Lecture – 5: Tubular Secretion

RENAL SYSTEM PHYSIOLOGY

Dr Shahab Shaikh PhD, MD

•••••••••••••••••••••••••••••••••• 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.

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• Three Basic Mechanisms (Renal Processes) of Urine Formation include:1.Glomerular filtration - GF2.Tubular reabsorption - TR3.Tubular secretion - TS

Urine Formation

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• 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.

Tubular Secretion

H+, K+, NH3

Organic acids and bases

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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

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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

Tubular Secretion

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• 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

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• 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

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Potassium Regulation

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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.

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

Potassium handling by nephron(continued)

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+

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 carriers1. For organic anions2. 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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