1. 1 Lecture-5 Dr. Zahoor

2. Objectives – Tubular Secretion Define tubular secretion Role of tubular secretion in maintaining K + conc. Mechanisms of tubular secretion. 2

3. Three Basic Mechanisms (Renal Processes) Of Urine Formation include: 1.Glomerular Filtration 2.Tubular Reabsorption 3.Tubular Secretion URINE FORMATION 3

4. TUBULAR SECRETION  Tubular Secretion is transfer of substances from the peritubular capillaries (capillaries surrounding the tubule) into the tubular lumen.  It helps to eliminate the compounds from the body 4

5. Tubular Secretion 5 First step is simple diffusion from peritubular capillaries to interstitial fluid Entry from interstitial fluid to tubular cell can be active or passive Exit from tubular cell to lumen can be active or passive Examples: potassium, hydrogen, organic acids, organic bases, NH 3

6. Calculation of Tubular Secretion Secretion = Excretion - Filtration H +, K +, NH 3 Organic acids and bases 6

7. Tubular Secretion 7 Tubular secretion is important for:  Disposing of substances not already in the filtrate  Eliminating undesirable substances such as urea and uric acid  Getting rid of excess potassium ions  Controlling blood pH by secreting H +

8. TUBULAR SECRETION  The most important substances secreted are - Hydrogen ion - Potassium ion - Para Amino Hippuric acid ( PAH) - Organic anion and cations - Drugs e.g. penicillin, aspirin, Cemitidine - Hormones e.g. erythropoietin, renin 8

9. TUBULAR SECRETION Hydrogen Ion Secretion:  Hydrogen Ion Secretion is important in acid base balance  Hydrogen ion is secreted in the tubular lumen and eliminated from the body in the urine  H+ ion is secreted in proximal, distal, and collecting tubule We will discuss H+ ion secretion in detail with acid base balance. 9

10. TUBULAR SECRETION Potassium Ion Secretion:  K + ion secretion is controlled by aldosterone  98% of K + is intracellular (ICF – K = 140meq/l)  ECF – K + = 4meq/l Slight changes in ECF – K + can affect the membrane excitability, therefore, plasma K + concentration is tightly controlled by the kidneys 10

11. TUBULAR SECRETION OF K +  K + is actively reabsorbed in PCT  Na + is actively reabsorbed and K + is actively secreted by principal cells in the distal and collecting tubules and controlled by Aldosterone.  Intercalated cells in DCT and CT actively secrete H + and K + ion  Intercalated cells work for acid base balance 11

12. Potassium handling by nephron

13. MECHANISM OF K + SECRETION  K + is secreted in the principal cell of DCT and CT. It is coupled to Na + reabsorption by energy dependent basolateral Na + - K + pump 13

14. 14 K + ion secretion

15. Principle cells in Late DCT & CT

16. CONTROL OF K + SECRETION  Most important control mechanism for K + secretion is by aldosterone  Aldosterone causes Na + reabsorption and K + secretion by principal cells  Increased K + concentration directly stimulates the adrenal cortex to increase aldosterone secretion  Decreased K + concentration in plasma – causes decreased aldosterone secretion NOTE – Aldosterone secretion by Na + is through Renin- Angiotensin Aldosterone mechanism 16

17. 17 Control Of Aldosterone Secretion By K + and Na +

18. 18 Sodium Reabsorption

19. Mechanism of Aldosterone Action Aldosterone : Aldosterone causes Na + re absorption and K + secretion by principle cell Aldosterone causes increased Na + entry through luminal membrane into principal cells Aldosterone causes Na + pumping out of principal cells by Na + -K + pump into interstial fluid at basolateral membrane Aldosterone causes K + entry into the cell by Na + - K + pump, it increases the concentration of K + in the cell, which is driving force for K + secretion (passively) 19

20. Changes in Distal K+ Secretion  Causes of increased Distal K + Secretion - High K + diet - Hyperaldosteronism - Alkalosis - Thiazide diuretics - Loop diuretics  Causes of decreased Distal K + Secretion - Low K + diet - Hypoaldosteronism - Acidosis - K + - sparing diuretics 20 NOTE Hyperaldosteronism – Hypokalemia Hypoaldosteronism – Hyperkalemia

21. EFFECT OF H + SECRETION ON K + SECRETION  During acid base regulation, intercalated cells in DCT secrete either K + or H +  When there is acidosis, H + ions secretion is increased and K + secretion is decreased  This decreased secretion of K + leads to K + retention in the body fluids, therefore, in acidosis, there is hyperkalemia {increased K + } 21

22. IMPORTANCE OF REGULATING PLASMA K + CONCENTRATION  K + plays important role in membrane potential  K + changes in ECF, when there is increase or decrease in K + level, it can affect the heart and can cause decreased cardiac excitability, decrease conduction, cardiac arrhythmia, fibrillation  K + changes not only affects cardiac muscle but it also affects skeletal muscle and nerve conduction 22

23. EFFECT OF DECREASED K +  Decreased K + causes hyperpolarization, which decreases the excitability of the nerve  In Skeletal muscle, K + depletion causes muscle weakness  K + depletion causes abdominal distension due to smooth muscle dysfunction 23

24. Organic Anion and Cation secretion  Proximal tubule contains two types of secretory carriers 1. For organic anions 2. 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

25. 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.

26. Thank you 26