Red Cells 1 Flashcards
What is anaemia?
Reduction in the number of blood cells or the haemoglobin content of the blood cells
Not a pathology itself but rather a result of something elsse (increased production / destruction, Blood loss)
Which metals are required for red cell production?
IRON
Copper
Cobalt
manganese
Which vitamins are required for red cell production?
B12
FOLIC ACID
Thiamine
Vitamin B6, C, E
Which hormones are required for red cell production?
ERYTHROPOIETIN
GM-CSF
Androgens
Thyroxine
Which physiological system is responsible for red cell breakdown? What is this system composed of?
Reticuloendothelial system
Composed of macrophages in the spleen*, liver, lymph nodes, lungs etc.
Describe the metabolism of red blood cells that have reached senescence
Amino acids from globin protein are reutilized
Iron is reutilized and reincorporated into haemoglobin
Haem is converted into unconjugated bilirubin which binds albumin in the plasma
Bilirubin is then conjugated by the liver and excreted in the urine
How does the type of bilirubin found in the plasma indicate different pathologies?
Excess unconjugated bilirubin - excess RBC breakdown
Conjugated bilirubin - hepatic pathology
What are the advantages to the biconcave shape of red blood cells?
Maximum surface area for oxygen exchange
Provides a squeezability and flexibility to the cell that allows RBCs to get through tight spaces
Which parts of the red cell are commonly affected by genetic abnormalities? What effect does this tend to have?
Red cell membrane
Metabolic pathways within the red cell
Haemoglobin
Tend to result in haemolysis
What is hereditary spherocytosis? How are the mutations transmitted?
A disroder in which there is a mutation in one of the genes coding for the cytoskeleton of red blood cells
Results in loss of bi-concave shape and cell becomes spherical
Transmitted in an autosomal dominant pattern
Other than the inefficient shape of the RBCs in hereditary spherocytosis, what effect does the mutation have?
Red cells are recognized by the reticuloendothelial system as being abnormal and so are removed from circulation much sooner
How does hereditary spherocytosis tend to present?
Varying severity - severity depends on the specific cytoskeleton protein mutation
- Anaemia (early or late onset)
- Jaundice (may be neonatal, or unnoticable)
- Splenomegaly
- Pigment gallstones
How is hereditary spherocytosis treated?
- Mild cases: folic acid supplementation
- Moderate cases: blood transfusions
- Severe cases: splenectomy (removing spleen slows removal of abnormal RBCs from circulation
What are some examples of other RBC membrane disorders?
- Hereditary Elliptocytosis
- Hereditary Pyropoikilocytosis
- South East Asian Ovalocytosis
What is the most common disorder of red blood cell enzymatic metabolism?
Deficiency in Glucose 6 Phosphate Dehydrogenase (G6PD)
Enzyme functions to protect red cell proteins (haemoglobin from oxidative damage)
How is G6PD deficiency transmitted? What accounts for the high prevalence of the mutation?
X linked - affects males, females are carriers
The mutation confers a protection against malaria and so is a survival advantage in areas where malaria is endemic
How does G6PD deficiency tend to present?
- Anaemia
- Jaundice (may be neonatal)
- Splenomegaly
- Pigment gallstones
- Intravascular haemolysis
Varying presentations, some people may only show signs when exposed to oxidative factors such as drugs / infections
What is pyruvate kinase deficiency? What is the effect of it? How does it present?
Mutation in the pyruvate kinase gene in glycolytic pathway of RBCs, causes reduced ATP and buildup of metabolites, especially 2,3 DPG
2,3 DPG makes cells rigid
- Anaemia
- jaundice
- Gallstones
Describe the structure of haemoglobin. When does the structure chamnge?
