1. Chapter 17
Physiology of the Kidneys
17-1

2. Kidney Function
• Is to regulate plasma & interstitial fluid by
formation of urine
• In process of urine formation, kidneys regulate:
– Volume of blood plasma, which contributes to BP
– Waste products in blood
– Concentration of electrolytes
• Including Na+, K+, HC03-, & others
– Plasma pH
17-3

3. Fig 17.5
17-13

4. Type of Nephrons
• Cortical nephrons
originate in outer
2/3 of cortex
• Juxtamedullary
nephrons originate
in inner 1/3 cortex
– Have long LHs
– Important in
producing
concentrated urine
Fig 17.6
17-17

5. Mechanisms of Urine Formation
• Urine formation
and adjustment
of blood
composition
involves three
major processes
– Glomerular
filtration
– Tubular
reabsorption
– Secretion
Figure 25.8

6. Glomerular Filtration
• Glomerular capillaries & Bowman's capsule
form a filter for blood
– Glomerular Caps are fenestrated--have large pores
between its endothelial cells
• 100-400 times more permeable than other Caps
• Small enough to keep RBCs, platelets, & WBCs from
passing
• Pores are lined with negative charges to keep blood
proteins from filtering
17-19

7. Glomerular Filtration continued
• To enter
tubule filtrate
must pass
through
narrow
filtration slits
formed
between
pedicels of
podycytes of
glomerular
capsule
Fig 17.8
17-20

8. Filtration
• Movement of fluid, derived from blood flowing through the glomerulus,
across filtration membrane
• Filtrate: water, small molecules, ions that can pass through
membrane
• Pressure difference forces filtrate across filtration membrane
• Renal fraction: part of total cardiac output that passes through the
kidneys. Varies from 12-30%; averages 21%
• Renal blood flow rate: 1176 mL/min
• Renal plasma flow rate: renal blood flow rate X fraction of blood that
is plasma: 650 mL/min
• Filtration fraction: part of plasma that is filtered into lumen of
Bowman’s capsules; average 19%
• Glomerular filtration rate (GFR): amount of filtrate produced each
minute. 180 L/day
• Average urine production/day: 1-2 L. Most of filtrate must be
reabsorbed

9. Glomerular Ultrafiltrate
• Is fluid that
enters
glomerular
capsule,
whose
filtration was
driven by
blood pressure
Fig 17.10
17-23

10. Filtration
• Filtration membrane: filtration barrier. It prevents blood cells and
proteins from entering lumen of Bowman’s capsule, but is many times
more permeable than a typical capillary
– Fenestrated endothelium, basement membrane and pores formed
by podocytes
– Some albumin and small hormonal proteins enter the filtrate, but
these are reabsorbed and metabolized by the cells of the proximal
tubule. Very little protein normally found in urine
• Filtration pressure: pressure gradient responsible for filtration; forces
fluid from glomerular capillary across membrane into lumen of
Bowman’s capsules
• Forces that affect movement of fluid into or out of the lumen of
Bowman’s capsule
– Glomerular capillary pressure (GCP): blood pressure inside
capillary tends to move fluid out of capillary into Bowman’s capsule
– Capsule pressure (CP): pressure of filtrate already in the lumen
– Blood colloid osmotic pressure (BCOP): osmotic pressure
caused by proteins in blood. Favors fluid movement into the
capillary from the lumen. BCOP greater at end of glomerular
capillary than at beginning because of fluid leaving capillary and
entering lumen
– Filtration pressure (10 mm Hg) = GCP (50 mm Hg) – CP (10 mm

11. Filtration Pressure

12. Filtration
• Colloid osmotic pressure in Bowman’s capsule normally close to zero.
During diseases like glomerular nephritis, proteins enter the filtrate
and filtrate exerts an osmotic pressure, increasing volume of filtrate
• High glomerular capillary pressure results from
– Low resistance to blood flow in afferent arterioles
– Low resistance to blood flow in glomerular capillaries
– High resistance to blood flow in efferent arterioles: small diameter vessels
• Pressure lower in peritubular capillaries downstream from efferent
arterioles
• Filtrate is forced across filtration membrane; fluid moves into
peritubular capillaries from interstitial fluid
• Changes in afferent and efferent arteriole diameter alter filtration
pressure
– Dilation of afferent arterioles/constriction efferent arterioles increases
glomerular capillary pressure, increasing filtration pressure and thus
glomerular filtration

