Flashcards in MEH - Haemopoiesis Deck (45):
Where are most red blood cells, platelets and white blood cells produced?
Where is bone marrow mainly distributed in adulthood?
Pelvis, sternum, skull, ribs, vertebrae
How are blood cells produced?
A multipotential haematopoietic stem cell becomes either a common myeloid progenitor or a common lymphoid progenitor.
The lymphoid progenitors form B and T lymphocytes, and the myeloid progenitors form thrombocytes, monocytes, basophils, neutrophils and eosinophils
What cells are included in the reticuloendothelial system (RES)?
Monocytes, macrophages, kupffer cells, tissue histiocytes, microglial cells in CNS
What do RES cells in the spleen dispose of?
Damaged or old red blood cells
What are the functions of red blood cells?
Primary - to deliver oxygen to the tissues
- carry haemoglobin
- maintain haemoglobin in its reduced (ferrous) state
- generate energy (ATP)
- maintain osmotic equilibrium
Do red blood cells have a cell membrane?
Yes, a lipid bilayer. They also have membrane proteins inserted into it
At what age does the switch from foetal to adult haemoglobin occur?
Around 3-6 months of age
What is the function of the globin chains?
- protect haem molecule from oxidation
- confer solubility
- permits variation in oxygen affinity
What shape is an oxygen dissociation curve?
Why do people with too many red blood cells get jaundiced?
Excess of red blood cell destruction causes an excess of bilirubin formation which leads to jaundice
What is the function of the RES?
Cells identify and mount an appropriate immune response to foreign antigens
What are the main organs of the RES?
Spleen and liver
What is a peripheral blood count of haemoglobin used to measure with regards to red blood cells?
Their effectiveness. Normal range is 130-180 g/L (or 115-165 g/L for females)
What is a red blood count used to measure with regards to red blood cells?
How many red blood cells are present. Normal range is 4.5-6.5 x 10^12/L (3.9-5.6 in women)
What is a peripheral blood count of mean cell volume used to measure with regards to red blood cells?
How large the cells are. Normal range is 80-100 fL
How large are red blood cells?
8 micrometres diameter, and they can fit through the capillaries with a diameter of 3.5 micrometres
True or false - haemoglobin exists in three configurations?
False - it exists in two (oxyhaemoglobin/relaxed, and deoxyhaemoglobin/tight)
Which chromosome is the gene for the globin chain formation found on?
The globin gene clusters on chromosome 11 and 16.
How is erythropoiesis controlled by oxygen levels in the body?
- reduced pO2 detected in interstitial peritubular cells in kidney
- increased production of erythropoietin (hormone)
- this stimulates maturation and release of red cells from bone marrow
- haemoglobin rises
- pO2 rises
- erythropoietin production falls
What are the two main metabolic pathways in red cells?
1) glycolysis - generates ATP
2) pentose phosphate - generates NADPH
True or false - there is no mechanism of excreting iron?
Give some examples of 'available' iron
- tissue iron (enzyme systems)
- transported iron ('serum iron')
Give some examples of 'stored' iron
- haemosiderin (macrophage iron)
How do macrophages obtain iron?
They 'eat' old senescent red blood cells. Mainly occurs in splenic macrophages and Kupffer cells of the liver
Roughly how much iron enters and leaves the body each day?
Roughly how much iron is required each day in the diet?
What is the diffference between haem and non-haem iron?
Haem iron is from meat sources, while non-haem is from beans, cereals etc
What form is haem iron in?
Enters enterocyte and released as Fe2+, so it is FERROUS
What form is non-haem iron in?
Mainly Fe3+ (FERRIC) - reduced to ferrous iron before being transported across the intestinal epithelium
How does iron enter the bloodstream from the stomach acid?
- found in Fe3+ form in stomach acid
- binds to transferrin and enters cells through apical surface of the duodenum and upper jejunum
- becomes Fe3+ again in cell
- reduced to Fe2+ then moves through cell membrane into blood via ferroportin
How is iron taken into cells (eg RBCs)?
Iron-transferrin complex binds to transferrin receptor (TfR). Erythroid cells contain the highest number of these receptors.
Which vitamin enhances absorption of iron?
Give some examples of regulators of iron absorption
- regulation of transporters
- expression of receptors
- hepcidin and cytokines
- crosstalk between the epithelial cells and other cells eg macrophages
How does hepcidin control iron uptake?
- high levels of iron are detected causing the liver to secrete hepcidin
- hepcidin degrades ferroportin, a protein involved in moving iron out of cells
- this prevents iron release from macrophages and iron absorption from the gut
What are the symptoms of anaemia?
- reduced O2 carrying capacity leading to pallor, reduced exercise tolerance
- angina, palpitations, heart failure
- epithelial changes
What would a test showing a lowered ferritin level show about an individual?
They are likely to be iron deficient
Give some features likely to be observed in a blood film of an anaemic patient
- hypochromic (low Hb content)
- microcytic (low mean cell volume)
- anisopoikilocytosis (change in size and shape of RBCs)
- low reticulocyte haemoglobin content
How is iron deficiency treated?
- dietary advice
- oral iron supplements
- intramuscular iron injections
- intravenous iron
- transfusion (only in severe cases)
Why is free iron considered dangerous?
When binding capacity of transferrin is exceeded, Fe2+ can produce highly reactive hydroxyl and lipid radicals, which damage the lipid membrane nucleic acids and proteins. Excess iron is deposited in tissues
What is haemochromatosis?
A disorder of iron excess resulting in end organ damage due to iron deposition
What does haemochromatosis cause?
Liver cirrhosis, diabetes mellitus, hypergonadism, cardiomyopathy, arthropathy and skin pigmentation
How is hereditary haemochromatosis inherited?
Autosomal recessive mutation in a gene designated HFE on the chromosomes
How does a gene mutation cause haemochromatosis?
- Normally, HFE protein competes with transferrin for binding to the transferrin receptor
- mutated HFE can't bind, so transferrin has no competition
- too much iron enters cells