Exam 3 - Diuretics Flashcards
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What is the nephron and it’s function?
- Functional unit of kidney that allows filtration, reabsorption, and secretion of substances from the blood.
- Consists of renal corpuscle and tubules, not including the collecting ducts
What is the renal corpuscle and it’s function?
- Contains the Bowman’s capsule and glomerulus where blood plasma is filtered
Bowmans’s capsule: surrounds the glomerulus and catches filtrate from it. Comprised of connective tissue and epithelial cells.
Glomerulus: the capillary network that that contains afferent and efferent vessels.
What is the function of the proximal tubule?
- Connects renal corpuscle to the descending loop of Henle
- Where 80% of filtrate is reabsorbed like bicarb, NaCl, glucose, amino acids, water, K+
What is the loop of Henle?
- Comprised of thick descending, thin descending, thin ascending and thick ascending limbs. Descends into the medulla
- Descending loop is permeable to water by diffusion
- Ascending loop is impermeable to water and has active transport of NaCl
What is the distal tubule?
Connects loop of Henle to the collecting tubule/ducts
Where does filtration occur?
- Occurs by the movement of fluids from the glomerulus to the bowmans capsule (renal corpuscle)
Where does reabsorption occur?
Primarily in the proximal tubule, involves the selective transfer of essential solutes and water back into the blood.
Where does secretion occur?
Mainly in the distal tubule, involves the movement of waste from the blood into the nephron.
Where is the macula densa?
What is it’s function?
- A group of cells in the distal tuble adjacent to the glomerulus
- Monitors the osmolality and volume of the fluid in the distal tubule, then transmits the information to JG cells by releasing nitric oxide in order to adjust GFR.
Where is the juxtaglomerular apparatus?
What is it’s function?
- Located at the vascular pole of the renal corpuscle in the afferent arteriole.
- Comprised of macula densa, juxtaglomerular cells, and extraglomerular mesangial cells.
- It regulates blood pressure by activating the renin-angiotensin-aldosterone system via renin secretion.
Describe how the kidneys regulate GFR?
- Controlled by the juxtaglomerular apparatus
- An increased GFR (high BP or increased Na+) sensed by the macula densa cells via increased delivery of Na+, Cl-, and H2O.
- The JGA decreases secretion of nitric oxide leading to constriction of afferent arteriole which decreases blood flow through the glomerulus, resulting in decreased GFR.
- GFR is overall regulated by adjusting blood flow, altering capillary surface area, and controlling arteriole diameter.
What is the function of NHE3?
- “Sodium hydrogen exchanger” : a pump in the proximal tubule that pumps Na+ from the tubule lumen into the cell and H+ from the cell into the tubule. Na+ is then reabsorbed back to the blood via the Na+/K+ ATPase.
- The H+ pumped into the urine binds to bicarbonate to form carbonic acid
What is the function of carbonic anhydrase?
- Sits on the cell wall of the proximal tuble facing the urine and converts carbonic acid to H2O and CO2.
- CO2 can then diffuse across the PCT cell wall where it can combine with water and be transformed back into carbonic acid by carbonic anhydrase.
- Now HCO3- is in the PCT and can be reabsorbed back into the blood.
How does kidney osmolality affect water movement?
- Osmolality increases as the loop of henle descends into the medulla
- This causes water to move from the descending loop into the medulla to balanace the osmolality
- Because water left, the tuble has a high osmolality and NaCl will be actively transported from the ascending loop into the medulla to rebalance.
The ascending loop is impermeable to water
Where do carbonic anhydrase inhibitors work?
What is their affect on urinary electrolytes?
Side effects?
- Site of Action: Proximal convoluted tubule by preventing conversion of H2CO3 via CA inhibition, inhibits functioning of the NHE3 secondary active transporter.
- Urinary Electrolytes: loss of K+, Na+, and lots of NaHCO3
- Side Effects: Toxicity and metabolic acidosis from NaHCO3 wasting, reactions in pt’s with sulfa allergies, kidney stones
Acetazolamide- rarely used now
Where do loop diuretics work?
What is their affect on urinary electrolytes?
Side effects?
- Site of Action: Thick ascending limb by inhibiting NaCl reabsorption by blocking NKCC2
- Urinary Electrolytes: Greatly increases NaCl loss in urine, wastes K+ leading to slight alkalosis.
- Side Effects: Allergic reactions d/t sulfa allergen, increased loss of Mg and Ca d/t decrease in K+ permeability in tubule
Where do thiazide diuretics work?
What is their affect on urinary electrolytes?
Side effects?
- Site of Action: Inhibit NaCl transport in distal convoluted tubule via NCC inhibition, some CA inhibition
- Urinary Electrolytes: NaCl, NaHCO3, and K+ wasting
- Side Effects: Increase in body pH, allergic reactions if sulfa allergy
Hydrochlorothiazide
Where/how do potassium sparing diuretics work?
What is their affect on urinary electrolytes?
Side effects?
- Spironolactone: Blocks aldosterone receptor which causes inhibition of ENaC and Na/K pump
- Amiloride: Inhibits sodium reabsorption via ENaC
- Site of Action: Collecting tubule
- Urinary Electrolytes: Na+ increased
- Side Effects: Hyperkalemia
Most useful in states of mineralcorticoid excess (Conn’s syndrome)
Overview of nephron segments, function , and sites of drug action
What is potassium wasting?
When Na+ and NaHCO3 are inhibited to reabsorb, their concentration increases in the collecting tubule. This causes more Na+ to be reabsorbed through ENaC. NaHCO3 is negatively charged molecule that does not get reabsorbed. Both of these together lead to a more electronegative state in the CT incresing K+ outflow
What is the mechanism of potassium and bicarb wasting with specific diuretics?
- Diuretics upstream result in excess Na+ in collecting tubule by blocking NaCl (loop diuretics and thiazides). Cl- can be reabsorbed via the paracellular route reducing the electronegativity of the urine lessening potassium wasting.
- Diuretics that block NaHCO3 (Acetazolamide) cause significant K+ wasting because HCO3 can’t exit via paracellular route increasing CT electronegativity further
What are the 2 drugs that reduce potassium loss during diuresis?
How do they work?
- Spironolactone: blocks the aldosterone receptor which inhibits the ENaC channel and the Na/K pump causing more Na and water in lumen of the nephron. Since Na+ reabsorption is blocked in the CT, less K+ is effluxed.
- Amiloride: inhibits the Na flux by directly inhibiting the ENaC channels in the collecting tubule.
Describe the use of diuretics in diabetes insipidus?
- DI is a state of insufficent ADH leading to excessive urination.
- Thiazide diuretics can cause a decrease in urine output because they initially increase NaCl and H2O loss. This leads to a decrease in extracellular volume which results in a decreased GFR, allowing more Na+ and H2O to be reabsorbed in the PCT, opposing the effects of DI.
What hormone acts at the collecting duct?
What is its MOA?
What is its antagonist?
- ADH (vasopressin)
- Increases water reabsorption by increasing the number of aquaporins on the apical membrane
- This increases blood volume and creates more concentrated urine
- Conivaptan antagonizes ADH receptor
