1. RENAL SYSTEM PHYSIOLOGY
Dr Shahab Shaikh PhD, MD
Lecture – 5: Tubular Secretion
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College of Medicine
Al Maarefa Colleges of Science & Technology

2. OBJECTIVES
Qualitatively describe the forces that determine movement of reabsorbed fluid from interstitium into peritubular capillaries.
State the major characteristics of the proximal-tubular systems for active reabsorption of organic nutrients.
Understand pressure natriuresis, pressure diuresis and osmotic diuresis.
List the approximate percentages of the filtered load of sodium reabsorbed by the various tubular segments.
Understand the active step of sodium reabsorption in all sodium-reabsorbing segments.
Understand the mechanisms of water reabsorption.
Understand the water permeability characteristics of each tubular segment.
Understand the maximum urinary osmolarity.
Define obligatory water loss, and understand its determinants.

3. Urine Formation
Three Basic Mechanisms (Renal Processes) of Urine Formation include:
Glomerular filtration - GF
Tubular reabsorption - TR
Tubular secretion - TS

4. Tubular Secretion
It is transfer of substances from peritubular capillaries into the tubular lumen.
It is a supplemental mechanism that hastens elimination of some substances from the body.
H+, K+, NH3
Organic acids
and bases

5. Tubular Secretion Tubular secretion is important for:
Disposing of substances not already in the filtrate
Eliminating undesirable substances such as urea and uric acid
Ridding the body of excess potassium ions
Controlling blood pH by secreting H+

6. Tubular Secretion Most important substances secreted by the tubules:
Important in regulating acid-base balance
Secreted in proximal, distal, and collecting tubules K+
Keeps plasma K+ concentration at appropriate level to maintain normal membrane excitability in muscles and nerves
Secreted only in the distal and collecting tubules under control of aldosterone
Organic ions
Accomplish more efficient elimination of foreign organic compounds from the body
Secreted only in the proximal tubule

7. Potassium Regulation
Approximately 98 per cent of the total body potassium is contained in the cells and only 2 per cent in the extracellular fluid.
The normal potassium level in the blood is milliEquivalents per liter (mEq/L).
An increase in plasma potassium concentration of only 3 to 4 mEq/L above the normal can cause cardiac arrhythmias, and higher concentrations can lead to cardiac arrest or fibrillation.
Potassium contained in a single meal is often as high as 50 milliequilivants, and the daily intake usually ranges between 50 and 200 mEq/day.
Likewise, a small loss of potassium from the extracellular fluid could cause severe hypokalemia.
A rapid and appropriate compensatory response mechanism is vital to avoid dangerous Hyperkalemia or Hypokalemia.

8. Potassium Regulation K+ is tightly controlled by kidney
K+ is Filtered, Reabsorbed and Secreted.
K+ excretion can vary widely from 1% to 100% of filtered load depending on dietary K+ intake, aldosterone level and acid base status.
K+ is filtered freely in glomerular capillaries
K+ is actively reabsorbed in PCT and actively secreted in principal cell in DCT and CT
K+ filtered is almost completely reabsorbed in PCT and thick ascending limb of loop of Henle.
In DCT and CT, K+ is secreted depending on dietary K+ intake

9. Potassium Regulation

10. Potassium Regulation
Secretion of K+ occurs in principal cells. Aldosterone acts on principal cells in DCT and CT and causes Na+ absorption and K+ secretion.
Increased K+ causes increase aldosterone from adrenal cortex directly.
At basolateral membrane of principal cell, K+ is actively transported into the cell by Na+-K+ pump.
At luminal membrane, K+ is passively secreted into the lumen through K+ channel.

11. Potassium handling by nephron(continued)
Distal tubule & collecting ducts :
Responsible for adjustment of K+ excretion by either re absorption or secretion as dictated by need
Intercalated cells : absorption of potassium if person is on low K+ diet
Principle cells : if person on normal or high K+ diet potassium is excreted by principle cells
The magnitude of potassium excretion is variable depending on diet & several other factors for eg.aldosterone,acid base status ,flow rate etc

12. Effect of H+ secretion on K+ secretion
During acidosis H+ secretion is increase lead to retention of K+.

13. Factors affecting K+secretion
Magnitude of K+ secretion is determined by the size of electrochemical gradient across luminal membrane
Diet:
High K+ diet concentration inside thus principle cells increases electrochemical gradient across membrane

14. Factors affecting K+secretion(continued)
Aldosterone :
Aldosterone Na+ re absorption by principle cell by inducing synthesis of luminal membrane Na+ channels & basolateral membrane Na+- K+ channel
more Na+ is pumped out of the cell simultaneously more K+ pumped into the cell
Thus increasing the electrochemical gradient for K+ across the luminal membrane that leads to increase K+ secretion

15. DUAL EFFECT OF ALDOSTERONE
Fall in Na+
- through RAAS
Increase in K+

16. Increases Na+ reabsorption - principal cells
Aldosterone Actions on Late Distal, Cortical and Medullary Collecting Tubules
Increases Na+ reabsorption - principal cells
Increases K+ secretion - principal cells
Increases H+ secretion - intercalated cells

17. Relationship between Na+ absorption & K+ secretion
High Na+ diet:
more Na+ will be delivered to principle cells ,more Na+ is available for Na+- K+ ATPase than more K+ is pumped into the cell which increases the driving force for K+ secretion
Diuretics :
loop & thiazide diuretics inhibit Na+ re absorption in part of tubule earlier to principle cells, so increases Na+ delivery to principle cells , more Na+ is reabsorbed & more K+ is excreted

18. Organic Anion and Cation secretion
Proximal tubule contains two types of secretory carriers
For organic anions
For organic cations
Organic ions such as Prostaglandin, epinephrine – after their action removed from blood
Non filterable organic ions also removed
Chemicals, food additives, non nutritive substances
Drugs – NSAID, antibiotics

19. PAH –EXAMPLE OF SECRETION
PAH is an organic acid
Used for measurement of renal plasma flow
Both filtered and secreted
PAH transporters located in peritubular membrane of proximal tubular cells.
There are parallel secretory mechanism for secretion of organic bases like quinine and morphine

20. References Human physiology by Lauralee Sherwood, 8th edition
Text Book Of Physiology by Guyton & Hall, 11th edition
Review of Medical Physiology by Ganong. 24th edition

21. THANK YOU