Anaemia Flashcards
Define anaemia (1½-3) (Super NB)
A decrease in the circulating haemoglobin per unit volume of blood when compared with the correct reference population for that patient (correct age and sex) OR A blood haemoglobin concentration lower than normal for the age and sex of the patient.
List six (6) clinical features that may be present in patients with anaemia (3)
Tiredness, Fainting, Pallor, Tachycardia, Shortness of breath, Weakness, Palpitations, Headaches, Intermittent claudication, Confusion, Bounding pulse
Classify the morphological types of anaemia (3x½). Give three examples (causes) of each type (3x3x½) AND state one laboratory investigation that would assist you to make the diagnosis of the cause of the anaemia (3x3x½) [10½] (Super NB)
Hypochromic (MCHC) Microcytic (MCV) Anaemia
Iron deficiency (acquired) - Iron studies
Thalassaemia (inherited) - Haemoglobin studies
Sideroblastic anaemia - Bone marrow for ring sideroblasts
Anaemia of chronic disease/inflammation (can be normocytic too)
Lead poisoning
Macrocytic (MCV) Anaemia Megaloblastic anaemia o Vit. B12 deficiency - Serum B12 level o Folic acid deficiency - RBC folate level Liver disease - Liver function tests Myelodysplastic Syndrome Drugs e.g. ARVs Hypothyroidism Pregnancy
Normochromic Normocytic Anaemia (Normal MCHC & MCV)
Haemolytic anaemia - Blood film morphology, reticulocyte count, haptoglobin
Anaemia of chronic disease - Iron studies, soluble transferrin receptor
Renal disease - Serum urea and creatine
Bone marrow failure
Anaemia can be classified according to the red blood cell size or mechanism. Name four (4) mechanisms that result in anaemia and list one clinical or laboratory finding that indicates/ suggests each causative mechanism (8)
Failure of bone marrow production: Low reticulocyte
Blood loss: Clinical evidence of blood loss, ed reticulocyte
Increased destruction: Increased retic. count (polychromasia), Haemolytic screen (Morphology)
Pooling or sequestration: Splenomegaly
Five specific signs associated with a particular type of anaemia are listed below. Please indicate for each sign which subtype of anaemia it would suggest (2½)
a) Jaundice
b) Loss of proprioception and vibration sense
c) Koilonychia (spoon nails)
d) Leg ulcers in conjunction with haemolytic anaemia
e) Bone deformities in conjunction with haemolytic anaemia
Jaundice. Haemolytic anaemia
Loss of proprioception and vibration sense. Vit B12 deficiency
Koilonychia (spoon nails). Iron deficiency
Leg ulcers in conjunction with haemolytic anaemia. Sickle cell anaemia
Bone deformities in conjunction with haemolytic anaemia. Beta thalassaemia
Mrs Xaba is a 50-year-old anaemic patient. Placed on iron supplementation and educated about menopause. Six months later, despite continuing with iron supplements, tiredness persists and notices weight loss.
State the type(s) of anaemia suggested by these biochemical findings (2x½ = 1)
Iron deficiency & anaemia of chronic disease.
Briefly explain the change seen in: (4x1 = 4) (CPATH) Transferrin
Ferritin
Soluble Transferrin Receptors
Hepcidin
Transferrin. decreased due to chronic inflammation
Ferritin. increased with inflammation & decereased with iron deficiency,
Soluble transferrin receptors. increased with iron deficiency,
Hepcidin. increased with inflammation
Mrs April is a 90-year-old living with her 80-year-old sister. She is generally frail but on one morning she is particularly pale and short of breath and dizzy. Enlarged heart and a hyperdynamic circulation. Hb is 6g/dL.
If Mrs April has a microcytic, hypochromic anaemia and a positive stool occult blood test, state the important investigation you should refer her for (½) (CPATH)
Colonoscopy
List three (3) additional investigations you may need to perform to determine the aetiology for the above anaemia, seeing as you have already ascertained that she is not a strict vegan (1½) (CPATH)
Plasma anti-parietal, Anti-intrinsic factor Abs, Gastroscopy plus gastric biopsy, Small bowel imaging studies
If Mrs April has a macrocytic anaemia, is a teetotaller and has normal red cell folate levels, state the type of anaemia that must be excluded (½) (CPATH)
Vit B12 deficiency anaemia
Samantha Scott is a 21-year-old anaemic patient. Menses have been heavier than usual for the past few months. She is also a vegan and drinks ten (10) mugs of tea per day. On examination she is pale with a tachycardia of 102 bpm.
