Download Kidney I

Nyrer
Ivana Novak
Menneskets Fysiologi 2007-2008
Kidney I
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Structure and function of kidney
Basic renal processes
Nephron
Glomerular filtration and blood flow
Tubular transport
Renal clearance
(Micturition)
Main kidney functions
• Homeostatic role – water, salt, acid/base, nutrient
balance
• Filter – removes metabolic products and toxins from
blood and excretes them in urine
• Endocrine function – produces hormones involved in
erythrogenesis, calcium metabolism and blood
pressure/flow
• Gluconeogenesis
Table 14-1 like
Binyre
Nyrebark
Nyremarv
Art. renalis
Nyrebækken
Ven. renalis
Nyre
Aorta
Ven. cava inferior
Ureter (urineleder)
Urinblæren
Urethra (urinrør)
Figure 14-1 like
Gross anatomy of kidney
Nyrebark
Nyremarv
Nyrekapsel
Nyrebækken
Figure 14-4 like
Nefronets opbygning
Nyrelegeme
glomerulus Bowmans kapsel
efferent
Distale tubulus
Arteriole
Proximale tubulus
afferent
Nyrebark
Nyremarv
Samlerør
Henles slynge
Figure 14-2 like
Main processes in kidney
• Filtration
• Absorption
• Secretion
Main elements of nephron function
filtration
Nyrebark
Nyremarv
The nephron forms an
ultrafiltrate of the blood
plasma and then selectively
reabsorbs the tubule fluid
and secretes solutes into it.
absorption
secretion
excretion
Figure 14-6 like
Filtration – renal corpuscle
Glomerulus, Bowman´s capsule and Juxtaglomerular apparatus
Macula densa
Distale tubulus
Figure 14-3 like
Filtration – renal corpuscle
Glomerulus, Bowman´s capsule and Juxtaglomerular apparatus
Afferent arteriole
Macula Densa
Mesangial cells
nerves
granula
Efferent arteriole
Basement membrane
Epithelial cell
Bowman´s capsule
Endothelium
Podocytes
Capillary
lumen
Mesangial cell
Ultrafiltrate
Figure 14-3 like
(Glomerular filtrate) Ultrafiltrate - limits
Ions
0.02-0.05 kDa
Urea 0.06 kDa
Glucose 0.18 kDa
1.0
Myoglobin
17 kDa
Inulin
5.5 kDa
[Ultrafiltrate]/[Plasma]
0.8
0.6
0.4
Albumin
Hemoglobin
69 kDa
0.2
0
0
1
2
3
Molecular radius (nm)
4
5
Figure X
Kidney vascular bed - important for filtrate formation and
concentrating mechanism
renal artery
afferent arteriole
glomerular capillary network
efferent arteriole
capillary network surrounding
renal tubules (peritubular
capillaries)
renal vein
Figure 14.2 like
Blood pressure in kidney vascular bed
Blood pressure (mm Hg)
150
125
100
75
50
25
0
Afferent
arteriole
Arteria
renalis
Arteria
arcuata
Efferent
arteriole
Glomerular
capillaries
Vena
arcuata
Peritubular
capillaries
Vena
renalis
Figure X
Filtration depends on hydrostatic (P) and
oncotic (Π) pressures
Glomerular filtration pressure ca. 16 mm Hg
PGC
ΠGC
PBS
ΠBS
60
29
15
0
16
Proximal tubulus
GC glomerular capillary
BS Bowman´s space
Net filtration pressure = [(PGC-PBS)-(ΠGC-ΠBS)] = 16 mm Hg
Figure 14-8 like
Rate of Glomerular Filtration
