GLOMERULAR FILTRATION &
Tubular reabsorption and
secretion
Sheen Bermudez
Glomerular
Filtration
Excretion
Tubular
Reabsorption &
Secretion
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GLOMERULAR FILTRATION
 Formation of urine
 Blood passes through the capillary
endothelium, the basement membrane,
and the epithelium of Bowman’s capsule
into Bowman’s space
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⊹ Starling forces - responsible for glomerular
filtration
- GFRs higher than the systemic
capillaries (due to glomerular capillary
barrier)
⊹ Hydrostatic pressure (HP) fluid out of capillary
⊹ Colloidal osmotic pressure (COP) opposes HP;
draws fluid in
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Ultrafiltrate of Plasma
⊹ filtered fluid, similar to interstitial fluid
⊹ contains water and all of the small solutes of
blood
⊹ but it does not contain blood cells and proteins
( mol weight of 70,000 and above)
Plasma haptoglobin (a plasma protein)
⊹ Binds to hemoglobin to prevent leakage at the
glomerulus.
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Hemoglobinuria
⊹ Hemoglobin begins to appear in the urine
⊹ Excessive intravascular lysis of RBC = haptoglobin
becomes saturated
Acute renal shutdown
⊹ Blocked tubules due to high tubular hemoglobin
concentration
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Factors that influence GFR
Changes in the diameter of the arterioles.
Dilation of afferent arteriole = ↑ BF to the glomerulus = ↑ HP = ↑ filtration.
Constriction of the efferent arteriole = ↑ glomerular HP; ↓ renal blood flow
(RBF).
Neural and humoral factors
capable of affecting these diameter changes.
Negative charge of Proteoglycans (basement membrane)
positively charged molecules are more readily filtered than negatively charged
molecules.
Poor perfusion of the kidneys
cans result in a change in the electrostatic charge of the membrane, and
molecules previously restricted from filtration can be filtered and gain entrance
to the capsular space.
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Autoregulation
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RBF and glomerular filtration rate (GFR) remain relatively
constant within a wide range of mean systemic arterial
pressure. (80 - 130 mmHg)
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intrinsic to the kidney and independent of renal nerve activity
Myogenic stretch receptor response in afferent arteriole
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↑BP = arteriole contracts = ↓ RBF and glomerular HP = ↓
GFR.
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↓ BP = arteriole dilate = ↑RBF and glomerular HP = ↑ GFR
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Tubuloglomerular feedback.
⊹ Afferent arteriolar feedback mechanism &
Efferent arteriolar feedback mechanism
⊹ ↓ GFR = ↓ FR in loop of Henle = ↑
reabsorption of Na and Cl ions in the
ascending limb = ↓ NaCl at the macula
densa cells.
⊹ Macula densa sends signal to afferent arterioles to
↓ resistance to blood flow = ↑ glomerular HP,
helping to return GFR to normal.
⊹ Macula densa cells sense changes in volume
delivery to the distal tubules
⊹ It also increases release of renin from the
juxtaglomerular (JG) cells of the afferent and
efferent arterioles (major storage sites for renin).
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Angiotensinogen converted to angiotensin I by renin
Renin, an enzyme, increases the formation of angiotensin I
Angiotensin‐converting enzyme (ACE) converts angiotensin I to
angiotensin II; from capillary endothelium of the lung, kidney
endothelium and other organ beds
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Angiotensin II constricts the efferent arterioles = ↑ GHP &
GFiltration; second most potent vasoconstrictor produced in the
body; stimulates the secretion of aldosterone, which causes
reabsorption of Na+.
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Vasopressin most potent vasoconstrictor
Angiotensinases rapidly destroys angiotensin II in the peripheral
capillary beds
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Angiotensinogen
Renin
Angiotensin I
Angiotensin-converting
enzyme
Angiotensin II
destroy
Angiotenases
constricts
Efferent
arterioles
↑ GHP & GFR
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Tubular transport
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refers to all phenomena
associated with tubular
fluid throughout the
nephron and collecting
ducts.
Transport from Bowman’s
capsule to the renal pelvis is
accomplished by a
difference in HP (high in
Bowman’s capsule, low in
renal pelvis).
Tubular reabsorption
⊹
Tubular reabsorption
involves transport of water
and solute from tubular fluid
to peritubular capillaries.
Tubular secretion
⊹
Tubular secretion is
associated with
transport of solute from
peritubular capillaries to
the tubular fluid.
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Peritubular capillaries
⊹ reabsorb fluid from tubules
⊹ Higher COP than the tubular fluid COP (proteins
not filtered)
⊹ Reduction in HP lessens its counteractive force to
the COP.
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Tubular reabsorption
⊹ Substances important to body function (Na+, glucose, &
AA) have relatively small molecular size
⊹ Concentrations in the filtrate are about equal to
plasma.
⊹ Excreted in the urine if not absorb
⊹ Energy is supplied by the Na+/K+‐ATPase pump
(sodium pump) on the basal and lateral surfaces of
the tubular epithelial cells.
