KIDNEY III - PRODUCTION OF DILUTE URINE BY THE KIDNEY
Describe the process of diuresis
OLIGURIA - Any output of urine below the minimum (0.428L/day)
POLYURIA - Excessive urine output (above 1-2L/day, maximum, around 23L/day)
OSMOLAR CLEARANCE - The clearance of all osmotically active particles, so the volume of plasma cleared of osmotically active particles per unit time of the fictive urine flow that would have resulted in a urine which was isomolar to plasma. - fasting osmolar clearance is 2-3ml/min
FREE WATER CLEARANCE - the ability of kidneys to excrete dilute or concentrated urine: 1.3-14.5ml/min C=V-(Vosm x V)/Posm
if the free water clearance is 0- then isomotic in relation to plasma, above that it is hyper osmotic and below it is hypo osmotic
Describe the control of ADH secretion from the pituitary gland and its effects on the kidney
Basically done in the previous post: osmoreceptors in brain hypothalamus: supraoptic and paraventricular nuclei detect high osmolarity, stimulate ADH release from the posterior pituitary gland, which then attaches to V2 receptors in the collecting duct which cause the exocytosis of the aquaporin-containing vesicles of the cells, increasing the permeability of the CD to water and allowing water reabsorption into the blood vessels, and therefore decreasing plasma osmolarity.
Explain the need to control osmolarity through thirst and urine production
Describe the role of the hypothalamus and osmoreceptors
Because our body cells, unlike those of plants, do not have cell walls, our cells are highly sensitive to changes in the osmolarity of their environment. It is therefore essential to maintain as constant as possible (dynamic equilibrium in reality) of blood plasma. This is done through changing the concentration of urine we produce: holding on to water when we need it and getting rid of it when we need it. This is coupled with a desire to drink water (polydipsia) when plasma osmolarity is high, ensuring that enough water is taken in the body while enough is allowed to be excreted with the waste we need to remove.
Osmolarity is detected by the supraoptic and paraventricular nuclei in the hypothalamus. Thirst is controlled by the lateral pre optic area. Not only are these cells capable of themselves detecting changes in plasma osmolarity, but also the presence of angiotensin II in the blood promotes their activation.
Describe diabetes insipidus and osmotic diuresis
What happens when this goes wrong?
Diabetes Insipidus "water diabetes": polyuria, polydipsia and nocturia
Can be either neurogenic (lack of ADH secretion due to congenital issues or head injury or brain tumour) or nephrogenic (inherited mutations in V2 receptors or aquaporin 2 channels, or acquired due to infection or side effects of drugs)
Osmotic diuresis?
Increased urination due to small molecules such as glycerol, mannitol and excess glucose in the renal tubule lumen (typical in untreated diabetes mellitus)
why?
1) Increased blood glucose
2) Increased glomerular filtration of glucose
3) Increased osmolarity in filtrate
4) Decreased water reabsorption from proximal tubule
and later portions of the nephron cannot compensate
Describe the renal handling of potassium
Let's think about how K+ acts in the body: it has high concentrations within cells and low concentrations in the ECF.
1) K+ is actively transported into the cell in the basolateral membrane by the Na+/K+ pump which we need to maintain the low Na+ concentration within the cell to drive reabsorption of everything else we need. There are K+ channels on this side that allow K+ not to accumulate within the cell.
2) On the luminal side, K+ is passively secreted into the lumen through K+ channels. The magnitude of this depends therefore on the electrical and chemical forces driving K+ across the luminal membrane.
- so if you increase the intracellular K+, you will increase the secretion: for example then aldosterone increasing the Na+ out and K+ in will also increase the K+ secretion into the lumen because its increasing the overall amount of K+ within the cell. (Aldosterone also increases the number of luminal membrane K+ channels). So hyperaldosteronism causes hypokalemia (and the opposite).
Acid-Base
K+ is tied to acid-base issues because K+ and H+ exchange for each other across the basolateral membrane.
Therefore, acidosis will increase the H+ concentration outside the cell, decrease the H+ excretion, and decrease the K+ absorption. So therefore, the amount of intracellular K+ will decrease (less is coming in from the basolateral side) and the driving force for K+ excretion into the lumen will decrease. Acidosis decreases K+ secretion into urine.
Alkalosis increases the amount of H+ secreted into the blood, increasing the amount of K+ entering the basolateral side of the cell, increasing the driving force for K+ to leave the cell, and increasing K+ secretion into the urine
Thiazide and loop diuretics
Increase K+ secretion
They increase the flow rate through the distal tubule and collecting ducts, causing dilution of the luminal K+ concentration, increasing the driving force for K+ secretion, causing hypokalemia.
K+ sparing diuretics
Antagonists of alsodsterone or act directly on principle cells: spironolactone. They decrease K+ secretion, used alone they cause hyperkalemia. They are usually used in combination with thiazide or loop directs to offset urinary K+ losses.
IMPORTANT CONCEPT
Increasing the amount of urine output, through for example diurectics, will decrease reabsorption (because less chance of colliding with the channels and pumps) and will increase the secretion (by increasing the driving forces through dilution of the luminal content).
Overall, 95% of K+ filtered through the kidneys is reabsorbed.
65% of it is reabsorbed passively in the proximal tubule, flowing through the spaces between cells with water and other ions.
30% of it is reabsorbed in the thick ascending limb in the NKCC contransproter
and then 5% of it is reabsorbed in the distal tubule via the K+/H+ exchanger
In the intercalated type A cells, more of it is absorbed in exchange for H+, but this is outweighs by K+ secretion by principle cells. Aldosterone stimulates this!
The channels are the ROMK - renal outer medullary channel and BK - the Ca2+ activated Big-conductance K+ channel
and also K+/Cl- cotransporters
What affects K+ flow?
1) How much Na+ enters the cell, so anything that affects Na+ flow
2) Aldosterone increases K+ secretion
3) Tubular flow rate. High flow rates favour secretion
4) Acid-base balance. Acidosis inhibits its and alkalosis enhances it