Glomerulære filtrationsrate
The Glomerular Filtration Rate (GFR) depends on:
•
Net filtration pressure
•
Permeability of corpuscular membranes
Kf
•
Surface area of filtration zone
GFR = Kf [(PGC-PBS)-(ΠGC-ΠBS)]
GFR in healthy person is ca. 125 ml/min (which makes
about 1/5th of renal plasma flow)
Assume that total volume of plasma is 3 l, it is filtered by kidney 60x per day
Autoregulation of renal blood flow and glomerular
filtration rate (GFR)
Glomerulære filtrationsrate = GFR
1200
Renal
Blood
Flow
(ml/min)
600
autoregulation
0
150
GFR
(ml/min)
75
0
0
40
80
120
Pressure (mm Hg)
160
200
Figure X
Myogenic control of renal blood flow and GFR
Glomerulære filtrationsrate = GFR
Figure 14-9
Tubuloglomerular feedback
Vasoconstrictor X
Myogenic control
Juxtaglomerular cells
Figure øvelse
Renin
Renal handling of substances – tubular transport
Filtered
Filtered and secreted
Filtered and reabsorbed
afferent
efferent
Inulin, creatinine
p- aminohippurate (PAH)
glucose
Figure 14-7 like
Renal handling of substances – solute mass
balance in nephron
amount filtered
amount reabsorbed
+
amount secreted
=
amount excreted in urine
Figure 14-6 like
Solute mass balance in the kidney
Arterial input
PS,a · RPFa
=
PS,v ·RPFv
Venous output
+
Urine output
P - concentrations in plasma
RPF - renal plasma flow
Ux · V
Figure 14-11 like
Renal Clearance
• The Clearance of a solute is the virtual
volume of blood that would be totally
cleared of a given solute in a given time
• Clearance can be used to determine:
– Glomerular Filtration Rate (GFR)
– Renal Plasma Flow (RPF)
Clearance
Clearance of substances can vary between:
0 ml/min - substances that do not appear in urine, because they are
reabsorbed (substance Z in Fig. 14-7)
and
up to 700 ml/min - substances that are totally removed from blood in a
single pass through kidney; can be used to estimate renal plasma flow
(substance X in Fig. 14-7)
in special case
ca. 125 ml/min – substances that are only filtered; can be used to
estimate glomerular filtration rate
Clearance and GFR
Arterial input of S
Venous output of S
Urine output of S
PS,a · RPFa
PS,v ·RPFv
·
US · V
=
mmol/ml · ml/min
+
mmol/ml · ml/min
mmol/ml · ml/min
If kidney clears all S from incoming blood,
we can replace RPFa with Clearance for S, i.e. CS
PS,a · CS
=
+
0
CS =
·
US · V
·
US · V
(ml/min)
PS,a
If substance S is inert, i.e. only filtered and not absorbed or secreted by kidney,
Cs becomes an estimate of Glomerular Filtration Rate - GFR
·
UIn · V
(ml/min)
GFRIn =
PIn,a
Kidney II
Na+ (and Cl-), water and K+ balance
Urine concentration
Regulatory mechanisms
Composition of glomerular filtrate and urine
Solute
excreted
Glomerular
filtrate
concentration
(mmol/l)
Amount
filtered
(mmol/day)
Urine
concentration
(mmol/day)
Amount
excreted
(mmol/day)
H2O
