URINARY SYSTEM


Primary functions

Excretion of metabolic wastes

Regulation of water and ion balances

Regulation of blood pressure

Vitamin D activation

Regulation of rbc’s (erythropoietin)

Gluconeogenesis
Major organs & structures




Kidneys
Ureters
Urinary bladder
Urethra
See Fig. 26-2
1
Body Fluids

Daily intake / output

Balanced
Tab. 25-1
2
Body Fluids


Fluid totals

~ 60% body weight

~ 42 L (70 kg male)
Major compartments

Intracellular fluid


Interstitial fluid


~ 67%
~ 26%
Plasma

~ 7%
Fig. 25-1
3
Body Fluids

4
Comparison of substance concentrations
Table. 25-2, Figs. 25-2,3
Osmosis & Osmotic Equilibrium

Osmosis?

Diffusion of H2O through a semipermeable membrane
from low solute conc. to high solute conc.
Fig. 4-9
5
Osmosis & Osmotic Equilibrium

Effect of solutions on cells

Isotonic

Hypertonic

Hypotonic
Figs. 25-5,6
6
Osmosis & Osmotic Equilibrium

Osmoles

Describes total number of solute particles in
solution (regardless of composition)
23
 1 osm = 1 mole (6.02x10 ) of solute particles
 Typically expressed a milliosmoles (mOsm)
 1 osm = 1000 mOsm
Osmolarity



Osmolar concentration of solution = osm/L solution
Osmolality

Osmolal concentration of solution = osm/kg H20
7
Osmosis & Osmotic Equilibrium

Osmotic pressure

The amount of pressure required to prevent osmosis
(pressure opposing osmosis)

Directly proportional to number of osmotically active
particles in solution

 particle concentration  osmotic pressure
8
Osmosis & Osmotic Equilibrium

van’t Hoff’s law

Relates osmotic pressure & osmolarity

 = CRT


 = osmotic pressure

C = solute concentration (osm/L)

R = ideal gas constant (mmHg)

T = normal body temp (310 K)
At 1 mOsm/L,  = 19.3 mmHg

p. 297
 for every 1 mOsm gradient across a membrane,
19.3 mmHg osmotic pressure exerted
9
Osmosis & Osmotic Equilibrium

Application…

What is the potential osmotic pressure of physiological saline
(0.9% NaCl)?

0.9% NaCl = 0.9g/100ml or 9g/L

9g/L NaCl  MW (58.5 g/mol) = 0.154 mol/L

Osmolarity (osm/L) = 0.154 mol/L x 2 = 0.308 osm/L = 308
mOsm/L


p. 297
Each molecule of NaCl = 2 osmoles (Na+ + Cl-)
Osmotic pressure = 308 mOsm/L x 19.3 mmHg/mOsm/L =
5944 mmHg
10
Gross Anatomy of the Kidney

Capsule

Renal cortex


Contains renal corpuscles
Renal medulla

Segmented into lobes (renal
pyramids)

Groups of collecting ducts draining
to renal pelvis

Renal calyces

Renal pelvis

Ureter
Fig. 26-2
11
Gross Anatomy of the Kidney

Blood supply

Renal artery & vein (at
hilum)

Interlobar arteries & veins

Arcuate arteries & veins



Feed / drain nephrons
Interlobular arteries &
veins
Blood flow

Receive ~22% of cardiac
output (1,100 ml/min)
See Fig. 26-2
12
The Nephron

Primary functional unit of the kidney

~ 1x106 / kidney but highly variable
Fig. 26-3
13
The Nephron

Renal corpuscle


14
Glomerulus

Capillary with afferent & efferent arterioles

Site of “filtration” membrane
Bowman’s capsule

Surrounds
glomerulus

Collects
“filtrate”
Fig. 26-4
The Nephron

Tubules

Proximal tubule
 Reabsorption of most nutrients
+
 Active: ex., glucose, aa’s, Na
 Passive: Cl , H2O
Fig. 26-4
15
The Nephron

Tubules

Loop of Henle
Fig. 26-4

Descending: H2O reabsorption

Ascending: Na+, Cl-, K+ reabsorption
16
The Nephron

Tubules

Distal tubule
Fig. 26-4

Reabsorption/secretion of Na+, Cl-

Site of aldosterone activity
17
The Nephron

Collecting ducts

Reabsorption of H20, urea

Site of ADH activity

~250/kidney; ~4,000 nephrons each
Fig. 26-4
18
The Nephron

Capillary beds

Glomerulus


Arterial capillary
bed
Peritubular capillaries

Surround renal
tubules

Reclaim filtrate

Some secretion
Fig. 26-3
19
The Nephron

Categories

Cortical nephrons

85%

Almost entirely in
cortex
Fig. 26-5
20
The Nephron

Categories

Juxtamedullary nephrons

Close to cortexmedullary junction

L of H extend deep into
medulla

Important in
concentrating urine

Peritubular capillaries
surrounding L of H
modified (vasa recta)
Fig. 26-5
21
Urine Formation

