Kidney And Diuretics Flashcards
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Kidney location
The kidneys are located either side of the vertebral column, between vertebrate T12 and L3
Main functions of the kidney
excretion of metabolic waste products
excretion of drugs
regulate the volume, electrolyte content (Na+/K+/Cl-) and pH of the extracellular fluid
Blood flow in the kidneys of average individual
1.2L per minute (~20-25% of cardiac output)
How much do kidneys filter per day?
~120L with 99% of water being reabsorbed
Gross structure of the kidney
Outer cortes, inner medulla, hollow pelvis
Nephron
Nephrons are the basic units of the kidney, with 400,000 - 800,000 present per kidney
Nephrons consist of:
Glomerulus, proximal convoluted tube, loop of Henle, distal convoluted tube, collecting duct
Where does blood enter the glomerulus?
Afferent arteriole (wide)
Where does blood leave the glomerulus?
Efferent arteriole (narrow)
Ultrafiltration
The high hydrostatic pressure forces small molecules in the tubular fluid such as water, glucose, amino acids, sodium chloride and urea through the filter, from the blood in the glomerular capsule across the basement membrane of the Bowman’s capsule and into the renal tubules
Resulting fluid of ultrafiltration
Called glomerular filtrate or ultrafiltrate
Virtually free of large proteins and blood cells
Further modification of ultrafiltrate leads to
Urine production
Regulation of osmolality
• Osmoreceptors in the anterior hypothalamus measure osmolality and stimulate release of vasopressin (ADH) from posterior pituitary gland in the brain.
• Vasopressin binds to V2 receptors on collecting duct cells and increases the number of aquaporins (water channels) facilitating water reabsorption by osmosis. Alcohol can reduce vasopressin release, acting like a diuretic.
Regulation of fluid volume
Baroreceptors in aortic arch respond to vascular stretch.
Macula densa cells of ascending loop of Henle sense NaCl concentration and flow. Decreased flow or reduced NaCl concentration causes the Juxtaglomerular granular cells in the kidney to release Renin resulting in activation of the Renin-Angiotensin System (RAS) and release of aldosterone from adrenal cortex, which leads to increased water reabsorption.
What influences water reabsorption?
Water permeability of the tubular epithelium
Osmotic gradient across the epithelium
Composition of filtrate
That of plasma, minus the proteins
65-70% of the volume of filtrate is reabsorbed from where?
The proximal tubule
There is the rest of the volume of filtrate reabsorbed?
Loop of Henle and distal tubule
Actions of diuretics
Diuretics generally work by reducing the reabsorption of NaCl, which results in the reduced reabsorption of H2O to maintain the osmotic balance.
Uses of diuretics
Used mainly in the treatment of oedema, hypertension and cardiac failure
5 main classes of diuretics
Carbonic a hydrate inhibitors
Loop inhibitors
Thiazides
Potassium-sparing aldosterone antagonists or Na+ channel blockers
Osmotics
Carbonic anydrase inhibitors
• Sodium bicarbonate (NaHCO3) is broken down into water and CO2 in the lumen of renal tubules
• The CO2 passes into the cells, where it is converted back into bicarbonate by carbonic anhydrase. This passes into the interstitial fluid and back into the blood
• Inhibition of carbonic anhydrase causes increased secretion of bicarbonate (along with accompanying Na+, K+ and water)
• Inhibitors of carbonic anhydrase (e.g. acetazolamide) are rarely used as diuretics now
• They are sometimes used to treat fluid build-up in glaucoma
Loop Diruretics
• Loop diuretics (e.g. furosemide) are the most powerful diuretics.
• They act at the thick segment of the loop of Henle.
• Normally the transport of Na+ and Cl- ions from the tubular lumen forms an osmotic gradient. This draws the water out of the nephron.
• Loop diuretics inhibit this ionic transport from the nephron into the interstitial fluid, therefore reducing re-uptake of water.
• e.g., furosemide inhibits a co-transport system that pumps Na+, K+ and 2Cl- ions into the cells.
• Loop diuretics are mainly used to treat oedema and cardiac failure.
Thiazides
• Thiazides (e.g. bendroflumethiazide) are moderately powerful diuretics.
• They act at the distal convoluted tubule.
• They inhibit the active reabsorption of Na+ and Cl-.
• They may act on an electroneutral Na+/Cl- co-transport system.
• They have no effect on the ascending loop of Henle.
Problems with loop diuretics and thiazides
Excessive potassium secretion, causing hypokalaemia.
• K+ loss is regulated by the principal cells of the collecting duct
• Increased Na+ in the tubular lumen (e.g. with loop diuretics, thiazides) increases K+ loss
• This causes disturbances in the heart, brain and skeletal muscle
• May therefore require oral K+ supplement
Potassium sparing diuretics
• Spironlactone and amiloride act on the principal cells of the collecting duct
• Spironlactone is a weak diuretic, acting as an antagonist at aldosterone receptors
• Aldosterone is an endogenous mineralocorticoid produced by adrenal glands. It enhances Na+ reabsorption from urine, and indirectly increases K+ excretion
• Aldosterone receptors act in the nucleus, stimulating mRNA transcription. Expression of Na+ channels and pumps is increased
• Release of aldosterone depends on the renin-angiotensin system
• Amiloride directly blocks the Na+ channels induced by aldosterone
Osmotic diuretics
• Osmotic diuretics (e.g. mannitol) are large molecules that are filtered into the glomerulus, but cannot be reabsorbed from the tubules.
• This reduces passive water reabsorption in the proximal tubule and descending loop of Henle.
• They are administered in large quantities intravenously.
