1. Regulation of Extracellular Fluid Osmolarity and Sodium Concentration
For the cells of the body to function properly, they must be bathed in extracellular fluid with a relatively constant concentration of electrolytes and other solutes.

2. Total Concentration Of Solutes
Osmolarity is determined by the amount of solute divided by the volume of the extracellular fluid.
Thus, to a large extent, extracellular fluid sodium concentration and osmolarity are regulated by the amount of extracellular water.

3. Level Of Body Water It is controlled by:
Fluid intake, which is regulated by factors that determine thirst.
Renal excretion of water, which is controlled by multiple factors that influence glomerular filtration and tubular reabsorption.

4. Functions of Kidney
The normal kidney has tremendous capability to vary the relative proportions of solutes and water in the urine in various states.

5. Kidney can excrete a large volume of dilute urine or small volume of concentrated urine without major changes in rates of excretion of solutes such as sodium and potassium.

6. This ability to regulate water excretion independently of solute excretion is necessary for survival, especially when fluid intake is limited.

7. Formation of Dilute and Concentration Urine
Osmolarity of glomerular filtrate is same as that of plasma i.e 300 mOsm/L.
Urine can be concentrated to a maximum of 1200mOsm/L.

8. The formation of a dilute or concentrated urine depends upon two factors:
Medullary gradient.
Antidiuretic hormone.

9. Anti-Diuretic Hormone
Rate of ADH secretion to a large extent determine, whether dilute or conc. urine is going to be excreted.

10. Osmolarity Of The Body Fluids:
Conc. body fluids due to increase solutes.
Secretion of ADH by Posterior pituitary
Increase permeability of water from distal tubules and collecting ducts.
Absorption of large amounts of water

11. Decreased urine volume ( without altering rate of renal excretion of the solutes).

14. Osmolarity Of The Body Fluids:
Excess water in the body fluids
Decrease ADH secretion
Reduce permeability of water from distal tubule and collecting ducts
Excretion of large amount of dilute urine.

16. Medullary Hyperosmolarity
Osmolarity of the interstitial fluid in the renal medulla near the cortex is 300 mOsm/L.
Towards the inner part of medulla, it increases gradually and reaches the maximum at the inner most part of medulla near renal sinus i.e 1200 mOsm/L

18. Medullary Gradient
The gradual increase in the osmolarity of the medullary interstitial fluid is called the medullary gradient.
The vertical osmotic gradient remains constant.

20. Development and Maintenance of Medullary Gradient
Kidney has some unique anatomical arrangements, which are responsible for the development of medullary gradient and for the hyperosmolarity of interstitial fluid in the inner medulla. These arrangements are together called Counter current system.

21. Counter Current System
In kidney, the structures which form the counter current system, are the Loop of Henle and the Vasa recta.
It is a system of “U” shaped tubules in which, the flow of fluid is in opposite direction in different limbs of the “U” shaped tubules.

23. In both, the direction of flow of fluid in the descending limb is just opposite to that in the ascending limb.
Loop of Henle forms the Counter Current Multiplier.
Vasa recta form the Counter Current Exchanger.

25. MOA Of The Counter Current System.

26. Long loops of Henle establish the vertical osmotic gradient.
Vasa recta , prevent the dissolution of this gradient while providing blood to the renal medulla.

27. Collectively, this entire functional organization is known as the Medullary Counter Current System.
Collecting tubules in conjunction with the vasopressin, use the gradient to produce urine of varying concentrations.

29. At The Level Of The Proximal Tubule
Immediately after the filtrate is formed, uncontrolled osmotic reabsorption of filtered water occurs in the proximal tubule secondary to active Na+ reabsorption.

31. By the end of the proximal tubule, about 65% of the filtrate has been reabsorbed.
35% remaining in the tubular lumen still has the same osmolarity as the body fluids.
Therefore, the fluid entering the loop of Henle is still isotonic.

34. At The Level Of loop of Henle
An additional 15% of the filtered H2O is obligatorily reabsorbed from the loop of Henle during the establishment and maintenance of the vertical osmotic gradient, with the osmolarity of the tubular fluid being altered in the process.

36. Descending Limb Of Loop Of Henle
It carries fluid from the proximal tubule down into the depths of the medulla.
Is highly permeable to water.
Does not actively extrude Sodium ions.

38. Ascending Limb Of Loop Of Henle

39. Carries fluid up and out of the medulla into the distal tubule.
Actively transports NaCl out of the tubular lumen into the surrounding interstitial fluid.
Impermeable to water so salt leaves the tubular fluid without water osmotically following along.

41. Ability of kidney to form a urine that is more concentrated than plasma is essential for survival.

42. Water is continuously lost from the body through various routes:
Lungs
Gastrointestinal tract
Skin
kidneys

43. Fluid intake is required to match this loss, ability of the kidney to form a small volume of concentrated urine minimizes the intake of fluid required to maintain homeostasis, this function is especially important when water is in short supply.

44. Obligatory Urine Volume

45. A normal 70-kg human must excrete about 600 milliosmoles of solute each day.
Maximal urine concentrating ability is 1200 mOsm/L.
Minimal volume of urine excreted is called Obligatory urine volume.

46. Obligatory Urine Volume
It is calculated by:

47. End Of Todays Lecture!!!