The ultimate garage sale:

Filtration…

Take out everything that fits through the door

Reabsorption…

Bring back everything you want

Secretion…

Take back out XS items

Excretion…

Everything left goes
22
Urine Formation

Filtration

Reabsorption

Secretion

Excretion
Fig. 26-8
Excretion = Filtration – Reabsorption + Secretion
nephron function
23
Urine Formation






24
Not all substances treated equally
A = freely filtered,
not reabsorbed
B = freely filtered,
partly reabsorbed
C = freely filtered,
completely
reabsorbed
D = freely filtered,
secreted
“E” = not filtered,
not secreted
Fig. 26-9
Glomerular Filtration

Blood flow


~1.1 L/min (~1,600 L/day)
Filtrate

~180 L/day


Process “entire” plasma volume ~60x/day
Urine formation

~1.5 L/day (<1% of filtrate)
Why the need for the high filtration rate?
25
Anatomy of the Filtration Apparatus

26
Blood supply through afferent & efferent
arterioles

Maintain & regulate pressure

Efferent arteriole

Smaller diameter

 resistance
Fig. 26-10
Anatomy of the Filtration Apparatus

Filtration membrane

Fenestrated capillary epithelium

27
Passage of fluids & small solutes
Fig. 26-10
Anatomy of the Filtration Apparatus

Podocytes


“Feet” attach to endothelium
Spaces between form “slit
pores”

Passage of filtrate to
capsular space
See Fig. 26-8
28
Podocytes
29
Glomerular Filtration

Essentially a passive process


Fluids/solutes forced out by hydrostatic pressure
Filterability based on…

Size of molecule

Pores ~8 nm diameter

Molecules <3 nm, freely pass


E.g., water, glucose, aa’s, N-wastes
Molecules >7-9 nm, usually blocked
30
Substance Filterability Based on MW
Substance
MW
Filterability
Water
18
1.0
Sodium
23
1.0
Glucose
180
1.0
Myoglobin
17,000
0.75
Albumin
69,000
0.005
See Tab. 26-1
31
Glomerular Filtration

Essentially a passive process


Fluids/solutes forced out by hydrostatic pressure
Filterability based on…


Size of molecule
Charge of molecule
 (+) filtered easier than (-) of
same size
 Proteoglycans (- charged) on
surfaces of…
Fig. 26-9
 Plasma membranes of capillaries
 Plasma membranes of Podocytes
 Within basement membrane
 E.g., albumin
 ~6 nm (small enough) but not filtered (- charged)
32
Glomerular Filtration

Forces favoring filtration

Glomerular hydrostatic pressure (PG)

~60 mmHg
Fig. 26-12
33
Glomerular Filtration

Forces opposing filtration


Bowman’s capsule hydrostatic pressure (PB)
 ~18 mmHg
Glomerular colloid osmotic pressure (G)
 ~32 mmHg
Fig. 26-12
34
Glomerular Filtration

Net filtration pressure

NFP = PG - PB - G

~10 mmHg
Fig. 26-12
35
Glomerular Filtration Rate (GFR)

GFR = Kf x NFP


Kf = glomerular capillary filtration
coefficient
 Reflects conductivity & capillary
surface area
 Kf = GFR / NFP
Normal GFR



GFR (both kidneys) ~125 ml/min (~180
L/day)
NFP ~10 mmHg
Kf ~12.5 ml/min/mmHg
36
Factors Affecting GFR


 Kf =  GFR

Reduction in glomerular capillaries

Increased thickness of glomerular capillary membrane
 NFP

 PG =  GFR


 PB =  GFR


 arterial pressure,  sympathetic activity
Urinary tract obstruction
 G =  GFR

 plasma proteins
See Table 26-2
37
Factors Affecting GFR

 arterial resistance

 efferent arteriole resistance



Fig. 26-14
Increases resistance to
outflow
 blood pressure
 glomerular
hydrostatic pressure
(PG)  GFR
38
Factors Affecting GFR

 arterial resistance

 afferent arteriole resistance



Fig. 26-14
Restricts blood flow to
glomerulus
 blood pressure
 glomerular
hydrostatic pressure
(PG)   GFR
39
Regulation of Filtration

Intrinsic control mechanisms (autoregulation)

Maintain relatively constant GFR under normal daily
arterial pressure fluctuations


Tubuloglomerular feedback mechanism


Prevents excessive / inadequate urine production that
would accompany large changes in GFR
Control GFR based on glomerular pressure and NaCl
concentrations
Extrinsic control mechanisms

ANS
40
Tubuloglomerular Feedback Mechanism

Involves specialized tubular arrangement

Juxtaglomerular apparatus (JGA)

