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138 Cards in this Set
- Front
- Back
which hormone stimulates the maturation of red blood cells?
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erythropoietin
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what is the lifespan of a RBC?
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120 days
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how is increased production of RBCs by the marrow achieved?
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expansion of the volume of red marrow and by shortening of transit time for red cell maturation
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with acute blood loss, what effect is there on platelets and WBCs?
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there may be a reactive thrombocytosis and leukocytosis
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what deficiency is the result of chronic blood loss?
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iron
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what are the last cells capable of division in the erythroid line?
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polychromatophilic erythroblasts
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what are the last cells of the erythroid line that can synthesise haemoglobin?
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reticulocytes
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what shape are erythrocytes?
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biconcave discs
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t/f... erythrocytes do not have organelles
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true
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which cells are the last in the erythroid line to have a nucleus?
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normoblasts
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where does haemopoiesis take place in the foetus?
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in the liver and spleen up to 7 months gestation and in the bone marrow after that
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what does the haemopoietic stem cell look like?
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small to intermediate sized lymphocyte
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t/f... commitment to a cell lineage is reversible
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true, but only under very specific circumstances with the correct factors (and only very recently)
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what is the source of erythropoietin?
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kidney
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what metals are required for normal haemopoiesis?
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iron, manganese, cobalt
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which vitamins are required for normal haemopoiesis?
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B12, folic acid, C, E, B6, thiamine, riboflavin, pantothenic acid
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what is the most common cause of anaemia?
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iron deficiency
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what is the laboratory hallmark of iron deficiency?
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microcytosis
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what is the definition of microcytosis?
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mean corpuscular volume less than 80 femtolitres
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what is the best measurement of overall iron stored in the body?
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serum ferritin
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which deficiencies result in megaloblastosis?
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vitamin B12 and folate
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hypersegmented neutrophils are a feature of which type of anaemia?
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megaloblastic anaemia
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what is the most common cause of macrocytosis?
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excess alcohol consumption
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which deficiency can cause profound neurological damage?
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Vitamin B12
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what is Vit B12 deficiency most commonly caused by?
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poor absorption from the bowel (often associated with pernicious anaemia)
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which cells are destroyed by antibodies in pernicious anaemia?
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gastric cells
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what substance is secreted by gastric cells?
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intrinsic factor
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name two non-immune causes of Vit B12 deficiency
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surgical removal of stomach or terminal ileum, poor diet lacking in animal products, proton pump inhibitor drugs
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where does folic acid absorption occur?
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jejunum
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which deficiency affects the peripheral nervous system only?
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folate
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Which two haematological conditions are associated with reduced haemoglobin concentration of the erythrocytes and are characterised by microcytic hypochromic erythrocytes?
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Iron deficiency and thalassaemia
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What is the best screening test for iron deficiency?
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serum ferritin
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What increases the secretion of erythropoietin?
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Fall in arterial oxygen tension, sensed by peritubular renal cells
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What is the term for the shortening of the lifespan on RBCs?
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haemolysis
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Which two conditions result in rapid falls in haemoglobin concentration?
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haemolysis and blood loss anaemia
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What are the clinical features of haemolysis?
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scleral jaundice, splenomegaly, increased reticulocytes, elevated LDH, asbence of serum haptoglobin, haemosiderin in urine
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What are some causes of haemolytic anaemia?
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hereditary spherocytosis, G-6-PDH deficiency, sickle cell anaemia, thalassaemia, immune disorders
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Where is haptoglobin produced?
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liver
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How does B12 deficiency result in neurological deficits?
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Causes Subacute Combined Degeneration of the Spinal Cord - B12 is made for fatty acid synthesis, and in deficiency fatty deposits are laid down very patchily within the myelin (demyelination) and APs are slowed
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Which two pathways in the white matter of the spinal cord are affected by B12 deficiency?
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the dorsal columns and the lateral corticospinal tract
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t/f... subacute combined degeneration of the spinal cord affects the transmission of pain information in the spinal cord
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false, pain travels in the lateral spinothalamic pathways which are not involved in subacute combined degeneration
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what is the prevalence of undernutrition in community living?
