RENAL SYSTEM
PHYSIOLOGY
Dr Shahab Shaikh PhD, MD
Lecture – 3: Tubular Reabsorption - I
••••••••••••••••••••••••••••••••••
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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Urine Formation
• Thus Urinary Excretion is total sum of the three
processess:
Urinary excretion
=
Glomerular filtration - Tubular reabsorption + Tubular secretion
WHERE & HOW
Tubular Reabsorption
• Reabsorption – It is return of most of the filtered water and
many solutes to the bloodstream.
• Water, Essential substances and electrolytes needed by the
body are reabsorbed but waste products are eliminated .
• Reabsorbed substances carried by the peritubular
capillaries to the venous system.
• Tubular reabsorption is highly selective process.
• Both active and passive processes are involved in
Reabsorption.
• GFR is 125ml/min, out of this 124ml/min is reabsorbed.
Only 1ml/min excreted.
– 99% of water is reabsorbed.
– 99.5% Na+ is reabsorbed.
– 100% glucose is reabsorbed.
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Tubular Reabsorption
Steps in Tubular Reabsorption:
– Substance must leave
tubular fluid by crossing
luminal membrane of
tubular cell.
– Substance must pass
through one side of
tubular cell to the other.
– Substance must cross basolateral membrane of tubular cell to
enter interstitial fluid.
– Substance must diffuse through the interstial fluid.
– It must penetrate the capillary wall to enter blood plasma.
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Tubular Reabsorption
Routes for Tubular Reabsorption:
• Reabsorption occurs either
via the tubular cells ‘the
transcellular
route’
or
between the cells ‘the
paracellular route’.
• The
reabsorption
and
secretion that occur via the
transcellular route are largely
the result of active transport
of solutes by the tubular
cells.
• Paracellular reabsorption is passive and occurs as a result of
concentration or electrical gradients that favor movement of
solutes out of the tubular fluid.
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Tubular Reabsorption
• Passive Reabsorption occurs from tubular lumen to
the plasma, when no energy is spent. Movement
occurs due to electro-chemical or osmotic gradient.
• Active Reabsorption is, when energy is required for
trans epithelial transport i.e. when there is
movement of substance from tubular lumen to
plasma against electro chemical gradient. e.g. Na+ ,
Glucose, Amino acid, Phosphate (PO4-3)
– Primary active transport
• E.g. Sodium-potassium pumps in basolateral membrane.
– Secondary active transport
• E.g. co-transport (glucose, amino acids)
• E.g. counter-transport (K+, H+)
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Tubular Reabsorption
Transport Mechanisms used:
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Tubular Reabsorption
Transport Mechanisms used:
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Tubular Reabsorption
Transport Mechanisms used:
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Tubular Reabsorption
Transport Mechanisms used:
12
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Role of Different Parts of Nephron
Reabsorption and Secretion :
Tubular Reabsorption
Proximal Convoluted Tubule
Role in Reabsorption
• GFR delivers ~125ml/min of filtered
plasma to the Proximal tubule.
• Nearly 65 - % of this volume is
reabsorbed by the proximal convoluted tubule and
returned back to the blood.
• Needed products such as glucose and amino acids
are reabsorbed 100% rapidly.
• Other products are slowly reabsorbed such as Urea
or not at all such as Creatinine.
• Proximal tubule also secretes some substances that
the body needs to get rid of rapidly. These include
toxins and drugs.
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Proximal Convoluted Tubule
Role in Reabsorption
Common Substances Reabsorbed in PCT:
–
–
–
–
–
–
–
–
Sodium
Chloride
Glucose
Water
Amino acid
Bicarbonate
Phosphate
Urea
65%
50%
100%
65%
100%
90%
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Proximal Convoluted Tubule
Role in Reabsorption
• Cells of the Proximal Convoluted Tubule (PCT):
– The Simple Cuboidal cells of the PCT are called Brush Border
cells because of their numerous Microvilli, which project into
the lumen of the tubule.
Mitochondria
Lumen
Interstitial
space
Basolateral
membrane
Luminal
membrane
Tight junction
Microvilli
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Loop of Henle
Role in Reabsorption
• The loop of Henle consists of
three
functionally
distinct
segments:
– The thin descending segment
– The thin ascending segment
– The thick ascending segment
• The descending limb of the loop is
highly permeable to water
• While the ascending limb,
including both the thin and the
thick
portions, is virtually
impermeable to water.
• This characteristic of the loop is
important for concentrating the
urine.
