Flashcards in Anaemia Deck (53):
Describe the structure of haemoglobin
tetramer made up of 2 alpha globin chains and 2 beta globin chains
one haem group attached to each globin chain
What are the 3 major forms of haemoglobin and their prevalence in adults?
HbA (two alpha chains and two beta chains) - 97%
HbA2 (2 alpha and two delta chains) - 2.5%
HbF (2 alpha and 2 gamma chains) - 0.5%
Which genes are responsible for control of globin chain production?
alpha like genes on chromosome 16
beta like genes on chromosome 11
When do babies achieve adult levels of HbA?
between 6-12 months of age
What are the bone marrow responses to haemolysis?
reticulocytosis and erythroid hyperplasia
Do reticulocytes have a nucleus? Do they pick up stain?
No (but does contain some RNA fragments causing some staining - polychromasia)
What causes increased reticulocyte production?
haemolysis, response to bleeding, response to iron therapy in iron deficient anaemia
What are the two types of haemolysis? Which is commoner?
extravascular (much commoner) and intravascular
What is haemolysis?
premature red cell destruction i.e. shortened red cell survival
What are the signs of intravascular haemolysis?
1. haemoglobinaemia - free Hb in circulation
3. haemoglobinuria (FREE Hb in the urine) - pink urine, turns black on standing,
4. haemosidrinuria - this can only be caused by intravascular haemolysis
What are the causes of intravascular haemolysis?
ABO incompatible blood transfusion
severe falciparum malaria (Blackwater Fever - called this because urine turns black)
rarer - PCH, PNH
all other causes of haemolysis cause extravascular haemolysis
What investigations can you do to confirm haemolytic state?
FBC (and blood film)
serum unconjugated biliruben
How is haemolysis classified by site of red cell defect?
1. Normal red cells, premature destruction (immune or mechanical)
2. abnormal red cell membrane
3. abnormal red cell metabolism
4. abnormal haemoglobin (e.g. sickle cell disease)
What are the two types of immune mediated haemolysis?
autoimmune and alloimmune
Describe the characterstics of Zeive's syndrome
Haemolysis, alcoholic liver disease, hyperlipidaemia
anaemia, polychromatic macrocytes, irregularly contracted cells
What is the commonest type of red cell membrane disorder resulting in haemolysis?
What is the commonest red cell metabolism defect?
G6PD enzyme deficiency - causes failure to produce antioxidants in RBCs and failure to cope with oxidant stress
Is intravascular or extravascular haemolysis more associated with chronic haemolytic states?
What are the bony consequences of beta thalassaemia major?
bony deformities of chronic erythroid hyperplasia and bone marrow cavity expansion (which also results in thinned cortical bone)
What are Heinz bodies?
red cell inclusions comprised of denatured Hb normally removed by the spleen (seen in G6PD)
How much iron do we absorb from our guts each day?
What is the normal red cell life span?
What protein transports iron from gut lumen into duodenal lining enterocytes?
What protein transports iron from enterocytes into bloodstream, passing the iron onto transferrin?
What protein limits iron absorption and how does it work?
Hepcidin - binds to ferroportin so prevents iron transport from enterocytes into bloodstream (rather than preventing absorption from the gut lumen into the enterocytes)
Name a nail change seen in iron deficiency
koilonychia (spooning of nail)
What are the commonest causes of hypochromic microcytic anaemia?
iron deficiency (causing haem deficiency) - most common
anaemia of chronic disease (have normal body iron but it is all stored rather than being used)
What are the causes of iron deficiency?
insufficient dietary intake to meet physiological need
- particularly children (growing) and women (menstruation and especially pregnancy as iron needs go up quite a bit)
losing too much - bleeding
not absorbing enough - malabsorption (rarer cause)
What are the causes of chronic blood loss?
GI (tumours, ulcers, NSAIDs, parasitic infection)
Explain how occult GI blood loss can cause iron deficient anaemia
GI bleeds of 8-10ml per day cause a loss of 4-5mg of iron per day and are usually symptomless
the maximum iron absorption per day is 4-5mg
if losing slightly more than this, can become iron deficieny
What are the features of hereditary haemochromatosis?
gradual onset iron overload of >5g
results in tissue damage
presents usually in middle age or older
- joint pains
What is the commonest genetic mutation that causes hereditary haemochromatosis?
