RENAL SYSTEM PHYSIOLOGY Dr Shahab Shaikh PhD, MD Lecture – 5: Tubular Secretion •••••••••••••••••••••••••••••••••• College of Medicine Al Maarefa Colleges of Science & Technology

OBJECTIVES Qualitatively describe the forces that determine movement of reabsorbed fluid from interstitium into peritubular capillaries. State the major characteristics of the proximal-tubular systems for active reabsorption of organic nutrients. Understand pressure natriuresis, pressure diuresis and osmotic diuresis. List the approximate percentages of the filtered load of sodium reabsorbed by the various tubular segments. Understand the active step of sodium reabsorption in all sodium-reabsorbing segments. Understand the mechanisms of water reabsorption. Understand the water permeability characteristics of each tubular segment. Understand the maximum urinary osmolarity. Define obligatory water loss, and understand its determinants.

Urine Formation Three Basic Mechanisms (Renal Processes) of Urine Formation include: Glomerular filtration - GF Tubular reabsorption - TR Tubular secretion - TS

Tubular Secretion It is transfer of substances from peritubular capillaries into the tubular lumen. It is a supplemental mechanism that hastens elimination of some substances from the body. 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 Regulation Approximately 98 per cent of the total body potassium is contained in the cells and only 2 per cent in the extracellular fluid. The normal potassium level in the blood is 3.5-5.0 milliEquivalents per liter (mEq/L). An increase in plasma potassium concentration of only 3 to 4 mEq/L above the normal can cause cardiac arrhythmias, and higher concentrations can lead to cardiac arrest or fibrillation. Potassium contained in a single meal is often as high as 50 milliequilivants, and the daily intake usually ranges between 50 and 200 mEq/day. Likewise, a small loss of potassium from the extracellular fluid could cause severe hypokalemia. A rapid and appropriate compensatory response mechanism is vital to avoid dangerous Hyperkalemia or Hypokalemia.

Potassium Regulation K+ is tightly controlled by kidney K+ is Filtered, Reabsorbed and Secreted. K+ excretion can vary widely from 1% to 100% of filtered load depending on dietary K+ intake, aldosterone level and acid base status. K+ is filtered freely in glomerular capillaries K+ is actively reabsorbed in PCT and actively secreted in principal cell in DCT and CT K+ filtered is almost completely reabsorbed in PCT and thick ascending limb of loop of Henle. In DCT and CT, K+ is secreted depending on dietary K+ intake

Potassium Regulation

Potassium Regulation Secretion of K+ occurs in principal cells. Aldosterone acts on principal cells in DCT and CT and causes Na+ absorption and K+ secretion. Increased K+ causes increase aldosterone from adrenal cortex directly. At basolateral membrane of principal cell, K+ is actively transported into the cell by Na+-K+ pump. At luminal membrane, K+ is passively secreted into the lumen through K+ channel.

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 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+.

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+

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

References Human physiology by Lauralee Sherwood, 8th edition Text Book Of Physiology by Guyton & Hall, 11th edition Review of Medical Physiology by Ganong. 24th edition

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