1. Chapter 17
Physiology of the
Kidneys
Lecture PowerPoint
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. Kidney Function
• 1. Maintain proper water balance in the body.
• 2. Regulate the concentrations of most ECF ions such as Na+, H+, K+, Cl-, HCO3-,
Mg++, PO4--etc.
• 3. Maintain the proper plasma volume and therefore helping to regulating blood
pressure.
• 4. Help maintain the proper acid-base balance of the body.
• 5. Maintain the proper osmolality of body fluids.
• 6. Excrete waste products of metabolism.
• 7. Excrete many foreign compounds such as drugs, food additives etc.
• 8. Secrete erythropoietin, the hormone that controls red blood cell production.
• 9. Secrete renin, an enzyme which participates in regulation of Na+ levels and blood
pressure.
• 10. Convert vitamin D into its active form which helps us absorb calcium from our
food.
17-3

3. Overview of Kidney Structure
17-4

4. Kidney Structure
• Paired kidneys are on either
side of vertebral column below
diaphragm
– About size of fist
• Urine made in the kidneys
pools into the renal pelvis, then
down the ureter to the urinary
bladder.
• It passes from the bladder
through the urethra to exit the
body.
• Urine is transported using
peristalsis.

5. Kidney Structure
• The kidney has two distinct regions:
– Renal cortex
– Renal medulla, made up of renal pyramids and
columns
• Each pyramid drains into a minor calyx  major calyx 
renal pelvis.

6. Nephron
17-9

7. Microscopic Kidney Structure
• Nephron: functional
unit of the kidney
– Each kidney has
more than a million
nephrons.
– Nephron consists of
small tubules and
associated blood
vessels.

8. Renal Blood Vessels
Renal artery 
Interlobar arteries 
Arcuate arteries 
Interlobular arteries 
Afferent arterioles
Glomerulus 
Efferent arterioles 
Peritubular capillaries 
Interlobular veins 
Arcuate veins 
Interlobar veins 
Renal vein

9. Nephron Tubules
• Glomerular (Bowman’s) capsule surrounds the glomerulus. Together,
they make up the renal corpuscle.
• Filtrate produced in renal corpuscle passes into the proximal convoluted
tubule.
• Next, fluid passes into the descending and ascending loop of Henle.

10. Nephron Tubules
• After the loop of Henle, fluid passes into the distal convoluted tubule.
• Finally, fluid passes into the collecting duct.
– The fluid is now urine and will drain into a minor calyx.

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Four Processes Take place In Nephrone
Non-filtered substances move Filtered substances
from peritubular capillaries move from tubular
into tubular lumen lumen into peritubular
capillaries Movement of protein
free plasma from
glomerular capillaries
into glomerular
capsule
Elimination of waste
products from the body into
urine
17-49

12. II. Glomerular Filtration

13. 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 Ultrafiltrate

14. Glomerular Filtration continued
• Filtrates must pass through:
1. Capillary fenestrae 2. Glomerular basement membrane
17-20

15. Glomerular Filtration continued
• Filtrates must pass through:
3. Visceral layer of the glomerular capsule composed of
cells called podocytes with extensions called pedicles
17-20

16. Ultrafiltrate
• Fluid in glomerular capsule gets there via
hydrostatic pressure of the blood, colloid osmotic
pressure, and very permeable capillaries.
Contains everything
except formed
elements and
plasma proteins

17. Filtration Rates
• Glomerular filtration rate (GFR): volume of
filtrate produced by both kidneys each
minute = 115−125 ml.
– 180 ml/ day
– Total blood volume filtered every 40 minutes
– Most must be reabsorbed immediately

18. 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

19. 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

20. 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.
Achieved via effects of locally produced
chemicals on afferent arterioles

21. Regulation of Filtration Rate
• Summary:

22. III. Reabsorption of Salt and
Water

23. 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.

24. Transepithelial Transport

25. Active Transport
• Cells of the proximal tubules are
joined by tight junctions on the
apical side (facing inside the
tubule).
– The apical side also contains
microvilli.
– These cells have a lower Na+
concentration than the filtrate
inside the tubule due to Na+/K+
pumps on the basal side of
the cells.
– Na+ from the filtrate diffuses
into these cells and is then
pumped out the other side.

26. Mechanism of H20 and Chloride
Reabsorption
• Na+ is actively transported out of the filtrate into
the peritubular blood to set up a concentration
gradient to drive osmosis of H2O. Chloride moves
by passive transport.

27. Proximal Tubular Fluid
• The pumping of sodium
into the interstitial space
attracts negative Cl− out of
the filtrate.
• Water then follows Na+ and
Cl− into the tubular cells
and the interstitial space.
• The increased
concentration of salts and
water diffuses into the
peritubular capillaries.

28. Proximal Tubular Fluid
• Reduced by 1/3 but
still isosmotic
– Plasma membrane
is freely permeable
to water and salts
– Because both H2O
and electrolytes are
reabasorbed here in
the same ratio, the
tubular fluid stays
isotonoic to blood

29. 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

30. Secondary active transport in the
Proximal Tubule
• Glucose, amino
acids, Ca++, etc.
are reabsorbed
in the proximal
tubule by
secondary active
transport.

31. 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 glucose & amino
acids 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

32. 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

33. 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

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

35. 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
17-75

36. 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

37. Descending Limb LH
• Is permeable to H20
• Is impermeable to, &
does not AT, 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
17-37

38. 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
17-38

39. Countercurrent Multiplier System
• Countercurrent flow & proximity allow descending & ascending
limbs of LH to interact in 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
17-41

40. Vasa Recta
• 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

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

42. 17-44

43. 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

44. Nephron sites of aquaporin (AQP) water channels (blue),
ion transporters (black), and urea transporters (green)
Schrier R W JASN 2006;17:1820-1832

45. 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

46. Collecting Duct (CD)
17-45

47. Osmolality of Different Regions of the Kidney
17-47

48. anim0082-rm_kidney_func.rm

49. Hormonal Effects
17-60

50. 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

51. 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

52. 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
17-63

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

54. 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

55. 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

56. 17-67

57. Macula Densa
• Is region of 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

58. Hormonal Control of Kidney by Negative
Feedback Circuits

59. 17-69

60. 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

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

62. 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
• In severe acidosis, H+ is
secreted at expense of
K+
17-72

63. 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