When the kidneys fail

1

2

People with kidney failure (腎衰竭 ) must be treated immediately.

3

They can eitherundergo a kidney transplant (移植 ).

transplanted kidney

4

They can eitheruse a kidney machine (洗腎機 ).

5

They can eitherundergo peritoneal dialysis (腹膜透析 ).

dialysis fluid in

dialysis fluid out

4 hours later

6

e.g. avoid taking too much fluid and high-protein food.

They also have to make some changes in their diet.

7

1.1 Importance of regulating water content

water intake

water loss

balanced

8

•Figure 20-2

Water Balance in the BodyWater Balance in the Body

9

• Land animals manage water budgets by drinking and eating moist foods and using metabolic water

•Water

•balance in a

•kangaroo rat

•(2 mL/day)

•Water

•balance in

•a human

•(2,500 mL/day)

•Water

•gain

•Water

•loss

•Derived from

•metabolism (1.8 mL)

•Ingested

•in food (0.2 mL)

•Derived from

•metabolism (250 mL)

•Ingested

•in food

•(750 mL)

•Ingested

•in liquid

•(1,500 mL)

•Evaporation (900 mL)

•Feces (100 mL)•Urine

•(1,500 mL)

•Evaporation (1.46 mL)

•Feces (0.09 mL)•Urine

•(0.45 mL)

10

• if water intake water loss affects water content in blood affects water potential of tissue fluid water enters or leaves cells by osmosis cells do not function properly or

even die


11

control of the water content in the body

control of the water content in the body

osmoregulation (滲透調節 )

osmoregulation (滲透調節 )

done by kidneys of urinary system (泌尿系統 )

done by kidneys of urinary system (泌尿系統 )


12

1 keeps the water potential of the tissue fluid and hence the water potential of the cells stable, so that cells can function properly to sustain life.

Osmoregulation


13

2 The of thesystem are the major organs for osmoregulation.

kidneys


urinary

14

1.2 The human urinary system

(dorsal aorta)

female

(posterior vena cava)

(renal artery)

(renal vein)

•Despite their small size, the two kidneys receive an enormous blood flow — about 1.2 litres/min /2000 litres per day in an adult — which is a quarter of the total output of the heart (5 litres/min).

15


female

kidneys

ureters

urinary bladder

16


female

sphincter muscles

control urinationcontrol

urination

17


female urethramale

18


male

ureters

urinary bladder

(vas deferens)

urethra

(penis)

19

1.1

Examination of the mammalian urinary system

Video


1 Examine the urinary system of a dissected rat.

2 Identify the structures.

20


Structure of the kidney3D model

cortex (皮質 )medulla ( 髓 )pelvis (腎盂 )

renal vein

renal artery

ureter

21


Structure of the kidney

22



cortex

medulla

23



branch from renal artery

branch from renal vein

24


Structure of the kidneynephron (腎元 )

25

•Filtration

•Reabsorption

•Secretion

•Excretion

•Excretory

•tubule

•Capillary

•Filtrate

•Urin

e

Key functions of most excretory systems:

•Filtration: pressure-filtering of body fluids

•Reabsorption: reclaiming valuable solutes

•Secretion: adding toxins and other solutes from the body fluids to the filtrate

26



Bowman’s capsule

proximal convoluted tubule

collecting duct

distal convoluted tubule

loope of Henle

kidney tubulekidney tubule

27



Bowman’s capsule

proximal convoluted tubule

collecting duct

distal convoluted tubule

flow of urine

from another nephron

loop of Henle

28



glomerulus

Bowman’s capsule

kidney tubule

29

Capillary Beds of the Nephron

• Every nephron has has twotwo capillary beds capillary beds– Glomerulus – Peritubular capillaries

• Each glomerulus is: – Fed by an afferent arteriole – Drained by an efferent arteriole

