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The Urinary System

Part B
Tubular Reabsorption
Our total plasma volume filters into the renal tubules about
every 22 minutes (i.e 2750ml/125ml = 22min)
Tubular Reabsorption is a transepithelial1 process
Most tubule contents are returned to the blood by reabsorption.
To reach back to blood , transported substances move through
three barriers
Luminal membrane of tubule cells
Basolateral membrane of tubule cells
Endothelium of peritubular capillaries
Tight junction between tubule cell, so movement between cells
is limited.
Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed via
paracellular pathways. i.e. (between cells)
Transcellular and paracellular routes of tubular reabsorption.

Movement from lumen to Peritubular capillaries through


Transcellular route
Paracellular route
The transcellular route consists of four steps:
Transport across the luminal membrane,
Diffusion through the cytosol,
Transport across the basolateral membrane,
Movement through the interstitial fluid and into the capillary.
Transcellular transport often involves the lateral intercellular
spaces because ATP-dependent pumps located on the
basolateral membrane pump ions into these spaces.
Water and solutes following the paracellular route move
through leaky tight junctions, particularly in the PCT.
Routes of Water and Solute Reabsorption
Tubular Reabsorption
Movement of substance across a memb. is by way of
Ion channels
Exchangers
Cotransporters
Pumps
Pumps and other units in the luminal membrane are
different from those in the basolateral membrane.
It is this different distribution that makes possible net
movement of solutes across the epithelia.
Transport Proteins across Apical membrane of renal tubule cells
Tubular Reabsorption
Reabsorption may be through
Active Transport (requiring ATP) (Transcellular)
Primary Active Transport (Direct use of ATP)
Secondary Active Transport( No direct Use of ATP)
Co-Transport or Symport (Uni-directional)
One along conc.gradient, other against in same direction
eg Na+/Glucose Co-Tranporter
Counter Transport or Antiport (Opposite Directions)
One along conc.gradient, other against in opposite directions
eg Na+/H+ Antiporter
Passive process (No ATP required)
Passive Diffusion (between cells) (Paracellular)
Facilitated Diffusion (Through Cells) (Transcellular)
Osmosis (Para, Trans both)
Sodium Reabsorption:
Primary Active Transport

Single most abundant ions in filtrate


80 % energy used for active transport is for Na+ reabs.
Sodium reabsorption is almost always by active
transport and via transcellular pathway
Two Basic Process
Na+ enters the tubule cells at the luminal membrane
Is actively transported out of the tubules by a
Na+-K+ ATPase pump in interstitial fluid
From here, Na+ is swept along by the bulk flow of water
into adjacent peritubular capillaries
Sodium Reabsorption: Primary Active
Transport
Its movement to peritubular capillaries due to:
Low hydrostatic pressure
High osmotic pressure of the blood
Active pumping of Na+ results in a strong
electrochemical gradient
It favors its passive entry at the luminal face via
cotransport (symport or antiport) carriers or via
facilitated diffusion through channels.
Sodium Reabsorption: Primary Active Transport

Passive entry of Na+ into cell is because


The pump maintains the intracellular Na+ concentration
at low levels, and (Cehmical Gradient)
The K+ pumped into the tubule cells almost immediately
diffuses out into the interstitial fluid via leakage
channels, leaving the interior of the tubule cell with a net
negative charge. (Electrical gradient)
Hence active Na+ reabsorption provides the energy and
the means for reabsorbing most other solutes
Reabsorption by PCT Cells
“Downhill” Na+ entry at the luminal surface is usually
coupled to the transport of another solute (a cotransport
process referred to as secondary active transport).
Active pumping of Na+ at the basolateral membrane
creates concentration and osmotic gradients that drive
reabsorption of
Water by osmosis
Anions and fat-soluble substances by diffusion,
Organic nutrients and selected cations by secondary
active transport (symport with Na+ at the luminal
membrane).
Most organic nutrients reabsorbed in the PCT by
facilitated diffusion.
Reabsorption by PCT Cells

