Erythrocytes (CKD) Flashcards

1
Q

What is haematopoiesis?

A

the process by which blood cells and blood plasma are formed
- erythrocytes (RBCs)
- leukocytes (WBCs)
- thrombocytes (platelets)

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2
Q

What are the steps in erythropoiesis?

A

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

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3
Q

What is the main characteristic of colony forming units (CFU-E)?

A

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

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4
Q

At what point during erythropoiesis does haemoglobin synthesis begin?

A

Hb synthesis starts when the erythroblast is formed

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5
Q

What are the different stages of erythroblast?

A

basophilic erythroblast is converted to polychromatophilic erythroblast

polychromatophilic erythroblast is converted to orthochromatic erythroblast

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6
Q

What are the features of erythrocytes?

A

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

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7
Q

What is the life cycle of erythrocytes?

A

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
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8
Q

What factors regulate erythropoiesis?

A

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

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9
Q

What factors are necessary for haemoglobin production?

A

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

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10
Q

What is erythropoietin? What is its role in erythropoiesis?

A

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

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11
Q

How does erythropoietin affect cells in the erythropoiesis cycle?

A

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

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12
Q

What is polycythemia?

A

an abnormally high number of red blood cells in the blood

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13
Q

How does blood oxygen levels affect erythropoietin synthesis?

A

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

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14
Q

What areas of the kidney is erythropoietin produced?

A

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

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15
Q

What cellular oxygen sensing mechanism controls EPO transcription?

A

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

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16
Q

What is number needed to treat?

A

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.

17
Q

What is number needed to harm?

A

describes the number of people that would need to be treated before one suffers from harm.

the bigger the NNH, the better.

18
Q

What is acute kidney injury?

A

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.

19
Q

What are the causes of pre renal AKI?
- decreased perfusion to kidneys

A

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

20
Q

What are the causes of post renal AKI?
- obstruction to urine outflow from the collecting ducts in the kidney to the urethra

A

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

21
Q

What are the causes of intra renal AKI?
- damage to the kidney itself

A

sustained hypo perfusion or exposure to nephrotoxic agents
- antibiotics = ahminoglycosides, amphotericin
- analgesics = paracetamol, salicylates
- ethylene glycol

autoimmune renal disease
- vasculitis, interstitial nephritis

22
Q

What drugs should you avoid or reduce dosing in AKI and renal damage?

A

avoid
- NSAIDs, ACEi, ARBs, diuretics, opioids, potassium sparing diuretics (eplerenone), aminoglycosides, trimethoprim, hypoglycaemic drugs, metformin

reduce dose
- pregabalin, gabapentin, acyclovir

23
Q

What is chronic kidney disease?

A

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.

24
Q

What medication reviews do people with CKD need?

A

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

25
Q

What is acute on chronic kidney disease?

A

people with pre-existing CKD can experience a sudden decline in kidney function