1. Faisal I. Mohammed, MD, PhD Yanal Shafagoj, MD, PhD
Renal system
Faisal I. Mohammed, MD, PhD
Yanal Shafagoj, MD, PhD
University of Jordan

2. Tubular reabsorption and tubular secretion
Reabsorption – return of most of the filtered water and many solutes to the bloodstream
About 99% of filtered water reabsorbed
Proximal convoluted tubule cells make largest contribution
Both active and passive processes
Secretion – transfer of material from blood into tubular fluid
Helps control blood pH
Helps eliminate substances from the body (K+)
University of Jordan

3. Reabsorption routes and transport mechanisms
Paracellular reabsorption
Between adjacent tubule cells
Tight junction do not completely seal off interstitial fluid from tubule fluid
Passive
Transcellular reabsorption – through an individual cell
Transport mechanisms
Reabsorption of Na+ especially important
Primary active transport
Sodium-potassium pumps in basolateral membrane only
Secondary active transport
Symporters, antiporters
Transport maximum (Tm)
Upper limit to how fast it can work
Obligatory vs. facultative water reabsorption
University of Jordan

4. Reabsorption routes: paracellular reabsorption and transcellular reabsorption
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5. Reabsorption and secretion in proximal convoluted tubule (PCT)
Largest amount of solute and water reabsorption
Secretes variable amounts of H+, NH4+
Most solute reabsorption involves Na+
Symporters with glucose, amino acids, lactic acid, water-soluble vitamins, phosphate and sulfate
Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be secreted
Solute reabsorption promotes osmosis – creates osmotic gradient
Aquaporin-1 in cells lining PCT and descending limb of loop of Henle
As water leaves tubular fluid, solute concentration increases
Urea and ammonia in blood are filtered at glomerulus and secreted by proximal convoluted tubule cells
University of Jordan

6. Reabsorption and secretion in the proximal convoluted tubule
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7. Reabsorption in the loop of Henle
Chemical composition of tubular fluid quite different from filtrate
Glucose, amino acids and other nutrients were already reabsorbed in PT
At the entranc of LH Osmolarity still close to that of blood
Reabsorption of water and solutes balanced
In the descending: For the first time reabsorption of water is NOT automatically coupled to reabsorption of solutes
Independent regulation of both volume and osmolarity of body fluids
Ascending: Na+-K+-2Cl- symporters function in Na+ and Cl- reabsorption – promotes reabsorption of cations
No water is reabsorbed in ascending limb – osmolarity decreases
University of Jordan

8. Na+–K+-2Cl- symporter in the thick ascending limb of the loop of Henle…Lasix
University of Jordan

9. Reabsorption and secretion in the late distale convoluted tubule and collecting duct
Reabsorption on the early distal convoluted tubule
Na+-Cl- symporters reabsorb Na+ and Cl- (Thiazide)
Major site where parathyroid hormone stimulates reabsorption of Ca+ depending on body’s needs
Reabsorption and secretion in the late distal convoluted tubule and collecting duct
90-95% of filtered solutes and fluid have been returned by now
Principal cells reabsorb Na+ and secrete K+
Intercalated cells reabsorb K+ and HCO3- and secrete H+
Amount of water reabsorption and solute reabsorption and secretion depends on body’s needs
University of Jordan

10. Hormonal regulation of tubular reabsorption and secretion
Angiotensin II - when blood volume and blood pressure decrease
Decreases GFR, enhances reabsorption of Na+, Cl- and water in PCT
Aldosterone - when blood volume and blood pressure decrease
Stimulates principal cells in collecting duct to reabsorb more Na+ and Cl- and secrete more K+ (Aldactone)
Parathyroid hormone
Stimulates cells in DCT to reabsorb more Ca2+
University of Jordan

11. Regulation of facultative water reabsorption by ADH
Antidiuretic hormone (ADH or vasopressin)
Increases water permeability of cells by inserting aquaporin-2 in last part of DCT and collecting duct
Atrial natriuretic peptide (ANP)
Large increase in blood volume promotes release of ANP
Decreases blood volume and pressure by inhibiting reabsorption of Na+ and water in PCT and collecting duct, suppress secretion of ADH and aldosterone
University of Jordan

12. ANP Produced by atria due to stretching of walls.
Antagonist to aldosterone.
Increases Na+ and H20 excretion.
Acts as an endogenous diuretic.

