urinary system - warner pacific collegeclasspages.warnerpacific.edu/bdupriest/bio 420/unit 6...

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

~ 67%

Interstitial fluid

~ 26%

Plasma

~ 7% Fig. 25-1

3

Body Fluids

Comparison of substance concentrations

Table. 25-2, Figs. 25-2,3 4

Osmosis & Osmotic Equilibrium

Osmosis?

Diffusion of H2O through a semipermeable membrane

from low solute conc. to high solute conc.

Fig. 4-9 5


Effect of solutions on cells

Isotonic

Hypertonic

Hypotonic

Figs. 25-5,6

6


Osmoles

Describes total number of solute particles in solution (regardless of composition)

1 osm = 1 mole (6.02x1023) 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


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


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

for every 1 mOsm gradient across a membrane,

19.3 mmHg osmotic pressure exerted

9 p. 297


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

Each molecule of NaCl = 2 osmoles (Na+ + Cl-)

Osmotic pressure = 308 mOsm/L x 19.3 mmHg/mOsm/L =

5944 mmHg

p. 297 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

Glomerulus

Capillary with afferent & efferent arterioles

Site of “filtration” membrane

Bowman’s capsule

Surrounds

glomerulus

Collects

“filtrate”

Fig. 26-4 14

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

Descending: H2O reabsorption

Ascending: Na+, Cl-, K+ reabsorption

16 Fig. 26-4

The Nephron

Tubules

Distal tubule

Reabsorption/secretion of Na+, Cl-

Site of aldosterone activity

17 Fig. 26-4

The Nephron

Collecting ducts

Reabsorption of H20, urea

Site of ADH activity

~250/kidney; ~4,000 nephrons each

18 Fig. 26-4

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

20

Fig. 26-5

The Nephron

Categories

Juxtamedullary nephrons

Close to cortex-

medullary 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…

Reabsorption…

Secretion…

Excretion…

Take out everything that fits through the door

Bring back everything you want

Take back out XS items

Everything left goes

22

Urine Formation

Filtration

Reabsorption

Secretion

Excretion

Excretion = Filtration – Reabsorption + Secretion

nephron function

Fig. 26-8

23

Urine Formation

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

Not all substances treated equally

24

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

Blood supply through afferent & efferent

arterioles

Maintain & regulate pressure

Efferent arteriole

Smaller diameter

resistance

Fig. 26-10 26


Filtration membrane

Fenestrated capillary epithelium

Passage of fluids & small solutes

Fig. 26-10 27


Podocytes

“Feet” attach to endothelium

Spaces between form “slit

pores”

Passage of filtrate to

capsular space

See Fig. 26-8

28

Podocytes

29


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


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…

Plasma membranes of capillaries

Plasma membranes of Podocytes

Within basement membrane

E.g., albumin

~6 nm (small enough) but not filtered (- charged)

Fig. 26-9

32


Forces favoring filtration

Glomerular hydrostatic pressure (PG)

~60 mmHg

Fig. 26-12

33


Forces opposing filtration

Bowman’s capsule hydrostatic pressure (PB)

~18 mmHg

Glomerular colloid osmotic pressure (G)

~32 mmHg

34

Fig. 26-12


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

See Table 26-2

NFP

PG = GFR

arterial pressure, sympathetic activity

PB = GFR

Urinary tract obstruction

G = GFR

plasma proteins

37


arterial resistance

efferent arteriole resistance

Increases resistance to

outflow

blood pressure

glomerular

hydrostatic pressure

(PG) GFR

Fig. 26-14

38


arterial resistance

afferent arteriole resistance

Restricts blood flow to

glomerulus

blood pressure

glomerular

hydrostatic pressure

(PG) GFR

39

Fig. 26-14

Regulation of Filtration

Intrinsic control mechanisms (autoregulation)

Maintain relatively constant GFR under normal daily

arterial pressure fluctuations

Prevents excessive / inadequate urine production that

would accompany large changes in GFR

Tubuloglomerular feedback mechanism

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

Walls of afferent (10) & efferent

arterioles

Fig. 26-17 41

Tubuloglomerular Feedback Mechanism

Involves specialized tubular arrangement

Juxtaglomerular complex

Juxtaglomerular cells

Macula densa

Initial portion of distal

tubule

Close contact with

afferent/efferent

arterioles

Fig. 26-17 42

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 Figs. 27-1, 3

49

cotransport

Transport Mechanisms

Na+

Reabsorbed primarily by transcellular active transport

H2O

Reabsorbed entirely by osmosis (passive)

50

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

Active Transport Rate

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

Fig. 27-11

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

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

Fig. 27-14 59

Reabsorbed

(needed)

Secreted (not

needed)

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

H2O

osmosis

[electrolytes]

Y Y cell swells

signal

post. pituitary

kidneys

ADH H2O not

reabsorbed [electrolytes]

X 65

Formation of Dilute Urine

Tubular activity

Cortical nephrons

Low [ADH]

Fig. 28-2

66

Max Output:

~ 20L/day @

50 mOsm/L

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

H2O

osmosis

[electrolytes]

Y Y cell shrinkage

signal

posterior pituitary

kidneys

ADH

reabsorb H2O [electrolytes] 68


Tubular activity

Juxtamedullary nephrons

High [ADH]

Fig. 28-4

69


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


Urine concentrating abilities of mammals

Human

~1200 mOsm/L

Aquatic mammals (beaver)

~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


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


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

76

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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

Supplies metabolic needs of medullary tissues but minimizes solute loss

Fig. 28-6

78

Renal Clearance

The volume of plasma completely cleared of a

substance per unit time

Use to quantify kidney function

79

Use to Estimate GFR

Conditions for accurate determination

Freely filterable

Not reabsorbed or secreted

GFR = Cs

Renal Clearance

Clearance rate (ml/min)

Cs = (Us x V) / Ps

Us = [urine]of substance, V = urine flow rate, PS = [plasma] of substance

80

Renal Clearance

Example: inulin

Administered IV

Cs = (Us x V) / Ps

Cs = (125 mg/ml x 1 ml/min)

1 mg/ml

Cs = GFR = 125 ml/min

Fig. 27-17

81

Renal Clearance

Compare other solutes to inulin

Cs = inulin

Filtered, not reabsorbed or secreted

Cs < inulin

Filtered & reabsorbed

Cs > inulin

Filtered & secreted

See p. 312

Substance Cs (ml/min)

Glucose 0.0

Na+ 0.9

Cl- 1.3

K+ 12.0

PO4- 25.0

Inulin 125.0

Creatinine 140.0

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

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