and ferritin/marrow shows no response to EPO
What is happening in anaemia of chronic disease (ACD)
1) iron is not being released by recycling macrophages for use by the bone marrow
2) RBC life span is reduced
3) marrow shows a lack of response to EPO
Defects in haemoglobin synthesis can also cause anaemia. What anaemia involves
a) a functional lack of iron
b) lack of folate (B12)
c) mutations in proteins encoding the globin chains
a) anaemia of chronic disease
b) megaloblastic anaemia
c) thalassaemia/sickle cell disease
How can defects in RBC membranes cause anaemia (haemolytic anaemias - reduced RBC lifespan)?
The cells are more flexible and are damaged more easily -> they break up in the circulation and are then removed by the RES in the spleen
Give a hereditary and an acquire cause of damage to RBC membrane structure
Hereditary - hereditary spherocytosis/eliptocytosis/pyropoikilocytosis
Acquired - heart valves/DIC/burns/vascular is
Also anaemia can be the result of defects in the enzymes of RBC metabolism. Give an example
Glucose-6-phosphate dehydrogenase
Pyruvate kinase deficiency
In haemolytic anaemias RBC’s are destroyed more quickly than they are absorbed because they are damaged or defective. What disease do cells in the RES recognise autoantibodies on the bodies RBC membranes?
Autoimmune haemolytic anaemia
In anaemia a reticulocytosis suggests what is working adequately?
The bone marrow
If there is a reticulocytosis in an anaemic patient we then must see if there is evidence of haemolysis and then work out the cause of that. If there is not haemolysis, what is the likely cause of the problem?
A bleed
If see a low reticulocytosis count in a potentially anaemic patient, The next step is to evaluate the Mean cell volume - low = microcytic/ normal = normocytic and high = macrocyclic. What are the 5 diseases associated with a microcytic anaemia with a low retic count
Thalasseamia trait Anaemia of chronic disease (though this is normally normocytic) Iron deficiency Lead poisoning Sideroblastic anaemia
TAILS mnemonic
Give an example of some of the important diseases associated with
a) macrocytic anaemia with low retic count
b) normocytic anemia with low retic count
a) vitamin b12 deficiency/ folate deficiency/alcoholism/myelodysplasia
b) anaemia of chronic disease/HIV/aplastic anaemia
Vitamin B12 and/or folate deficiency cause a deficiency in the building blocks for DNA, what kind of anaemia does this cause and what class of anaemia would this be?
Megaloblastic anaemia - macrocytic anaemia
What are deficiencies in iron/b12 or folate called?
Haematinic deficiencies
What does B12 bind in the small intestine that is necessary for its absorption in the terminal ileum?
Intrinsic factor
List two causes of low vitamin B12 (B12 is rich in animal products)
Dietary deficiency - commonly vegans or poor diet
pernicious anaemia - Lack of intrinsic factor
Ileum diseases e.g. crohns disease
Congenital deficiency of transcobalamin
Give two example of how a patient would get a folate deficiency
Poor diet (leafy greens are a good source of folate)
Pregnancy/haemolytic anaemia (increased use of folate)
Crohns
Why are vb12 and folate dependent on one another?
Folate requires b12 to be in its active form
Megaloblastic anaemia is characterised by macrocytic red cells with abnormally large nuclei and open chromatin. Explain the pathogenesis behind this
B12 and folate are necessary for thymine production this a deficiency cause a thymine deficiency. Uracil is incorporated instead, detected as error and DNA destroyed -> normal cytoplasm, no loss of nucleus and large nucleus forms
Name three features on a megaloblastic anaemic blood film
Macrocytic RBC’s
Anisopoikilocytosis with tear drops
Hypersegmented neutrophils
Can see white cell precursors
Eventually causes a pancytopenia
What would we see clinically in a FBC of a megaloblastic anaemic patient?
Low Hb High MCV (macrocytic) High bilirubin and LDH (both increased in increased cell destruction) Low B12/folate Blood film has megaloblastic features
What is the treatment for
a) folate deficiency
b) b12 deficiency
What
A) oral folic acid
B) Intramuscular b12 in pernicious anaemia (autoantibodies)
Patients with vitamin b12 deficiency get it over a long time cos we have big stores of it. Thus transfusion of b12 in those patients we need to be careful of why?
Cos it can cause cardiac failures
what triggers the release of eryhtropoietin?
Reduced pO2 detected at the kidney -> release of EPO -> stimulates the bone marrow to increase production of RBC’s -> more oxygen delivered -> feedback loop turns off EPO.
When might we see tear drop RBC’s?
Vitamin B12/folate deficiency or myelofibrosis (fibrotic marrow)
Vitamin B12 is required for folic acid to be converted to its active form in the body. Vitamin B12 binds haptocorrin in the salivary glands. This complex then travels to the terminal ileum where it binds intrinsic factor -> haptocorrin released. Complex internalised T/F
`T
Be able to recognise a megaloblastic anaemia on a blood film. B12 and folate deficienct cause a defect in DNA development. The red cells have very large nucleia and open chromatin, is this a microcytic, normocytic or macrocytic anaemia? What other features might we see on a megaloblastic anaemia blood iflm
Macrocytic
tear drop cells/hypersegmented neutrophils/presence of white cell precursors/
What are some problems with a) long term untreated b12 deficiency b) long term untreated B12/folate deficiency
c) folate deficiency in pregnancy
a) demyelination
b) neurological disease
c) neural tube defects