13. Net Filtration Pressure (NFP)
• The pressure responsible for filtrate formation
• NFP equals the glomerular hydrostatic
pressure (HPg) minus the oncotic pressure of
glomerular blood (OPg) combined with the
capsular hydrostatic pressure (HPc)
NFP = HPg – (OPg + HPc)

14. Glomerular Filtration Rate (GFR)
• Is volume of filtrate produced by both
kidneys/min
– Averages 115 ml/min in women; 125 ml/min in men
– Totals about 180L/day (45 gallons)
• So most filtered water must be reabsorbed or death
would ensue from water lost through urination
• GFR is directly proportional to the NFP
• Changes in GFR normally result from changes in
glomerular blood pressure
17-24

15. Regulation of Glomerular
Filtration
• If the GFR is too high:
– Needed substances cannot be reabsorbed
quickly enough and are lost in the urine
• If the GFR is too low:
– Everything is reabsorbed, including wastes
that are normally disposed of

16. Regulation of Glomerular
Filtration
• Three mechanisms control the GFR
– Renal autoregulation (intrinsic system)
– Neural controls
– Hormonal mechanism (the renin-
angiotensin system)

17. Intrinsic Controls
• Under normal conditions, renal autoregulation
maintains a nearly constant glomerular
filtration rate
• Autoregulation entails two types of control
– Myogenic – responds to changes in pressure in
the renal blood vessels
– Flow-dependent tubuloglomerular feedback –
senses changes in the juxtaglomerular apparatus

18. Renal Autoregulation
• Is also maintained by negative feedback between afferent
arteriole & volume of filtrate (tubuloglomerular feedback)
– Increased flow of filtrate sensed by macula densa (part of
juxtaglomerular apparatus) in thick ascending LH
• Signals afferent arterioles to constrict
17-29

19. Renal Autoregulation
• Allows kidney to maintain a constant GFR over wide
range of BPs
• Achieved via effects of locally produced chemicals on
afferent arterioles
• When average BP drops to 70 mm Hg afferent
arteriole dilates
• When average BP increases, afferent arterioles
constrict
17-27

20. Extrinsic Controls
• When the sympathetic nervous system
is at rest:
– Renal blood vessels are maximally dilated
– Autoregulation mechanisms prevail

21. Extrinsic Controls
• Under stress:
– Norepinephrine is released by the sympathetic
nervous system
– Epinephrine is released by the adrenal medulla
– Afferent arterioles constrict and filtration is
inhibited
• The sympathetic nervous system also
stimulates the renin-angiotensin mechanism

22. Renin-Angiotensin Mechanism
• Is triggered when the JG cells release renin
• Renin acts on angiotensinogen to release
angiotensin I
• Angiotensin I is converted to angiotensin II
• Angiotensin II:
– Causes mean arterial pressure to rise
– Stimulates the adrenal cortex to release
aldosterone
• As a result, both systemic and glomerular
hydrostatic pressure rise

23. Sympathetic Effects
• Sympathetic
activity
constricts
afferent arteriole
– Helps maintain
BP & shunts
blood to heart &
muscles
Fig 17.11
17-26

24. 17-28

25. Tubular Reabsorption: Overview
• Tubular reabsorption: occurs as filtrate flows through the
lumens of proximal tubule, loop of Henle, distal tubule, and
collecting ducts
• Results because of
– Diffusion
– Facilitated diffusion
– Active transport
– Cotransport
– Osmosis
• Substances transported to interstitial fluid and reabsorbed
into peritubular capillaries: inorganic salts, organic
molecules, 99% of filtrate volume. These substances return
to general circulation through venous system

26. Routes of Water and Solute Reabsorption
Figure 25.11

27. 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

28. Nonreabsorbed Substances
• A transport maximum (Tm):
– Reflects the number of carriers in the renal
tubules available
– Exists for nearly every substance that is
actively reabsorbed
• When the carriers are saturated, excess
of that substance is excreted

