CKD Pathophysiology Flashcards
What is ESRD?
Categorised by irreversible loss of function of the nephrons and the need for treatment (dialysis or transplant)
What is the reason for the CKD epidemic?
Increasing age of society (lose 0.9GFR per yea after 40)
Increasing diabetes, obesity and hypertension
Increased diversity (increased risk of ESRD if you are black/asian)
What determines the progression from CKD to ESRD?
Nature of original disease
Proteinuria
Hypertension
What is the hallmark of ESRD?
Renal fibrosis - irreversible loss of function of the nephron (glomerulosclerosis, tubulointerstitial fibrosis and vascular fibrosis)
What are the two most common causes of ESRD?
Hypertension - narrowing of renal artery - lowers BP in afferent arteriole - low GFR - release of GFR and RAAS system - increase in BP - further narrowing of artery - further increase in hypertension - reduced oxygen to glomerulus - hypoxia - activation of HIF-1a which activates TBF-B and VEGF leading to fibroblast proliferation and ECM deposition - loss of function of glomerulus
Diabetes - high glucose can lead to generation of ROS leading to damage to membrane between glomerulus and bowmans capsule
What is the consequence of glomerulosclerosis?
Proteinuria - protein can leak into the urine - compliment protein can lead to insertion of MAC in tubule cells and release anaphylotoxin - activation of inflammatory and profibrotic genes - leads to inflammatory cell infiltrates and fibrosis in interstitial - fibrosis
How is TBF-B released?
In response to inflammation and scarring, TGF-B is released to attempt to repair the tissue - leads to further fibroblast proliferation (Pericyte activation, fibrocyte activation, epithelial/endothelial mesenchymal transition)
What is the overall result of renal fibrosis?
Imbalance between ECM production and degradation
How can limit the progression of CKD
Treat underlying diseases (Hypertension (ACE inhibitors), Diabetes (metformin/exercise)
Treat complications (renal anaemia/bone metabolism/poor nutrition)
What are the two methods of treating ESRD?
Dialysis - Haemodialysis and Peritoneal Dialysis
Transplant
What are the differences between Haemodialysis and Peritoenal Dialysis?
Peritoneal dialysis uses the periotineal lining in the abdomen as the membrane. Insert dialysate into the space and filter urine through the membrane - exchange fluid when used. Can we performed by patient at home, during the day or overnight - every day
Haemodialysis - 3 times per week - have to visit a clinic - have to restrict your diet
What are the disadvantages of dialysis?
Time consuming
Low Survival rate
High symptom burden
Fatigue
Haemodialysis - Low BP, Sepsis, Muscle cramps, itchy skin, low labido
Peritoneal Dialysis - Peritonitis (if equipment isn’t clean), Hernia (due to strain on your abdomen muscles), Weight Loss (dialysate contains sugars which can be absorbed)
How many people in the UK are on dialysis?
30,000
What is the average wait for a kidney transplant?
2-3 years
When was the first transplant?
1954