Figure 25.12
Reabsorption of Water, Ions, and Nutrients
Obligatory water reabsorption
Water moves by osmosis into the peritubular capillaries,
by water channels called aquaporins.
There are thirteen known types of aquaporins in mammals,
and six of these are located in the kidney.
Aquaporin-1 is localized in the proximal tubules
Aquaporin-1 facilitates water transport @ a rate of
approx. 3 billion H2O molecules/second
Completely impermeable to charged species eg (Protons)
Reabsorption of Anions:
Na+ ions establish an electrical gradient that favors
passive reabsorption of anions (Cl– and HCO3– for
example) to restore electrical neutrality in the filtrate and
plasma.
Reabsorption of Water, Ions, and Nutrients
Phenomenon of Solute Following Solvents
Filtrate becomes conc. as water leaves
Passive absorption of lipid-Soluble Drugs, Cations, fatty
acids and some urea.
Secondary Active Transport
Luminal carrier moves Na+ down its concentration
gradient as it transports another solute against its conc.
gradient.
Co-Transport (Symport) Same direction
Counter Transport (Antiport) Opposite direction
Glucose, Lactate, Amino acids, Vitamins, Cations are
transported by secondary active transport
Reabsorption of Glucose
Secondary Active Transport
Transport maximum
Transport maximum (Tm):
Reflects the number of carriers in the renal tubules
available
Exists for nearly every substance that is actively
reabsorbed
Expressed in mg/min
When the carriers are saturated, excess of that substance
is excreted eg
Glucose Tm = 375mg /min in nephrons, excess will be
excreted in urine causing Glucosuria resulting in osmotic
diuresis.
Nonreabsorbed Substances
Substances are not reabsorbed if they:
Lack carriers
Are not lipid soluble
Are too large to pass through membrane pores
Urea, creatinine, and uric acid are the most important
nonreabsorbed substances
Absorptive Capabilities of Renal Tubules and
Collecting Ducts
Proximal Convoluted tubule:
PCT cells are most effective reabsorbers:
All Glucose, Lactate, Amino acids
65 % Na+ and water
90 % HCO3-1 (Bicarbonate)
60 % Cl- & 55% K+
All of the uric Acid which is later secreted back
Absorptive Capabilities of Renal Tubules and Collecting Ducts

Loop of Henle reabsorbs:

Decending Limb Water Osmosis

Na+, Cl- and K+ Secondary active


Ascending limb transport via Na+,
K+ and 2Cl-
cotransport
Na+/H+ Anitport
Paracellular diff.
Ca2+, Mg2+
Passive
paracellular diff
Loop of Henle
Decending limb:
Water can leave the descending limb (Aquaporin-1) but solutes can
not.
Ascending limb:
Water can not leave the ascending limb, aquaporins are less or
absent in the tubule membrane, but solutes can.
Thin portion of the ascending limb,
Na+ moves passively down the concentration gradient created by
water reabsorption.
Thick portion of the ascending limb,
Na+-K+-2Cl– symporter
Na+-H+ antiporters,
50% of Na+ passes via the paracellular route.
A Na+-K+ ATPase operates at the basolateral membrane
Distal Convoluted Tubule and Collecting Duct
10% of NaCl and 25% of the water remain in the tubule.
Some NaCl reabsorption in the DCT via Na+-Cl– symporters.
Most reabsorption depends on the body’s needs and is regulated
by hormones
1) ADH for water, 2) Aldosterone for Na+, 3) PTH for Ca2+
No hormones, the DCT and collecting duct are almost
impermeable to water.
Water Reabsorption (ADH)1
Based on presence of ADH, by inserting aquaporins into the
collecting duct luminal membranes.
Sodium Reabsorption: (Aldosterone Mediated)2
Decreased blood volume or blood pressure,
Low extracellular Na+ concentration (hyponatremia),
High extracellular K+ concentration (hyperkalemia)
can cause the adrenal cortex to release aldosterone to the blood.
Distal Convoluted Tubule and Collecting Duct
Actions of Aldosterone
Targets the principal cells of the collecting ducts and
cells of the distal portion of the DCT
Urging them to open or synthesize more luminal Na+
and K+ channels, and more basolateral Na+-K+
ATPases.
Facilitate water reabsorption:
After Na+ is reabsorbed, water follows it back into the
blood (if it can).
Reduces blood K+ concentrations as Na+ enters, K+
moves into the lumen.
In absence of aldosterone about 2% of filtered Na+ is
lost daily.
Atrial Natriuretic Peptide Activity
Atrial natriuretic peptide (ANP) or atriopeptin released
by cardiac atrial cells when blood volume or blood
pressure is elevated
ANP reduces blood Na+ which:
Decreases blood volume
Lowers blood pressure
ANP lowers blood Na+ by:
Acting directly on medullary ducts to inhibit Na+
reabsorption
Counteracting the stimulatory effect of angiotensin II on
aldosterone secretion by the adrenal cortex,
Indirectly stimulating an increase in GFR reducing water
reabsorption
Na+ Entry into Tubule Cells
In the PCT:
facilitated diffusion using symport and antiport carriers
In the ascending loop of Henle:
facilitated diffusion via Na+-K+-2Cl− symport system
In the DCT:
Na+-Cl– symporter
In collecting tubules:
Diffusion through membrane pores
Tubular Secretion
Reverse of reabsorption which was from tubule to peritubular
capillaries,
In tubular secretion substances move from peritubular capillaries
or tubule cells into filtrate
Tubular secretion is important for:
Disposing of substances, which are tightly bound to plasma
proteins. E.g. certain drugs and metabolites,
Eliminating undesirable substances or end products that have been
reabsorbed by passive processes (urea and uric acid).
Ridding the body of excess K+.
Virtually all K+ present in the filtrate is reabsorbed in the PCT and
ascending loop of Henle,
All K+ in urine is from aldosterone-driven active tubular secretion
into the late DCT and collecting ducts.
Controlling blood pH.
Acidic pH, the renal tubule cells actively secrete more H+ into the
filtrate and retain more HCO3–– (a base). blood pH rises
Blood pH alkaline, Cl– is reabsorbed instead of HCO3–
Regulation of Urine Concentration and Volume
Osmolality
The number of solute particles dissolved in 1L of water
Reflects the solution’s ability to cause osmosis
Body fluids are measured in milliosmols (mOsm)
The kidneys keep the solute load of body fluids constant
at about 300 mOsm
This is accomplished by the countercurrent mechanism
Countercurrent Mechanism
Interaction between the flow of filtrate through the loop
of Henle (countercurrent multiplier) and the flow of
blood through the vasa recta blood vessels
(countercurrent exchanger)
The solute concentration in the loop of Henle ranges
from 300 mOsm to 1200 mOsm
Dissipation of the medullary osmotic gradient is
prevented because the blood in the vasa recta
equilibrates with the interstitial fluid
Osmotic Gradient in the Renal Medulla

