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TUBULAR REABSORPTION URINARY BLOCK 313 Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College Objectives Define tubular secretion Role of tubular secretion in maintaining K+ conc. Mechanisms of tubular secretion. URINE FORMATION • Three Basic Mechanisms (Renal Processes) Of Urine Formation include: 1. Glomerular Filtration 2. Tubular Reabsorption 3. Tubular Secretion Tubular secretion • Secretion – transfer of material from blood into tubular fluid – Helps control blood pH – Helps eliminate substances from the body 4 Tubular Secretion • First step is simple diffusion from peritubular capillaries to interstitial fluid • Enter 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 Calculation of Tubular Secretion Secretion = Excretion - Filtration H+, K+, NH3 Organic acids and bases 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+ Tubular Secretion • Most important substances secreted by the tubules: – H+ • 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 Potassium balance 98% of K+ is in ICF & 2% in ECF ICF = 150 m Eq/L & in ECF = 4.5 mEq/L Balance → intake = out put Maintenance of K balance is important in normal functioning of excitable tissue Importance of regulating plasma K+ concentration • K+ plays a key role in the membrane potential of excitable tissues. • Both increase and decrease in plasma K+ can change intracellular to extracellular K+ conc. Gradient which can change the RMP. • Its impact on the heart – decreased cardiac excitability • Rise in ECF K+ conc. decreases excitability of the neurons & skeletal muscle cells. • Decrease in ECF K+ lead to skeletal muscle weakness, diarrhea and abdominal distension. Potassium handling by nephron 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 α -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 Effect of H+ secretion on K+ secretion During acidosis H+ secretion is increase lead to retention of K+. Principle cells in Late DCT & CT 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 principle cells increases thus electrochemical gradient across membrane 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 DUAL EFFECT OF ALDOSTERONE •Fall in Na+ - through RAAS •Increase in K+ Late Distal, Cortical and Medullary Collecting Tubules Principal Cells Tubular Lumen H20 (+ ADH) Na + Na + K+ ATP K+ Cl - Aldosterone 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 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 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 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 UREA & Uric acid • Urea is freely filtered – 50% reabsorbed in PCT. • Urate is freely filtered • In PCT there is reabsorption and secretion takes place. • In the initial & middle part of PCT reapsorption is more than secretion • In the distal portion of PCT moderate amount of urates are secreted. References • Human physiology by Lauralee Sherwood, seventh edition • Text book of physiology by Linda .s contanzo,third edition • Text book physiology by Guyton &Hall,11th edition