Renal Flashcards
What proportion of sodium ions are reabsorbed in the proximal tubule?
Approximately 70%
How do sodium ions pass through the tubule epithelia?
Co-transported with organic molecules
What is the main cause of water reabsorption?
Sodium ion movement results in the reabsorption via passive diffusion
How do kidneys regulate acid-base balance?
Controlled secretion of protons and carbonic anhydrase
How do kidneys correct alkalosis?
Secretion of protons from the plasma reduces the pH, leading to a build up of carbon dioxide which is removed via the lungs
How is sodium regulated in the kidneys?
Aldosterone is released increasing the number of sodium channels in the apical membrane and sodium-potassium ATPase channels in the basolateral membrane
Briefly describe the effect of low sodium on the RAAS?
Low sodium causes juxtaglomerular cells to release renin allowing conversion of angiotensin to angiotensin I.
Kidney and lung capillaries secrete ACE allowing conversion of angiotensin I to the active form of angiotensin II.
Angiotensin II stimulates release of aldosterone from the adrenal cortex.
What is the outer region of the kidney?
Cortex
What is the inner region of the kidney?
Medullar
Where are the kidneys found in the body?
Lie against the back of the abdominal wall, not found in the peritoneal cavity
What are the three major functions of the kidney?
Homeostasis
Excretion
Endocrine
Describe the journey of the blood/plasma through the kidney. (4 main points)
Enters glomerulus via afferent arteriole
Filtration occurs into the Bowman’s capsule before entry into the lumen of the nephron
Follows proximal and straight convoluted tubules into the Loop of Henle
Travels to bladder via cortical and medullar collecting ducts
What allows glomerular filtration to occur at a reasonable rate?
Efferent arteriole is narrower than the afferent arteriole, increasing blood pressure in the glomerulus
Where do molecules travel to if they are not filtered into the Bowman’s capsule?
Through efferent arteriole to vasa recta
What are the three layers that plasma travels through to enter Bowman’s capsule?
Capillary endothelium Basement membrane Capsule cells (podocytes)
How are molecules filtered into Bowman’s capsule?
Pores of 30kDa diameter act as a molecular sieve
Why is albuminuria common in reduced GFR?
Filtration becomes less efficient, allowing larger molecules such as albumin to filter into the nephron and be excreted in urine
What is secretion?
Movement of molecules from the vasa recta peritubular capillary into tubules
What is reabsorption?
Movement of molecules from tubules back into peritubular capillaries. Generally small molecules such as glucose and amino acids
Under what circumstances can molecules not be filtered?
If they are bound to plasma proteins
What are diuretics?
Compounds that increase excretion of sodium and water
Why are diuretics used in cardiac failure?
Increase in interstitial fluid volume with reduced cardiac output, increases venous pressure. By reducing fluid volume, blood pressure is reduced, reducing cardiac workload.
Why are diuretics used in hyperaldosteronism?
Increased sodium retention causes increase in plasma volume raising blood pressure. Diuretics promote excretion of excess sodium
What is the action of loop diuretics?
Inhibit the Na/K/Cl carrier in the ascending loop of henle
Give examples of loop diuretics.
Furosemide
Bumetanide
Why is there a risk of alkalosis with loop diuretics?
Carbonic acid excretion is not affected, increasing the plasma concentration thus raising pH
What effects do loop diuretics have on small molecule concentrations?
Increased excretion of magnesium and calcium
Reduced secretion of uric acid
What is the effect of loop and thiazide diuretics on proton concentrations?
Na/H exchanger is not affected thus entry of sodium drives the excretion of protons
Why is hypokalaemia a common side effect of diuretics?
The K/Cl transporter is blocked, reducing uptake of these ions from the tubule
What is the mechanism of action of thiazide like diuretics?
Inhibit the Na/Cl co-transporter in the distal tubule
Give examples of thiazide like diuretics?
Bendroflumethiazide
Indapamide
Metolazone
Why is indapamide preferred to other thiazide diuretics?
Lowers blood pressure at subdiuretic doses
Does not have as many metabolic effects
What effects do thiazide like diuretics have on small molecule concentrations?
Increase magnesium excretion
Reduce secretion of calcium and uric acid
What is the mechanism of action of potassium sparing diuretics?
Aldosterone antagonists, blocking the reabsorption of sodium and Na/K exchange in the collecting tubule
Give examples of potassium sparing diuretics.
Spironolactone
Eplerenone
What is the mechanism of action of amiloride?