13. Production of dilute and concentrated urine
Even though your fluid intake can be highly variable, total fluid volume in your body remains stable
Depends in large part on the kidneys to regulate the rate of water loss in urine
ADH controls whether dilute or concentrated urine is formed
Absent or low ADH = dilute urine
Higher levels = more concentrated urine through increased water reabsorption
University of Jordan

14. Formation of dilute urine
Glomerular filtrate has same osmolarity as blood 300 mOsm/liter
Fluid leaving PCT is isotonic to plasma
When dilute urine is being formed, the osmolarity of fluid increases as it goes down the descending loop of Henle, decreases as it goes up the ascending limb, and decreases still more as it flows through the rest of the nephron and collecting duct
University of Jordan

15. Formation of dilute urine
Osmolarity of interstitial fluid of renal medulla becomes greater, more water is reabsorbed from tubular fluid so fluid become more concentrated
Water cannot leave in thick portion of ascending limb but solutes leave making fluid more dilute than blood plasma
Additional solutes but not much water leaves in DCT
Low ADH makes late DCT and collecting duct have low water permeability
University of Jordan

16. Formation of concentrated urine
Urine can be up to 4 times more concentrated than blood plasma
Ability of ADH depends on presence of osmotic gradient in interstitial fluid of renal medulla
3 major solutes contribute – Na+, Cl-, and urea
2 main factors build and maintain gradient
Differences in solute and water permeability in different sections of loop of Henle and collecting ducts
Countercurrent flow of fluid though descending and ascending loop of Henle and blood through ascending and descending limbs of vasa recta
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17. Countercurrent multiplication
Process by which a progressively increasing osmotic gradient is formed as a result of countercurrent flow
Long loops of Henle of juxtamedullary nephrons function as countercurrent multiplier
Symporters in thick ascending limb of loop of Henle cause buildup of Na+ and Cl- in renal medulla, cells impermeable to water
Countercurrent flow establishes gradient as reabsorbed Na+ and Cl- become increasingly concentrated
Cells in collecting duct reabsorb more water and urea
Urea recycling causes a buildup of urea in the renal medulla
Long loop of Henle establishes gradient by countercurrent multiplication
University of Jordan

18. Countercurrent exchange
Process by which solutes and water are passively exchanged between blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow
Vasa recta is a countercurrent exchanger
Osmolarity of blood leaving vasa recta is only slightly higher than blood entering
Provides oxygen and nutrients to medulla without washing out or diminishing gradient
Vasa recta maintains gradient by countercurrent exchange
University of Jordan