29. Reabsorption of Salt & H20
• In PCT returns most molecules & H20 from
filtrate back to peritubular capillaries
– About 180 L/day of ultrafiltrate produced; only 1–2 L
of urine excreted/24 hours
• Urine volume varies according to needs of body
• Minimum of 400 ml/day urine necessary to excrete
metabolic wastes (obligatory water loss)
17-31

30. Reabsorption of Salt & H20 continued
• Return of filtered
molecules is called
reabsorption
• Water is never
transported
– Other molecules
are transported &
water follows by
osmosis
Fig 17.13
17-32

31. PCT
• Filtrate in PCT is
isosmotic to blood
(300 mOsm/L)
• Thus reabsorption of
H20 by osmosis
cannot occur without
active transport (AT)
– Is achieved by AT of
Na+ out of filtrate
• Loss of + charges
causes Cl- to passively
follow Na+
• Water follows salt by
osmosis
Fig 17.14
17-33

32. Na+ Entry into Tubule Cells
• Passive entry: Na+-K+ ATPase pump
• 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

33. Insert fig. 17.14
Fig 17.15
17-34

34. Significance of PCT Reabsorption
• ≈65% Na+, Cl-, & H20 is reabsorbed in PCT &
returned to bloodstream
• An additional 20% is reabsorbed in descending
loop of Henle
• Thus 85% of filtered H20 & salt are reabsorbed
early in tubule
– This is constant & independent of hydration levels
– Energy cost is 6% of calories consumed at rest
– The remaining 15% is reabsorbed variably,
depending on level of hydration
17-35

35. Absorptive Capabilities of Renal
Tubules and Collecting Ducts
• Substances reabsorbed in PCT include:
– Sodium, all nutrients, cations, anions, and water
– Urea and lipid-soluble solutes
– Small proteins
• Loop of Henle reabsorbs:
– H2O, Na+, Cl−, K+ in the descending limb
– Ca2+, Mg2+, and Na+ in the ascending limb

36. Absorptive Capabilities of Renal
Tubules and Collecting Ducts
• DCT absorbs:
– Ca2+, Na+, H+, K+, and water
– HCO3− and Cl−
• Collecting duct absorbs:
– Water and urea

37. Concentration Gradient in Kidney
• In order for H20 to be reabsorbed, interstitial
fluid must be hypertonic
• Osmolality of medulla interstitial fluid (1200-
1400 m O sm) is 4X that of cortex & plasma
(300 m O sm)
– This concentration gradient results largely from loop
of Henle which allows interaction between
descending & ascending limbs
17-36

38. Osmotic Gradient in the Renal
Medulla
Figure 25.13

39. Osmolality of Different Regions of the Kidney
Fig 17.20
17-47

40. Descending Limb LH
• Is permeable to H20
• Is impermeable to salt
• Because deep regions
of medulla are 1400
mOsm, H20 diffuses out
of filtrate until it
equilibrates with
interstitial fluid
– This H20 is reabsorbed by
capillaries
Fig 17.17
17-37

41. Ascending Limb LH
• Has a thin segment in
depths of medulla &
thick part toward
cortex
• Impermeable to H20;
permeable to salt;
thick part ATs salt out
of filtrate
– AT of salt causes
filtrate to become
dilute (100 mOsm) by
end of LH
Fig 17.17
17-38

42. AT in Ascending Limb LH
• Fig 17.16
• NaCl is actively
extruded from thick
ascending limb Insert fig. 17.15
into interstitial fluid
• Na+ diffuses into
tubular cell with
secondary active
transport of K+ and
Cl-
• Occurs at a ratio of
1 Na+ & 1 K+ to 2 Cl-
17-39

43. AT in Ascending Limb LH continued
• Na+ is AT across
basolateral
membrane by
Na+/ K+ pump
• Cl- passively
follows Na+ down
electrical gradient
• K+ passively
diffuses back into
filtrate
Fig 17.16
17-40

44. 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

45. Countercurrent Multiplier System
• Countercurrent flow & proximity allow descending & ascending
limbs of LH to interact in a way that causes osmolality to build
in medulla
• Salt pumping in thick ascending part raises osmolality around
descending limb, causing more H20 to diffuse out of filtrate
– This raises osmolality of filtrate in descending limb which causes more
concentrated filtrate to be delivered to ascending limb.
– As this concentrated filtrate is subjected to AT of salts, it causes even
higher osmolality around descending limb (positive feedback)
– Process repeats until equilibrium is reached when osmolality of medulla
is 1400 mOsm.
17-41