30


Blood supply of a nephron

branch from renal artery

afferent arteriole

glomerulus

efferent arteriole

Peritubular

capillary

branch from renal vein

31

1.2

Examination of the mammalian kidney


1 Put a fresh pig’s kidney on a dissection tray.

2 Examine whether there are tubes coming from the kidney. Remove any fatty tissues and identify the tubes.

32

1.2


3 Cut the kidney longitudinally.

33

1.2


4 Identify various structures of the kidney.

5 Draw a labelled diagram of the longitudinal section of the kidney.

34


1 Parts of urinary system

Function

Purify blood and form urine

Carry urine from kidneys to urinary bladder

Kidneys

Ureters

35


1 Parts of urinary system

Function

Stores urine temporarily

Carries urine from urinary bladder to the outside

Urinary bladder

Urethra

36

a A nephron consists of the

2 Structure of a nephron:

Bowman’s capsule


, theproximal convoluted tubulethe

, distal convoluted tubule

and the .

collecting duct

37

b The Bowman’s capsule encloses a network of capillaries called the

2 Structure of a nephron:

glomerulus


. The kidney tubule

is surrounded by another network of capillaries which is continuous with the glomerulus.

38

ultrafiltration(超濾 )

reabsorption(重吸收 )

1.3 Functioning of a nephron• urine is formed by mainly two

processes:

39

Active secretionActive secretion

1.3 Functioning of a nephron• and:

ultrafiltration reabsorption

40

Mechanism of Urine Formation• Urine formation

and adjustment of blood composition involve three major processes – Glomerular

filtration– Tubular

reabsorption– Active

Secretion

•Figure 24.9

41

1 Ultrafiltration• blood is under high

hydrostatic pressure

1.3 Functioning of a nephron

glomerulus

forces small molecules through the thin walls

Bowman’s capsule

• capillary wall is differentially permeable

42

1 Ultrafiltration1.3 Functioning of a nephron

glucose

amino acids

water

salts

urea

43

1 Ultrafiltration• fluid filtered into the

Bowman’s capsule: glomerular filtrate


to proximal convoluted tubule

44

1 Ultrafiltration1.3 Functioning of a nephron

to proximal convoluted tubule

water

glucose

amino acids

salts

urea

plasma proteins

• composition similar to plasma

45

Net Filtration Pressure (NFP) _ref only

• The pressure responsible for filtrate formation• NFP equals the glomerular hydrostatic pressure

(HPg) minus the osmotic pressure of glomerular blood (OPg) combined with the capsular hydrostatic pressure (HPc)

NFP = HPg – (OPg + HPc)

46

Glomerular Filtration Rate (GFR)

•Figure 24.10

47

2 Reabsorption• absorption of useful substances and most

of the water from the filtrate to the blood


•Your kidneys filter approximately 200L of plasma/day

•99% of the filtrate gets reabsorbed, leaving 1 -2 L of urine per day

•Your kidneys filter approximately 200L of plasma/day

•99% of the filtrate gets reabsorbed, leaving 1 -2 L of urine per day

48

2 Reabsorption1.3 Functioning of a nephron

from renal artery

flow of urine

to renal vein

49

Sodium Reabsorption: Sodium Reabsorption: PrimaryPrimary Active Transport_ Active Transport_ ref onlyref only

Tubule lumen with renal fluid

50

Glucose Reabsorption: Glucose Reabsorption: SecondarySecondary Active TransportActive Transport

51

Reabsorption: Both Primary and Reabsorption: Both Primary and secondary Active Transportsecondary Active Transport

• Sodium reabsorption is almost always by active transport– Na+ enters the tubule cells

from the lumen / filtrate– Na+ is actively transported

out of the tubules by a Na+-K+ ATPase pump

• From there it moves to peritubular capillaries

• Na+ reabsorption provides the energy and the means for reabsorbing most other solutes