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5-12%
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what is anaemia?
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reduction in red cell number, haemoglobin or haematocrit
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why does haemoglobin reduce in pregnancy?
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haemodilution - increase in plasma volume is greater than increase in rbc
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what is the normal range for % reticulocytes in a blood film?
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0.5% - 1.5%
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what fraction of a red blood cell is normally central pallor?
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1/3
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t/f... reticulocytes contains some RNA
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true
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what is required for haemoglobin synthesis?
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haem synthesis, globin synthesis, iron
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what is required for red cell production?
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erythropoietin, vit B12, folic acid, metals
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where is erythropoietin produced?
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kidney (and to a lesser extent the liver)
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what effect does hypoxia have on the production of EPO?
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production is increased by hypoxia (related to HIF)
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what are the haematinics?
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iron, B12, folate
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what happens to senescent RBCs?
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removed to the spleen by macrophages
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what percentage of RBCs need to be replaced daily to maintain steady state?
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1%
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t/f... cardiac output increases in response to anaemia
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true
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list the symptoms of anaemia
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tiredness, headaches, dizziness, SOB, palpitations, angina (with pre-existing heart disease)
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what are the signs of anaemia?
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pallor (conjunctival, palmar crease), cardiac decompensation (tachycardia, postural hypotension, CCF)
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what effect does anaemia have on viscosity of blood?
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anaemia reduces viscosity of blood
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what is the effect of reduced O2 delivery to tissues on blood vessels?
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dilatation (except at lungs)
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which deficiency leads to both peripheral and central neurological signs?
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B12
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will deficiency of the haematinics be associated with a low or high reticulocyte count?
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low
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will haemolysis be associated with a low or high reticulocyte count?
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high
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list some causes of haemolysis
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immune attack on red cells (autoimmune, drugs e.g. methyldopa, alloimmune e.g. incompatible red cell transfusion, Rh disease), abnormal red cell membrane (HS), abnormal red cell metabolism (G6PDH deficiency), mechanical (malfunctioning prosthetic heart valve, DIC, malignancy)
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list 3 causes of macrocytic normochromic anaemia
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B12 deficiency, folate deficiency, myelodysplasia, alcohol consumption
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what is the appearance of the rbc on a blood film from a patien with anaemia from marrow suppression/aplasia?
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normocytic, normochromic
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what type of anaemia do defects in Hb synthesis cause?
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microcytic hypochromic
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what is the normal size of a RBC compared to a lymphocyte?
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RBC should be size of lymphocyte nucleus
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What do target cells indicate?
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hypochromia - excess membrane relative to haemoglobin (found in thalassaemia, asplenia, liver disease, severe iron deficiency)
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How many lobes does a hypersegmented neutrophil have?
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>5
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What do oval macrocytes indicate?
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B12 or folate deficiency (megaloblastic anaemia)
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When does rouleaux occur?
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increased plasma proteins usually from inflammation e.g. myeloma
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which leakaemia is associated with Auer rods?
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AML
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t/f... most people with anaemia receive a transfusion
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false, the only indication for transfusion is tissue hypoxia (severe anaemia)
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what is the commonest form of anaemia?
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iron deficiency
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what are the two stores of iron in the body?
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ferritin, haemosiderin
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t/f... there is no effective excretion mechanism for iron
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true
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how is iron balance controlled?
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iron absorption
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what regulates iron absorption?
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mucosal cells of proximal small intestine
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what are the two pathways for dietary iron absorption?
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iron attached to haem, iron in ferrous form
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t/f... haem/ferrous iron absorption is enhanced by ascorbate and meat and inhibited by phytates, bovine milk, tea and coffee
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false, this is true for non-haem/ferric iron absorption as it is insoluble (haem iron absorption is unaffected by composition of diet)
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what assists solubilisation, mucin binding and reduction of ferric iron to the ferrous form?
