Anaemia Flashcards
What is the definition of anaemia?
Defined as the condition whereby there is a reduction in the number of erythrocytes and haemoglobin within circulation
What are the main cases of anaemia?
Reduced production of erythrocytes/haemoglobin in bone marrow
Reduced survival of erythrocytes in the circulation - haemolysis
Loss of blood from the body
Pooling of erythrocytes within the spleen - splenic sequestration (Splenomegaly)
What are the three main causes for reduced red cell survival?
Hereditary spherocytosis
Autoimmune haemolytic anaemia
G6PD deficiency
What are the three main causes for a reduced red cell production?
Iron deficiency anaemia Anaemia of chronic disease Megaloblastic anaemia (Vitamin B12 deficiency)
What is associated with microcytic anaemia and hypochromia?
characterised with relatively smaller erythrocytes with a larger area of central pallor. (MCHC is low).
Which cells are associated with microcytic anaemia?
Target cells
Elliptocytes
What are the causes of microcytic anaemia?
Iron deficiency
Anaemia of chronic disease
Thalassemia
What is thalassemia?
Impaired beta and alpha chain synthesis
What is normocytic anaemia?
Anaemia with standard sized erythrocytes
What the main causes of normocytic anaemia?
Recent blood loss
Failure of production of red cells - leukaema
Pooling of red cells in the spleen - hyperspenism (liver cirrhosis), splenic sequestration in sickle cell anaemia
What is macrocytic anaemia?
Associated with normochromia, anaemia with comparatively larger erythrocytes.
What are the causes of macrocytic anaemia?
Vitamin B12/Folate deficiency Use of drugs interfering with DNA synthesis Liver disease and ethanol toxicity Haemolytic anaemia (reticulocytes increased)
What is anaemia of chronic disease?
Anaemia of chronic disease is a disease entity in which anaemia occurs on a background of chronic disease (e.g. rheumatoid arthritis). It is thought to occur due to the abundance of pro-inflammatory cytokines (e.g. IL-1 and TNF-alpha) in chronic disease. These cytokines suppress the absorption and transport of iron thereby limiting the ability of the body to use this iron in red cell production. (Hepcidin is elevated)
• Malignancy, rheumatoid arthritis and infections including TB & HIV are common causes.
Which pro-inflammatory cytokines are elevated in anaemia of chronic disease?
IL-1 and TNF-alpha
Which hormone is up-regulated in anaemia of chronic disease?
Hepcidin
Which conditions are implicated in anaemia of chronic disease?
Malignancy, rheumatoid arthritis and infections (TB & HIV)
What are the ferritin levels in iron deficiency anaemia?
Low
Describe the level of transferrin in iron deficiency anaemia?
High
What is hereditary spherocytosis?
An inherited disorder of the red cell membrane which results in spherical red blood cells that have lost their biconcave shape, spherocytes can be identified on blood film.
Why does haemolytic anaemia arise in hereditary sphereocytosis?
Due to the fragile nature of spherocytes (spherical shape is less flexible) - removed and destroyed by the spleen
What symptoms arise due to hereditary sphereocytosis?
Jaundice - hyperbillrubinaemia
Elevated reticulocyte count
Gallstones
Why are reticulocytes elevated in hereditary spherocytosis?
Compensatory mechanism in response to increased rate of red-cell destruction
What is the treatment for hereditary spherocytosis?
Folic acid supplementation (because of increased need)
Splenectomy (if severe), to increase red cell life span
Why is there an increased risk of gallstones in patients with hereditary spherocytosis?
Increased haemolytic breakdown of haemoglobin to bilirubin.
Elevated in conjugated bilirubin indicates obstruction jaundice within the common bile duct (gall stones), since the liver has the capacity to conjugate BR however not adequately being delivered from the bile ducts and gallbladder into the duodenum
What is autoimmune haemolytic anaemia?
Caused by the generation of antibodies that target red cell antigens.
What are the common causes of autoimmune haemolytic anaemia?
lymphoproliferative and autoimmune diseases
N.B: May be idiopathic
What happens to the reticulocyte count in autoimmune haemolytic anaemia?
Elevated
What test is done in patients with autoimmune haemolytic anaemia?
DAT test
Direct anti-globulin test
Why is MCV raised in autoimmune haemolytic anaemia?
Raised reticulocyte count as a compensatory mechanism to the raised rate of haemolysis. Reticulocytes have a larger diameter, thus increasing the average MCV
What evidence is there for haemolysis?
- Unconjugated hyperbilirubinemia
- Lactate dehydrogenase is raised
- Reduced haptoglobins
What are the non-immune causes of haemolytic anaemia?
- Microangiopathic
- Haemolytic uraemic syndrome
- Malaria
- Snake venom
- Drugs
What is microangiopathic haemolytic anaemia?
Microangiopathic haemolytic anaemia is a form of haemolytic anaemia in which red blood cells lyse due to the shear forces encountered as they pass through small blood vessels It would cause a raised reticulocyte count.
What are the immune-mediated causes of haemolytic anaemia?
- Auto immune (SLE)
* Allo immune (Post blood transfusion)
What is iron deficiency anaemia?
Iron is required for haemoglobin synthesis, myoglobin and cytochromes, and therefore is crucial for erythrocyte production. Iron store depletion occurs because more iron is lost or used than can be absorbed Impairing RBC production.
In iron deficiency anaemia, a blood film will reveal what?
The blood film reveals hypochromia, poikilocytosis (Target cells & elliptocytes) and microcytosis.