46. Loop of Henle: Countercurrent Mechanism
Figure 25.14

47. 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

48. Formation of Dilute Urine
• 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)

49. 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

50. Formation of Concentrated
Urine
• 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

51. Formation of Dilute and Concentrated Urine
Figure 25.15a, b

52. Vasa Recta Fig 17.18
• Is important component of
countercurrent multiplier
• Permeable to salt, H20 (via
aquaporins), & urea
• Recirculates salt, trapping
some in medulla interstitial
fluid
• Reabsorbs H20 coming out
of descending limb
• Descending section has
urea transporters
• Ascending section has
fenestrated capillaries
17-42

53. Effects of Urea
• Urea contributes
to high osmolality
in medulla
– Deep region of
collecting duct is
permeable to
urea & transports
it
Fig 17.19
17-43

54. 17-44

55. Collecting Duct (CD)
• Plays important role in water conservation
• Is impermeable to salt in medulla
• Permeability to H20 depends on levels of ADH
17-45

56. ADH
Fig 17.21
• Is secreted by post
pituitary in response to
dehydration
• Stimulates insertion of
aquaporins (water
channels) into plasma
membrane of CD
• When ADH is high, H20 is
drawn out of CD by high
osmolality of interstitial
fluid
– & reabsorbed by vasa
recta
17-46

57. Glucose & Amino Acid Reabsorption
• Filtered glucose & amino acids are normally
100% reabsorbed from filtrate
– Occurs in PCT by carrier-mediated cotransport with
Na+
• Transporter displays saturation if ligand concentration in
filtrate is too high
– Level needed to saturate carriers & achieve maximum transport
rate is transport maximum (Tm)
– Glucose & amino acid transporters don't saturate
under normal conditions
17-58

58. Glycosuria
• Is presence of glucose in urine
• Occurs when glucose > 180-200mg/100ml plasma
(= renal plasma threshold)
– Glucose is normally absent because plasma levels stay
below this value
– Hyperglycemia has to exceed renal plasma threshold
– Diabetes mellitus occurs when hyperglycemia results in
glycosuria
17-59

59. Hormonal Effects
17-60

60. Electrolyte Balance
• Kidneys regulate levels of Na+, K+, H+, HC03-, Cl-,
& PO4-3 by matching excretion to ingestion
• Control of plasma Na+ is important in regulation
of blood volume & pressure
• Control of plasma of K+ important in proper
function of cardiac & skeletal muscles
17-61

61. Role of Aldosterone in Na+/K+ Balance
• 90% filtered Na+ & K+ reabsorbed before DCT
– Remaining is variably reabsorbed in DCT & cortical
CD according to bodily needs
• Regulated by aldosterone (controls K+ secretion & Na+
reabsorption)
• In the absence of aldosterone, 80% of remaining Na+ is
reabsorbed in DCT & cortical CD
• When aldosterone is high all remaining Na+ is reabsorbed
17-62

62. K+ Secretion
• Is only way K+
ends up in urine
• Is directed by
aldosterone &
occurs in DCT &
cortical CD
– High K+ or Na+
will increase
aldosterone & K+
secretion
Fig 17.25
17-63

63. Juxtaglomerular Apparatus (JGA)
• Is specialized region in each nephron where afferent arteriole
comes in contact with thick ascending limb LH
Fig 17.26
17-64

64. Renin-Angiotensin-Aldosterone
System
• Is activated by release of renin from granular
cells within afferent arteriole
– Renin converts angiotensinogen to angiotensin I
• Which is converted to Angio II by angiotensin-converting
enzyme (ACE) in lungs
• Angio II stimulates release of aldosterone
17-65

65. Regulation of Renin Secretion
• Inadequate intake of NaCl always causes
decreased blood volume
– Because lower osmolality inhibits ADH, causing
less H2O reabsorption
– Low blood volume & renal blood flow stimulate renin
release
• Via direct effects of BP on granular cells & by Symp
activity initiated by arterial baroreceptor reflex (see Fig
14.26)
17-66