From the case history, identify two (2) possible causes for Ms Scott’s anaemia, and for each state the health or lifestyle factor that may have led to this anaemia (2)
Iron deficiency from blood loss due to heavy menses & from excessive tea drinking, Vit B12 deficiency from vegan diet
Explain the possible relevance of excessive tea-drinking in this case (3) (CPATH)
Tea is rich in tannins which bind elemental iron (as opposed to haem iron) in the bowel lumen, preventing its absorption. In a vegan, elemental iron is the only form of dietary iron available, and could be a contributory factor (along with blood loss) to her iron-deficiency anaemia.
Ms Kowa (folate deficient) says her new baby boy has been jaundiced since birth. He is also anaemic and is found to have G6PD-deficiency. Reticulocyte counts performed.
Interpret and explain these results, considering what you know about each patient (3)
Ms Kowa is deficient in folic acid and therefore cannot mount a RCC, so her result is very low. Baby Kowa has a haemolytic anaemia & his bone marrow is trying to compensate for this by releasing increased numbers of reticulocytes, so his result is high.
In what form is iron… & Indicate the total quantity of iron (in mg or g) normally present in each form (2) (CPATH)
a) Carried in plasma
b) Stored in cells
a) Carried in plasma. Bound to transferrin (~3mg)
b) Stored in cells. Within the storage protein ferritin (~1g)
Describe the function of transferrin and name one condition other than IDA in which transferrin is decreased (2) (CPATH)
Transferrin transports iron in circulation – almost all iron is circulation is bound to transferrin
Conditions: Protein loss i.e. protein losing enteropathy or nephrotic syndrome, Liver disease
Transferrin & ferritin are acute phase responders. State in which direction they will change (increase, decrease, no change) in the presence of inflammation (1) (CPATH)
Transferrin - decrease
Ferritin - increase
List four (4) groups of causes of IDA, and state two (2) specific examples for each (½x12 = 6)
Chronic blood loss (bleeding peptic ulcer, heavy menses)(aggravated by NSAIDS), ed demands (pregnancy, premature infants), Malabsorption (gastrectomy), Undernutrition (poverty)
List six (6) biochemical and haematological markers of iron deficiency (3) (CPATH) (Super NB)
Decreased Serum iron, Increased Serum transferrin (or total binding capacity), Decreased% Transferrin saturation, DecreasedSerum ferritin, Decreased Hb
Blood smear features: Hypochromia (decreased MCHC), Microcytosis (decreased MCV), Pencil cells, Occasional target cells, Thrombocytosis
In the presence of inflammation, state which test would be useful in identifying iron deficiency anaemia (½) (CPATH)
Soluble transferrin receptors
Explain why iron deficiency typically gives rise to small red cells (microcytosis) whereas folate deficiency gives rise to larger than normal red cells (macrocytosis) (2) (CPATH)
Fe required to synthesise haemoglobin, the major protein in RBCs (>95%). Insufficient Hb ‘filling’ leads to small red cells. Folate is required for DNA synthesis; thus insufficient folate impairs division of red cell precursors (normoblasts) which continue to grow without dividing, leading to larger than normal mature red cells.
Name an inherited disease that gives rise to a microcytic anaemia, and name two (2) laboratory tests used to distinguish it from iron deficiency anaemia (2) (CPATH)
Thalassaemia (α or β)
Any 2: Serum Fe, total iron binding capacity (TIBC), transferrin, ferritin, relative rates of α or β-globin chain synthesis in reticulocytes or bone marrow cells
The haematological findings below are compatible with both iron deficiency and thalassaemia.
Identify the underlying defect in thalassaemia, and show how serum iron studies can distinguish the two conditions by completing the following table (use ↓↓ (very low), ↓ (low), N (normal), ↑ (high), or ↑↑ (very high) rather than actual numbers) (10) (CPATH)
Deletion of one or more β or α globin genes, hence impaired haemoglobin synthesis.
Mr Bonga Shoba is 54 years old. Very dark stools for several weeks. Been feeling tired when he climbs the stairs to his flat or runs for a taxi. On examination, pale, has mild tachycardia (90/min) and a poorly defined, tender mass in his epigastrium. The initial laboratory results show: Reticulocyte count: 0.1% (N = 0.5-2.5%), Occult Blood test: (+)
State the most likely specific cause of Mr Shoba’s anaemia and its probable underlying cause, giving one (1) clinical and three (3) laboratory features to justify your answers (3)
Cause: Iron deficiency. Underlying cause: GIT blood loss.