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Loop of Henle
Role in Reabsorption
Descending Limb:
• The descending part of the thin
segment is highly permeable to
water and moderately permeable
to most solutes, including urea
and sodium.
• About 20 per cent of the filtered water is reabsorbed in
the loop of Henle, and almost all of this occurs in the thin
descending limb.
• The thin descending limb does not reabsorb significant
amounts of the solutes.
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Loop of Henle
Role in Reabsorption
Ascending Limb:
• The ascending limb, including
both the thin and the thick
portions, is virtually impermeable
to water.
• It absorbs mainly solutes:
– Na+, Cl-, K+ active transport
– Ca2+, Mg2+ passive transport
– Na+- H+ Counter-transport
• The thick ascending limb of the
loop of Henle is the site of action
of loop diuretics
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Distal Convoluted Tubule - DCT
Role in Reabsorption
J-G Apparatus:
• The very first portion of the distal
tubule forms part of the
juxtaglomerular complex that
provides feedback control of GFR
and blood flow in this same
nephron.
Early DCT:
•
•
•
•
Na+ : symporter mediated
Ca2+ : PTH mediated
Cl- : diffusion
Water : impermeable
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Late DCT and Cortical Collecting Tubule
Role in Reabsorption
• The second half of the distal
convoluted tubule and the
subsequent cortical collecting
tubule have similar functional
characteristics.
• They have two distinct cell types,
the Principal cells and the
Intercalated cells
• Principal cells:
• Intercalated cells:
– Na+ : Aldosterone mediated
– Ca2+ : PTH mediated
– Water : ADH mediated
– H2CO3 reabsorption
– K+ reabsorption
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Late DCT and Cortical Collecting Tubule
Functional characteristics:
Role in Reabsorption
• The tubular membranes of both segments are almost completely
impermeable to urea.
• The rate of reabsorption of sodium ions in both the segments is controlled
by hormones, especially aldosterone.
• These segments secrete potassium ions into the tubular lumen, a process
that is also controlled by aldosterone and by other factors.
• The intercalated cells of these nephron segments avidly secrete hydrogen
ions by an active hydrogen-ATPase mechanism. It can do so against a large
concentration gradient, as much as 1000 to 1 in contrast to the relatively
small gradient (4- to 10-fold) that can be achieved by secondary active
secretion proximal tubule. Thus, the intercalated cells play a key role in
acid-base regulation of the body.
• The permeability of the these segments to water is controlled by the ADH
also called vasopressin. In the absence of ADH, they are virtually
impermeable to water. This plays an important role in controlling the
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degree of dilution or concentration of the urine.
Medullary Collecting Duct
Role in Reabsorption
• Although the medullary collecting ducts
reabsorb less than 10 per cent of the
filtered water and sodium, they are the
final site for processing the urine.
• The permeability of the medullary
collecting duct to water is controlled by
the level of ADH.
• The medullary collecting duct is
permeable to urea.
• The medullary collecting duct is capable of secreting hydrogen ions
against a large concentration gradient, as in the cortical collecting
tubule. Thus, it also plays a key role in regulating acid-base balance.
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Regulation of Tubular Reabsorption
Mechanisms of regulation:
• Glomerulotubular Balance
– The Ability of the Tubules to Increase Reabsorption Rate in Response to
Increased Tubular Load
• Peritubular Capillary and Renal Interstitial Hydrostatic and
colloid osmotic forces.
– Reabsorption = Kf X Net reabsorptive force
• Effect of Arterial Pressure on Urine Output
– The Pressure-Natriuresis and
– Pressure-Diuresis Mechanisms
• Hormonal Control:
–
–
–
–
–
aldosterone
angiotensin II
antidiuretic hormone (ADH)
natriuretic hormones (ANF)
parathyroid hormone
• Sympathetic Nervous System
• Osmotic factors
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Regulation of Tubular Reabsorption
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Regulation of Tubular Reabsorption
Pressure Natriuresis & Pressure Diuresis:
• When the body contains too much extracellular fluid, the blood
volume and arterial pressure Increases. The rising pressure in turn
has a direct effect to cause the kidneys to excrete the excess
extracellular fluid, thus returning the pressure back toward normal.
• An increase in arterial pressure in the human of only a few
millimeters of mercury can double renal output of water, which is
called pressure diuresis, as well as double the output of salt, which
is called pressure natriuresis.
Osmotic Diuresis:
• high rate of water excretion resulting from osmosis caused by the
filtered solutes in lumen such as mannitol.
