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Kidney Functions
• Regulation of the extracellular fluid environment in the body, including:– Volume of blood plasma (affects blood
pressure)– Wastes – Electrolytes– pH
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Afferent arteriole
Efferent arteriole
Renal corpuscle
Cortical nephron
Peritubularcapillaries
Peritubularcapillaries
Collectingduct
Nephronloop
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Afferent arteriole
Efferent arteriole
Glomerulus
Nephronloop
Collectingduct
Distal convolutedtubule DCT
Proximal convolutedtubule PCT Peritubular capillaries
Vasa recta
Juxtamedullary nephron
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NEPHRON
Proximal convoluted tubule Distal convoluted tubule
Reabsorption of water,ions, and all
organic nutrients
• Secretion of ions, acids, drugs, toxins
Glomerulus
Efferent arteriole
Afferent arteriole
Renal tubule
Loop beginsLoop ends
Renal corpuscle
Production of filtrate
Descendinglimb of loop
Ascendinglimb of loop
Nephron loop
KEY
Water
Solutes
Filtrate
Variablereabsorptionor secretion
Further reabsorption of waterdescending limb and both
sodium and chlorideions ascending limb
Papillary duct
Towardureter
Delivery of urineto minor calyx
Variable reabsorptionof water and
reabsorption orsecretion of sodium,
potassium, hydrogen,and bicarbonate ions
Collecting duct
COLLECTING SYSTEM
• Variable reabsorption of water and sodium ions
under hormonal control
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Juxtaglomerularcomplex
Juxtaglomerularcells
Macula densa
Distal convolutedtubule
Efferent arteriole
Afferentarteriole
Capsularspace
Glomerularcapillary
Parietal layer
Visceralepitheliumpodocyte
Proximalconvoluted
tubule
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Control of Micturition
• Detrusor muscles line the wall of the urinary bladder.– Innervated by parasympathetic neurons,
which release acetylcholine onto muscarinic ACh receptors
• Sphincters surround urethra.– Internal urethral sphincter: smooth muscle– External urethral sphincter: skeletal muscle
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Control of Micturition
• Stretch receptors in the bladder send information to S1−S4 regions of the spinal cord.– These neurons normally inhibit
parasympathetic nerves to the detrusor muscles, while somatic motor neurons to the external urethral sphincter are stimulated.
– Called the guarding reflex– Prevents involuntary emptying of bladder
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Control of Micturition
• Stretch of the bladder initiates the voiding reflex.– Information about stretch passes up the spinal
cord to the micturition center of the pons. – Parasympathetic neurons cause detrusor
muscles to contract.– Sympathetic innervation of the internal
urethral sphincter causes it to relax.– Person feels the need to urinate and can
control when with external urethral sphincter.
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Glomerular Corpuscle
• Capillaries of the glomerulus are fenestrated.– Large pores allow water and solutes to leave
but not blood cells and plasma proteins.
• Fluid entering the glomerular capsule is called filtrate
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Glomerular Corpuscle
• Filtrates must pass through:
1. Capillary fenestrae (the primary cause for not passing the Protein by the glomerulus)
2. Glomerular basement membrane
3. Visceral layer of the glomerular capsule composed of cells called podocytes with extensions called pedicles
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Glomerular Corpuscle
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Glomerular Corpuscle
• Slits in the pedicles called slit diaphragm pores are the major barrier for the filtration of plasma proteins.
– Defect here causes proteinuria = proteins in urine.
– Some albumin is filtered out but is reabsorbed by active endocytosis.
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Ultrafiltrate
• Fluid in glomerular capsule gets there via hydrostatic pressure of the blood, colloid osmotic pressure, and very permeable capillaries.
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Filtration Rates
• Glomerular filtration rate (GFR): rate of filtrate produced by both kidneys each minute = 115−125 ml.
– 180 l/ day
– Total blood volume filtered every 40 minutes
– Most must be reabsorbed immediately
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Net Pressure that driving the
glomerular filtration. How to calculate?How to calculate
clearance?
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Regulation of Filtration Rate
• Vasoconstriction or dilation of afferent arterioles changes filtration rate.
– Extrinsic regulation via sympathetic nervous system
– Intrinsic regulation via signals from the kidneys; called renal autoregulation
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Sympathetic Nerve Effects
• In a fight/flight reaction, there is vasoconstriction of the afferent arterioles.
– Helps divert blood to heart and muscles
– Urine formation decreases
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Renal Autoregulation
• GFR is maintained at a constant level even when blood pressure (BP) fluctuates greatly.– Afferent arterioles dilate if BP < 70.– Afferent arterioles constrict if BP > normal.