Clinical feature: Dark stools. Lab features: Microcytosis, Hypochromia, Positive stool occult blood
Would the level of soluble transferrin receptors be normal, increased or decreased in Mr Shoba’s case (1) (CPATH) [iron deficiency due to blood loss]
Increased
Explain the pathogenesis of beta-thalassaemia briefly and list four (4) smear features of beta-thalassaemia major (3)
Genetic disease/Congenital. Decreasing the production of Beta chains of globin molecule in haemoglobin
Hypochromia, Microcytosis, Target cells, Basophilic stippling, Nucleated red cells
Briefly describe the mechanism of anaemia in beta thalassaemia major (3)
Defective synthesis of beta chains results in an excess of alpha chains. These precipitate in the cell, causing the developing red cell to be destroyed in the bone marrow (intramedullary haemolysis). Those red cells which survive have a decreased amount of Hb compared to normal, hence the hypochromic microcytic picture.
Give two (2) causes of acquired sideroblastic anaemia (2)
MDS, Drugs, Ethanol, Toxins, Nutritional deficiencies
Explain the molecular mechanism for anaemia of chronic disorders (e.g. due to chronic sepsis or auto-immune disease) (4) (CPATH)
The cytokine, interleukin-6 (IL-6), released from the site of inflammation, acts on the liver to increased hepcidin production. Hepcidin blocks iron release from the reticulo-endothelial system which eventually limits iron availability to the bone marrow.
Briefly explain anaemia of chronic disorders and specifically name the hormone that is instrumental in the pathophysiology as well as where this hormone is produced (4)
Hepcidin: liver
Inflammatory reaction/ cytokines released. IL-6 stimulates hepcidin production shutting down iron transport via ferroportin, reducing access of the bone marrow erythroid cells to iron
List the biochemical results that portray an anaemia of chronic disorder (2) (CPATH)
Low serum iron, low transferrin, normal transferrin saturation & high ferritin
Name a laboratory investigation used to confirm… (CPATH) Folate deficiency (1) Vitamin B12 deficiency (1)
Folate deficiency - Red cell folate
Vitamin B12 deficiency - Serum vitamin B12
Name two (2) nutritional causes for a megaloblastic anaemia (1) & Explain why neurological disturbance/degeneration (subacute combined degeneration of the spinal cord) is often present in one but absent in the other (4) (CPATH) (NB)
In folate deficiency, folate is diverted away from DNA synthesis into a form, methyl tetrahydrofolate (methyl-THF), which can sustain methionine recycling required for myelin production. Thus, myelin synthesis is spared at the expense of impaired DNA synthesis and megaloblastic anaemia.
In vitamin B12 deficiency there is insufficient methionine recycling to maintain myelin synthesis (B12 required for methionine synthesis from homocysteine and methyl-THF). Thus, myelin synthesis (hence neurologic function) is impaired PLUS folate is diverted away from DNA synthesis (trapped as metabolically useless methyl-THF), resulting in megaloblastic anaemia and neurological disease.
Outline three (3) peripheral blood features which may suggest a megaloblastic anaemia (3)
High MCV, Decrease in white cell count and platelets, Smear features: Oval macrocytes, teardrops, basophilic stippling, hypersegmented neutrophils
(No case) Give two (2) reasons why megaloblastic anaemia would be the most likely cause in this setting (2)
Poor diet, Growing child with high folate demands. The other causes of macrocytosis (liver disease, pregnancy, hypothyroidism) are unlikely (½)
List three (3) causes of folate deficiency (1½)
Haemolysis, Malabsorption (Crohn’s disease, Jejunal resection), Excess utilisation (pregnancy, lactation, malignant diseases), Drugs (anticonvulsants)
List four (4) groups of causes of deficiency of folic acid, and state two (2) specific examples for each (½x12 = 6)
Nutritional e.g. old age (Ess Haem p49), Malabsorption, Excess Utilisation, Excess urinary loss
Briefly explain why folate deficiency causes anaemia (2)
Folate is essential for the synthesis of DNA. In the absence of folate, DNA synthesis is decreased, and tissues with a rapid cell turnover are affected. The bone marrow is one such tissue (More detailed biochemical explanations regarding the conversion of dUMP to dTMP were also completely acceptable.)
