Lectures

• Major roles of the kidneys are: maintaining water, electrolyte and acid-base balance.
• About 25% of cardiac output is received by the kidneys
• Kidneys balances excretion and absorption
• Kidneys create relative homeostasis by assisting in regulation of blood volume/pressure/pH and electrolytes and metabolites
• Reabsorption of molecules from filterate occurs in the PCT
• Blood vessels receiving reabsorbed molecules are peritubular capillaries
• Water leaves in the descending loop of henle
• salt leaves in the ascending loop of henle
• Secretion occurs in the DCT of the kidney
• In tubular secretion; additional wastes are removed from the blood and added to the filterate
• In tubular reabsorption, useful solutes are removed from the filtrate and returned to the blood
• Filtration is the first line of defence in the kidney
• Tubular reabsorption and secretion can occur at the PCT, LoH or DCT but each section does more of the specific action
• Filtrate is everything that enters the nephron
• 99% of Na in the kidneys is reabsorbed
• There are 2 mechanisms for Na reabsorption: Cation exchange and chloride ion transport
• Cation exchange: occurs at the PCT and DCT in which Na+ gets reabsorbed while H+ gets secreted
• For cation exchange, in the DCT specifically: Na+ is reabsorbed while K+ is secreted and this is controlled by the hormone aldosterone
• H+ in kidneys is produced in tubular cells when the enzyme Carbonic anhydrase catalyzes the reaction of CO2 and H2O into H2CO3 which is broken down into HCO3- and H+; this allows the kidney to maintain the blood pH
• Chloride Ion transport: occurs in the loop of Henle in which Cl- is reabsorbed which causes Na+ to also be reabsorbed(follows it); changes the charge association and water follows wherever Na+ goes.
• Within Chloride ion transport; water is pulled out of the urine back into circulation at the collecting ducts
• ADH works by widening the pores at the collecting ducts to allow water to be retained
• 5 types of Diuretic drugs: osmotic diuretics, carbonic anhydrase inhibitors, organic acid diuretics, thiazide diuretics and potassium sparing diuretics
• Osmotic diuretics: filtered by the glomerulus but can't be reabsorbed by the renal tubules; get trapped in the tubular lumen which creates an osmotic gradient that forces water towards the tubules rather than the circulation.
• Osmotic diuretics have no affect on Na+ so electrolyte balance nor pH balance is affected by them
• Osmotic diuretics cause mild diuresis without significant changes to acid/base or electrolyte imbalance
• Mannitol(Osmitrol) is the most common osmotic diuretic that's given IV to attract fluid from swollen tissues.
• Mannitol(Osmitrol) is used to stimulate urine flow in oliguria before irreversible renal damage and indicated for renal failure, drug toxicity and cerebral swelling
• Carbonic anhydrase inhibitors inhibits the enzyme carbonic anhydrase to prevent production of H+ and HCO3- which causes less H+ to be available for Na+ exchange so Na+ and water get excreted(decreases Na+ reabsorption).
• Refractory diuretics: given but there's no response because there's an acid-base imbalance.
• Acetazolamide(Diamox) is a carbonic anhydrase inhibitor and it is also a weak acid
• Acetazolamide(Diamox) and carbonic anhydrase inhibitors are refractory diuretics
• Thiazide/Thiazide-like diuretics: largest group of diuretics that are used in edema with hypertension but can alleviate it in CHF/CRF. They work by reducing plasma volume and relaxing vascular smooth muscle
• Thiazide and Thiazide-like diuretics are not chemically related but produce the same effects
• Thiazide and Thiazide-like diuretics work by inhibiting Na+ transport in the distal portion of the nephron; causing a significant loss of Na+ and water. This causes K+ and Cl- to also be excreted which may cause hypochloremic alkalosis and hypokalemia
• The adverse effects of thiazide and thiazide-like diuretics are hypotension and hyponatramia
• Thiazide diuretics are hydrochlorothiazide and chlorothiazide
• Thiazide-Like diuretics are metolazone(Zaroxolyn) and Indapamide(Lozide)
• Coversyl+ is indapamide(Lozide) and perindopril(Coversyl) combined
• Potassium sparing diuretics AKA aldosterone antagonists: inhibit K+ secretion in the DCT by blocking aldosterone receptors. This causes a loss of Na+ but no loss of K+.