pharma fouda 1_p101-103.pdf

Part 1 1: Basiic inform mation ▌TUBU ULAR FUN NCTION AN ND URINE E FORMAT TION  Thee renal bloo od flow (RB BF) is 1.1 L /min (~ 22%...

Part 1 1: Basiic inform mation ▌TUBU ULAR FUN NCTION AN ND URINE E FORMAT TION  Thee renal bloo od flow (RB BF) is 1.1 L /min (~ 22% 2 of CO OP).  Thee glomerulaar filtration n rate (GFRR) is 125 ml/min. m  Thee capillary tuft filtrate es ~ 180 L of fluid per day. 99% of thhe filtered fluid is reab bsorbed ag gain during g passage e in the renal tubules..  Watter reabso orption is usually u 2ryy to Na+ re eabsorptioon (exceptt in the co ollecting ug that ↓ Na reabs tubules; ‘CT’)). Any dru + = ↑ Na lo sorption (= + oss), also ↓ water bsorption (= ↑ water loss or ‘di uresis’). reab Tubular reabsorrption and sites of ac ction of 3 ty ypes of diuuretics 87  Proximal convoluted tubules (PCT):  Reabsorption: (75% of the glomerular filtrate). – Active reabsorption of Na+ (~65%). – Passive (2ry to Na+) reabsorption of equiosmotic amount of water. – Reabsorption of all filtered K+, glucose, amino acids, and drugs.  Secretion: active secretion and reabsorption of organic acids and bases into tubular fluid. Loop of Henle (LOH):  Descending limb: passive reabsorption of water due to hypertonicity of the medullary interstitium.  Ascending limb: active reabsorption of Na+ (~25%) (this causes hypertonicity of the medullary interstitium), Ca2+ and Mg2+. Distal convoluted tubules (DCT):  Proximal part: – Active reabsorption of Na+ (5-7%). – Passive (2ry to Na+) reabsorption of equiosmotic amount of water. – Active reabsorption of Ca2+ (under the influence of parathormone ‘PTH’).  Distal part: – Active reabsorption of Na+ (2–5%) in exchange with K+ (under the influence of aldosterone). – Passive (2ry to Na+) reabsorption of equiosmotic amount of water. Collecting tubules (CT): Reabsorption of water under the influence of ADH. ▌EDEMA AND EDEMATOUS CONDITIONS  Edema is defined as the accumulation of fluid in the interstitial space due to either: – Increased capillary hydrostatic pressure – Decreased plasma oncotic pressure. – Increased capillary permeability.  Edema can be either exudative (having high protein content) or transudative (having low protein content).  Exudative edema results from increased capillary permeability as part of the acute inflammatory response. It is usually localized to the site of inflammation and will not be considered in this chapter. 88  Transudative edema is usually generalized and is associated with renal Na+ retention. The three most common clinical causes are: – Congestive heart failure (CHF): the decreased COP causes renal ischemia which stimulates the renin-angiotensin-aldosterone system (RAAS) → Na+ and water retention → edema. – Liver cirrhosis: the cirrhotic liver cannot synthesize sufficient albumin and other plasma proteins → ↓ plasma oncotic pressure. Hypoalbuminemia together with portal hypertension and 2ry stimulation of RAAS cause fluid retention (edema) and accumulation of fluid in the peritoneal cavity (ascites). – Nephrotic syndrome: glomerular dysfunction causes excessive loss of plasma proteins in urine → ↓ plasma oncotic pressure → edema. Part 2: Diuretic classes and agents Diuretics are drugs that increase urine volume and Na+ excretion. Natriuretic: a drug that increase Na+ excretion by the kidney. Classification of diuretics: Renal diuretics E x t r a - r e n a l di u r e t i c s They act directly on the kidney: They act indirectly on the kidney: Thiazide diuretics: act on the Water diuresis: ↑ water intake → ↓ proximal part of the DCT e.g. ADH release → diuresis. hydrochlorothiazide. Digitalis in CHF: ↑ the COP Loop diuretics: act on the leading to ↑ RBF → diuresis. ascending limb of loop of Henle e.g. i.v. albumin in ascites or furosemide. nephrotic edema: to increase K+ sparing diuretics: act on the plasma osmotic pressure → distal part of the DCT e.g. mobilization of edema fluid toward spironolactone. the vascular compartment → ↑ RBF Osmotic diuretics: substances that → diuresis. ↑ the osmotic pressure of tubular fluid → ↓ water reabsorption by renal tubules e.g. mannitol. N.B. Carbonic anhydrase inhibitors e.g acetazolamide: they are weak diuretics that ↓ NaHCO3 reabsorption from the PCT and may cause metabolic acidosis. They also ↓ aqueous humor secretion and can be used in the treatment of glaucoma (see pharmacology of the eye). 89