1. The Urinary System
Muse 2440
lecture #9
6/26/12

2. Overview of kidney functions
Regulation of blood ionic composition
Regulation of blood pH
Regulation of blood volume
Regulation of blood pressure (hormone: Renin)
Maintenance of blood osmolarity
Production of hormones (calcitrol and erythropoitin)
Regulation of blood glucose level
Excretion of wastes from metabolic reactions and foreign substances (drugs or toxins)

3. Anatomy and histology of the kidneys
External anatomy
Renal hilium – indent where ureter emerges along with blood vessels, lymphatic vessels and nerves
3 layers of tissue
Renal capsule – deep layer – continuous with outer coat of ureter, barrier against trauma, maintains kidney shape
Adipose capsule – mass of fatty tissue that protects kidney from trauma and holds it in place
Renal fascia – superficial layer – thin layer of connective tissue that anchors kidney to surrounding structures and abdominal wall

4. Organs of the urinary system in a female

5. Position and coverings of the kidneys

6. Internal anatomy Renal cortex – superficial
Outer cortical zone
Inner juxtamedullary zone
Renal columns – portions of cortex that extend between renal pyramids
Renal medulla – inner region
Several cone shaped renal pyramids – base faces cortex and renal papilla points toward hilium
Renal lobe – renal pyramid, overlying cortex area, and ½ of each adjacent renal column

7. Anatomy of the kidneys Parenchyma (functional portion) of kidney
Renal cortex and renal pyramids of medulla
Nephron – microscopic functional units of kidney
Urine formed by nephron drains into
Papillary ducts
Minor and major calyces
Renal pelvis
Ureter
Urinary bladder

8. Internal anatomy of the kidneys

9. Blood and nerve supply of the kidneys
Blood supply
Although kidneys constitute less than 0.5% of total body mass, they receive 20-25% of resting cardiac output
Left and right renal artery enters kidney
Branches into segmental, interlobar, arcuate, interlobular arteries
Each nephron receives one afferent arteriole
Divides into glomerulus – capillary ball
Reunite to form efferent arteriole (unique)
Divide to form peritubular capillaries or some have vasa recta
Peritubular venule, interlobar vein and renal vein exits kidney
Renal nerves are part of the sympathetic autonomic nervous system
Most are vasomotor nerves regulating blood flow i

10. Blood supply of the kidneys

11. Cortical radiate artery
Cortical radiate vein
Cortical radiate artery
Arcuate vein
Arcuate artery
Interlobar vein
Interlobar artery
Segmental arteries
Renal vein
Renal artery
Renal pelvis
Ureter
Renal medulla
Renal cortex
(a) Frontal section illustrating major blood vessels
Figure 25.4a

12. Nephron-associated blood vessels
Aorta
Inferior vena cava
Renal artery
Renal vein
Segmental artery
Interlobar vein
Interlobar artery
Arcuate vein
Cortical radiate
vein
Arcuate artery
Peritubular
capillaries
and vasa recta
Cortical radiate artery
Afferent arteriole
Efferent arteriole
Glomerulus (capillaries)
Nephron-associated blood vessels
(b) Path of blood flow through renal blood vessels
Figure 25.4b

13. The nephron – functional units of kidney
2 parts
Renal corpuscle – filters blood plasma
Glomerulus – capillary network
Glomerular (Bowman’s) capsule – double-walled cup surrounding glomerulus
Renal tubule – filtered fluid passes into
Proximal convoluted tubule
Descending and ascending loop of Henle (nephron loop)
Distal convoluted tubule i

14. Nephrons
Renal corpuscle and both convoluted tubules in cortex, loop of Henle extend into medulla
Distal convoluted tubule of several nephrons empty into single collecting duct
Cortical nephrons – 80-85% of nephrons
Renal corpuscle in outer portion of cortex and short loops of Henle extend only into outer region of medulla
Juxtamedullary nephrons – other 25-20%
Renal corpuscle deep in cortex and long loops of Henle extend deep into medulla
Receive blood from peritubular capillaries and vasa recta
Ascending limb has thick and thin regions
Enable kidney to secrete very dilute or very concentrated urine

15. The structure of nephrons and associated blood vessels

16. Histology of nephron and collecting duct
Glomerular capsule
Visceral layer has podocytes that wrap projections around single layer of endothelial cells of glomerular capillaries and form inner wall of capsule
Parietal layer forms outer wall of capsule
Fluid filtered from glomerular capillaries enters capsular (Bowman’s) space

17. Histology of a renal corpuscle

18. Glomerular capsule: visceral layer
Basement
membrane
Podocyte
Fenestrated
endothelium
of the glomerulus
Glomerular capsule: visceral layer
Figure 25.5

19. Renal tubule and collecting duct
Proximal convoluted tubule cells have microvilli with brush border – increases surface area
Juxtaglomerular appraratus helps regulate blood pressure in kidney
Macula densa – cells in final part of ascending loop of Henle
Juxtaglomerular cells – cells of afferent and efferent arterioles contain modified smooth muscle fibers
Last part of distal convoluted tubule and collecting duct
Principal cells – receptors for antidiuretic hormone (ADH) and aldosterone
Intercalated cells – role in blood pH homeostasis

20. Overview of renal physiology
Glomerular filtration
Water and most solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubule
Tubular reabsorption
As filtered fluid moves along tubule and through collecting duct, about 99% of water and many useful solutes reabsorbed – returned to blood
Tubular secretion
As filtered fluid moves along tubule and through collecting duct, other material secreted into fluid such as wastes, drugs, and excess ions – removes substances from blood
Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted
Excretion of any solute = glomerular filtration + secretion - reabsorption