Juxtaglomerular cells

41
Walls of afferent (10) & efferent
arterioles
Fig. 26-17
Tubuloglomerular Feedback Mechanism

Involves specialized tubular arrangement

42
Juxtaglomerular complex

Juxtaglomerular cells

Macula densa

Initial portion of distal
tubule

Close contact with
afferent/efferent
arterioles
Fig. 26-17
Juxtaglomerular Cells

Modified smooth muscle

Produce & store renin

Respond to pressure changes

Decreased arterial pressure
promotes renin release

Angiotensin II constricts
efferent arterioles

Results in 
glomerular
hydrostatic
pressure
Figs. 19-9, 26-17
43
Macula Densa

Sense changes in volume via changes in Na+
& Cl- concentrations


Decreased flow through L of H
 Slower flow
 Increased ion reabsorption
 Decreased ion concentration in
filtrate
Response to  Na+ & Cl

Vasodilate afferent arterioles
Stimulate renin release from JG cells
 Vasoconstriction of efferent
arterioles
 Results in  glomerular hydrostatic
pressure
44
Tubuloglomerular Feedback Overview
Fig. 26-18
45
Autonomic Control of GFR

Sympathetic division

Strong stimulus =  GFR

Constriction of renal arterioles


Slower flow
Parasympathetic division

Stimulus = ?
46
Tubular Processing of Filtrate


Reabsorption & secretion processes

Reclaim desired filtrate components

Discard additional/excess plasma components
Structures involved

Proximal tubule

Loop of Henle

Distal tubule

Collecting ducts
47
Typical F, R & E Rates
Tab. 27-1
48
Transport Mechanisms

Paracellular and transcellular pathways

Active & passive processes

Benefits of active transport?

Primary & secondary active transport

Pumps, channels or endocytosis
 cotransport
Figs. 27-1, 3
49
Transport Mechanisms

Na+


Reabsorbed primarily by transcellular active transport
H2O

Reabsorbed entirely by osmosis (passive)
50
Active Transport Rate

Rate of transport dependent on limitations of
transport mechanisms

Transport maximum

Point at which transport mechanisms are saturated

Solutes in concentration above this point will be
excreted
Substance
Transport Maximum
glucose
320 mg/min
amino acids
1.5mM/min
plasma proteins
30 mg/min
creatinine*
16 mg/min
See p.331
51
Glucose Transport
Fig. 27-4
52
Proximal Tubule

Primary site of reabsorption

Nearly all “nutrients” & other substances reabsorbed

E.g., glucose, aa’s, vitamins, electrolytes
Substance
% Reabsorbed in PT
K+
> 90
HCO3-
~ 90
Na+
~ 70
H2O
~ 70
Cl-
~ 50
53
Proximal Tubule

Extensive brush border

Increased surface area for transport

E.g., glucose, aa’s, vitamins, electrolytes
Fig. 27-6
54
Loop of Henle


Descending limb

“Thin” segment

Very permeable to H2O

Reabsorption

Concentrates filtrate
Ascending limb

“Thick” segment

Impermeable to H2O

Active reabsorption…

Na+, K+, Cl-

Dilutes filtrate
Fig. 27-8
55
Ascending Loop – Thick Segment
Fig. 27-9
56
Distal Tubule

Additional reabsorption dependent on body needs



Only ~10% Na+ & ~20%
H2O from original filtrate
remaining
Na+ reabsorption
enhanced by aldosterone
Site of atrial naturietic
peptide activity

 Na+ reabsorption
  blood vol. & pressure
Fig. 27-11
57
Collecting Duct

Reabsorption of H2O

ADH

Reabsorption of urea

Acid (H+) & base (HCO3-) regulation
Fig. 27-13
58
Solute Concentrations Through the Tubular System
Secreted (not
needed)
Reabsorbed
(needed)
Fig. 27-14
59
Urine Composition

~ 95% H2O

~ 5% solutes
urea
Na+
K+
phosphates
uric acid
creatinine

Normal osmolarity ~500 mOsm/L
60
Diuresis
Fig. 28-1
61
Urine Formation

Kidneys can regulate water excretion independent
of solute excretion. Therefore…

Can excrete large volumes of dilute urine

Can excrete small volumes of concentrated urine

Can do both without major changes in rates of solute
excretion
62
Concentrating Urine

Dependent on…

Nephron structure

Hyperosmotic interstitial concentration gradient of the
medulla
63
Formation of Dilute Urine

Purpose: excretion of excess water

Primary influence = ADH

 plasma osmolarity…

 ADH secretion   H2O reabsorption   [urine] /
 output
Fig. 28-1
64
ADH
 [electrolytes]
H2O
osmosis
Y
cell swells
Y
signal
post. pituitary
 [electrolytes]
H2O not
reabsorbed
X ADH
kidneys
65
Formation of Dilute Urine