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⊹ Cotransport (symport)
simultaneous transport of two or
more compounds on the same
carrier & same direction
(e.g., Na+ plus glucose, or Na+ plus amino
acid)
⊹ Countertransport (antiport)
movement of a compound in
opposite direction of the second
compound
(e.g., Na+–H+ countertransport).
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Sodium absorption
⊹ About 65% occurs in the proximal tubule by three
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major mechanisms.
25% in the ascending limb
10 % in distal tubule
Proximal tubule to the peritubular capillaries.
Reabsorption is accompanied by anions to maintain
electrical neutrality (75% Cl– & 25% HCO3–)
tightly coupled to passive water reabsorption,
meaning when sodium moves, water follows
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First mechanism
⊹ Na+ readily diffuses because of:
⊹ When Na+ is actively transported, electrochemical
gradient between the tubular epithelial cells and the
tubular lumen
⊹ The membrane contains carrier proteins specific for Na+
coupled with either glucose or an amino acid
(cotransport).
⊹ Peritubular space become electropositive due to Na+
transport
⊹ To maintain electrical neutrality, Cl– ions readily diffuse
from the tubular lumen to the peritubular space
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second mechanism
⊹ Countertransport with H+
⊹ The epithelial cells of the proximal and distal tubules,
and collecting ducts all secrete H+ ions (hydration of
CO2 within the epithelial cells = H+ and HCO3 –)
⊹ The HCO3 – ions diffuses through the membranes
into the peritubular space to maintain electrical
neutrality with the Na+ that was countertransported
with the H+.
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third mechanism
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chloride‐ driven Na+ transport
occurs in more distal portions of the proximal tubules.
There is more HCO3 – being reabsorbed into the
peritubular space as anion rather than Cl–
Cl– concentration increase in the tubule creates a
gradient for its diffusion into the peritubular space
through the “leaky” tight junctions.
This is accompanied by diffusion of Na+ in the same
direction to maintain electrical neutrality
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Glucose and amino acid reabsorption
⊹ reabsorbed by cotransport
⊹ They are coupled with specific carriers that require
Na+ binding and diffuse to the cell interior because
of the electrochemical gradient for Na+.
⊹ Inside the cell, the Na+ and glucose or amino acids
separate from the carrier.
⊹ specific carriers are present for facilitated diffusion
of glucose and amino acids into the peritubular
space.
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Transport of water and nonactively
reabsorbed solutes
⊹ ↑ solute in peritubular space = ↑ effective osmotic
pressure in peritubular space = water diffuses to the
peritubular space.
⊹ Urea and other nonactively reabsorbed solutes are
concentrated in the lumen (chemical gradient) and they
are reabsorbed down their concentration gradient.
⊹ Reabsorption is dependent on the permeability of the
proximal tubular epithelium for the solute.
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Reabsorption of proteins and peptides
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Most proteins are reabsorbed in the proximal tubule and
are not lost in the urine but a small quantity of protein is
present in normal urine.
Proteins (and polypeptides) are reabsorbed by endocytosis
and degraded by lysosomes to AA.
The amino acids reabsorb by facilitated diffusion.
Small peptides are hydrolyzed and the amino acids are
taken into the cell by the cotransport mechanism
Small‐peptide hydrolysis is a high‐capacity mechanism
capable of returning to the body large amounts of amino
acids
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Tubular secretion
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Transport of solute from peritubular capillaries to the tubular
fluid.
Example: counter transport of H+ with Na+ reabsorption
Distal nephron H+ secretion an active process that occurs in
the intercalated cells of the collecting duct; No Na+ absorption
Renal K+ transport is reabsorbed in some parts of the tubule
and secreted in others.
⊹ ↓ dietary potassium intake = ↑ K+ reabsorption in distal
tubule
⊹ ↑ dietary potassium intake = ↑ K+ secretion.
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Penicillin is lost from the body fluids because of tubular
secretion.
A longer‐acting penicillin that has been developed
persists in the body for longer periods because its rate of
secretion has been slowed.
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Tubular transport maximum (Tm)
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maximum rate at which substances can be reabsorbed
Tm is exceeded, the substance will appear in the urine.
Diabetes mellitus
⊹ lack of insulin causing impaired movement of glucose from plasma into
body cells
⊹ ↑ glucose concentration in plasma = ↑ tubular loads of glucose
⊹ Excess glucose continues its flow into the urine.
⊹ Glucose retained within the tubules = ↑ effective osmotic pressure of
the tubular fluid
⊹ Diuresis increased urine formation
⊹ Osmotic diuresis retention of water due to ↑ effective osmotic pressure
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Glomerulotubular balance
⊹ Property of the proximal tubule to reabsorb a
consistent fractional amount of glomerular filtrate
(about 65% for water & NaCl)
⊹ If the GFR is low, only a fractional amount of
filtrate is reabsorbed and the remaining fraction
(about one‐third) continues to the distal nephron
where the regulatory processes are given a chance
to operate.
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The End…
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