Figure 25.13
Loop of Henle: Countercurrent Multiplier
The descending loop of Henle:
Is relatively impermeable to solutes
Is permeable to water
The ascending loop of Henle:
Is permeable to solutes
Is impermeable to water
Collecting ducts in the deep medullary regions are
permeable to urea
Loop of Henle: Countercurrent Exchanger
The vasa recta is a countercurrent exchanger that:
Maintains the osmotic gradient
Delivers blood to the cells in the area

Urinary System: Early Filtrate Processing


Loop of Henle: Countercurrent Mechanism

Figure 25.14
Formation of Dilute Urine
Filtrate is diluted in the ascending loop of Henle
Dilute urine is created by allowing this filtrate to
continue into the renal pelvis
This will happen as long as antidiuretic hormone (ADH)
is not being secreted
Collecting ducts remain impermeable to water; no
further water reabsorption occurs
Sodium and selected ions can be removed by active and
passive mechanisms
Urine osmolality can be as low as 50 mOsm (one-sixth
that of plasma)
Formation of Concentrated Urine
Antidiuretic hormone (ADH) inhibits diuresis
This equalizes the osmolality of the filtrate and the
interstitial fluid
In the presence of ADH, 99% of the water in filtrate is
reabsorbed
ADH-dependent water reabsorption is called facultative
water reabsorption
ADH is the signal to produce concentrated urine
The kidneys’ ability to respond depends upon the high
medullary osmotic gradient
PLAY
Urinary System: Late Filtrate Processing
Formation of Dilute and Concentrated Urine

Figure 25.15a, b
Diuretics
Chemicals that enhance the urinary output include:
Any substance not reabsorbed
Substances that exceed the ability of the renal tubules to
reabsorb it
Substances that inhibit Na+ reabsorption
Osmotic diuretics include:
High glucose levels – carries water out with the glucose
Alcohol – inhibits the release of ADH
Caffeine and most diuretic drugs – inhibit sodium ion
reabsorption
Lasix and Diuril – inhibit Na+-associated symporters
Renal Clearance
The volume of plasma that is cleared of a particular
substance in a given time
Renal clearance tests are used to:
Determine the GFR
Detect glomerular damage
Follow the progress of diagnosed renal disease
RC = UV/P
RC = renal clearance rate
U = concentration (mg/ml) of the substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance in plasma
Physical Characteristics of Urine
Color and transparency
Clear, pale to deep yellow (due to urochrome)
Concentrated urine has a deeper yellow color
Drugs, vitamin supplements, and diet can change the
color of urine
Cloudy urine may indicate infection of the urinary tract
Odor
Fresh urine is slightly aromatic
Standing urine develops an ammonia odor
Some drugs and vegetables (asparagus) alter the usual
odor
Physical Characteristics of Urine
pH
Slightly acidic (pH 6) with a range of 4.5 to 8.0
Diet can alter pH
Specific gravity
Ranges from 1.001 to 1.035
Is dependent on solute concentration
Chemical Composition of Urine
Urine is 95% water and 5% solutes
Nitrogenous wastes include urea, uric acid, and
creatinine
Other normal solutes include:
Sodium, potassium, phosphate, and sulfate ions
Calcium, magnesium, and bicarbonate ions
Abnormally high concentrations of any urinary
constituents may indicate pathology