Erythrocytes (CKD) Flashcards
What is haematopoiesis?
the process by which blood cells and blood plasma are formed
- erythrocytes (RBCs)
- leukocytes (WBCs)
- thrombocytes (platelets)
What are the steps in erythropoiesis?
in the BONE MARROW
- pluripotent haematopoietic stem cell (HSC) give rise to burst forming unit (BFU-E)
- BFU differentiates into colony forming unit (CFU-E)
- CFU-E changes into proerythroblast
- proerythroblast converts to erythroblast
- erythroblast loses its nucleus and organelles to become a reticulocyte
in the BLOOD
- reticulocyte are released into the blood and mature into erythrocytes
What is the main characteristic of colony forming units (CFU-E)?
pluripotent HSC - BFU-(E) - CFU-E
the differentiation to CFU-(E) is irreversible
- at this point they are committed to becoming an erythrocyte
- are highly sensitive and dependent on erythropoietin for further differentiation
At what point during erythropoiesis does haemoglobin synthesis begin?
Hb synthesis starts when the erythroblast is formed
What are the different stages of erythroblast?
basophilic erythroblast is converted to polychromatophilic erythroblast
polychromatophilic erythroblast is converted to orthochromatic erythroblast
What are the features of erythrocytes?
are
- non-nucleated cells
- reddish, circular and biconcave in shape
- cytoplasm has a paler centre and occupies 1/3 of cell area
- no visible internal structure
- high haemoglobin content
- outline is regular
What is the life cycle of erythrocytes?
red blood cells die and undergo phagocytosis
- via macrophages in spleen, liver or red bone marrow
RBC is split into heme and globin
- heme is broken down into bilirubin which is taken up by the liver and excreted via faeces (stercobilin) or urine (urobilin)
- heme is broken down into iron which is stored in ferritin for reuse in erythropoiesis in the red bone marrow
- globin is broken down into amino acids which are reused for protein synthesis
What factors regulate erythropoiesis?
hypoxia - under hypoxic conditions, the kidneys produce and secrete more erythropoietin (EPO) to increase the production of erythrocytes
growth factors
vitamins - B12 and folic acid for DNA synthesis, riboflavin
What factors are necessary for haemoglobin production?
vitamin C - helps in iron absorption from the gut
proteins - amino acids for globin synthesis
pyridoxine (VB6) - heme synthesis
iron and copper - heme synthesis
calcium, cobalt, nickel, zinc and bile salts
What is erythropoietin? What is its role in erythropoiesis?
erythropoiesis is an essential hormone for red cell production
role is to increase RBC production in 3 ways
- promotes proerythroblast production
- shortens transition time through erythroblast stage (BE, PE, OE)
- promotes the early release of reticulocytes
How does erythropoietin affect cells in the erythropoiesis cycle?
promotes the survival of RBC progenitors and precursors by protecting these cells from apoptosis
- BFU-(E) starts EPO receptors expression
- EPO binds to CFU-(E), proerythroblasts and basophilic erythroblasts
What is polycythemia?
an abnormally high number of red blood cells in the blood
How does blood oxygen levels affect erythropoietin synthesis?
hypoxia
- caused by decreased RBC count, decreased availability of oxygen to blood and increased tissue demand for oxygen
hypoxia
- kidney produces and secretes more EPO
- EPO
stimulates red bone marrow
- enhanced EPO increases RBC count which increases oxygen carrying ability of the blood
typically EPO levels are low in the absence of anaemia but increase during hypoxia
What areas of the kidney is erythropoietin produced?
during normal blood oxygen concentration
- synthesis of EPO occurs in scattered cells located predominately in the inner cortex
during hypoxia
- interstitial cells within almost all zones of the kidney begin to produce EPO
= increased EPO is due to an increase in the number of cells that produce it which is regulated by an ON/OFF switch
What cellular oxygen sensing mechanism controls EPO transcription?
gene for EPO is located on chromosome 7 and is regulated by transcriptions factors known as hypoxia inducible factors (HIF)
HIF is composed of an alpha subunit (unstable at high oxygen levels) and a beta subunit (present in the nucleus)
during hypoxia
- hydroxylation is inhibited so HIF alpha is not degraded and is instead stabilised
- HIF alpha translocates to the nucleus and forms a heterodimer with HIF beta
- the heterodimer is transcriptionally active and binds to specific DNA recognition sequences
- activates transcription and increases EPO production
What is number needed to treat?
describes the number of people that would need to be treated over the specified amount of time to make it useful.
the smaller the NNT, the better.
What is number needed to harm?
describes the number of people that would need to be treated before one suffers from harm.
the bigger the NNH, the better.
What is acute kidney injury?
a reversible state characterised by a rapid decline in kidney function over hours or days
it can result in failure to maintain fluid, electrolytes, and acid-base balance.
What are the causes of pre renal AKI?
- decreased perfusion to kidneys
volume depletion
- excessive diuresis, haemorrhage, burns, severe trauma, shock
cardiovascular disorders
- congestive heart failure, acute myocardial infarction
obstruction of renal arteries
- renal thrombosis, renal artery stenosis
What are the causes of post renal AKI?
- obstruction to urine outflow from the collecting ducts in the kidney to the urethra
deposition of crystals in the tubules
- uric acid, sulphonamides, acyclovir, cisplatin
renal stones in the ureter or bladder
tumour either within the tract or pressing on it from another organ
- bladder cancer, bowel cancer
What are the causes of intra renal AKI?
- damage to the kidney itself
sustained hypo perfusion or exposure to nephrotoxic agents
- antibiotics = ahminoglycosides, amphotericin
- analgesics = paracetamol, salicylates
- ethylene glycol
autoimmune renal disease
- vasculitis, interstitial nephritis
What drugs should you avoid or reduce dosing in AKI and renal damage?
avoid
- NSAIDs, ACEi, ARBs, diuretics, opioids, potassium sparing diuretics (eplerenone), aminoglycosides, trimethoprim, hypoglycaemic drugs, metformin
reduce dose
- pregabalin, gabapentin, acyclovir
What is chronic kidney disease?
an irreversible and gradual loss of renal function over time.
it is defined as abnormalities in kidney structure or function present for greater than 3 months.
What medication reviews do people with CKD need?
offer lipid lowering therapy with a statin for the primary or secondary prevention of CVD
offer antiplatelets for secondary prevention of CVD
offer immunisations for the influenza and pneumococcal viruses
