Anaemia Flashcards
What is anaemia defined as?
Hb two standard deviations below mean for age and sex. Less than 13 g/dL for men over 15, and more than 12 g/dL in women.
What is the normal range for MCV?
80-96 fl
What is microcytic anaemia?
Anaemia associated with low MCV (less than 80)
What is the aetiology of microcytic anaemia? (x5 (x5, x3, x5))
- IRON DEFICIENCY: most common cause; from reduced absorption (small bowel disease, post-gastrectomy), increased demand (growth or pregnancy), reduced intake (vegans), increased loss (GI tract, urogenital tract, menstruation), or hookworm infection. Leading to defect in HAEM SYNTHESIS.
- ANAEMIA OF CHRONIC DISEASE: usually normocytic; occurs in chronic inflammatory or autoimmune disease. Leading to defect in HAEM SYNTHESIS.
- THALASSAEMIA. Leading to defect in GLOBIN synthesis.
- SIDEROBLASTIC ANAEMIA: abnormality of haem synthesis. Can be X-linked recessive or secondary to alcohol, drugs, lead or myelodysplasia (bone marrow dysplasia). Leading to defect in HAEM SYNTHESIS.
- LEAD POISONING: interferes with globin and haem synthesis; in scrap metal or smelting workers.
What is the process of iron metabolism?
Iron is lost through menstrual bleeding, sweating, skin desquamation, and urinary/faecal excretion. The body replenishes iron stores by recycling iron from destroyed/senescent RBCs and regulating dietary intake and absorption. Dietary iron is absorbed mostly in the duodenum and jejunum where it is transported by transferrin and stored in either ferritin or haemosiderin forms.
What is the pathophysiology of iron deficiency anaemia?
Haemoglobin formation and RBC formation are impaired resulting in hypochromic and microcytic RBCs.
What is the pathophysiology of anaemia of chronic disease?
- Inflammation/infection/autoimmune disease cause release in pro-inflammatory cytokines and subsequent changes in intracellular iron metabolism.
- One of these changes is up-regulation of hepcidin synthesis. Hepcidin inhibits iron transport by binding to the iron export channel ferroportin on basal surface of enterocytes. Hepcidin also causes iron-trapping in macrophages, splenic sequestration of iron, and impaired bone marrow responsiveness to erythropoietin.
- Another change is up-regulation of ferritin transcription
- Finally, ACD also reduces RBC lifespan die to increased erythrophagocytosis from raised macrophages
What is the pathophysiology of lead poisoning?
- Lead poisoning is a SLOW process
- It competes with minerals, particularly calcium and zinc, therefore inhibiting many of these processes. Lead is mostly stored in in bones, nervous system and kidneys. Hence, toxicity typically observed in these systems:
- It interferes with calcium-dependent processes in the brain, resulting in deranged neurotransmitter function and Protein kinase C inhibition which may contribute to neurotoxicity
- Potent toxin in proximal renal tubules resulting in Fanconi’s syndrome
- Competing with zinc inhibits several enzymes involved in haem synthesis
- Lead interferes with mitochondrial function in vitro by interfering with calcium uptake
- Also perpetuates hypertension
What is the pathophysiology of sideroblastic anaemia?
It is a form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy RBCs. In sideroblastic anemia, the body has iron available but cannot incorporate it into Hb, which red blood cells need in order to transport oxygen efficiently.
What is the epidemiology of microcytic anaemia: Common?
Most common form of anaemia worldwide.
What are the symptoms of microcytic anaemia? (x5)
Tiredness, dyspnoea, pallor, exacerbation of pre-existing angina or intermittent claudication. Pica in 55% of patients with iron-deficiency anaemia (unusual cravings for non-foods like dirt, ice, paint)
What are the signs of microcytic anaemia? (x5)
- Pallor of skin and mucous membranes
- Brittle nails and hair. Koilonychia if long-standing
- Glossitis
- Cheilitis (angular stomatitis)
- Signs of thalassaemia
What are the signs and symptoms of lead poisoning? (x9)
Anorexia, nausea + vomiting, abdominal pain, constipation, peripheral nerve lesions (foot and wrist drop), blue gumline, encephalopathy, convulsions, decreased consciousness.
What are the blood investigations for microcytic anaemia?
FBC: low Hb, MCV, MCH, MCHC, haematocrit and reticulocytes
How do you differentiate between IDA, lead poisoning, ACD and sideroblastic anaemia with blood investigations?
- Iron deficiency: low serum iron, ferritin, transferrin, high iron binding capacity.
- ACD: WBC and platelets may be raised, low serum iron, IRON BINDING CAPACITY, transferrin, high FERRITIN.
- Lead poisoning: high serum lead
- Sideroblastic anaemia: high IRON, FERRITIN, TRANSFERRIN, low total iron binding capacity
How does microcytic anaemia present on blood film: IDA? ACD? Sideroblastic anaemia? Lead poisoning?
