Page created on December 14, 2018. Last updated on May 11, 2020 at 15:26
This topic mostly discusses the mechanisms and causes of polyuria and oliguria, and the function of diuretics.
Oliguria is defined as a urine production of less than 400 – 500 mL per day. At this point is the urine maximally concentrated (1200 – 1300 mOsm/kg), meaning that this is the least amount of urine a healthy kidney in a not-dehydrated body can produce. Oliguria can occur due to:
- Low GFR
- Very few functional nephrons, so that even increased SNGFR can’t compensate
- Kidney disease
- Too high tubular reabsorption
Anuria is a urine production below 50 mL per day.
Polyuria is defined as urinary output above 2 L per day. We differentiate primary and secondary polyuria:
Primary polyuria occurs when there is a primary fluid loss that later causes secondary polydipsia (increased thirst). Common causes include:
- Diabetes mellitus
- Diabetes insipidus
- Compensatory (early) phase of chronic renal failure
- Acquired tubulopathies that decrease reabsorption
- Treatment with diuretics
These conditions cause increased water excretion, which causes the fluid level in the body to drop, which will then trigger thirst. The person will then drink more.
Secondary polyuria occurs in response to large fluid intake, often due to primary polydipsia. It can occur in:
- Psychological causes
- Physiological causes
- Autoimmune chronic hepatitis
- Excessive salt intake
Diuretics are part of the pharmacology curriculum and shouldn’t be asked during the pathophysiology exam.
You can find a better overview of diuretics here.
There exist no drugs that increase the GFR (they wouldn’t be useful anyway, as increased GFR can damage the glomeruli). Most diuretics work by enhancing tubular salt loss, which makes water follow. The emptied water is non-reabsorbed filtrate, meaning that it originated from the intravascular space (the blood) and not the extracellular space. Diuretics are usually used to decrease the fluid volume in the extracellular space, and they do this because decreasing the intravascular volume causes extracellular fluid to “refill” the intravascular space.
Osmotic diuretics are osmotically active substances that are filtered but not reabsorbed in the tubules. They will therefore bind water, disallowing much of the water from leaving passively in the descending loop, and increase the volume of the filtrate that reaches the distal tubule. Here will more NaCl and bicarbonate be reabsorbed than normal, while K+ and H+ loss increases. Hypokalaemia and alkalosis may follow.
Loop diuretics are not filtered but secreted into the filtrate through the proximal tubules. They inhibit the salt reabsorption in the ascending loop of Henle. This messes with the countercurrent multiplication system, which decreases the cortico-medullary osmotic gradient and therefore causes hyposthenuria. More water reaches the distal tubule, where more NaCl and bicarbonate will be reabsorbed while K+ and H+ loss occurs, like for osmotic diuretics. Hypokalaemia and alkalosis may follow.
Carbonic anhydrase inhibitors inhibit carbonic anhydrase inside proximal tubule cells. This causes less bicarbonate to be reabsorbed, which will act as an osmotic diuretic. Due to less bicarbonate reabsorption will acidosis develop, and increased fluid in the distal tubules causes K+-loss. Acidosis and hypokalaemia may occur.
Thiazides inhibit salt reabsorption in distal tubules, causing more salt and therefore water to be excreted. K+ is still lost.
Epithelial sodium channel blockers like amiloride block sodium uptake in the last portion of distal tubules, meaning that H+ and K+ will be retained. However, because they act just the most distal tubules is there less time to affect the fluid composition of the filtrate, so the diuretic effect is only moderate.
Aldosterone antagonists like spironolactone do what the name suggest and prevent aldosterone from binding to mineralocorticoid receptors in renal tubules. Aldosterone increases sodium and water retention but increases potassium and H+ secretion. By blocking these effects can we increase diuresis while sparing potassium. However, the potassium sparing may be significant enough to cause hyperkalaemia.
Renal functions in the elderly
Renal size and volume decrease with age, along with the number of glomeruli. The result is a decrease in GFR.
Tubular function decreases, especially the ability to conserve sodium, along with a decreased cortico-medullary gradient, which causes hyposthenuria.
In elderly is the secretion of sodium and potassium higher at night, which causes nocturnal polyuria.