Outline the biochemical basis of the anaemia in folate deficiency (2)
Folate is required for the synthesis of thymidine monophosphate from dexyuridine monophosphate. The latter is required for DNA synthesis.
Outline the reason for raised lactate dehydrogenase (LDH) in folate deficiency (1) (CPATH)
Intramedullary haemolysis due to ineffective erythropoiesis.
Ms Kowa, 25 years old, has been feeling very tired since the birth of her baby one month ago. One day she faints while cooking the supper. Ms Kowa has 3 children. She is breast-feeding the youngest and has two other children, aged 11 months and 2 years. She says she had been feeling tired throughout the pregnancy and had only stopped breast-feeding the 11-month-old when the new baby arrived. She and her partner and children live in an informal settlement outside Paarl. On examination, she is very pale, with a tachycardia (110bpm). Her systems examination reveals no abnormalities. The blood smear shows red cell macrocytosis, with numerous oval macrocytes. Many of the neutrophils have hypersegmented nuclei. Serum LDH 1500 IU/L (100-300 IU/L)
From the laboratory results, identify the morphological type of anaemia present in Ms Kowa (½)
Macrocytic anaemia
State the most likely cause of Ms Kowa’s anaemia (½)
Folate deficiency
Outline three (3) factors that probably led to her anaemia (3)
Poverty/ poor nutrition, 3 pregnancies in 3 years, Breast-feeding
Name two sources of naturally occurring vitamin B12 for humans (1)
Meat, fish, dairy products
Describe the mechanism of vitamin B12 absorption (3)
Dietary Vit B12 combines with Intrinsic Factor (½) synthesized by gastric parietal cells (1). This IF-B12 complex then binds to specific surface receptors in the distal ileum and is absorbed (1½).
List the two (2) essential biochemical functions of vitamin B12 (2) (CPATH)
Methylation - nucleotides/amino acids (methionine production) (methionine synthase)
Catabolism of certain (branched chain) amino acids/fatty acids for introduction into the Kreb cycle (methylmalonyl mutase)
Name and briefly explain the mechanism of two (2) non-dietary causes of vitamin B12 deficiency (3) (CPATH)
Pernicious anaemia due to lack of intrinsic factor secretion by the stomach
Terminal ileal disease where the intrinsic factor-B12 complex is absorbed
Pancreatic insufficiency where undigested ‘R’-factors prevent access of intrinsic factor to B12
Small bowel bacterial overgrowth which utilise dietary B12 before it can be absorbed
Fish tapeworm infestation (Diphyllobothrium latum) by the same mechanism.
List six (6) causes of Vitamin B12 deficiency (3) (½x6)
Congenital metabolic defects
Nutritional: Lack of animal products in diet (meat, dairy)
Malabsorption
o Gastric: Pernicious anaemia (lack of IF), gastrectomy
o Intestinal: Stagnant loop, tropical sprue, resection of ileum, Crohn’s disease
Explain how a vitamin B12 deficiency causes macrocytosis (2) (CPATH)
Lack of vitamin B12 leads to ‘trapping’ of folate as methyl tetrahydrofolate, which is a form unable to support DNA synthesis, and hence cell division, so cells become abnormally large.
Explain the mechanism of the jaundice in anaemia caused by vitamin B12 deficiency (4)
Caused by unconjugated hyperbilirubinaemia. Because of the impaired DNA synthesis, abnormal red cell precursors are formed in the bone marrow, and many are destroyed there (ineffective haemopoiesis). In addition, the mature red cells are abnormal and have a shortened life span (haemolysis). As a result, there is increased breakdown of haemoglobin and production of unconjugated bilirubin.
State which test can be used to confirm the cause of vitamin B12 deficiency and explain the result (2) (CPATH)
Schilling test. A low urinary excretion of orally administered radiolabelled vitamin B12, unchanged by co-administration of intrinsic factor.
State which plasma enzyme would be markedly elevated in the bloodstream of a vitamin B12 deficient patient. How can different forms of this enzyme be distinguished and which form would you expect in such a patient? (2) (CPATH)
LDH. Isoenzyme analysis, specific increase in the fastest moving isoform on electrophoresis (LDH1)
Briefly explain why the reticulocyte count is not raised in response to anaemia due to vitamin B12 deficiency (1)
She is deficient in Vitamin B12 and therefore cannot make red cells.