1. Myogenic constriction: Smooth muscles in arterioles sense blood pressure.
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Renal Autoregulation
2. Tubuloglomerular feedback: Cells in the ascending limb of the loop of Henle called macula densa sense a rise in water and sodium as occurs with increased blood pressure (and filtration rate).– They send a chemical signal to constrict
the afferent arterioles.
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What happen to urine concentration in low blood pressure or blood volume?
Which compound would increase most in case of drop of GFR?
Which happen in case of renal artery stenosis?
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III. Reabsorption of Salt and Water
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Reabsorption
• 180 ml of water is filtered per day, but only 1−2 ml is excreted as urine.– This will increase when well hydrated and
decrease when dehydrated.– A minimum 400 ml must be excreted to rid
the body of wastes = obligatory water loss.– 85% of reabsorption occurs in the proximal
tubules and descending loop of Henle.This portion is unregulated.
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Reabsorption in the Proximal Tubule
• The osmolality of filtrate in the glomerular capsule is equal to that of blood plasma.
• Na+ is actively transported out of the filtrate into the peritubular blood to set up a concentration gradient to drive osmosis.
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Proximal Tubular Fluid
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Descending Loop of Henle
• An additional 20% of water is reabsorbed here.– Happens continuously and is unregulated– The final 15% of water (~27 L) is absorbed
later in the nephron under hormonal control.
• Fluid entering loop of Henle is isotonic to extracellular fluids.
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Ascending Loop of Henle
• Salt (NaCl) is actively pumped into the interstitial fluid.– Movement of Na+ down its electrochemical
gradient from filtrate into tubule cells powers the secondary active transport of Cl− and K+.
– Na+ is moved into interstitial space via Na+/K+ pump. Cl− follows Na+ passively due to electrical attraction, and K+ passively diffuses back into filtrate.
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Ascending Loop of Henle
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Ascending Loop of Henle
• Walls are not permeable to water, so osmosis cannot occur from the ascending part of the loop.
• Surrounding interstitial fluid becomes increasingly solute concentrated at the bottom of the tube.
• Tubular fluid entering the ascending loop of Henle becomes more hypotonic as it ascends the loop.
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Descending Loop of Henle
• Is not permeable to salt but is permeable to water
• Water is drawn out of the filtrate and into the interstitial space where it is quickly picked up by capillaries.
• As it descends, the fluid becomes more solute concentrated.
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Loop of Henle: Solute and Water Transport
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Countercurrent Multiplication
• Positive feedback mechanism is created between the two portions of the loop of Henle.
– The more salt the ascending limb removes, the saltier the fluid entering it will be (due to loss of water in descending limb).
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Vasa Recta
• Specialized blood vessels around loop of Henle, which also have a descending and ascending portion
• Help create the countercurrent system because they take in salts in the descending region but lose them again in the ascending region– Keep salts in the interstitial space
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Vasa Recta
• High salt concentration at the beginning of the ascending region pulls in water, which is removed from the interstitial space.
– Also keeps salt concentration in the interstitial space high
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Vasa Recta
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Renal Tubule Osmolality
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Collecting Duct and ADH
• Last stop in urine formation
• Also influenced by hypertonicity of interstitial space – water will leave via osmosis if able to
• Permeability to water depends on the number of aquaporin channels in the cells of the collecting duct– Availability of aquaporins determined by ADH
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Collecting Duct and ADH
• ADH binds to receptors on collecting duct cells
cAMP
Protein kinase
Vesicles with aquaporin channels fuse to plasma membrane.
• Water channels are removed without ADH.
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Collecting Duct and ADH
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Role of ADH in Plasma Concentration
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Summary of ADH Action
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IV. Renal Plasma Clearance
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Clearance of Inulin
• Inulin is a compound found in garlic, onion, and artichokes.– Great marker of glomerular filtration rate
because it is filtered but not reabsorbed or secreted
V X UGFR = ----------
P
V = rate of urine formation
U = inulin concentration in urine
P = inulin concentration in plasma
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Reabsorption of Glucose and Amino Acids
• Easily filtered out in the glomerular capsule
• Completely reabsorbed in the proximal tubule via secondary active transport with sodium, facilitated diffusion, and simple diffusion
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Transporter Saturation
• Glucose/Na+ cotransporters have a transport maximum.– If there is too much glucose in the filtrate, it
will not be completely reabsorbed.– Glucose in the urine = glycosuria and is a sign
of diabetes mellitus.– Extra glucose in the blood also results in
decreased water reabsorption and possible dehydration.
