1. Reabsorption & secretion Part - II

2. RENAL HANDLING OF WATER
180 liters of plasma filtered / day. But, only 1.5 liters of urine are excreted. 99% of water is reabsorbed.
Water reabsorption in PCT (70%):
Passive (secondary to active transport of NaCL, glucose & amino acids).
Obligatory water reabsorption (independent of ADH effect).
Helped by aquaporin 1 (= water channels) in luminal border of PCT.

3. RENAL HANDLING OF WATER
Water reabsorption in loop of Henle (15%):
In thin descending limb (permeable to water & less permeable to solutes) fluid reaching renal medulla becomes hypertonic.
In thick part of ascending limb (impermeable to water and allow some solutes to pass out to medullary interstitium)  fluid reaching into DCT becomes hypotonic.

4. RENAL HANDLING OF WATER
Water reabsorption in DCT & CD:
In first portion of DCT (5%):
as a continuation of thick ascending limb of loop of Henle.
Relatively impermeable to water & allow passage of solutes.
In late portion of DCT & CD (10%):
10% of H2O is reabsorbed.
Facultative water reabsorption (dependent on ADH effect).
ADH acts on aquaporin 2 in luminal border of CD (in principal cells).

5. At normal rate of ADH secretion:
10% of H2O is reabsorbed in Cortical CDs.
4.2% in Medullary CDs (changeable).
Total water reabsorption = 99.2 %
Urine volume = 1.5 L/day
Urine osmolality = 400 mosmol/litre (concentrated urine).

6. Hypervolemia & Overhydration.
ADH secretion
(= Urine Dilution)
Hypervolemia & Overhydration.
↓ Water-permeable area in MCDs → ↓ H2O reabsorbtion → excretion of a large volume of diluted urine with low osmolality.
In diabetes insipidus (= Impaired ADH secretion): Late parts of DCTs & whole length of CDs become water-impermeable → ↓ H2O reabsorption. While, Na+ reabsorption is continuous → ↓ osmolality of tubular fluid in CCDs to 90 mosmol/L.
- Large diluted Urine volume.
- Osmolality of Diluted urine < 80 mosmol/litre.

7. (= Urine Concentration)
ADH secretion
(= Urine Concentration)
Hypovolaemia (e.g. haemorrhage & dehydration)
& blood hypertoncity (e.g.  salt intake).
↑ H2O-permeable parts of Medullary collecting ducts (MCDs) → ↑ water reabsorbtion → excretion of concentrated urine with high osmolality.
In cases of maximal ADH secretion (severe haemorrhage): whole length of MCDs becomes water-permeable → 4.7 % of water is reabsorbed (instead of normal 4.2%) → total water reabsorption of 99.7%
- Urine volume = 0.5 L/day.
-Urine osmolality = 1400 mosmol/litre.

8. Renal Handling of K+ Functions of K+: K+ reabsorption:
Controls osmotic pressure inside cells & regulate ICF content.
Maintain resting membrane potential & repolarization processes.
Maintain intracellular pH (acidosis moves K+ outside cell).
K+ reabsorption:
65% is reabsorbed actively by PCT.
25% is reabsorbed by secondary active co-transport carrier (1Na+, 1K+, 2 Cl-) in thick ascending part of loop of Henle.
10% is reabsorbed from CD, only if aldosterone is absent.

9. K+ secretion & excretion:
Amount of K+ excreted in urine is derived from secretion rather than from filtration.
K+ is secreted in exchange with Na+ by aldosterone at principal cells in DCT & CD.
At principal cells, Na+ - K+ ATPase pumps Na+ outside basolateral membrane and K+ to inside the cell. Then, K+ diffuses out to the lumen.

10. Factors that  K+ excretion Factors that  K+ excretion
↑ K+ intake (fresh fruits & vegetables )
↓ Amount of K+ intake.
↑ Aldosterone.
↓ Aldosterone.
↑ Tubular flow rate via distal parts.
↓ Tubular flow via distal parts.
Some diuretics.
Aldactone
Chronic acidosis
Acute acidosis
↑ H+ secretion at DCT & ↓ K+ secretion (competition).
↑ Excretion of anions as Cl-, HCO3-.
Endothelins, IL-1, PGE2 & ANF.

11. Renal Handling of Glucose
Glucose is “preferred fuel” for many tissues and “only fuel” for brain & cornea.
Glucose is nearly completely reabsorbed by PCT (glucose clearance is nearly zero) & only negligible milligrams may be found in urine over 24 hours.
Mechanism: reabsorbed by Secondary active transport (= co-transport mech.) coupled with Na+ reabsorption in the first half of PCT.

12. Renal Handling of Glucose
At luminal border:
Common carrier (SGLT2 = Sodium- Dependent Glucose Transporter) binds both Na+ & glucose.
Na+ diffuses to inside cell along electro chemical gradient.
Glucose is carried into cell actively against concentration gradient.
Energy needed for this transport is derived from energy released by Na+- K+ ATPase at basalateral border of cells.
Insulin is not essential for glucose transport in PCT.

