Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College 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: Glomerular Filtration Tubular Reabsorption Tubular Secretion

Tubular secretion Secretion – transfer of material from blood into tubular fluid Helps control blood pH Helps eliminate substances from the body

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: 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 thus principle cells increases 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 + ATP ATP K+ K+ Cl - Aldosterone

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

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 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

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