TUBULAR SECRETION

1. Lecture-5 Dr. Zahoor TUBULAR SECRETION

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

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

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

5. Tubular Secretion • 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, NH3

6. Calculation of Tubular Secretion Secretion = Excretion - Filtration H+, K+,NH3 Organic acids and bases

7. Tubular Secretion • 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

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.

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

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

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

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

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

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)

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 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+}

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

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

24. 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

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