urine production

Urine production

If body fluids are hypo osmolar, then kidney will produces hypo osmolar urine. (Dilute urine)
If body fluids are hyper osmolar (dehydration) then kidney produces hyperosmolar urine. (concentrated urine)
In the renal cortex the osmolarity of interstitial fluid is 300mOs/L going to 1200mOs/L in the papilla.
From the cortex to the papilla there is an increasing hyper osmolarity of the interstitial fluid. Cortico papillary osmolarity gradient.
Urine with osmolarity more than 300mOs/l is hypertonic.
Urine with osmolarity 300mOs/l is isotonic.
Urine of osmolarity below 300mOs/l is hypotonic.

How is cortico papillary gradient is made

1. Counter Current multipliers

Descending part of loop of Henley is thin and ascending is thick.
Osmolarity in plasma is 300mOs/l.
65% of the Na+ Cl , water, 100% glucose AA and 90-95% of the bi carbs are absorbed in the proximal tubule.
The osmolarity of the fluid leaving the proximal convoluted and going into the loop of Henley is the same as the proximal tubule, which is freely permeable to water.
Solutes and solvent are reabsorbed in the same proportions (Iso osmotically- osmolarity does not change.) and therefore the osmolarity remains the same (300mOs/l)
The cells in the baso lateral side of the ascending part of loop of Henley contain sodium/potassium ATP ase, these constantly remove NA+ and accumulate K+.
The Na+ and K+ carrier protein (Sodium/potassium cotransporter) is present on the luminal membrane of the ascending part of loop of Henley.
This carrier protein will transport 1 Na+, 1 K+ and 2 Cl- into cells.
This part of the nephron is water impermeable. Tubular fluid with therefore become diluted as the solutes are being removed
The medullary interstitial fluid is now more concentrated.
The thick ascending part of the loop of Henley is making the interstitial fluid progressively more hyper osmoler and the decending part by releasing water into the interstitial fluid is constantly providing more and more hyper osmoler fluid to the ascending part of the loop.
The current of the fluid is moving is an counter direction.
The descending part is the water loosing part and the ascending part is the solute losing part especially the thick part.
This multiplies the capability of the system to make hyper osmoler interstitial fluid.
The fluid that enters the cortico area of the nephron is usually 100mOs/l
The proximal convoluted tubule and the descending part of the loop are always water permeable. There are tight junctions present but they are only able to keep the solutes in not water.
The thick ascending part is always water impermeable.
In the last part of the nephron, the water permeability is based on the presence of ADH.
In the distal tubule the is further loss of Na+ and Cl- , further diluting the tubular fluid to roughly 60mOs/l.
As the ascending area of the loop is present in the medulla then the this is referred to as medullary hyper osmolarity
The counter current multiplier system contains an active transport of solutes.
It is responsible for generating the hyper osmolarity of the medullary interstitial fluid.

2. Urea recycling in renal medulla.

Urea is a waste product of protein and AA catabolism.
Urea becomes highly concentrated as it moves through the loop and the distal tubule is urea impermeable.
Towards the end of the nephron urea becomes very concentrated.
In the last part of the nephron (papilla), in the inner medullary collecting tubule (cells have urea transporters), the cells are highly permeable to urea and some of it is reabsorbed just before most of it is lost into urine.
The reabsorbed urea contributes to about 30-35% of the hyper osmolality of the interstitial fluid in the medulla.
The reabsorbed urea diffuses back into the thin part of the ascending limb and is recycled through the loop once again

*Both of these mechanisms are amplified and more active in the presence of ADH and less active in the absence of ADH.

How cortico papillary gradient is maintained

1. Vasa recta as counter current exchangers

Vasa recta also has a counter current.
Its long thin walled vessel is parallel to the nephron loops of the medulla.
The vasa recta maintain the hypertonicity of the interstitial fluid by a mechanism called the counter current exchange.
As the vasa recta capillary descends it freely equilibrates with the interstitial fluid as its walls are freely permeable to water and solutes.
It there fore starts to lose water and absorbs solutes.
As it move from medullary interstitial fluid to cortical interstitial fluid, it then starts to absorb water and is removing solutes.
At the start of the vasa recta the osmolarity is 300 mOs/l
The solute has an osmolality of 325 mOs/l at the end of the
Counter current exchanger contains passive transport.
It is responsible for maintaining the hyper osmolarity.

Role of ADH

Principle cells are present in the late distal tubule, cortical collecting tubule and the medullary collecting tubule.
These principle nephron cells are ADH sensitive and also aldosterone sensitive.
If principle cells of the nephron are under the influence of aldosterone then they retain Na+ and water, and secrete K+.
If they are under the influence of ADH then they retain water only.
The receptor for ADH is present on the baso lateral membrane of the principle cell and the receptor is a 7-path receptor (passes the membrane 7 times).
Aldosterone is a lipid soluble hormone and can therefore directly inter into the principle cells, so its receptor is present within the cell.
ADH is a peptide hormone and it cannot enter into the cell, and therefore its receptor is on the surface of the cell.
The ADH stimulates the G stimulatory, which activates adenylyl cyclase, which can convert ATP into the cyclic AMP.
ADH therefore increases the AMP in the principle cells.
The AMP stimulates the enzyme protein kinase A.(A= AMP driven)
Protein kinase A is going to phosphorylate and activate certain transporter proteins.
AQUAPORIN TWO
Intracellular protein channels, theses are present in the cytoplasm, inserted in certain type of vesicles.
They are attached with transporter proteins.
Protein kinase A phosphorylates the transporter proteins on the vesicles containing the water channels.
When the proteins get phosphorylated the microfilaments start moving towards the lumen of the membrane.
When the membrane of the vesicle fuses with lumen of the lumen of the membrane, the water channels on the vesicle part make the membrane makes the membrane water permeable. This is dependent on ADH presence.
Aquaporin 3 and 4 are always present on the baso lateral membrane, which makes is highly permeable to water, but luminal membrane water permeability is dependent on the presence of ADH.
This mean that if ADH is not present then there are no aquaporin 2 channels on the luminal side and the person would pass the diluted urine, as none of the H2O can be absorbed due to lack of ADH.
In the absence of ADH the last part of the nephron is water impermeable.

When there are increased levels of ADH in the body then the last part of the nephron is very permeable to water.

The interstitial fluid in around the last part of the nephron is hyperosmolar and pulls the water from the diluted tubular fluid through osmosis, leading to more concentrated urine excreted.

ADH not only makes the last part of the nephron more water permeable, but it also increases the medullary interstitium, by enhancing the counter current multiplier system and also enhancing the urea recycling.

Thirst dehydration

When the body is losing water in a dehydrated state the blood osmolality can increase.
The hypothalamus has osmo receptors that are very sensitive to blood osmolality (hyperosmolor).
This hyper osmolarity stimulates the osmo receptors, they in turn, stimulate the supra optic nuclear neurons.
This leads to the release of ADH by the posterior pituitary.
Increasing the ADH levels in the blood.
ADH is synthesized in the hypothalamus, but it is stored in the posterior pituitary.

Thirst over hydration
Plasma osmolarity is low(hyposmolar blood)
No ADH secreted, which means the last part of the nephron becomes impermeable to water.
Patient passes hypoosmolar urine.