Explain why it is ill-advised to treat anaemia empirically with iron without first establishing whether iron deficiency is actually present (2) (CPATH)
To prevent iron overload in non-iron deficient disorders e.g. thalassaemia.
Describe the clinical presentation of acute iron poisoning (6)
Early (0.5-2 hrs): Vomiting, haematemesis, abdominal pain, diarrhoea, lethargy, shock, metabolic acidosis & coagulopathy (2)
Quiescent (up to 12 hrs): Deceptive recovery and stabilisation (2)
12-48 hrs: Haematemesis, melaena, perforation, vascular collapse, severe acidosis, hypoglycaemia, cyanosis, pulmonary oedema, convulsions, coma, hepatorenal failure (2)
State the four (4) biochemical parameters used to assess iron status and their direction of change in acute iron toxicity (8x½ = 4) (CPATH)
Iron, Transferrin (normal), Ferritin (normal), ed % transferrin saturation, Soluble transferrin receptors (normal)
Indicate two (2) blood tests that permit one to distinguish acute iron poisoning from chronic iron overload (e.g. haemochromatosis), stating for each test how the results would differ (3) (CPATH)
Ferritin normal in acute poisoning, high in chronic overload. Transferrin normal in acute poisoning, low in chronic overload.
The SCA patient’s father had a brother who died in childhood from SCA. The couple has two other healthy children: a six and a four-year-old boy and girl, respectively.
Draw the genetic pedigree of this family (3)
State the most likely genetic condition found in this family (1)
State the mode of inheritances of this disease
State the most likely genetic condition found in this family (1) Sickle cell disease
State the mode of inheritances of this disease (1) Autosomal recessive
The parents of the affected child are not anaemic. She has four (4) siblings. Outline the possibility of one of the siblings also having SCA. May use a diagram (4)
Each of Mariam’s parents must have heterozygous sickle cell anaemia as they are clinically well. When each parent has a normal gene and an abnormal gene, each child has; a 25% chance of inheriting two normal genes; a 50% chance of inheriting one normal gene and one abnormal gene; and a 25% chance of inheriting two abnormal genes.
List two (2) laboratory tests that may be used to confirm the diagnosis of SCA (2)
Hb electrophoresis & The sickling test or sickle solubility test.
Name x tests that would confirm SCA (3)
Blood smear would confirm sickle cells, Screening test – expose blood to conditions of low ozygen (sodium metabisulphite) and induce sickling, Hb electrophoresis confirms HbSS, with absence of HbA
Outline the molecular defect that is responsible for SCA (2)
SCA is a haemoglobinopathy, caused by the presence of abnormal beta haemoglobin chains. It is a genetic disorder, where the child inherits an abnormal B-globin gene from each parent
The underlying problem in SCA.
Genetic alteration of the beta chain of Hb results in a molecule which polymerises under conditions of low oxygen tension. This causes the cells to “sickle”.
Its effects on the body.
Sickle cells block the small vessels causing ischaemia and painful crises. The sickle cells have a short lifespan, hence the haemolysis.
Outline the most likely cause of (painful) swollen fingers and feet in a child with SCA (2)
Vaso-occlusive crisis (1) owing to blockage of blood vessels (½) by sickled red blood cells in these regions (½)
List 2 clinical features, other than anaemia, associated with SCA (2)
Splenic infarcts resulting in autosplenectomy, Proliferative retinopathy, Osteomyelitis (Salmonella spp)
List four (4) complications of SCA and for each explain the underlying pathological process (6)
Infections
Painful vaso-occlusive crises precipitated by cold/dehydration/ infection/stress
Neurological complications (TIAs and CVAs) due to vaso-occlusion
Pulmonary: Acute chest syndrome and pulmonary hypertension (acute vaso-occlusion and chronic repeated episodes)
Gallstones due to chronic haemolysis
Leg ulcers: vaso-occlusion and infarction
Glomerular injury with proteinuria, papillary necrosis, CRF (kidneys vulnerable to infarction)
Aplastic crises: Parvovirus/ folate deficiency with decreased RBC lifespan
Sequestration syndromes: Respiratory distress [chest syndrome], splenic sequestration - young children (blood pooling in spleen) and later hyposplenism (auto-splenectomy), hypoxia
State two (2) reasons why a child with SCA may be folate deficient (1)
Poor nutrition, Haemolysis