What are the symptoms associated with iron-deficiency anaemia?
- Fatigue
- Low energy level
- Dyspnoea on exertion
- Pica Abnormal craving or appetite for non-food substances.
- Nail changes Thinning, flattening and spooning of nails.
What is pica?
Abnormal craving or appetite for non-food substances
What nail changes are evident in iron deficiency anaemia?
Thinning, flattening, and spooning of nails
Why is tranferrin elevated in iron deficiency anaemia?
Transferrin is elevated in individuals with iron-deficiency anaemia is a compensatory mechanism to optimise iron transport to the bone marrow; however, transferrin saturation is low considering the iron-binding sites are not completely filled.
What are the causes for increased blood loss and IDA?
Hookwork
Menorrhagia
Gastrointestinal (occult)
What can cause insufficient iron intake?
- Dietary: Vegetarian/vegan.
* Malabsorption: Coeliac disease (gluten-induced enteropathy); H. Pylori gastritis
What is Coeliac’s disease?
(gluten-induced enteropathy); H. Pylori gastritis
What can increase the physiological demand for iron?
Pregnancy
Infancy
What investigations are conducted in patients with IDA?
• Upper gastrointestinal endoscopy Oesophagus, stomach and duodenum
-Take duodenal biopsy
-Colonoscopy Can reveal carcinoma.
• Coeliac antibody testing
• Investigating for blood in the stool (Faecal immunochemical test, FIT).
What is megaloblastic anaemia?
Folic acid and B12 deficiency can cause megaloblastic anaemia. B12 is essential for DNA synthesis, so a deficiency results in impaired nuclear maturation and cell division within the bone marrow. This results in the release of large, immature red blood cells in the circulation, known as megaloblasts.
What type of deficiency is associated with megaloblastic anaemia?
Folic acid
B12 deficiency
Why is B12 important?
Essential for DNA synthesis and the integrity of the nervous sytem
What are the consequences of a B12 deficiency?
Impaired nuclear maturation and cell division within the bone marrow- megaloblastic anaemia
What are megaloblasts?
Immature red blood cells
What does a bone marrow aspirate show in a patient with megaloblastic anaemia?
Megaloblastic faetures
- Megaloblasts are large with nucleocytoplasmic dissociation (asynchronous)
- Impaired DNA synthesis, nuclear maturation and cell division.
- Adequate cytoplasmic maturation and cell growth.
Which drugs are linked with megaloblastic anaemia by impairing DNA synthesis?
Azathioprine -cytotoxic chemotherapy
Folate antagonists- methotrexate
What does a blood test reveal in megaloblastic anaemia?
Low Hb
High MCV
Inappropriately normal reticulocytes (vitamin B12 or folate deficient)
What is the function of folic acid?
DNA synthesis and homocysteine metabolism
What are the dietary causes of B12 and folate deficiency?
Inadequate diet
Veganism
What treatment is available for patients with dietary induced B12 deficiency?
Oral supplements
What are the gastric causes of vitamin-B12 deficiency?
Gastrectomy
Autoimmune: Pernicious anaemia (Anti-GPC and IF antibodies).
Which factor is released by gastric parietal cells to support b12 transport?
Intrinsic factor
What is the treatment for gastric induced vitamin b12 deficiency?
Hydroxocobalamin injections (IM)
Which bowel related issues cause b12 deficiency?
Crohn’s disease
Ileal resection
What is a gastectomy?
A gastrectomy is a surgical procedure in which part or all of the stomach is removed. It may be performed due to stomach cancer or morbid obesity
What is the function of intrinsic factor?
IF-B12 complexes, prevents B12 degradation and helps transport it to the terminal ileum
Where within the small bowel is B12 absorbed?
Terminal ileum
What transport protein does B12 bind to once in circulation?
Transcobalamin II
What reduces the availability of b12?
Dietary: Poverty & alcoholism
Malabsorption
• Coeliac disease
• Jejunal resection
What neurological disorder can occur in neonates due to a folate deficiency?
Development of neural tube defects
What neurological disorders can occur due to vitamin b12 deficiency?
• Vitamin B12: Dementia and sub-acute combined degeneration (SACD) of the spinal cord.
What are the inherited causes of haemolytic anaemia?
- Abnormal red cell membrane Hereditary spherocytosis
- Abnormal Hb Sickle cell anaemia
- Defect in glycolytic pathway Pyruvate kinase deficiency
- Defect in enzyme of pentose shunt G6PD deficiency
Which type of anaemia is associated with Heinz bodies?
Glucose-6-phosphate dehydrogenase deficiency
Which food can cause Glucose-6-phosphate dehydrogenase deficiency?
Broad beans (fava)
What is Glucose-6-phosphate dehydrogenase deficiency?
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency is a form of haemolytic anaemia that results from an inability of red cells to generate glutathione. Glutathione is the red cell’s main defence mechanism against oxidative damage, so a deficiency of glutathione results in increased susceptibility to oxidative damage and cell death. Heinz bodies are lumps of denatured haemoglobin within red cells - they are a marker of oxidative damage. Haemolysis can be precipitated by various agents that can increase the risk of oxidative damage (e.g. antimalarial drugs). An increase in red cell breakdown means that there will be an increase in bilirubin generation. This will exceed the capacity of the liver to metabolise bilirubin, so it will manifest as jaundice.
What are ghost cells?
A marker of intravascular haemolysis?
What are Heinz bodies?
Heinz bodies are precipitated oxidised haemoglobin.
