TUBULAR SECRETION Lecture-5 Dr. Zahoor 1 Objectives –Tubular Secretion Define tubular secretion Role of tubular secretion in maintaining K+ conc. Mechanisms of tubular secretion. 2 URINE FORMATION • Three Basic Mechanisms (Renal Processes) Of Urine Formation include: 1. Glomerular Filtration 2. Tubular Reabsorption 3. Tubular Secretion 3 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 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 5 Calculation of Tubular Secretion Secretion = Excretion - Filtration H+, K+, NH3 Organic acids and bases 6 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+ 7 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 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 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 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 Potassium handling by nephron 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 K+ ion secretion 14 Principle cells in Late DCT & CT 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 ReninAngiotensin Aldosterone mechanism 16 Control Of Aldosterone Secretion By K+ and Na+ 17 Sodium Reabsorption 18 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 Changes in Distal K+ Secretion Causes of increased Causes of decreased Distal K+ Secretion Distal K+ Secretion - High K+ diet - Low K+ diet - Hyperaldosteronism - Hypoaldosteronism - Alkalosis - Acidosis - Thiazide diuretics - K+ - sparing diuretics - Loop diuretics NOTE Hyperaldosteronism – Hypokalemia Hypoaldosteronism – Hyperkalemia 20 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 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 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 Organic Anion and Cation secretion Proximal tubule contains two types of secretory carriers For organic anions 2. For organic cations 1. 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 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. Thank you 26