52

Reabsorption by PCT CellsReabsorption by PCT Cells

•Figure 24.12

53


• Active pumping of Na+ drives reabsorption of: – Water by osmosis– Anions by diffusion– Organic nutrients and selected ions by

secondary active transport

54


•Figure 24.12

55


proximal convoluted tubule blood

glucose

amino acids

water

salts

amino acids

56


Substance Substance reabsorbed reabsorbed

Process Process Region where Region where reabsorption occurs reabsorption occurs

Glucose (100%)

Amino acids (100%)

Water (99%)

Salts (80%)

Urea (50%)

Diffusion, active transport

Osmosis



Diffusion

At proximal convoluted tubule, loop of Henle, distal convoluted tubule & collecting duct

At proximal convoluted tubule only

57

•Figure 19-5

Filtration FractionFiltration Fraction

58


• kidney tubule is highly coiled to increase the surface area and the time for reabsorption

59


• remaining glomerular filtrate in collecting duct is called urine

mostly water with salts, urea and other

metabolic waste

60

Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate

• Tubular secretion is important for:– Eliminating undesirable substances such as

urea and uric acid– Controlling blood pH

3. Secretion

61


Proteins pass through the walls of the glomerulus and the Bowman’s capsule.

62


It is the amino acids that are filtered into the Bowman’s capsule and reabsorbed later.

63

1 In ultrafiltration, the highhydrostatic pressure


glomerulus forces small molecules out of the blood into the Bowman’s capsule.

inside the

64

The capillary wall of the glomerulus is1

differentially permeable


only allows small molecules to pass through.

and

65

2 The composition of the glomerular filtrate is similar to that of plasma but it contains no .

plasma proteins


66


a All and

3 Reabsorption along the kidney tubule:

glucose amino acidsin the glomerular filtrate are reabsorbed into the blood by diffusion and active transport.

67


b Most is reabsorbed by osmosis.


water

68


c Some are reabsorbed by diffusion and active transport.


salts

69


d Some is reabsorbed by diffusion and the rest is removed in the urine.


urea

70

1.4 The role of the kidneys

• kidneys carry out osmoregulation by controlling the amount of water reabsorbed from the glomerular filtrate

Osmoregulation

71

• http://health.clevelandclinic.org/2013/10/what-the-color-of-your-urine-says-about-you-infographic/• http://health.clevelandclinic.org/2013/10/what-the-color-of-your-urine-says-about-you-infographic/

What The Color of Your Urine Says About Your Health

•http://health.clevelandclinic.org/2013/10/what-the-color-of-your-urine-says-about-

you-infographic/

72

• the amount of water reabsorbed is controlled by antidiuretic hormone (ADH) (抗利尿激素 )


• secretion of ADH is controlled by the hypothalamus (下丘腦 )

73

Diuresis• Diuretics are a group of drugs given to

help the body eliminate excess fluid through the kidneys. e.g. to treat hypertension, glaucoma, etc

• Natural diuretic foods and drinks• Melon• Watercress• Coffee• Tea• Coke (caffeinated soda)

74


hypothalamus• has receptors to

detect water content in blood

• controls secretion of ADH

75


pituitary gland• secretes ADH

• ADH is transported by blood

76

• under the action of ADH


permeability of the wall of the collecting duct to water increases

a greater proportion of water is reabsorbed from the filtrate

• urine in different volumes and concentrations can be formed

77

•Figure 20-4

Urine ConcentrationUrine ConcentrationOsmolarity changes as filtrate flows through the

nephron

78

Formation of Dilute Urine / Formation of Dilute Urine / hypotonic urinehypotonic urine

• Filtrate is hypotonic after passing through the loop of Henle

• Dilute urine is created by allowing this filtrate to continue into the renal pelvis

• This will happen as long as antidiuretic hormone (ADH) is not being secreted

• Collecting ducts remain impermeable to water; no further water reabsorption occurs

• Diuresis – hypotonic urine (large volume of)

79

•Figure 20-5b

Water ReabsorptionWater Reabsorption

80

•Figure 20-5a

Water ReabsorptionWater ReabsorptionWater movement in the collecting duct in the

presence of vasopressin (ADH)