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acid (e.g. gastric juice, ascorbic acid)
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What enzyme reduces ferric iron to ferrous form?
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Dcytb (duodenal cytochrome b1)
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What is the role of DMT1 (divalent metal transporter) in dietary iron absorption?
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apical uptake at duodenum
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What transfers iron into the plasma from the enterocyte?
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ferroportin (transfer is facilitated by hephaestin)
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What is hepcidin?
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peptide hormone secreted by liver
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what is the function of hepcidin?
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decreases functional activity of ferroportin, reducing Fe leaving a cell
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how does intestinal absorption of Fe relate to liver hepcidin expression?
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absorption varies inversely with expression
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what is the sole physiologic means of iron transport?
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transferrin
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what is the average daily loss of iron in men and non-menstruating women?
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1 mg/day
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what is the average daily iron loss in menstruating women?
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2 mg/day
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how much iron do pregnant women lose every day?
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3.5 mg/day
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what is the most important lab marker of iron deficiency?
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serum ferritin
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what effect does iron deficiency have on serum transferrin?
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raised
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what percentage of oxygen in the blood is dissolved?
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1.5%
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list 4 factors that will decrease oxygen affinity for Hb
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increased PCO2
acidosis increased temp increased 2,3-DPG |
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t/f... reduced affinity of oxygen for Hb is equivalent to a shift to the left of the O2-Hb curve
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false, it is a shift to the right
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what is the Bohr effect?
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oxygen carrying capacity of Hb at a particular PO2 is decreased by increased PCO2
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what is the affinity of CO for Hb compared to oxygen?
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200 times
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what type of anaemia occurs in thyroid disease?
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macrocytic
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what volumes define microcytic, normocytic and macrocytic?
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microcytic: <80 fl
normocytic: 80-99 fl macrocytic: >99 fl |
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what type of anaemia occurs with impaired DNA synthesis?
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megaloblastic (vit B12 or folate deficiency)
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list some blood film changes in megaloblastic anaemia
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oval macrocytes, aniso/poikilocytosis, hypersegmented neutrophils, may have low WCC and low platelets
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how long do body stores of vitamin B12 last?
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3-4 years
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what is vitamin B12 bound to in the plasma?
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transcobalamin (TC II)
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where is vitamin B12 absorbed?
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terminal ileum
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what secretes intrinsic factor?
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gastric parietal cells
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What does B12 bind to in the stomach to travel to the terminal iluem for absorption?
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intrinsic factor
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Which columns of the spinal cord are affected in B12 deficiency?
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posterior and lateral
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Which peripheral fibres are affected in B12 deficiency?
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peripheral sensory nerves
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t/f... inadequate intake is a common cause of vitamin B12 deficiency
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false, it is a very rare cause (only in true vegans)
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What is the most common cause of vitamin B12 deficiency?
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malabsoption due to inadequate intrinsic factor or disorders of terminal ileum
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What is pernicious anaemia?
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severe lack of intrinsic factor due to autoimmune disease affecting gastric parietal cells
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Is pernicious anaemia more common in men or women?
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women (M:F 1:1.6)
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Which antibody is highly specific for pernicious anaemia?
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anti-intrinsic factor (found in 95% patients)
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How long do the body stores of folate last?
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3-4 months
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Where is the body's store of folate?
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liver
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Where is folic acid absorbed?
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proximal jejunum
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t/f... folic acid is absorbed via specific receptors
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false, folic acid is absorbed via concentration dependent diffusion (B12 is absorbed via specific receptors)
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When is there an increased need for folic acid?
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pregnancy, prematurity, haemolysis, malignancy (anything causing increased cellular proliferation)
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Which disease causes malabsorption of folate?
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Coeliac disease
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Name some antifolate drugs.
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methotrexate, anticonvulsant, trimethoprim, alcohol
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Which measure of folate tests body stores not just recent intake?
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red cell folate
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Name three situations in which serum folate will be raised.
