‫بسم هللا الرحمن الرحيم‬
‫‪Tubular function‬‬
TUBULAR FUNCTION
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General Considerations
The amount of any substance (X) that is filtered is the product of
the GFR and the plasma level of the substance (ClnPX).
The tubular cells may add more of the substance to the filtrate
(tubular secretion), may remove some or all of the substance from
the filtrate (tubular reabsorption), or may do both.
The amount of the substance excreted per unit time (UXV.) equals
the amount filtered plus the net amount transferred by the
tubules.
This latter quantity is conveniently indicated by the symbol TX .
The clearance of the substance equals the GFR if there is no net
tubular secretion or reabsorption, exceeds the GFR if there is net
tubular secretion, and is less than the GFR if there is net tubular
reabsorption.
Tubular function
Mechanisms of Tubular
Reabsorption & Secretion
• Small proteins and some peptide hormones are
reabsorbed in the proximal tubules by endocytosis.
• Other substances are secreted or reabsorbed in the
tubules by passive diffusion between cells and through
cells by facilitated diffusion down chemical or
electrical gradients or active transport against such
gradients .
• Movement is by way of ion channels, exchangers,
cotransporters, and pumps.
• Mutations of individual genes for many of them cause
specific syndromes such , Bartter's syndrome, and
Liddle's syndrome, and a large number of mutations
have been described.
Mechanism for Na+ reabsorption in the proximal tubule. Solid lines indicate active transport;
dashed lines indicate cotransport; and the dotted line indicates passive diffusion.
Note that Na+ moves from the lumen into the cells by cotransport and that Na+ and H2O
diffuse into the tubular lumen at the intercellular tight junctions.
Mechanisms of Tubular
Reabsorption & Secretion
• It is important to note that the pumps and other units in the
luminal membrane are different from those in the basolateral
membrane.
• It is this different distri-bution that makes possible net movement
of solutes across the epithelia.
• Like transport systems elsewhere, renal active transport systems
have a maximal rate, or transport maximum (Tm), at which they
can transport a particular solute.
• Thus, the amount of a particular solute transported is
proportionate to the amount present up to the Tm for the solute,
but at higher concentrations, the transport mechanism is saturated
and there is no appreciable increment in the amount transported.
• However, the Tms for some systems are high, and it is difficult to
saturate them.
Mechanisms of Tubular
Reabsorption & Secretion
• It should also be noted that the tubular epithelium, like
that of the small intestine and gallbladder, is a leaky
epithelium in that the tight junctions between cells permit
the passage of some water and electrolytes.
• The degree to which leakage by this paracellular pathway
contributes to the net flux of fluid and solute into and out
of the tubules is controversial since it is difficult to
measure, but current evidence seems to suggest that it is a
significant factor.
• One indication of this is that paracellin-1, a protein
localized to tight junctions, is related to Mg2+ reabsorption,
and a loss-of-function mutation of its gene causes severe
Mg2+ and Ca2+ loss in the urine.
Mechanism for Na+ reabsorption in the proximal tubule. Solid lines indicate active transport;
dashed lines indicate cotransport; and the dotted line indicates passive diffusion.
Note that Na+ moves from the lumen into the cells by cotransport and that Na+ and H2O
diffuse into the tubular lumen at the intercellular tight junctions.
Renal handling of various plasma constituents
in a normal adult human on an average diet.
Na+ Reabsorption
• The reabsorption of Na+ and Cl- plays a major role in body electrolyte
and water metabolism .
• In addition, Na+ transport is coupled to the movement of H+, other
electrolytes, glucose, amino acids, organic acids, phosphate, and other
substances across the tubule walls.
• The principal cotransporters and exchangers in the various parts of the
nephron are shown in table.
• In the proximal tubules, the thick portion of the ascending limb of the
loop of Henle, the distal tubules, and the collecting ducts, Na+ moves
by cotransport or exchange from the tubular lumen into the tubular
epithelial cells down its concentration and electrical gradients and is
actively pumped from these cells into the interstitial space.
• Thus, Na+ is actively transported out of all parts of the renal tubule
except the thin portions of the loop of Henle.
• Na+ is pumped into the interstitium by Na+-K+ ATPase.
• It extrudes three Na+ in exchange for two K+ that are pumped into the
cell.
Transport proteins involved in the movement of Na+ and Cl- across
the apical membranes of renal tubular cells
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Na
Reabsorption
• The tubular cells are connected by tight junctions at their luminal edges,
but there is space between the cells along the rest of their lateral borders.
• Much of the Na+ is actively transported into these extensions of the
interstitial space, the lateral intercellular spaces .
• Proximal tubular reabsorbate is, slightly hypertonic and water moves
passively along the osmotic gradient created by its absorption into tubular
epithelial cells.
• It is now known that the apical membranes of proximal tubule cells
contain water channels which aid the movement of water .
• From the cells, the water moves into the lateral intercellular spaces.
• The rate at which solutes and water move into the capillaries from the
lateral intercellular spaces and the rest of the interstitium is determined
by the Starling forces determining movement across the walls of all
capillaries, ie, the hydrostatic and osmotic pressures in the interstitium
and the capillaries .
• Na+ and H2O leak back to the tubular lumen via the intercellular
junctions, especially when the lateral intercellular spaces are distended.
Glucose Reabsorption
• Glucose, amino acids, and bicarbonate are reabsorbed
along with Na+ in the early portion of the proximal tubule .
• Farther along the tubule, Na+ is reabsorbed with Cl-.
• Glucose is typical of substances removed from the urine by
secondary active transport.
• It is filtered at a rate of approximately 100 mg/min .
• Essentially all of the glucose is reabsorbed, and no more
than a few milligrams appear in the urine per 24 hours.
• The amount reabsorbed is proportionate to the amount
filtered and hence to the plasma glucose level (PG) times
the GFR up to the transport maximum (TmG); but when the
TmG is exceeded, the amount of glucose in the urine rises .
• The TmG is about 375 mg/min in men and 300 mg/min in
women.
Top: Relation between the plasma level (P) and excretion (UV.) of
glucose and inulin. Bottom: Relation between the plasma
glucose level (PG) and amount of glucose reabsorbed (TG).
Glucose Reabsorption
• The renal threshold for glucose is the plasma
level at which the glucose first appears in the
urine in more than the normal minute amounts.
• However, the actual renal threshold is about 200
mg/dL of arterial plasma, which corresponds to a
venous level of about 180 mg/dL .
Glucose Transport
Mechanism
• Glucose reabsorption in the kidneys is similar to
glucose reabsorption in the intestine .
• Glucose and Na+ bind to the common carrier SGLT 2 in
the luminal membrane , and glucose is carried into the
cell as Na+ moves down its electrical and chemical
gradient.
• The Na+ is then pumped out of the cell into the lateral
intercellular spaces, and the glucose is transported by
GLUT 2 into the interstitial fluid.
• Thus, glucose transport in the kidneys as well as in the
intestine is an example of secondary active transport.
Glucose Transport
Mechanism
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