19. Mechanism of urine concentration in long-loop juxtamedullary nephrons
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20. (b) Recycling of salts and urea in the vasa recta
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferent
arteriole
Efferent
Glomerulus
Distal convoluted tubule
Proximal
convoluted
tubule
Symporters in thick
ascending limb cause
buildup of Na+ and Cl–
Interstitial fluid
in renal medulla
300
1200
1000
800
Osmotic
gradient
600
400 H 2 O
200
980
780
580
380
100
Loop of Henle
Concentrated urine
320
H2O
Urea
Papillary
duct
Urea recycling
causes buildup
of urea in the
renal medulla
Collecting
Countercurrent flow
through loop of Henle
establishes an osmotic
Principal cells in
collecting duct
reabsorb more
water when ADH
is present
500
700
900
1100
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symporters
Interstitial
fluid in
renal cortex
Juxtamedullary nephron
and its blood supply
together
Vasa
recta
Loop of
Henle 1 3 4
(b) Recycling of salts and urea in the vasa recta
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferent
arteriole
Efferent
Glomerulus
Distal convoluted tubule
Proximal
convoluted
tubule
Symporters in thick
ascending limb cause
buildup of Na+ and Cl–
Interstitial fluid
in renal medulla
300
1200
1000
800
Osmotic
gradient
600
400 H 2 O
200
980
780
580
380
100
Loop of Henle
Concentrated urine
320
H2O
Urea
Papillary
duct
Collecting
Countercurrent flow
through loop of Henle
establishes an osmotic
Principal cells in
collecting duct
reabsorb more
water when ADH
is present
500
700
900
1100
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symporters
Interstitial
fluid in
renal cortex
Juxtamedullary nephron
and its blood supply
together
Vasa
recta
Loop of
Henle 1 3
(b) Recycling of salts and urea in the vasa recta
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferent
arteriole
Efferent
Glomerulus
Distal convoluted tubule
Proximal
convoluted
tubule
Symporters in thick
ascending limb cause
buildup of Na+ and Cl–
Interstitial fluid
in renal medulla
300
1200
1000
800
Osmotic
gradient
600
400 H 2 O
200
980
780
580
380
100
Loop of Henle
Concentrated urine
320
H2O
Urea
Papillary
duct
Collecting
Countercurrent flow
through loop of Henle
establishes an osmotic
500
700
900
1100
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symporters
Interstitial
fluid in
renal cortex
Juxtamedullary nephron
and its blood supply
together
Vasa
recta
Loop of
Henle 1
(b) Recycling of salts and urea in the vasa recta
(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferent
arteriole
Efferent
Glomerulus
Distal convoluted tubule
Proximal
convoluted
tubule
Symporters in thick
ascending limb cause
buildup of Na+ and Cl–
Interstitial fluid
in renal medulla
300
1200
1000
800
Osmotic
gradient
600
400 H 2 O
200
980
780
580
380
100
Loop of Henle
Concentrated urine
320
H2O
Urea
Papillary
duct
Collecting
500
700
900
1100
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symporters
Interstitial
fluid in
renal cortex
Juxtamedullary nephron
and its blood supply
together
Vasa
recta
Loop of
Henle 1
University of Jordan

21. Summary of filtration, reabsorption, and secretion in the nephron and collecting duct
University of Jordan

22. Na+ Reabsorption Insert fig. 17.26 90% filtered Na+ reabsorbed in PCT.
In the absence of aldosterone, 80% of the remaining Na+ is reabsorbed in DCT.
Final [Na+] controlled in CD by aldosterone.
When aldosterone is secreted in maximal amounts, all Na+ in DCT is reabsorbed.
Insert fig

23. K+ Secretion
90% filtered K+ is reabsorbed in early part of the nephron.
Secretion of K+ occurs in CD.
Amount of K+ secreted depends upon:
Amount of Na+ delivered to the region.
Amount of aldosterone secreted.
As Na+ is reabsorbed, lumen of tubule becomes –charged.
Potential difference drives secretion of K+ into tubule.
Transport carriers for Na+ separate from transporters for K+.

24. K+ Secretion (continued)
Final [K+] controlled in CD by aldosterone.
When aldosterone is absent, no K+ is excreted in the urine.
High [K+] or low [Na+] stimulates the secretion of aldosterone.
Only means by which K+ is secreted.
Insert fig

25. Renal Acid-Base Regulation
Kidneys help regulate blood pH by excreting H+ and reabsorbing HC03-.
Most of the H+ secretion occurs across the walls of the PCT in exchange for Na+.
Antiport mechanism.
Moves Na+ and H+ in opposite directions.
Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03- and excrete H+.
Returns blood pH back to normal range.

26. Reabsorption of HCO3-
Apical membranes of tubule cells are impermeable to HCO3-.
Reabsorption is indirect.
When urine is acidic, HCO3- combines with H+ to form H2C03-, which is catalyzed by ca located in the apical cell membrane of PCT.
As [C02] increases in the filtrate, C02 diffuses into tubule cell and forms H2C03.
H2C03 dissociates to HCO3- and H+.
HCO3- generated within tubule cell diffuses into peritubular capillary.