Na+
ClK+
Ca2+
HCO3Phosphates
D-Glucose
Amino acids
Urea
Urate
Creatinine
H+
Proteins
Osmolality
55 556 (1 kg/l)
145
120
5
1.5
25
2
5
2
5
0.3
0.1
10-4
10 mg/l
(180 l)
26 000
20 000
900
250
4250
360
900
350
900
54
18
10-2
1.8 g
300 mosm/kg
55 556 (1kg/l)
30-150
30-150
33-300
3-6
1
3-20
0.05-0.5
2-8
280-400
3
11
0.01
40 mg/l
(1-3 l)
100-300
100-500
50-450
0.5-20
1
5-30
0-1
3-12
420-600
5
17
30
60 mg
50-1500 mosm/l
Table 14-2 like
Composition of glomerular filtrate and urine
Solute
excreted
Glomerular
filtrate
concentration
(mmol/l)
Amount
filtered
(mmol/day)
Urine
concentration
(mmol/day)
Amount
excreted
(mmol/day)
H2O
Na+
ClK+
Ca2+
HCO3Phosphates
D-Glucose
Amino acids
Urea
Urate
Creatinine
H+
Proteins
Osmolality
55 556 (1 kg/l)
145
120
5
1.5
25
2
5
2
5
0.3
0.1
10-4
10 mg/l
(180 l)
26 000
20 000
900
250
4250
360
900
350
900
54
18
10-2
1.8 g
300 mosm/kg
55 556 (1kg/l)
30-150
30-150
33-300
3-6
1
3-20
0.05-0.5
2-8
280-400
3
11
0.01
40 mg/l
(1-3 l)
100-300
100-500
50-450
0.5-20
1
5-30
0-1
3-12
420-600
5
17
30
60 mg
50-1500 mosm/l
Table 14-2 like
Water distribution and balance in the human body
Intake:
Drink 1200 ml
Food 1000 ml
Metabolic 350 ml
0.015
Transcellular water
0.045
Plasma
0.19
Interstittium
Extracellular
fluid
Cell
Intracellular
fluid
r
te
a
w
u
lrE
ce
xta
0.35
Water = 0.6
r
te
a
w
Output:
u
lrIn
e
c
ta
Man
Water
0.46-0.75 l/kg
body weight
Baby
0.64
0.53
Young
Old
0.75
Woman
0.53
0.46
Young
Old
Urine 1500 ml
Feces 100 ml
Sweat 50 ml
insensible loss
(skin, lungs) 900 ml
Table 14-3 like
Elektrolyt øvelse - like
The kidneys (and Digestive system)
Comprise of epithelia
Regulate salt, water and
nutrient balance
and
Other cell types (smooth
muscle, nerves, endocrine
cells, blood vessels)
Epithelial transport
Interstitium
serosa
Lumen
mucosa
ATP
Na+
K+
absorption
solute and H2O
secretion
Tight junction
blood vessel
Na+ distribution in the body
Na+ has a central role in salt and water homeostasis
Sweat
10-15 mmol/day
Diet
120 mmol/day
Absorb
110 mmol/day
Gut
Feces
5-10 mmol/day
Filter
25,500
mmol/day
ECF
2460 mmol
Kidneys
ICF
375 mmol
Reabsorb
25,400
mmol/day
Urine
100 mmol/day
Table 14-4 like
Recovery of Na+ (and Cl-) along the nephron
Figure X
Na+, Cl- and water
• Different nephron segments use different
transporters and channels for Na+ absorption
• Cl- absorption follows via transcellular or
paracellular route
• Water reabsorption is passive and secondary to
solute transport (if epithelium is water permeable)
Coupling of Na+ and water transport in proximal tubulus
lumen
interstitium
blood vessel
Na+
solute
ATP
Na+
K+
Aquaporin
K+
H2O
Figure 14-14 like
Na+-dependent absorption – Cortical Collecting Duct (CCD)
interstitium
lumen
Na+
regulation
ATP
Na+
K+
K+
K+
AQP2
H2O
Na+ and water (also K+ and H+) transport can be regulated. Fine tuning.