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Tubular Reabsorption
Some Major Substances Reabsorbed:
–
–
–
–
–
–
–
Sodium
Water
Glucose
Amino acid
Bicarbonate
Phosphate
Urea
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Tubular Reabsorption - Sodium
• 99.5% of filtered Na+ is reabsorbed back in the tubule.
• Na+ is reabsorbed variedly throughout the tubule except
descending limb of Loop of Henle as follows:
• Proximal convoluted tubule
• Loop of Henle (thick ascending limb)
• Distal and Collecting Tubule
65 - 67%
25 %
8%
• Na+ Reabsorption in proximal convoluted tubule helps in
reabsorption of Water, glucose, amino acid, Cl-, Urea.
• Na+ Reabsorption in DCT and CT (8%) is under control of
hormone Aldosterone, thus plays a key role in regulating
ECF volume, which is important in long-term control of
arterial blood pressure.
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Tubular Reabsorption - Sodium
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Tubular Reabsorption - Sodium
Na+ Reabsorption Mechanism:
• Luminal side: Movement of
Na+
from
lumen
to
intracellular
fluid
by
electrochemical gradient.
• Basolateral membrane: Na+
- K+ ATPase (3 Na+ out/ 2 K+
in)  Na+ leak out of the
cell  results in low
intracellular
Na+
concentration
and

osmolarity in the interstitial
space.
• Peritubular side: (Bulk flow)
Movement
of
hyperosmotic fluid from
interstitial
space
into
peritubular capillaries.
%
Mechanism of Na+ entry
Proximal tubule
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Na+ K+ Pump
Na+-H+ exchange,
Na+ cotransport with AA &
Glucose,
Na+/H+-Cl/anion exchange
Henle’s loop
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1Na+-K+-2Cl cotransport
Distal tubule
~5
Na+-Cl cotransport
Late distal tubule &
collecting duct
~4
Na+ channels
Segment
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Tubular Reabsorption - Sodium
Substances Reabsorbed with Na+:
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Tubular Reabsorption - Sodium
Substances Reabsorbed with Na+:
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Tubular Reabsorption - Sodium
Renin–Angiotensin–Aldosterone system (RAAS)
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Tubular Reabsorption - Sodium
Control of Aldosterone Secretion By Na+ and K+ : The RAAS System
• RAAS
activity
if
abnormally increased can
cause hypertension.
• RAAS is also responsible
for fluid retention and
EDEMA
occurring
in
congestive heart failure.
• Angiotensin
Converting
Enzyme inhibitor – ACE
inhibitor drugs are used
for hypertension and
congestive heart failure
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Tubular Reabsorption - Sodium
Role of ATERIAL NATRIURETIC PEPTIDE (ANP) in (Na+)
Reabsorption:
• Hormone ANP is Natriuretic i.e causes Na+ loss, therefore,
decreases BP.
• Site of production of ANP – Atria of heart.
• Site of action of ANP – distal part of nephron (DCT and CT),
causes decreased Na+ reabsorption, therefore, increased
Na+ and water loss in urine.
• Inhibits aldosterone secretion from adrenal cortex.
• Inhibits renin secretion, therefore, has negative effect on
RAAS.
• Inhibits vasopressin secretion and its action, therefore
causes decreased water reabsorption.
• Dilates afferent arteriole and constricts efferent arteriole,
therefore, increases GFR.
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Tubular Reabsorption - Water
• 99 – 99.7% water is reabsorbed
• Average urine volume – 1 to 1.5 liter/day
• Minimum urine needed per day to get rid of waste
products 500ml/day.
• Proximal convoluted tubule (PCT) – 60-70%. It is passive,
due to osmotic gradient due to active reabsorption of
solutes e.g. Na+
• Loop of Henle(Descending Limb) – 15% of water is
reabsorbed.
• DCT and CT – 20% of filtered water is reabsorbed. DCT –
5% water reabsorbed. CT – 15% water reabsorbed.
• In DCT and CT, water is reabsorbed under the action of
ADH (Anti-Diuretic Hormone) or Vasopressin.
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Tubular Reabsorption - Water
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Tubular Reabsorption - Water
Mechanism of
Action of ADH
(Vasopressin):
• In absence of ADH, collecting
tubule epithelium is relatively
impermeable to water.
Diabetes Insipidus (DI):
• occurs due to deficiency of ADH
• Nephrogenic DI
• occurs when V2 receptors in
collecting tubule fail to
respond to ADH.
• Central DI
• occurs due to deficiency of
ADH
• In both cases, person will pass
dilute urine up to 22 liters/day
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Regulation of Water Reabsorption
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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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