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:
1.Glomerular filtration - GF
2.Tubular reabsorption - TR
3.Tubular secretion - TS
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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
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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+
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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
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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.
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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
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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.
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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
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+
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
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
THANK YOU
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