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Renal Principles


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Renal Principles

  1. 1. Renal Revision Renal Revision
  2. 2. Learning objectives • Blood supply to the kidneys • Function of the kidneys • RAAS and hypertension • Acidosis and alkalosis • UTIs and treatment • Renal failure and dialysis • Mechanism of action of diuretics
  3. 3. Functions of the kidney • Regulation of body fluid volume and osmolality • Regulation of electrolyte balance • Regulation of acid-base balance • Excretion of waste products (urea, ammonia, drugs, toxins) • Production and secretion of hormones • Regulation of blood pressure  Maintaining balance
  4. 4. Blood supply
  5. 5. A. Renal Vein B. Renal Artery C. Ureter D. Medulla E. Renal Pelvis F. Cortex 1. Ascending loop of Henle 2. Descending loop of Henle 3. Peritubular capillaries 4. Proximal tubule 5. Glomerulus 6. Distal tubule Structure of the kidney and nephron
  6. 6. The Nephron • Functional unit of the kidney (1,000,000) • Responsible for urine formation:
  7. 7. • Glomerulus • Afferent and Efferent arterioles • Proximal Tubule • Loop of Henle • Distal Tubule • Collecting Duct Components of the nephron
  8. 8. Overview of nephron function
  9. 9. • Components of plasma cross the 3 layers of the glomerular barrier • Capillary endothelium • Basement membrane (net negative charge) Plasma is filtered through the glomerular barrier • Epithelium of Bowman’s Capsule (Podocytes –filtration slits allow size <60kD) • The ability of a molecule to cross the membrane depends on size, charge, and shape • Glomerular filtrate therefore contains all molecules not contained by the glomerular barrier - it is NOT URINE YET!
  10. 10. Filtration barrier Capillary hydrostatic pressure Podocytes with foot processes Fenestrated endothelium Bowman’s space Glomerular capillary Basement membrane Intracapsular pressure Colloid osmotic pressure of plasma Pb
  11. 11. K+ Secretion • Final [K+] controlled in collecting duct by aldosterone – When aldosterone is absent, no K+ is excreted in the urine • High [K+] or low [Na+] stimulates the secretion of aldosterone • Only means by which K+ is secreted Insert fig. 17.24
  12. 12. Glomerular Filtration Rate (GFR) • Measure of functional capacity of the kidney • Volume of plasma from which a substance (e.g. creatinine) is completely removed in 1 min by excretion in the urine • Dependent on difference in pressures between capillaries and Bowman’s space • Normal = 120 ml/min = 7.2 L/h = 180 L/day!! 179 L of fluid filtered is reabsorbed!
  13. 13. Glomerular Filtration Rate (GFR) GFR = U x V P • U = concentration of substance in urine • V = urine volume per minute • P = concentration of substance in plasma • Estimated GFR ([Creatinine], age, sex (M↑F↓), ethnicity)
  14. 14. Clearance of Urea • Urea is secreted into blood and filtered into glomerular capsule • Urea clearance is 75 ml/min, compared to clearance of creatinine at 120 ml/min – 40-60% of filtered urea is always reabsorbed • Passive process because of the presence of carriers for facilitative diffusion of urea
  15. 15. Reabsorption • Active Transport (requires ATP) – Na+, K+ ATP pumps • Passive Transport – Na+ symporters (glucose, amino acids, etc) – Na+ antiporters (H+) – Ion channels – Osmosis
  16. 16. Factors influencing reabsorption • Saturation: Transporters can get saturated by high concentrations of a substance - failure to resorb all of it results in its loss in the urine (eg, renal threshold for glucose is about 180mg/dl) • Rate of flow of the filtrate: affects the time available for the transporters to reabsorb molecules
  17. 17. What is reabsorbed where? • Proximal tubule - reabsorbs 65 % of filtered Na+ as well as Cl-, Ca2+, PO4, HCO3 -. 75-90% of H20. Glucose, carbohydrates, amino acids, and small proteins are also reabsorbed here • Loop of Henle - reabsorbs 25% of filtered Na+ • Distal tubule - reabsorbs 8% of filtered Na+ and reabsorbs HCO3- • Collecting duct - reabsorbs the remaining 2% of Na+ only if the hormone aldosterone is present. H20 depending on hormone ADH
  18. 18. Secretion • Proximal tubule – uric acid, bile salts, metabolites, some drugs, some creatinine • Distal tubule – Most active secretion takes place here including organic acids, K+, H+ and drugs
  19. 19. Hormones produced by the kidney • Renin: – Released from juxtaglomerular apparatus when low blood flow or low Na+. Renin leads to production of angiotensin II, which in turn ultimately leads to retention of salt and water • Erythropoietin: – Stimulates red blood cell development in bone marrow. Will increase when blood oxygen low and anemia (low hemoglobin) • Vitamin D3: – Enzyme converts Vit D to active form 1,25(OH)2VitD. Involved in calcium homeostasis