81

Formation of Concentrated / Formation of Concentrated / hypertonic Urine hypertonic Urine

• Antidiuretic hormone (ADH) inhibits diuresis

• In the presence of ADH, 99% of the water in filtrate is reabsorbed

• ADH is the signal to produce concentrated urine

• The kidneys’ ability to respond depends upon the high medullary osmotic gradient

82

The kidneys’ ability to make hypertonic urine depends upon the high medullary osmotic gradient

•Click the diagram to

see an animation

83


receptors in hypothalamus

water content increases

normal water content in blood

wall of collecting duct

pituitary glandless ADH

detected by

less permeablesmaller proportion

of water reabsorbed

larger volume of dilute urine

84

receptors in hypothalamus

water content decreases


wall of collecting duct

pituitary glandmore ADH

detected by

more permeable

smaller volume of concentrated urine

greater proportion of water

reabsorbed


85

•Filtrate

•H2O

•Salts (NaCl and others)

•HCO3– ; H+ (control pH)

•Urea

•Glucose; amino acids

•Some drugs

•Key

•Active transport

•Passive transport •INNER

•MEDULLA

•OUTER

•MEDULLA

•NaCl

•H2O

•CORTEX

•Descending limb

•of loop of

•Henle

•Proximal tubule

•NaCl •Nutrients•HCO3

–

•H+

•K+

•NH3

•H2O

•Distal tubule

•NaCl •HCO3–

•H+•K+

•H2O

•Thick segment

•of ascending

•limb•NaCl

•NaCl

•Thin segment

•of ascending

•limb

•Collecting

•duct

•Urea

•H2O

86

•Figure 20-6

Water Reabsorption Water Reabsorption (reference)(reference)

The mechanism of vasopressin action

Collecting

duct

lumen

Filtrate

300 mOsmH2O

Exocytosis

of vesicles

Cross-section of

kidney tubule

Collecting duct cell

Second

messenger

signal

H2O

cAMP

Storage vesicles

Aquaporin-2

water pores

600 mOsM

H2O

Medullary

interstitial

fluid

Vasopressin

receptor

600 mOsM

Vasa

recta

H2O

700 mOsM

Vasopressin

Vasopressin

binds to mem-

brane receptor.

Receptor activates

cAMP second

messenger system.

Cell inserts AQP2

water pores into

apical membrane.

Water is absorbed

by osmosis into

the blood.

1 2 3 4

1

2

3

4

87

•Figure 20-6, step 1


Collecting

duct

lumen

Filtrate

300 mOsm

Cross-section of

kidney tubule

Collecting duct cellMedullary

interstitial

fluid

Vasopressin

receptor

Vasa

recta

Vasopressin

Vasopressin

binds to mem-

brane receptor.

1

1

600 mOsM

600 mOsM

700 mOsM

88

•Figure 20-6, steps 1–2

Collecting

duct

lumen

Filtrate

300 mOsm

Cross-section of

kidney tubule


Second

messenger

signal

cAMP

Medullary

interstitial

fluid

Vasopressin

receptor

Vasa

recta

Vasopressin

Vasopressin

binds to mem-

brane receptor.

Receptor activates

cAMP second

messenger system.

1 2

1

2

600 mOsM

600 mOsM

700 mOsM


89


Collecting

duct

lumen

Filtrate

300 mOsm

Exocytosis

of vesicles

Cross-section of

kidney tubule


Second

messenger

signal

cAMP

Storage vesicles

Aquaporin-2

water pores

Medullary

interstitial

fluid

Vasopressin

receptor

Vasa

recta

Vasopressin

Vasopressin

binds to mem-

brane receptor.

Receptor activates

cAMP second

messenger system.

Cell inserts AQP2

water pores into

apical membrane.