66. Fig 17.27
17-67

67. Macula Densa
• Is region of Fig 17.26
ascending limb
in contact with
afferent arteriole
• Cells respond to
levels of Na+ in
filtrate
– Inhibit renin
secretion when
Na+ levels are
high
– Causing less
aldosterone
secretion, more
Na+ excretion
17-68

68. Renin Release
Figure 25.10

69. 17-69

70. Atrial Natriuretic Peptide (ANP)
• Is produced by atria due to stretching of walls
• Acts opposite to aldosterone
• Stimulates salt & H20 excretion
• Acts as an endogenous diuretic
17-70

71. Na , K , H , & HC03
+ + + -
Relationships
17-71

72. Na+, K+, & H+ Relationship
• Na+ reabsorption in
DCT & CD creates
electrical gradient for
H+ & K+ secretion Insert fig. 17.27
• When extracellular H+
increases, H+ moves
into cells causing K+ to
diffuse out & vice versa
– Hyperkalemia can cause
acidosis
Fig 17.28
• In severe acidosis, H is
+
secreted at expense of
K+
17-72

73. Renal Acid-Base Regulation
• Kidneys help regulate blood pH by excreting H +
&/or reabsorbing HC03-
• Most H+ secretion occurs across walls of PCT in
exchange for Na+ (Na+/H+ antiporter)
• Normal urine is slightly acidic (pH = 5-7)
because kidneys reabsorb almost all HC0 3- &
excrete H+
17-73

74. Reabsorption of HCO3- in PCT
• Is indirect because apical membranes of PCT
cells are impermeable to HCO3-
17-74

75. Reabsorption of HCO3- in PCT continued
• When urine is acidic, HCO3- combines with H+ to form H2C03
(catalyzed by CA on apical membrane of PCT cells)
• H2C03 dissociates into C02 + H2O
• C02 diffuses into PCT cell & forms H2C03 (catalyzed by CA)
• H2C03 splits into HCO3- & H+ ; HCO3- diffuses into blood
Fig 17.29
17-75

76. Urinary Buffers
• Nephron cannot produce urine with pH < 4.5
• Excretes more H+ by buffering H+s with HPO4-2 or
NH3 before excretion
• Phosphate enters tubule during filtration
• Ammonia produced in tubule by deaminating
amino acids
• Buffering reactions
– HPO4-2 + H+ → H2PO4-
– NH3 + H+ → NH4+ (ammonium ion)
17-76

77. 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

78. Physical Characteristics of
Urine
• Odor
– Fresh urine is slightly aromatic
– Standing urine develops an ammonia odor
– Some drugs and vegetables (asparagus)
alter the usual odor

79. 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

80. Urethra
Figure 25.18a. b

81. Micturition (Voiding or
Urination)
• The act of emptying the bladder
• Distension of bladder walls initiates spinal
reflexes that:
– Stimulate contraction of the external urethral
sphincter
– Inhibit the detrusor muscle and internal sphincter
(temporarily)
• Voiding reflexes:
– Stimulate the detrusor muscle to contract
– Inhibit the internal and external sphincters

82. Micturition (Voiding or Urination)

83. Kidney Diseases
• In acute renal failure, ability of kidneys to
excrete wastes & regulate blood volume, pH, &
electrolytes is impaired
– Rise in blood creatinine & decrease in renal plasma
clearance of creatinine
– Can result from atherosclerosis, inflammation of
tubules, kidney ischemia, or overuse of NSAIDs
17-80

84. Kidney Diseases continued
• Glomerulonephritis is inflammation of glomeruli
– Autoimmune attack against glomerular capillary
basement membranes
• Causes leakage of protein into urine resulting in
decreased colloid osmotic pressure & resulting edema
17-81

85. Kidney Diseases continued
• In renal insufficiency, nephrons have been destroyed
as a result of a disease
– Clinical manifestations include salt & H20 retention & uremia
(high plasma urea levels)
• Uremia is accompanied by high plasma H+ & K+ which can cause
uremic coma
– Treatment includes hemodialysis
• Patient's blood is passed through a dialysis machine which separates
molecules on basis of ability to diffuse through selectively permeable
membrane
• Urea & other wastes are removed
17-82