Tubular activity

Cortical nephrons

Low [ADH]
Max Output:
~ 20L/day @
50 mOsm/L
Fig. 28-2
66
Formation of Concentrated Urine

Purpose: water conservation

ADH influence

 plasma osmolarity…


 ADH secretion   H2O reabsorption   [urine]
/  output
Influence of the hyperosmotic environment of
renal medulla
ADH
 [electrolytes]
H2O
osmosis
Y
cell shrinkage
Y
signal
posterior pituitary
ADH
 [electrolytes]
reabsorb H2O
kidneys
68
Formation of Concentrated Urine

Tubular activity

Juxtamedullary nephrons

High [ADH]
Fig. 28-4
69
Formation of Concentrated Urine

Maximum concentrating ability of kidney dictates
how much urine volume must be excreted daily to
rid body of metabolic wastes


“Normal” human (70 kg)

Need to excrete ~600 mOsm/day

Max. concentrating ability ~1200 mOsm/L
Obligatory (minimal) urine volume

600 / 1200 = 0.5 L/day
70
Formation of Concentrated Urine

Urine concentrating abilities of mammals

Human


Aquatic mammals (beaver)


~1200 mOsm/L
~500 mOsm/L
Desert mammals (kangaroo rat)

~10,000 mOsm/L
71
So You’re Adrift at Sea…

Sea water



~3% salt (~ 2000-2400 mOsm/L)
Human drinking 1 L of sea water

Solute intake of 2400 mOsm

Max. concentrating ability 1200 mOsm

2400 / 1200 = 2 L urine output
Kangaroo Rat drinking sea water

2400 / 10,000 = .24 L urine output
72
Countercurrent Mechanism

Generates & maintains hyperosmotic environment
of medulla


Countercurrent multiplier system

Establishes hyperosmotic state

Loop of Henle & collecting ducts
Countercurrent exchange system

Maintains hyperosmotic state

Vasa recta
See Fig. 26-5
73
Countercurrent Multiplier System

Major factors contributing to solute buildup in
medulla

Active transport of Na+, K+, Cl- & other ions out of the
loop of Henle (ascending limb)

Active transport of ions from collecting ducts

Diffusion of urea from collecting ducts

Diffusion of only small amounts of water relative to
reabsorption of other solutes
74
Countercurrent Multiplier System




Assume all concentrations equal (starting point)
Active transport of ions in ascending limb
Osmosis of H2O out of descending limb
Additional fluid flow through loop
Fig. 28-3
75
Countercurrent Multiplier System

With time & continued concentration of filtrate…


Active pumping of ions multiplies interstitial solute concentrate
Net effect

Solutes added to medullary interstitium in excess of water
www.studentconsult.com
76
Countercurrent Multiplier System

Impact of urea
 Concentrates in distal
tubule & superior
collecting duct
(impermeable)
 Inferior collecting
duct permeable
 Urea diffuses into
medulla
 Further increases
concentration
gradient
 Recirculation into
descending loop helps
“trap” urea in
medulla
Fig. 28-5
77
Countercurrent Exchange System


Major factor in the preservation / maintenance of
the medullary solute concentration
Involves vasa recta


Special characteristics
 Low blood flow
 U-shape
 High permeability to
H2O, Na+ & Cl- along
entire length
Fig. 28-6
Supplies metabolic needs of medullary tissues but
minimizes solute loss
78
Renal Clearance

The volume of plasma completely cleared of a
substance per unit time

Use to quantify kidney function
79
Renal Clearance

Clearance rate (ml/min)
Cs = (Us x V) / Ps
Us = [urine]of substance, V = urine flow rate, PS = [plasma] of substance

Use to Estimate GFR

Conditions for accurate determination

Freely filterable

Not reabsorbed or secreted
GFR = Cs
80
Renal Clearance

Example: inulin

Administered IV
Cs = (Us x V) / Ps
Cs = (125 mg/ml x 1 ml/min)
1 mg/ml
Fig. 27-17
 Cs = GFR = 125 ml/min
81
Renal Clearance

Compare other solutes to inulin

Cs = inulin


Cs < inulin


Filtered, not reabsorbed or secreted
Filtered & reabsorbed
Cs > inulin

Filtered & secreted
Substance
Glucose
Na+
ClK+
PO4Inulin
Creatinine
Cs (ml/min)
0.0
0.9
1.3
12.0
25.0
125.0
140.0
See p. 312
82
Kidney Failure & Hemodialysis

Loss of kidney function


Infection, trauma, toxin poisoning, inadequate blood
flow
Hemodialysis

Use semipermeable membrane to facilitate solute
transfer between patient blood and dialyzing fluid
83
Dialyzing Fluid
Tab. 31-7
84
Artificial Kidney
Fig. 31-8
85