27. Acidification of Urine
Insert fig

28. Urinary Buffers Nephron cannot produce a urine pH < 4.5.
In order to excrete more H+, the acid must be buffered.
H+ secreted into the urine tubule and combines with HPO4-2 or NH3.
HPO4-2 + H H2PO4-
NH3 + H NH4+

29. Diuretics Increase urine volume excreted. Loop diuretics:
Increase the proportion of glomerular filtrate that is excreted as urine.
Loop diuretics:
Inhibit NaCl transport out of the ascending limb of the LH.
Thiazide diuretics:
Inhibit NaCl reabsorption in the 1st segment of the DCT.
Ca inhibitors:
Prevent H20 reabsorption in PCT when HC0s- is reabsorbed.
Osmotic diuretics:
Increase osmotic pressure of filtrate.

30. Clinical Diuretics Sites of Action
Insert fig

31. Evaluation of kidney function
Urinalysis
Analysis of the volume and physical, chemical and microscopic properties of urine
Water accounts for 95% of total urine volume
Typical solutes are filtered and secreted substances that are not reabsorbed
If disease alters metabolism or kidney function, traces if substances normally not present or normal constituents in abnormal amounts may appear
University of Jordan

32. Evaluation of kidney function
Blood tests
Blood urea nitrogen (BUN) – measures blood nitrogen that is part of the urea resulting from catabolism and deamination of amino acids
Plasma creatinine results from catabolism of creatine phosphate in skeletal muscle – measure of renal function
Renal plasma clearance
More useful in diagnosis of kidney problems than above
Volume of blood cleared of a substance per unit time
High renal plasma clearance indicates efficient excretion of a substance into urine
PAH administered to measure renal plasma flow
University of Jordan

33. Urine transportation, storage, and elimination
Ureters
Each of 2 ureters transports urine from renal pelvis of one kidney to the bladder
Peristaltic waves, hydrostatic pressure and gravity move urine
No anatomical valve at the opening of the ureter into bladder – when bladder fills it compresses the opening and prevents backflow
University of Jordan

34. Ireters, urinary bladder, and urethra in a female
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35. Urinary bladder and urethra
Hollow, distensible muscular organ
Capacity averages mL
Micturition – discharge of urine from bladder
Combination of voluntary and involuntary muscle contractions
When volume increases stretch receptors send signals to micturition center in spinal cord triggering spinal reflex – micturition reflex
In early childhood we learn to initiate and stop it voluntarily
Urethra
Small tube leading from internal urethral orifice in floor of bladder to exterior of the body
In males discharges semen as well as urine
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36. Comparison between female and male urethras
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37. Glucose and Amino Acid Reabsorption
Filtered glucose and amino acids are normally reabsorbed by the nephrons.
In PCT occurs by secondary active transport with membrane carriers.
Carrier mediated transport displays:
Saturation.
Tm.
[Transported molecules] needed to saturate carriers and achieve maximum transport rate.
Renal transport threshold:
Minimum plasma [substance] that results in excretion of that substance in the urine.
Renal plasma threshold for glucose = mg/dl.

38. Kidney Diseases Acute renal failure: Glomerulonephritis:
Ability of kidneys to excrete wastes and regulate homeostasis of blood volume, pH, and electrolytes impaired.
Rise in blood [creatinine].
Decrease in renal plasma clearance of creatinine.
Glomerulonephritis:
Inflammation of the glomeruli.
Autoimmune disease by which antibodies have been raised against the glomerulus basement membrane.
Leakage of protein into the urine.

39. Kidney Diseases (continued)
Renal insufficiency:
Nephrons are destroyed.
Clinical manifestations:
Salt and H20 retention.
Uremia.
Elevated plasma [H+] and [K+].
Dialysis:
Separates molecules on the basis of the ability to diffuse through selectively permeable membrane.

40. University of Jordan 40