- IDA/ACD: microcytic, hypochromic (central pallor), anisocytosis (variable cell size), poikilocytosis (variable cell shape)
- SIDEROBLASTIC: dimorphic blood film (two populations of cells – one population normal and one population hypochromic, microcytic)
- LEAD POISONING: basophilic stippling (coarse dots represent condensed RNA in the cytoplasm)
What is an additional investigation for microcytic anaemia?
Hb electrophoresis: for thalassemia, and presence of ring sideroblasts in the bone marrow in sideroblastic anaemia (iron deposited in mitochondria of erythroblasts, stain blue-green with Perl’s stain).
What investigations should be ordered if IDA in post-menopausal women and over 40 years? (x3)
Upper GI endoscopy, colonoscopy, and investigations for haematuria to rule out blood loss cause.
How is IDA managed? (x4)
Oral iron supplements (ferrous sulphate). Consider parenteral when oral not tolerated or malabsorption. Ascorbic acid promotes absorption of non-haema iron. Transfusion indicated if cardiac compromise.
How is sideroblastic anaemia managed? (x4)
Treat cause (stop the causative drugs). Pyridoxine can be used if the disease is inherited. Consider blood transfusion and iron chelation (remember it is associated with high iron) if no response.
How is lead poisoning managed? (x3)
Remove the source, dimercaprol and Ca2+ EDTA or D-penicillamine (lead chelation therapy).
What are the complications of microcytic anaemia?
High cardiac output heart failure, complications of the cause.
What is normocytic aneamia?
Low Hb associated with normal MCV (between 80 and 96 fl).
What are the classifications of normocytic anaemia? (x2)
- HYPERPROLIFERATIVE (reticulocyte count over 2%) – the proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction/loss of RBCs. Cause is usually ACUTE blood loss of haemolysis.
- HYPOPROLIFERATIVE (reticulocyte count below 2%) – primarily in disorders of decreased RBC production
What is the aetiology of normocytic anaemia? (x4 (x5))
- BLOOD LOSS
- FAILURE OF PRODUCTION: such as in early stages of iron deficiency and ACD, renal failure from lack of erythropoietin, aplastic anaemia from bone marrow failure or suppression, bone marrow infiltration (cancer)
- HYPERSPLENISM: can be from liver cirrhosis leading to pooling of red cells in the spleen
- HAEMOLYTIC ANAEMIA
What is the epidemiology of normocytic anaemia: Aetiology is most common? Age?
Anaemia of chronic disease is the most common. Increased prevalence with age.
What are the investigations for normocytic anaemia?
Peripheral blood smear: reticulocyte count is done to determine cause. High reticulocyte count signifies bone marrow processes are normal; low reticulocyte count would signify there is a problem with the bone marrow which produces the stem cells.
How is normocytic anaemia treated? (x3)
- If aetiology is ACD, then treat cause first
- Erythropoietin may be considered if anaemia is severe – to stimulate the bone marrow to make more blood cells
- Blood transfusions in acute management
What is macrocytic anaemia?
Anaemia associated with high MCV of erythrocytes (at least 96 fl)
What is the aetiology of macrocytic anaemia? (x2)
- MEGALOBLASTIC: defect in DNA synthesis or maturation resulting in appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation
- NON-MEGALOBLASTIC: encompasses all other causes in which DNA synthesis in normal.
What is the aetiology of megaloblastic anaemia? (x3)
Vitamin B12 deficiency and Folate deficiency. Also, some drugs that interfere with DNA synthesis such as cancer drugs for leukaemia.
What is the aetiology of non-megaloblastic anaemia? (x8)
Alcohol excess, liver disease, myelodysplasia, multiple myeloma, hypothyroidism, haemolytic anaemia (shift to immature red cells: reticulocytosis), drugs (tyrosine kinase inhibitors: imatinib, sunitinib), aplastic anaemias (usually inherited aetiologies).
What are the possible mechanisms of macrocytic anaemia? (x2)
- Results from ABNORMAL HEMOPOIESIS, so the red blood cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally. As a result, the red cells end up larger than normal. 2. Premature release of cells from the bone marrow. Young red blood cells are about 20% larger than mature RBCs, so if there’s an increased number of these premature cells (reticulocytes), then MCV is increased.
What is a megaloblast?
An abnormal bone marrow erythroblast (precursor of an erythrocyte with a nucleus). It is larger than normal and shows nucleocytoplasmic dissociation i.e. the maturation of the cytoplasm is mismatched with maturation of nucleus e.g. cytoplasm with dense Hb, but nucleus not condensed. NB: Megaloblastic refers to changes that occur ONLY in the BONE MARROW, but you can SEE the consequences of the megaloblastic changes by studying peripheral blood.