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
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.
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.
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.
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
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
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.
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
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
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
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
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
Notas del editor
Nephron sites of aquaporin (AQP) water channels (blue), ion transporters (black), and urea transporters (green). ROMK, renal outer medullary potassium channel; UT, urea transporter.