Inhibits reabsorption of sodium in collecting tubules by blocking luminal sodium channels
What is the mechanism of action of osmotic diuretics?
Increase osmolarity of filtrate, increasing sodium and water excretion, mainly in the proximal convoluted tubule, ascending loop of henle and collecting ducts
Give an example of an osmotic diuretic.
Mannitol
What are the two main methods of measuring kidney function?
1- creatinine produced by muscles and freely filtered by kidneys, increase in serum creatinine is suggestive of reduced kidney function
2- inulin administered IV is a fructose polymer that is freely filtered by kidneys, if concentration does not reduce quickly then likely to be kidney issues
What is renal clearance?
The volume of plasma from which a substance is completely removed over unit time
How does glucose reabsorption occur?
Uptake via active transport from tubular fluid to vasa recta via transporters requires sodium
What is dapagliflozin used for? How does it work?
Treatment of diabetes mellitus aiming to reduce plasma levels of glucose. Blocks SGLT2 glucose transporter to reduce reabsorption from tubules
Name 3 efflux transporters found in the cells of the kidney. Which membrane do they lie on?
Multidrug resistance associated polypeptide
Breast cancer resistance protein
P-glycoprotein.
Found on basolateral membrane
What is chronic kidney disease?
Damage for over 3 months as evidenced by structural or functional abnormalities Abnormal GFR (may not be present) <60mL/min/1.73m
What is the main quantitative marker of kidney disease?
Albumin-creatinine-ratio >3mg/mmol
Why is serum creatinine not always accurate?
Proportional to muscle mass
Under what circumstances is a correction factor applied to GFR values? What is this correction factor?
African and Afro-Caribbean patients
Correction factor of x1.159
What test can be used where an improved assessment of risk is required?
Cystatin C based GFR
Give complications of reduced renal function.
Anaemia
CVD
Disordered bone mineral metabolism
Calcification of blood vessels
Give risk factors of chronic kidney disease.
Diabetes Hypertension Acute kidney injury CVD Family history Structural disease Systemic Lupus Haematuria
What are the standard management aims/treatments for chronic kidney disease?
BP <140/90mmHg or below 130/80mmHg with proteinuria
Good glycaemic control
Statin therapy
Avoid nephrotoxic drugs
ACE/ARB not to be used together
Three or more antihypertensive agents
Anticoagulants for secondary prevention of CVD
What are the risk factors for acute kidney injury?
Over 65 Acute illness/sepsis Hypovalaemia Hypotensive CKD Heart failure Diabetes Liver failure
How is acute kidney injury detected?
Rise in serum creatinine of >26umols/L in 48 hours
50% or more rise in creatinine over 7 days
Urine output <0.5mL/kg/hr over 6 hours (8 hours in children)
25% or more reduction in eGFR in young people over 7 days
What is the main benefit of haemodialysis?
Good/efficient removal of electrolytes
What are the disadvantages of haemodialysis?
Anaemia Hypotension Air embolism Infection Pruritis
What are the disadvantages of peritoneal dialysis?
Constipation
Pleural effusion
Sclerosing peritonitis
What is the standard protocol for immunosuppressant therapy post kidney transplant?
Ciclosporin/tacrolimus
With or without prednisone and mycophenolate/azothioprine
What is the treatment for rejection of transplantation in hospital?
Sirolimus
Methylprednisolone
Plasma exchange
Rituximab
What is the treatment for renal anaemia?
Serum ferritin 200-500mcg/L
Iron and erythropoietin replacement
What is mineral bone disease?
Osteoporosis etc
Deranged calcium, raised phosphate and increased levels of parathyroid hormone
When does acidosis generally occur? How is it treated?
With a GFR <30mL/min/1.73m
Corrected with oral sodium bicarbonate
What are the common side effects of haemodialysis? How can they be managed?
Hypotension due to rapid fluid removal, counteracted with bolus NaCl 0.9%
Cramps due to hypotension can be improved with quinine tablets
Chest and back pain due to complement activation can occur, a more biocompatible dialysed would be preferred
Give examples of drugs can can increase levels of cyclosporin/tacrolimus.
Amiodarone Erythromycin Ketoconazole Diltiazem Nifedipine Progestogens
Give examples of drugs can can decrease levels of cyclosporin/tacrolimus.
Rifampicin Carbamazepine Phenytoin Phenobarbitone St John's Wort
What are the nephrotoxic drugs?
Contrast agents Aminoglycosides NSAIDs Amphotericin Diuretics ACE inhibitors/ARBs
