Anaemia Flashcards
What could cause reduced erythopoiesis?
Chronic kidney disease, empty bone marrow, parvovirus infection, marrow infiltrated by cancer cells
What is dyserythropoiesis?
Defective development of erythocytes
What conditions is anaemia of chronic disease often seen in?
Inflammatory conditions eg rheumatoid arthritis, lupus, IBS
TB, bronchiectasis
What are some features of anaemia of chronic disease?
Iron stored in macrophages is not released for use in bone marrow
Circulating red cells have reduced lifespan
Marrow lacks response to erythropoietin
Anaemia may be microcytic, normocytic or macrocytic
What is a clinical clue that it may be anaemia of chronic disease?
Often raised CRP and ferritin
What causes myelodysplastic syndromes?
Production of abdnormal clones of marrow stem cells
What is often detected in myelodysplastic syndromes?
Genetic change by looking at chromosomes in marrow cells
What happens to the red cells in myelodysplastic syndromes?
Red cells are defective and large so are prematurely destroyed
What usually develops as a result of myelodysplastic syndromes?
Acute leukaemia
What could cause haemoglobin abnormalities?
Lack of iron, deficiency in building blocks for DNA synthesis (eg vit B12, folate) and mutations in the genes that encode the globin protein
What is megaloblastic anaemia?
Macrocytic anaemia that results from inhibition of DNA synthesis during red blood cell production
How is anaemia defined?
Anaemia is defined as a haemoglobin concentration lower than the normal range.
Why can anaemia develop?
1) Abnormal erythorpoiesis
2) Abnormal haemoglobin synthesis
3) Abnormal function, structure or metabolism
4) Abnormal function of the RES
5) Excessive blood loss
What is pancytopenia?
Lack of red cells, white cells and platelets
What is aplastic anaemia?
Deficiency of all types of blood cell caused by failure of bone marrow development
What is thalassemia?
Results from decreased or lack of alpha or beta chain production, causing an imbalance in the composition of the a2b2 tetramer.
What does deficiency of Vit B12 and folate lead to?
Megaloblastic anaemia due to an inability of red cell precursor cells to synthesise DNA and therefore divide. Since nuclear maturation and cell division lag behind cytoplasm development, large (“mega”) partially replicated red cell precursors are released into the bloodstream with inappropriately, large nuclei and open chromatin.
What is folate converted to once absorbed?
Tetrahydrofolate (by intestinal cells before entering the portal circulation and much of this is taken up by the liver which acts a store)
What is the role of tetrahydrofolate in metabolism?
To act as a one-carbon carrier, accepting carbon units from sources such as serine, glycine, histidine and formate
What is the collection of the various one carbon
forms of tetrahydrofolate referred to as?
One carbon pool
What do recipient reactions of carbon from the one carbon pool include?
Synthesis of the base thymidine required for DNA synthesis, synthesis of the purine bases adenine and guanine required for both DNA and RNA synthesis and transfer of methyl groups to vitamin B12
What can folate deficiency lead to in pregnancy?
Neural tube defects in the fetus
True or False:
Vitamin B12 can only be obtained from food of animal origin
True
What two metabolic reactions is vitamin B12 responsible for?
It transfers a methyl group from L-methylmalonyl-CoA to form SuccinylCoA and is also required for the transfer of a methyl group from tetrahydrofolate to homocysteine to form methionine
What can lead to functional folate deficiency?
Vit B12 deficiency as it required from the transfer of a methyl group from tetrahydrofolate to homocysteine - if this doesn’t happen, folate is essentially ‘trapped’ in the methyl-FH4 state so cannot take part in other reactions
What is produced by parietal cells in the stomach that binds to B12?
Intrinsic factor
What is B12 bound to in the portal blood?
Transcoalamin - delivers B12 to bone marrow and other tissues
What could B12 deficiency result from?
Dietary deficiency, lack of intrinsic factor, disease of terminal ileum (eg crohn’s), congenital deficiency is transcobalamin
What compound are dietary folates all converted to?
Methyltetrahydrofolate
Why can folate deficiency occur?
Dietary deficiency, proximal small bowel disease (eg coeliacs), alcoholism, drugs which inhibit dihydrofolate reductase enzyme
What is the mutation that causes sickle cell disease?
Point mutation - substitution of valine for glutamic acid in position 6 in the beta chain
What is hereditary spherocytosis?
Autosomal dominant abnormality of erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape
What is haemolytic anaemia?
Increased red cell destruction
What are some key laboratory features of autoimmune haemolytic anaemia?
Increased reticulocytes (as marrow tries to compensate)
Raised bilirubin (breakdown of haem)
LDH (red cells rich in this enzyme)
What is myelofibrosis?
Myelofibrosis is a serious bone marrow disorder that disrupts your body’s normal production of blood cells
How can anaemia be classified?
Mechanism, size, presence or absence of reticulocytes
When is there often a high reticulocyte count?
When there is an increased production of red blood cells to overcome chronic or severe loss of mature red blood cells, such as in a haemolytic anemia, there is often a markedly high number and percentage of reticulocytes
What is essential thrombocytosis?
A rare chronic blood disorder characterised by the overproduction of platelets by megakaryocytes in the bone marrow
What is polycythaemia vera?
A neoplasm in which the bone marrow makes too many red blood cells.
What is the diagnostic criteria of polycythaemia vera?
High haematocrit or raised red cell mass
How is polycythaemia vera managed?
Venesection, aspirin, manage cvs risk factors
How does the body adapt to anaemia?
Epo stimulation, increase cardiac output, make more Hb, increase BPG in tissues
What effect might gaviscon have on abdorption of an iron supplement?
Reduces iron absorption as acidic pH increases iron absorption
What would low Hb and normal reticulocytes suggest?
Problem with bone marrow
What is sideroblastic anaemia?
A form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells
What are patients with G6PD deficiency at risk of?
Haemolytic anaemia
What should you ask the lab to screen for before starting your patient on drugs with a known risk of haemolysis?
G6PDH deficiency
How can pyruvate kinase deficiency cause haemolytic anaemia?
Pyruvate kinase catalyses final step of glycolysis
Blocks the RBCs only metabolic mathway which can supply ATP for cellular processes
Sodium pump stops working, water moves out of cells causing them to shrink
True or False:
Bite cells or blister cells are classically seen on the blood film if patients are Vitamin B12 deficient.
FALSE.
These abnormal red cells are seen classically in
patients with G6PD deficiency
What are some causes of microcytic anaemia?
Iron deficiency anaemia, thalassaemia, congenital sideroblastic anaemia, anaemia of chronic disease (although this could also be normocytic or macrocytic)
What are the megaloblastic causes of macrocytic anaemia?
Folate and vitamin B12 deficiency
What are some normoblastic causes of macrocytic anaemia?
Alcohol, liver disease, hypothyroidism, pregnancy
What are some causes of normocytic anaemia?
Anaemia of chronic disease, chronic kidney disease, aplastic anaemia, haemolytic anaemia
What is reticulocytosis?
Reticulocytosis is a condition where there is an increase in reticulocytes, immature red blood cells.
What is chronic lymphocytic leukaemia?
Caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
What conditions are associated with the appearance of target cells?
Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease
What conditions are associated with the appearance of heinz bodies?
G6PD deficiency
Alpha-thalassaemia