13. Renal Handling of Glucose
At basolateral border:
Glucose is passively transported into interstitium by facilitated diffusion helped by carrier GLUT2 (Sodium- independent).
N.B. Glucose reabsorption is inhibited by Phlorizin that competes with glucose
For carrier (SGLT) & Oubain that blocks Na+- K+ ATPase  Glucosuria.

14. Facilitated diffusion
Glucose Reabsorption
% 100% of glucose is reabsorbed in PCT
This process is saturable and rate limited, due to saturation of the carrier, and it has a Tm.
The excess filtered glucose is excreted in urine as in DM.
Na-K ATPase
2ry active transport
Facilitated diffusion

16. Renal threshold of glucose
Renal threshold of glucose: = 180 mg %.
Plasma level of glucose (=180 mg/dl) above which glucose starts to appear in urine. Below it, glucose does not appear in urine (= completely reabsorbed).
Above 180 mg/dl, glucose starts to appear in urine (glucosuria) and capacity of kidney to reabsorb glucose is increased due to enhanced activity of carries system of glucose transport.
At a certain glucose level, the carrier in the kidney becomes fully saturated and cannot transport any more glucose and thus any excess glucose is excreted totally in urine, this level is called tubular maximum transport of glucose “TmG”.

17. Tubular load of glucose
Tubular load of glucose: = GFR x glucose conc. in 1 ml Plasma.
Amount of glucose filtered to renal tubules per min. (= 125 mg/minute
if normal plasma glucose level = 100 mg %).

18. Tubular maximum transport of glucose (TmG)
Tubular maximum transport of glucose (TmG): = 375 mg/minute.
Def. Maximal amount of glucose reabsorbed by tubular cells per minute.
Value: it equals 375 mg/minute in males which is corresponding to plasma level = 300 mg/dl (300 mg/minute in females).
It is limited by number of substance-specific carriers.
Number of glucose carriers is not equal in all nephrons  TmG is not equal in different nephrons.

19. GLUCOSURIA GLUCOSURIA: Appearance of glucose in urine. Causes:
Diabetes mellitus due to severe hyperglycaemia.
Diet (Very high carbohydrate)  temporary glucosuria.
Renal Glucosuria (deficiency in carrier system of renal tubules)  glucose appears in urine while its plasma level is normal.
Pregnancy ( GFR) transient mild glucosuria.
No glucosuria despite high blood glucose level in chronic old diabetics may be due to  GFR   tubular of load glucose  reabsorbed completely.

20. Renal handling of proteins
Normally, 1% of albumin is filtered in the kidney but it is completely reabsorbed by Pinocytosis at PCT.
In nephritis,  negative charge in glomerular membrane  albuminuria.

21. Renal handling of amino acids
Renal handling of amino acids is similar to glucose reabsorption.
In PCT.
Secondary active transport.
Tm amino acids = 30 mg/min. (due to carrier saturation).

22. Amino acids Reabsorption
Amino acids e.g. glutamate and glycine are absorbed Na-dependent 2ry active transport
The transport is limited due to saturation of the carrier

23. Renal Handling of Calcium
Normal blood calcium level between 9-11 mg / 100 ml.
Forms:
50% in ionized form and performing most of calcium functions in body.
10% bound to other anions (as citrate and phosphates) and they can be filtered with the ionized form.
40% bound to plasma proteins acting as a pool for the ionized amount and this part can not be filtered like ionized calcium.

24. Renal Handling of Calcium
The most important functions of calcium:
Excitability of nerve and muscle.
Muscle contraction (cardiac, skeletal and smooth muscles).
Blood coagulation Bone and teeth formation.
Activation of many enzymes Controls cell membrane permeability.
Secretions of many hormones are calcium-dependent (as insulin).

25. Renal Handling of Calcium
99% of filtered Ca++ is reabsorbed as follow:
65% in PCT
25% in loop of Henle
10% in DCT

26. Renal Handling of Calcium
Factors affecting Ca++ reabsorption:
 Ca++ intake   Ca++ excretion.
Parathormone  Ca++ reabsorption in DCT & CD.
 Na+ reabsorption by PCT   Ca++ reabsorption by PCT.
 Phosphate in plasma   Parathormone secretion   Phosphate reabsorption in PCT and  Ca++ reabsorption in DCT & CD. This keeps solubility product constant.

27. Renal handling of Phosphate
Forms:
Inorganic: as calcium salts in bone and teeth (about 85%).
Organic: as ATP & creatine phosphate for energy supply and PH buffers.
Renal handling of phosphate:
Parathormone   Phosphate reabsorption in PCT &  Ca++ reabsorption in DCT & CD. This keeps solubility product constant.
Normally, dietary intake of phosphate is high and non-reabsorbed amount is used in distal tubular fluid as a Buffer for H+ ion.