1 2 3

1

2

3

600 mOsM

600 mOsM

700 mOsM


90


Collecting

duct

lumen

Filtrate

300 mOsmH2O

Exocytosis

of vesicles

Cross-section of

kidney tubule


Second

messenger

signal

H2O

cAMP

Storage vesicles

Aquaporin-2

water pores

600 mOsM

H2O

Medullary

interstitial

fluid

Vasopressin

receptor

600 mOsM

Vasa

recta

H2O

700 mOsM

Vasopressin

Vasopressin

binds to mem-

brane receptor.

Receptor activates

cAMP second

messenger system.

Cell inserts AQP2

water pores into

apical membrane.

Water is absorbed

by osmosis into

the blood.

1 2 3 4

1

2

3

4


91

•Figure 20-7

Factors Affecting Vasopressin ReleaseFactors Affecting Vasopressin Release

92

•Figure 20-8

Water BalanceWater Balance

The effect of plasma osmolarity on vasopressin secretion by the posterior pituitary

93

smaller amount of salts and greater proportion of water reabsorbed

higher concentration of salts in blood

smaller volume of urine with a high salt concentration formed

(hypertonic urine)

taking in excess salts


94

Regulation of Kidney FunctionRegulation of Kidney Function

• The osmolarity of the urine is regulated by nervous and hormonal control of water and salt reabsorption in the kidneys

• Antidiuretic hormone (ADH) increases water reabsorption in the distal tubules and collecting ducts of the kidney

95

Osmoreceptors

in hypothalamus

Hypothalamus

ADH

Pituitary

•gland

Increased

permeability

Distal

tubule

Thirst

Drinking reduces

blood osmolarity

to set point

•Collecting duct H2O reab-

sorption helps

prevent further

osmolarity

increase

Homeostasis:

Blood osmolarity

STIMULUS

The release of ADH is

triggered when osmo-

receptor cells in the

hypothalamus detect an

increase in the osmolarity of the blood

96

What’s the effect of the following on urine output :

• 1. a lot of water

• 2. a lot of salty foods

• 3. a large volume of salty solution. E.g seawater

AssignmentAssignment: 1.Explain why we cannot survive on seawater as drinking water. 2. Write an essay on how one can survive without drinking water while drifting on a raft in the open ocean (>300 words)

97

• by forming urine

Excretion1.4 The role of the kidneys

to remove metabolic waste (e.g. urea)

98

• by forming urine

Excretion1.4 The role of the kidneys

to remove metabolic waste (e.g. urea)

• constantly produced• high concentration is toxic

99

Diuretics Diuretics (reference)(reference)

• Chemicals that enhance the urinary output include:– Any substance not reabsorbed– Substances that exceed the ability of the renal

tubules to reabsorb it• Osmotic diuretics include:

– High glucose levels – carries water out with the glucose

– Alcohol – inhibits the release of ADH– Caffeine and most diuretic drugs – inhibit sodium ion

reabsorption– Lasix – inhibits Na+-K+-2Cl symporters

100

Physical Characteristics of Physical Characteristics of Urine (reference)Urine (reference)

• Color and transparency

– Clear, pale to deep yellow (due to urobilin) -from the breakdown of heme

– Concentrated urine has a deeper yellow color

– Drugs, vitamin supplements, and diet can change the color of urine

– Cloudy urine may indicate infection of the urinary tract

101

Concentrated urine has a deeper yellow color

102

Physical Characteristics of Physical Characteristics of UrineUrine

• Odor / smell– Fresh urine is slightly

aromatic– Standing urine develops an

ammonia odor– Some drugs and vegetables

(asparagus) alter the usual odor

103

Physical Characteristics of Physical Characteristics of UrineUrine

• pH – Slightly acidic (pH 6) with a

range of 4.5 to 8.0– Diet can alter pH

• Specific gravity– Ranges from 1.001 to 1.035 – Dependent on solute

concentration

104

Chemical Characteristics of Chemical Characteristics of UrineUrine

• Urine is 95% water and 5% solutes• Nitrogenous wastes include urea, uric acid, and

creatinine• Other normal solutes include:

– Sodium, potassium, phosphate, and sulfate ions– Calcium, magnesium, and bicarbonate ions

• Abnormally high concentrations of any urinary constituents may indicate pathology

• Disease states alter urine composition dramatically

105

Functions of the KidneysFunctions of the Kidneys

• Regulation of extracellular fluid volume and blood pressure

• Regulation of osmotic potential in blood

• Maintenance of ion balance

• Homeostatic regulation of pH

• Excretion of wastes

106

secretes less ADHpituitary gland


1 Regulation of water content by negative feedback mechanism:


high water content in blood

hypothalamus kidneys

107


In the kidneys:

a wall of collecting duct becomespermeable to water

less

b a proportion of water reabsorbed

smaller

c a volume of urine is formed

larger

dilute

108

secretes less ADHpituitary gland




high water content in blood


water content in blood falls

109

secretes more ADHpituitary

gland




low water content in blood


110


In the kidneys:

a wall of collecting duct becomespermeable to water

more

b a proportion of water reabsorbed

greater

c a volume of urine is formed

smaller

concentrated

111

secretes more ADHpituitary

gland




low water content in blood


water content in blood rises

112

2 After excess salts are taken into the body, the excess salts have to be excreted. A amount of salts and a proportion of water are reabsorbed. As a result, a

smaller


greater

small

volume of urine with a high salt concentration is formed.

113

3 Excretion is necessary because metabolic waste is constantly produced and a high concentration of this waste is to the body. The kidneys form to remove metabolic waste (e.g. urea) from the blood.


toxic urine

114

1.5 The dialysis machine

• kidney machineAnimation

• helps remove metabolic waste by haemodialysis (血液透析 )

115


1 blood with metabolic waste

pump dialysis tubing

fresh dialysis fluid

116


dialysis tubing


same concentration of solutes as normal plasma but has no metabolic waste

same concentration of solutes as normal plasma but has no metabolic waste

117


dialysis tubing


constant temperature bath

dialysis fluid

118


differentially permeable membrane of dialysis tubing

119


2 urea diffuses through the pores to the dialysis fluid

120


3 glucose is retained in blood (no net movement from blood to dialysis fluid

121


4 plasma proteins and blood cells are too large to pass through the pores

122


5 ‘cleaned’ blood

used dialysis fluid (with urea)

123


• each treatment lasts for 4-6 hours• three times a week• costly

124

Peritoneal dialysis

Peritoneal dialysis (PD) is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood.

125

Kidney transplant

126

1 A dialysis machine removesmetabolic waste

patient’s blood.

from the


127

2 The dialysis fluid has the same concentration of solutes as normalplasma


This allows metabolic waste to diffuse from the patient’s blood to the dialysis fluid while

but no metabolic waste.

glucoseand other useful substances are retained in the blood.

128

Why may a person die quickly if thekidneys fail to function?1When the kidneys fail to function, the body cannot keep the water content in blood stable for cells to function properly.

129

Why may a person die quickly if thekidneys fail to function?1Besides, metabolic waste builds up in blood which can cause death.

130

How does a kidney machine treatkidney failure?2A kidney machine removes metabolic waste from the patient’s blood by haemodialysis.

131

Why can’t people with kidneyfailure take in too much fluid and high-protein food?

3

Excess proteins in the body are converted to urea by the liver.

132

3

The failed kidney cannot remove excess fluid and urea from the body.


133

3

Therefore, excessive intake of fluid and high-protein food must be avoided.


134

detected by

is the maintenance of a stable

Osmoregulation

water content in blood

hypothalamus

urinary system

done by

kidneys

main parts include

135

hypothalamus kidneyscontrols secretion of

antidiuretic hormone

functional units

nephrons

controls concentration and volume of

form

urine

136

by

ultrafiltration

kidneysurine

reabsorption helps body remove

fail to function can be treated by

metabolic waste

contains

dialysis machine

When the kidneys fail

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