21. Structures and functions of a nephron simplified schematic
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Tubular secretion
from blood into fluid
Tubular reabsorption
from fluid into blood
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1 2 3
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Tubular reabsorption
from fluid into blood
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1 2
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1

22. Glomerular filtration
Glomerular filtrate – fluid that enters capsular space
Daily volume liters – more than 99% returned to blood plasma via tubular reabsorption
Filtration membrane – endothelial cells of glomerular capillaries and podocytes encircling capillaries
Permits filtration of water and small solutes
Prevents filtration of most plasma proteins, blood cells and platelets
3 barriers to cross – glomerular endothelial cells fenestrations, basal lamina between endothelium and podocytes and pedicels of podocytes create filtration slits
Volume of fluid filtered is large because of large surface area, thin and porous membrane, and high glomerular capillary blood pressure

23. The filtration membrane

24. Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Basal lamina of glomerulus:
prevents filtration of larger proteins
Slit membrane between pedicels:
prevents filtration of medium-sized
proteins
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1 2 3
Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Basal lamina of glomerulus:
prevents filtration of larger proteins
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1 2
Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1

25. Net filtration pressure
Net filtration pressure (NFP) is the total pressure that promotes filtration
NFP = GBHP – CHP – BCOP
Glomerular blood hydrostatic pressure is the blood pressure of the glomerular capillaries forcing water and solutes through filtration slits
Capsular hydrostatic pressure is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and represents “back pressure”
Blood colloid osmotic pressure due to presence of proteins in blood plasma and also opposes filtration

26. The pressures that drive glomerular filtration

27. NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
BLOOD COLLOID
OSMOTIC PRESSURE
(BCOP) = 30 mmHg
CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1 2 3
Proximal convoluted tubule
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1 2
Proximal convoluted tubule
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1
Proximal convoluted tubule

28. Glomerular filtration
Glomerular filtration rate GFR – amount of filtrate formed in all the renal corpuscles of both kidneys each minute
Homeostasis requires kidneys maintain a relatively constant GFR
Too high – substances pass too quickly and are not reabsorbed
Too low – nearly all reabsorbed and some waste products not adequately excreted
GFR directly related to pressures that determine net filtration pressure

29. 3 Mechanisms regulating GFR
Renal autoregulation
Kidneys themselves maintain constant renal blood flow and GFR using
Myogenic mechanism – occurs when stretching triggers contraction of smooth muscle cells in afferent arterioles – reduces GFR
Tubuloglomerular mechanism – macula densa provides feedback to glomerulus, inhibits release of NO causing afferent arterioles to constrict and decreasing GFR

30. Tuboglomerular feedback

31. Mechanisms regulating GFR
Neural regulation
Kidney blood vessels supplied by sympathetic ANS fibers that release norepinephrine causing vasoconstriction
Moderate stimulation – both afferent and efferent arterioles constrict to same degree and GFR decreases
Greater stimulation constricts afferent arterioles more and GFR drops
Hormonal regulation
Angiotensin II reduces GFR – potent vasoconstrictor of both afferent and efferent arterioles
Atrial natriuretic peptide increases GFR – stretching of atria causes release, increases capillary surface area for filtration

32. 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

33. 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

34. Reabsorption routes: paracellular reabsorption and transcellular reabsorption

35. Reabsorption and secretion in proximal convoluted tubule (PCT)
Largest amount of solute and water reabsorption
Secretes variable amounts of H+, NH4+ and urea
Most solute reabsorption involves Na+
Symporters for 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

36. Reabsorption and secretion in the proximal convoluted tubule

37. Highly infolded plasma membrane
Microvilli
Mitochondria
Highly infolded plasma
membrane
Proximal convoluted tubule cells
Figure 25.5

38. Reabsorption in the loop of Henle
Chemical composition of tubular fluid quite different from filtrate
Glucose, amino acids and other nutrients reabsorbed
Osmolarity still close to that of blood
Reabsorption of water and solutes balanced
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
Na+-K+-2Cl- symporters function in Na+ and Cl- reabsorption – promotes reabsorption of cations
Little or no water is reabsorbed in ascending limb – osmolarity decreases

39. Na+–K+-2Cl- symporter in the thick ascending limb of the loop of Henle

40. 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-
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

41. 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 Proximal Convoluted Tubule
Aldosterone - when blood volume and blood pressure decrease
Stimulates principal cells in collecting duct to reabsorb more Na+ and Cl- and secrete more K+
Parathyroid hormone
Stimulates cells in Distal Convolute Tubule to reabsorb more Ca2+

42. 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

43. 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

44. 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 (concentrates) 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

45. 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

46. 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

47. 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
organisms that adapt to deserts have long loops of Henle

48. 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

49. Mechanism of urine concentration in long-loop juxtamedullary nephrons

50. i 1 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
(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 i

51. Summary of filtration, reabsorption, and secretion in the nephron and collecting duct

52. Summary: Renal Function
Figure 26–16a A Summary of Renal Function.

53. Summary: Renal Function
Figure 26–16b A Summary of Renal Function.

54. 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
look for pH, protein, urea, blood, ketone.

55. 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

56. 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

57. Ureters, urinary bladder, and urethra in a female

58. 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

59. Comparison between female and male urethras

60. Urine Transport, Storage, and Elimination
The Micturition Reflex and Urination
Begins when stretch receptors stimulate parasympathetic preganglionic motor neurons
Volume >500 mL triggers micturition reflex

61. Age-Related Changes in Urinary System
Decline in number of functional nephrons
Reduction in GFR
Reduced sensitivity to ADH
Problems with micturition reflex
Sphincter muscles lose tone leading to incontinence
Control of micturition can be lost due to a stroke, Alzheimer disease, and other CNS problems
In males, urinary retention may develop if enlarged prostate gland compresses the urethra and restricts urine flow