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severe vitamin B12 deficiency
folic acid therapy (methotrexate) sample haemolysed |
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When might red cell folate be falsely normal?
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blood transfusion
increased reticulocytes |
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When will the peak reticulocyte response be observed after starting therapy for megaloblastic anaemia?
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6-7 days
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How long will it take after beginning treatment for megaloblastic anaemia for the bone marrow to be normoblastic?
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48 hours
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At what rate will the Hb rise after commencing treatment for megaloblastic anaemia?
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Hb should rise by 10g/L per week
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t/f... B12 deficiency will cause a deficiency in homocysteine
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false, it causes a rise
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What is used to treat Methaemoglobin?
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When Haem has Fe3+/ferric iron (e.g. from high oxidants in broadbeans, drugs etc), it is reduced to the Fe2+/ferrous iron by IV methylene blue.
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t/f... folate should always be given before B12 in deficiencies where both are to be given
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false, if folate is given first, B12 supplies can be converted into methylcoalbumin, and won't be able to take place in fatty acid metabolism, facilitating subacute degeneration of the spinal cord
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Describe haematopoiesis and where it takes place.
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The formation of cells for the blood, these include lymphoid cells (T, B, NK cells) and myeloid cells (granulocytes, monocytes, megakaryocytes, erythrocytes).
It begins in the yolk sac, then migrates to the liver and spleen, then the bone marrow during gestation. As an adult, in times of severely increased demand, haematopoietic centres can be re-established in the liver, spleen and lymph nodes. |
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What ability is missing in the division of neoplastic haematopoietic cells?
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Neoplastic haematopoietic cells are able to self renew but are unable to differentiate into further cell types.
Coaxing cells into differentiation can be a form of treatment for some cancer types e.g retinoic acid in APML. |
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What is erythropoietin, what does it act on, where is it made, and when is it released?
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Erythropoietin (EPO) is a cytokine responsible for maturation of all red cells by inhibiting apoptosis. It also inhibits hepcidin, and so enhances Iron absorption.
EPO binds to EPO to elicit its actions. EPO-R are not present in the earliest RC progenitors, but are in subsequent nucleated progenitors after and are last seen in erythroblasts. It is made by peritubular cells in the kidney (and cells in the liver to a smaller extent) in response to low O2. |
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What myelolid cell lineage do the following factors cause to clonally expand?
1) ILF 2) GM-CSF 3) G-CSF 4) M-CSF 5) EPO 6) TPO |
1) All myloid lineage cells in early stages
2) Neutrophils, macrophages, eosinophils 3) Neutrophils alone 4) Macrophages alone 5) Erythrocytes alone 6) Megakaryocytes alone |
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Name 3 important factors needed for haematopoiesis.
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Iron, Magnesium, cobalt
B1 (thiamine), B2 (riboflavin), B5 (pantothenic acid), B6 (PLP), B9 (folic acid), B12 (cobalamin), C, E Amino acids Hormones Cytokines - ILFs, CSFs Stromal cells MicroRNAs (downregulate gene transcription) |
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Describe how most bone marrow replacements are done currently (2012)?
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Peripheral blood bone progenitor collection - cells are coaxed out using niche factors usually secreted by stromal bone marrow cells (CSFs, IL4). Blood is then collected and put through leukophoresis to siphon out WBC. These can be stored on elastic beds (physically similar to bone marrow) while the patient is irradiated, then over 28 days given progenitor cell transfusions.
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Describe the structure of haemoglobin?
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4 polypeptide globin chains, each around a central haem bound to a Fe2+ (Fe3+ = methaemoglobin and is inefficient). The haem group is non-protein, and is known as a porphyrin.
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What tests/investigations can you use to detect the presence of a haemolytic anaemia?
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Low levels of free haptoglobin (usually binds to free haemoglobin in plasma).
High LDH (used in RC glycolysis, realeased when they lyse) High bilirubin (what haem breaks down into) Increased reticulocytes (to keep up with increased demand) Haemosiderin in urine. Heinz bodies from denatured Hb in oxidative stress. |