Mutations of HFE gene (incomplete penetrance)
How is hereditary haemochromatosis diagnosed?
Risk of iron loading: >50% saturation of transferrin
Iron load: serum ferritin >300 micrograms/L in men; >200 micrograms for pre-menopausal women
liver biopsy - only if uncertain about iron load or to assess tissue damage
What is the treatment for hereditary haemochromatosis?
-450-500ml (200-250 mg iron)
- initially aiming to exhaust iron stores to
What is the result of regular red cell transfusions for anaemia, and how can it be treated?
venesection is not really an option as patients are already anaemic
so iron chelating agents are used e.g. desferrioxamine (IV or subcut), deferiprone oral
What are the consequences of vitamin B12 or folate deficiency
Macrocytic anaemia (reduced red cell mass, and abnormally large cells)
hypersegmented neutrophils - more than 6 lobes to to nucleus (+ neutropenia if severe enough)
reduced platelet production --> thrombocytopenia
Where is vitamin B12 absorbed?
What protein is essential for vitamin B12 absorption?
Intrinsic factor (IF)
Where is intrinsic factor produced?
gastric parietal cells
What can cause vitmamin B12 deficiency?
reduced intake e.g. poor diet (rare since body has large stores)
impaired absorption e.g. gastrectomy (no intrinsic factor produced), Crohn's disease ( affects area of absorption esp associated with terminal ileitis), ileal resection (lost area of absorption), pernicious anaemia (intrinsic factor destroyed)
Bacterial overgrowth - overuse of B12 by bacteria in the gut
What is cobalamin?
What are the causes of microcytic anaemia?
IRON DEFICIENCY, thalassaemia, anaemia of chronic disease, lead poisoning, pyridoxine responsive anaemias, sideroblastic anaemia
What are the causes of macrocytic anaemia?
Myelodysplasia, myleoma, aplastic anaemia, reticulocytosis, cold agglutinins, (macrocytosis often without anaemia: alcohol liver disease, hypothyroidism)
What are the causes of normochromic normocytic anaemia?
acute blood loss, early iron deficiency (might be in normal range of MCV but it might be low for them - if can compare to previous result, a drop in 10 fl would suggest microcytic even if in normal range)
hypoproliferative (low retic count):
- chronic inflammatory, infective, malignant disorders
- renal failure
- hypo-metabolic states (e.g. hypothyroidism)
- marrow failure (aplastia or infiltration)
Where is myoglobin on the oxygen dissociation curve compared to haemoglobin and what does this mean?
It is shifted to the left so it has a higher affinity for oxygen (holds onto oxygen at lower saturations, less good at giving it up to the tissues)
If the oxygen delivery curve shifts to the right, what does this mean for oxygen delivery to tissues?
Hb will give up oxygen to the tissues more readily at greater O2 sats - this is protective in chronic anaemia is there is less Hb so need to give more oxygen to tissues per molecule
What can shift the oxygen dissociation curve to the right?
Increased temperature, increased 2,3-DPG, Reduced pH (more acidic)
Explain the importance of glutathione and the consequence of a lack of it
glutathione helps protect against the toxic effects of reactive oxygen species (free radicals)
reduced glutathione is essential to detoxify hydrogen peroxide, the primary intermediate in oxidative damage
NADPH from the pentose phosphate pathway is needed to produce reduced glutathione
In RBCs, a lack of reduced glutathione (e.g. due to G6PD insufficiency resulting in NADPH deficiency) can lead to cell damage. This could result in haemolysis.
A 58 year old lady with a family history of hypothyroidism and atrophic gastritis presents with fatigue, macrocytosis and pancytopenia. What is the most likely diagnosis?
Explain the blood results.
B12 deficiency impairs DNA synthesis so can affect replication of all cell lineage, thus can result in a pancytopenia (not just a macrocytic anaemia)
A 25 year old male has recurrent admissions to hospitals with pain in his legs and chest wall. On one occasion, he became extremely breathless and required a red cell exchange transfusion. What is the most likely diagnosis?
Sickle cell anaemia
How is a vaso-occlusive sickle cell crisis in the pulmonary vasculature treated?
Prompt exchange transfusion
Where is folate absorbed?
What can impair its absorption?
- Bacterial overgrowth, small bowel disease (e.g. coeliac, Crohn's)