4 protein subunits each with their own haem and iron group
In relaxed position it binds oxygen via the haem group
When bound by 2,3 DPG the protein changes shape and releases the oxygen to the target tissue
What are some important factors that influence the affinity of haemoglobin for oxygen?
pH - more acidic condition lower affinity. When at tissues that have been active acid is produced and haemoglobin lets go of oxygen to provide it to cells that need it
DPG conc. - Low DPG means lower affinity for oxygen. DPG binding causes release of oxygen, therefore higher DPG means less oxygen binding
Temperature - higher temperature means lower oxygen affinity, probably to do with protein structural integrity
Which protein chains make up haemoglobin?
Alpha component:
- Made up of 2 alpha chains encoded by 4 alpha genes
Beta component:
- 2 beta chains encoded by 2 beta genes
Beta component can be replaced by gamma or delta genes, encodes different types of haemoglobin
HbA (aabb) - 97% of Hb
Hb A2 (aadd) - 2% of Hb
HbF (aagg) - 1% of Hb
What are haemoglobinopathies? What are the different types?
inherited abnormalities of haemoglobin synthesis (abnormal haemoglobin)
Thalassaemia - reduced or absent globin chain production. (eg. alpha chain thalassaemia = alpha thalassaemia)
Mutations leading to structurally abnormal haemoglobin chains (eg HbS - sickle cell)
Where do haemoglobinopathies tend to be more common?
In areas where malaria is or was endemic
Sickle cell - Africa
Thalassaemia - central belt around equator ish
Who confers the benefit of haemoglobinopathies in as far as malaria resistance is concerned?
Carriers of the recessive allele
- those who are affected do not benefit
- carriers don’t suffer the disease but are protected against malaria
Describe the pathophysiology of sickle cell disease
Mutation in beta chain, causes cells to become deformed into a sickle shape when deoxygenated. Can damage microvasculature
Damage to microvasculature causes inflammation which can cause coagulation and dysregulation of vasomotor tone by vasodilator mediators
All ends up in occluded vessels (vaso-occlusion)
How does sickle cell anaemia tend to present?
Often precipitayed by sickling mediator eg. infection
- Bone pain
- Hypoxia
- Stroke
- Hyposplenism (increases risk of infection)
- Gallstones
- Aplastic crisis
- Sequestration crises
How are flare ups of sickle cell anaemia treated?
Opiates for pain management Hydration Oxygen Antibiotics if infection Blood Transfusion
How is sickle cell anaemia treated long term?
- Vaccination (hyposplenism)
- Penicillin and malarial prophylaxis
- Folic acid
- Hydroxycarbamide (increases foetal haemoglobin and stops sickling)
- Bone marrow transplantation
What is the prognosis for homozygous alpha zero thalassaemia?
Not compatible with life
If you have no alpha genes you cannot synthesize haemoglobin and won’t survive
What is the prognosis for homozygous beta thalassaemia? (beta thalassaemia major)
Can’t make beta chains, but due to gamma and delta chains still synthesize a small amount of haemoglobin
Will rely on transfusions for life but will survive
If irregular transfusions / untreated life expectancy is <10 years
What is non-transfusion dependent thalassaemia?
Range of different genotypes, but generally thalassaemia that is not dependent on trnasfusions to survive
What is thalassaemia minor? How does it present?
Missing part of a chain coding gene / one copy of a chain coding gene
Mild anaemia (with small red cells on microscopy)
How does homozygous beta zero thalassaemia present? (beta thalassaemia major)
Present at 3-6 months because foetal Hb is sufficient in early life, but when become dependent on beta genes that are mutated become anaemic
- Anaemia
- Expansion of ineffective bone marrow
- Bony deformities
- Splenomegaly
- Growth retardation
How is beta thalassaemia major treated?
- Blood transfusions every 4-6 weeks for life
- Iron chelation therapy due to iron overloading from repeat transfusions
- oral deferasirox or desferrioxamine infusions
Bone marrow transplantation is curative
What is sideroblastic anaemia?
Anaemia due to defects in mitochondrial steps of haem synthesis
Very rare
