Urinary L5.2 Flashcards
1) What is natriuresis?
2) What is kaliuresis?
3) What is aquaretics?
1) Increased sodium excretion
2) Increased potassium excretion
3) Subtance causing net excretion of water
1) What is duiresis?
2) What is a diuretic?
3) What is the clinical use of diuretics?
1) Increased formation of urine by kidney
2) Drug promoting diuresis
3) In conditions where Na+ and water retention cause expansion of ECF volume (heart faiulre)
Structure of nephron
Describe the stages involved in the tubular reabsorption of sodium
- Na+ pumped into ECF across basolateral membrane by Na-K-ATPase
- Na+ moves across apical (luminal membrane) down concentration gradient
- Movement of Na+ utilises a membrane transporter / channel on apical memvrane
- Water moves down osmotic gradient created by Na+ reabsorption
1) Which transporter is common to all segments of the tubule (i.e. PCT, TAL, DCT)?
2) Different segments of the tubule have their own unique transporters and channels in apical membrane. What are the channels?
Na-KATPase
Diuretics - site of action
Describe the classification of diuretics by site of action
1) What is the site of action of carbonic anhydrase inhibitors?
2) In the PCT, which cells do they target?
3) Describe the mechanism of action of carbonic anhydrase inhibitors
1) PCT
2) PCT + brush border cells
3) Inhibits action of carbonic hydrase.
Causes Na+ to not be reabsorbed and stay in lumen, so more water stays in lumen
LEADS TO METABOLIC ACIDOSIS due to loss of HCO3
Useful in treatment of glaucoma (reduces formation of aqueous humour in eye)
1) What is the site of action of osmotic diuretics?
2) Describe their mechanism of action
3) State an example
4) What is the difference between osmotic diuretics and cabronic anhydrase inhibitors?
5) What condition are osmotic diuretics specially used for?
1) PCT, loop of henle (thin ascending limb)
2) Increase plasma osmolarity. Draw out fluid from tissues cand cells. The mannitol is freely filtered at glomerulus but is not reabsorbed. This increases osmolarity of filtrate. Cause loss of Na, K, water in urine.
3) Mannitol
4) Not inhibitors of enzymes / transport proteins
5) Cerbral edema. Water is drawn froma cross blood brain barrier, reducing cerebral edema + cranial pressure
1) What is the site of action of loop diuretics?
2) Desribe their mechanism of action
1) Thick asecnding limb
2. Inhibit action of Na2KCl transporter
1) What is the site of action of thiazide diuretics?
2) Mechanism of action
3) Why are thiazide diuretics less potent than loop diuretics?
1) Early DCT
2)Inhibit NaCl symporter. This increases Na + water loss. REDUCES CA LOSS IN URINE
3) Only 5% Na+ reabsorbed in DCT anyway. In fact, 25% in loop of henle
1)What is the site of action of potassium sparing diuretics + aldotseroen antagonists?
2) Why are these described as mild diuretics?
3) Mechanism of action
4) Why are they called potassium sparing diuretics?
5) What is the risk of potassium sparing drugs?
1) Late DCT, collectig duct
2) As you move through nephron, less Na being reabsorved. These diuretics only affect 2% of Na being reabsorbed
3) Target ENaC channels in late DCT and CCT (cortical collecting duct). Reduce Na channel acvity. Reduce loss of K.
4) Cause diuresis without loss of potassium in urine.
5) They can produce hyperkalemia
This is because they are blocking the loss of K in the urine. This means the extracellular conc of k in the ECF can increase.
Hyperkalemia can severely affect the heart
The risk is increased even further in patients who are taking potassium sparing drugs alongside ACE inhibitors or in patients with renal impairment.
1) What is the mechanism of action of aldosterone antagonists?
2) What cells of the LATE DT and CD does aldosterone act on?
1) Antagonise action of aldosterone
Competitively inhibit aldosterone receptor on collecting tubule cell, reducing expression of Na hannels and Na K pump. Reduces amount Na uptake and therefore, water uptake causing Na + water to be lost in urine
2) Principal cells
State a clinical situation where diuretics are used?
Edema
Describe the formation of tissue fluid
How does liver cirrhosis lead to ECF expansion and oedema?
How does liver cirrhosis lead to ASCITES?
TREATMENT
- Less albumin production in liver due to liver cirrhosis
- Low oncotic pressure
- Less pressure drawing water into capillaries
- Fluid accumulates in interstitial fluid
- Low circulatory volme, low plasma vol
- Triggers RAAS, More Na, water retention, = edema
ASCITES: condition in which fluid collects in spaces within abdomen
- Hypertenstion in portal vein
- Invrease venous pressure in splanchnic circualtion
- High venous pressure, low oncotic pressure
- Results in ascites
SPIRONOLACTONE
1)What type of diuretics are used in hypertension?
2)What type of diuretics are used in chronic kidney disease?
3) What type of diuretics are used in primary hyperaldosteronism (Conn’s syndrome)?
1) Thiazide
2) Loop diuretics
3) Potassium sparing diuretic = spironolactone
What are the adverse effects of diuretics?
- Primarily electrolyte imbalances, mainly potassium disturbances leading to hyperkalemia, hpokalemia
- Hypovolemia - loop diuretics.
Reduced ECF vol due to exccessive Na + water loss. - Hyponatremia
- Increase URIC acid levels in blood = GOUT
- Erectile disfunction (THIAZIDE)
Loop + thiazide diuretics increase loss of potassium in urine, therefore, cause HYPOKALEMIA
K+ sparing diuretics + aldosterone antagonists reduce excretion of potassium in urine, cause hyperkalemia
