Anaemia Flashcards
What is anaemia?
Condition where haemoglobin conc is lower than normal range
Symptoms of anaemia
Shortness of breath
Angina
Claudication
Weakness
Pallor
Lethargy
Palpitations
Signs of anaemia
Pallor
Hypotension
Tachypnoea
Tachycardia
Signs of iron deficiency anaemia
- Kolionychia - spoon shaped nails
- Angular stomatitis - inflammation of corners of mouth
Sign of vitamin B12 deficiency
Glossitis - inflammation of tongue
Sign of thalassaemia
Abnormal facial bone development
What is koilonychia and what is it a sign of?
Spoon shaped nails
Iron deficiency anaemia
What is angular stomatitis and what is it a sign of?
Inflammation of corners of mouth
Iron deficiency anaemia
What is glossitis and what is it a sign of?
Inflammation of tongue
Vitamin B12 deficiency
Reasons for anaemia to develop
In bone marrow:
- reduced erythropoiesis
- abnormal haem synthesis»_space; sideroblastic anaemia
- abnormal globin chain synthesis»_space; thalassaemia
In peripheral RBCs: - removed by spleen
- abnormal structure
- mechanical damage
- abnormal metabolism
Excessive bleeding
Increased removal by reticuloendothelial system
What is a sideroblast?
Immature RBC with nuceli
What can decreased or dysfunctional erythropoiesis be due to?
-
lack of response from haemostasis loop
e.g. chronic kidney disease - kidney stops producing EPO - bone marrow not responding to erythropoietin
- myelodysplastic syndrome (blood cancer) - bone marrow produces abnormal blood cells
- anaemic of chronic disease - iron not available for RBC production
What is erythropoietin?
Hormone secreted by the kidneys that increases the rate of erythropoiesis in response to falling level of O2 in tissues
What type of anaemia can be caused by defects in haemoglobin synthesis?
Sideroblastic anaemia
Iron deficiency anaemia
Anaemic of chronic disease»_space; functional iron deficiency
What is functional iron deficiency?
Sufficient iron but not available for erythropoiesis
What does microangiopathic haemolytic anaemia result from?
Mechanical damage»_space; schistocytes
- shear stress
- snagging on fibrin strands
Heat damage - severe burns
Osmotic damage - freshwater drowning
What causes haemolytic anaemia?
Abnormal structure
Mechanical damage
Explain inherited haemolytic anaemia
- Mutations in genes coding for proteins involved in interactions between plasma membrane and cytoskeleton e.g. ankyrin, spectrin
- Abnormal structure
- Less flexible + more easily damaged
- Break up in circulation or removed by RES
How can G6PDH deficiency cause anaemia?
- Used in the pentose phosphate pathway to generate NADPH
- deficiency»_space; less NADPH made
- NADPH needed for reduction of GSSG to GSH to manage oxidative stress
- if an able to do that > RBCs get damage
- damaged RBCs removed
- anaemia
How can pyruvate kinase deficiency cause anaemia?
- Enzyme in glycolysis
- RBCs lack mitochondria so need glycolysis for energy production
- lack of pyruvate kinase > reduced glycolysis > deficient in ATP > RBCs undergo haemolysis
Examples of chronic bleeding that can cause anaemia
Chronic bleeding - small amount of bleeding over a long period of time
- heavy menstrual bleeding
- repeated nosebleeds
- haemorrhoids
- gastrointestinal bleeding > blood lost in stool
- kidney or bladder tumours > blood lost in urine
Side effect of chronic NSAID usage
Induce GI injury + bleeding via
- inhibition of cyclooxgenase activity
- direct cytotoxic effects on epithelium
Examples of NSAIDs
aspirin
ibuprofen
naproxen
2 key features which can help work out the cause of anaemia
RBC size - macrocyctic, microcytic, normocytic
Presence or absence of reticulocytosis
What are reticulocytes?
Immature RBCs
Slightly larger than mature RBCs so more reticulocytes will increase mean cell volume
Why is reticulocytes count useful in evaluating anaemia?
Shows if marrow is capable of responding
What are the microcytic anaemias?
What is the MCV?
Small RBCs - low MCV <80fL
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia
What are the macrocytic anaemias?
What is the MCV?
Large RBCs - high MCV >100fL
- megaloblastic anaemia: B12/folate deficiency
- macronormoblastic erythropoiesis: liver disease, alcohol toxicity
- stress erythropoiesis: recovery from haemolytic anaemia or haemorrhage
What are the normocytic anaemias?
MCV
Abnormal but same size - 80-100fL
Sickle cell disease
Anaemic of chronic disease
Blood loss
Types of macrocyctic anaemias
Megaloblastic anaemias
Macronormoblastic erythropoiesis
Stress erythropoiesis
Outline anaemia of chronic disease
Patient has an inflammatory condition which causes cytokine release e.g. IL6 causing:
- inhibition of EPO production
- increases hepcidin production > inhibiton of ferroportin > decreases iron release from RES + absorption in gut > plasma iron reduced
All inhibits erythropoiesis in bone marrow
What is the underlying pathophysiology behind hereditary spherocytosis
Increased RBC rigidity - spherocyte shape
Mutations in loss of function of proteins - ankyrin, spectrin, band 3 + protein 4.2
What is haemoglobinanemia ?
Excess haemoglobin in blood
What does the Coombs test measure?
When is it used?
Antibodies bound directly to the surface of RBCs
When immune-mediated haemolytic anaemia is suspected
What are two causes of anaemia due to defects in red blood cell metabolism?
G6PDH deficiency
Pyruvate kinase deficiency
What can be seen on a blood film of a patient with G6PDH?
Why?
Heinz bodies
- Aggregates of cross linked haemoglobin due to oxidative stress
Describe Megaloblastic anaemias
Examples
- type of macrocytic anaemia MCV >100fL
- interference with DNA synthesis > decreased nucleus development compared to cytoplasm > delayed cell division > megaloblasts > larger RBCs
- e.g. B12/folate deficiency
Describe macronormoblastic erythropoiesis
Examples
- type of macrocytic anaemia MCV >100fL
- normal relationship between nucleus + cytoplasm
- erythroblastosis are larger than normal > larger RBC
- e.g liver disease, alcohol toxicity
Describe megaloblasts
- much larger than usual erythroblasts in bone marrow
- very large immature nuceli
Describe stress erythropoiesis
Examples
- type of macrocytic anaemia MCV >100fL
- high levels of EPO > increased erythropoiesis > high reticulocyte count (larger than mature RBCs)
e.g. recovery from haemolytic anaemia or blood loss due to haemorrhage
Where is EPO released from?
Kidneys
What is aplastic anaemia?
Condition where the bone marrow fails to produce enough blood cells