  20. 20. Renin-Angiotensin-Aldosterone system: Regulation of Salt/Water Balance
  21. 21. ACE
  22. 22. Acid-base regulation
  23. 23. DETERMINE STATUS OF pH: pH > 7.45 = alkalaemic pH < 7.35 = acidaemic Step 1
  24. 24. DETERMINE RESPIRATORY COMPONENT: Normal PaCO2 = 4.5-6.0 kPa (below = respiratory alkalosis, above = respiratory acidosis) Step 2
  25. 25. DETERMINE METABOLIC COMPONENT: Normal HCO3 = 22-26mmol/L (below = metabolic acidosis, above = metabolic alkalosis) Normal base excess (BE) = -2 to 2 Step 3
  26. 26. COMBINE THE INFORMATION FROM STEPS 1-4 Interpret in clinical context Which is main component and which is compensatory? Is the compensation full or attempted? Step 4
  27. 27. Typically E. Coli (also Proteus, Klebsiella, Staph e.g. epidermidis) Risk Factors: • Gender (ascending infection- shorter urethra in females) • Stasis of urine (eg renal calculi, reflux, tumours) • Medical plastic (catheters) P/C: Lower UTI (cystitis & urtheritis)- frequency, urgency, dysuria Upper UTI (pyelonephritis)- as above plus fever, loin pain, rigors Ix: • Pre-treatment MSSU for microscopy & culture. Urine dipstick • May need structural /functional imaging to rule of reflux & renal scarring if UTIs recurrent UTI
  28. 28. Common causes of UTI
  29. 29. Clinical features of UTI Upper UTIs - Fever, nausea, malaise, loin pain, tenderness Acute lower UTIs cause: - Dysuria, urgency, frequency, nocturia, haematuria, suprapubic pain, smell
  30. 30. Types of UTI • Uncomplicated - UTI by a usual pathogen in a normal urinary tract in a person with normal renal function • Complicated - UTI where there is anatomical, functional, pharmacological factors predisposing to persistent infection
  31. 31. Complicated UTI • Anatomical: stones, vesicoureteric reflux, neurogenic bladder, catheter, urinary obstruction • Virulent microorganism: S aureus • Impaired host defence: diabetes mellitus, immunosuppressed • Impaired renal function or post renal transplant
  32. 32. Laboratory diagnosis – urine collection • Urine in bladder is normally sterile • Clean-MSU – before antibiotics • Collected into sterile container • Cultured within one hour or held at 4C
  33. 33. Infection Properly collected MSU contain >105 CFU/ml of single bacterial spp Vs Contamination 104 CFU/ml – more than one spp
  34. 34. Dipstick • Detects urinary nitrite • Detects urinary leucocyte esterase • Not suitable in pregnant women +/+ =UTI very likely – treat empirically -/- = UTI unlikely – no treatment -/+ = Possible UTI – consider culture…..
  35. 35. Renal drugs
  36. 36. Identify the main site of action of: - loop diuretics - thiazide diuretics - aldosterone antagonists
  37. 37. Site of Action of Diuretics
  38. 38. Mechanisim of Action of Diuretics
  39. 39. Diuretics: thiazide Bendroflumethiazide • MOA: inhibit Na reabsorption in DCT • Indications: Hypertension, heart failure • Cautions: can worsen gout, diabetes • NOT IN PREGNANCY • Side effects: postural hypotension, hypok+, hypona+, hypomg+, hyperca2+,gout (hyperuricaemia)
  40. 40. Furosemide • MOA: Na/K/2Cl co-transporter blocker • Indications: oedema e.g. HF, resistant hypertension • Cautions: can worsen gout, diabetes • Contra-indications: hypok+, anuria • Side effects: postural hypotension, hypok+, hypona+, hypomg+ Diuretics: loop
  41. 41. Spironolactone • MOA: aldosterone receptor antagonist • Indications: oedema/ascites from liver cirrhosis, heart failure, primary hyperaldosteronism • Cautions: look out for hyperk+ • Contra-indications: hyperk+, Addison’s disease • Side effects: gynacomastia, testicular atrophy, menstrual disorders, alopecia, hirsutism Diuretics: K+ sparing
  42. 42. Amiloride and Triamterene • MOA: block luminal Na channels in collection system (usually controlled indirectly by aldosterone) • Indications: oedema, K conservation (amiloride: CCF, hepatic cirrhosis) • Cautions: monitor electrolytes • Contra-indications: hyperk+, Addison’s disease Diuretics: K+ sparing
  43. 43. Renal Effects of Drugs
  44. 44. Glomerular filtration - gentamicin digoxin Proximal tubular secretion - methotrexate salicylates Renal excretion of drugs
  45. 45. Should be avoided in renal failure e.g. NSAIDs, ACE-I, ARBs, aminoglycosides, large doses of penicillins, ciclophosphamide, ciclosporine A, gold, penicillamine What are the general principles of prescribing in renal failure? • Reduced dose and/or increase the dosage interval according to renal function, especially with drugs which have a small therapeutic index • Base changes on measures of renal function i.e. glomerular filtration rate, serum creatinine • Use plasma levels if possible – digoxin, gentamicin, ciclosporin. • Avoid drugs which are nephrotoxic Nephrotoxic drugs