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V. Renal Control of Electrolyte and Acid-Base Balance
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Aldosterone
• About 90% of filtered Na+ and K+ is reabsorbed early in the nephron.– This is not regulated.
• An assessment of what the body needs is made, and aldosterone controls additional reabsorption of Na+ and secretion of K+ in the distal tubule and collecting duct.
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Potassium Secretion
• Aldosterone independent response: Increase in blood K+ triggers an increase in the number of K+ channels in the cortical collecting duct.
– When blood K+ levels drop, these channels are removed.
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Potassium Secretion
• Aldosterone-dependent response: Increase in blood K+ triggers adrenal cortex to release aldosterone.
– This increases K+ secretion in the distal tubule and collecting duct.
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Sodium and Potassium
• Increases in sodium absorption drive extra potassium secretion.
• Due to:– Potential difference created by Na+
reabsorption driving K+ through K+ channels– Stimulation of renin-angiotensin-aldosterone
system by water and Na+ in filtrate– Increased flow rates bend cilia on the cells of
the distal tubule, resulting in activation of K+ channels
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Control of Aldosterone Secretion
• A rise in blood K+ directly stimulates production of aldosterone in the adrenal cortex.
• A fall in blood Na+ indirectly stimulates production of aldosterone via the renin- angiotensin-aldosterone system.
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Juxtaglomerular Apparatus
• Located where the afferent arteriole comes into contact with the distal tubule
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Juxtaglomerular Apparatus
• A decrease in plasma Na+ results in a fall in blood volume.– Sensed by juxtaglomerular apparatus– Granular cells secrete renin into the afferent
arteriole.– This converts angiotensinogen into
angiotensin I.– Angiotensin-converting enzyme (ACE)
converts this into angiotensin II.
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Angiotensin II
• Stimulates adrenal cortex to make aldosterone
– Promotes the reabsorption of Na+ from cortical collecting duct
– Promotes secretion of K+
– Increases blood volume and raises blood pressure
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Regulation of Renin Secretion
• Low salt levels result in lower blood volume due to inhibition of ADH secretion.– Less water is reabsorbed in collecting ducts
and more is excreted in urine.
• Reduced blood volume is detected by granular cells that act as baroreceptors. They then secrete renin.– Granular cells are also stimulated by
sympathetic innervation from the baroreceptor reflex.
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Macula Densa
• Part of the distal tubule that forms the juxtaglomerular apparatus
• Sensor for tubuloglomerular feedback needed for regulation of glomerular filtration rate– When there is more Na+ and H2O in the
filtrate, a signal is sent to the afferent arteriole to constrict limiting filtration rate.
– Controlled via negative feedback
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Macula Densa
• When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to inhibit the production of renin.
– This results in less reabsorption of Na+, allowing more to be excreted.
– This helps lower Na+ levels in the blood.
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Atrial Natriuretic Peptide
• Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched.
– Stimulates kidneys to excrete more salt
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Plasma Sodium Balance
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Relationship Between Na+, K+, and H+
• Reabsorption of Na+ stimulates the secretion of other positive ions.– K+ and H+ compete.
• Acidosis stimulates the secretion of H+ and inhibits the secretion of K+ ions.– Acidosis can lead to hyperkalemia.
• Alkalosis stimulates the secretion and excretion of more K+.
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Acid-Base Regulation
• Kidneys maintain blood pH by reabsorbing bicarbonate and secreting H+.– Urine is thus acidic.
• Proximal tubule uses Na+/H+ pumps to exchange Na+ out and H+ in.– Some of the H+ brought in is used for the
reabsorption of bicarbonate.
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Secretion of H+
• Aside from the Na+/H+ pumps in the proximal tubule, the distal tubule has H+ ATPase pumps to increase H+ secretion.
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pH Disturbances
• Alkalosis: Less H+ is available to transport bicarbonate into tubule cells, so less bicarbonate is reabsorbed.
– Extra bicarbonate secretion compensates for alkalosis.
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pH Disturbances
• Acidosis: Proximal tubule can make extra bicarbonate through the metabolism of the amino acid glutamine.
– Extra bicarbonate enters the blood to compensate for acidosis.
– Ammonia stays in urine to buffer H+.
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Urinary Buffers
• Nephrons cannot produce urine with a pH below 4.5.
• To increase H+ secretion, urine must be buffered.– Phosphates and ammonia buffer the urine.– Phosphates enter via filtration.– Ammonia comes from the deamination of
amino acids.
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