Figure 14-13, 14-14 like
Water permeability along the nephron
AQP1
H2O
H2O
AQP2
Impermeable to H2O
AQP - aquaporins
Figure X
Countercurrent multiplier system 1
Using selective NaCl and water permeability to
concentrate urine in the loop of Henle
Ascending limb of loop of Henle
transports NaCl
Descending limb of loop of Henle
is water permeable
Figure text book
Countercurrent multiplier system 2
Regulation of Na+ and water permeability in collecting ducts
Aldosterone
(Na+ and K+ transport)
+ Vasopressin –
(water transport)
urea
Figure 14-15
Concentrated urine
Dilute urine
Countercurrent multiplier system 3
Urea recycling maintains hypertonicity in the inner medulla
Figure 14-17
Countercurrent multiplier system 4
Vasa recta are permeable to salt and water
Figure 14-16
Regulation of Na+ and water homeostasis - overview
Plasma volume
Baroreceptors
BP Direct
Myogenic
effect
JGA
osmoreceptors
Renin
Sympathetic
nerves
Angiotensin II
+
+
Posterior
pituitary
Vasopressin
(Antidiuretic hormone)
Aldosterone
+
Atrial
myocytes
+
Atrial natriuretic
Peptide (ANP)
-
+
Changes in hemodynamics
and tubular transport
GFR
Na+ and H2O absorption
Na+ and H2O
excretion
Figures 14-18 to 14-23
Juxtaglomerular apparatus
Tubulo-Glomerular Feedback
Myogenic control
Single nephron
Acute effects
Vasoconstrictor X
Myogenic control
Juxtaglomerular cells
Renin
Figure øvelse
Figure 14-5 and 14-19 like
Renin-Angiotensin-Aldosterone
System
Whole body
Chronic effects
Renin-Angiotensin-Aldosterone Axis
hemorrhage
diarrhea
excessive sweat
lack of salt
Thirst
Vasopressin
Aldosterone
Plasma volume
Angiotensin II
Angiotensin I
Effect:
cortical collecting
ducts
Na+ and H2O
reabsorption
JGA
Angiotensin
Converting
Enzyme
Renin
Angiotensinogen
Na+ and H2O
excretion
Figure 14-19 and 14-22 like
Cellular actions of Aldosterone on epithelial Na+ channels in
principal cells of cortical collecting tubules
Mineralocorticoid
receptor
Na+
Aldosterone
MR
ATP
Na+
Na+ and H2O
absorption
K+
K+
K+
lumen
interstitium
Figure 14-13 like
Renal sympathetic nerve activity
• Increase renal vascular pressure
• Increase release of renin
• Increase tubular absorption of Na+
Atrial Natriuretic Peptide (ANP)
• Cardiac myocytes store and release ANP in
response to stretch (increase volume)
• ANP promotes natriuresis, i.e. Na+ excretion
• Therefore, lower plasma volume causes lower
release of ANP and thus Na+ retension
Vasopressin – (Antidiuretic Hormone - ADH)
osmolality
H2O reabsorption
Vasopressin
Figure 14-21 like
Urine volume
Water absorption in principal cells of Cortical Collecting tubules
and Ducts
interstitium
lumen
Na+
ATP
Na+
K+
K+
K+
AQP2
H2O
Figure X
K+ homeostasis
Diet
100 mmol/day
Cell damage
Acid/base
disturbances
Absorb
90 mmol/day
Gut
ICF
3,400 mmol
140 mM
ECF
65 mmol
4.5 mM
Secreted 50 mmol/day
Feces
10 mmol/day
Reabsorb
770
mmol/day
Kidneys
Filter
810
mmol/day
Urine
90 mmol/day
Figure X
K+ load and regulation of K+ excretion
Diet
K+ load
Aldosterone
Large intestine
Plasma and cellular K+
interstitium
lumen
MR
Na+
ATP
Aldosterone
K+ secretion
Na+
K+
K+
K+
AQP2
H2O
Principal cell of collecting duct
K+ secretion
(and Na+ absorption)
Figure 14-28 like
Mineralocorticoid
receptor
MR
Na+
ATP
Aldosterone
Na+
Na+ and H2O
absorption
K+
K+
K+
GR
MR
11β-HSD
lumen
Cortisol
interstitium
Glycyrrhetinic acid (licorice)
Figure XX
Kidney III
•
•
•
•
•
•
Ca2+ homeostasis and transport
Absorption of nutrients
Organic cation and anion transport
Acid/base homeostasis
Excretion of Nitrogen compounds
Diuretics and kidney diseases
Ca2+ homeostasis
fra Ugeskrift for Læger 2006
Figure 14-30-32 like
Absorption of nutrients and small organic molecules
in proximal tubulus
Example for glucose
lumen
Na+
glucose
Na+
ATP
AQP1
H2O
K+
K+
Figure
Secretion of organic anions and cations
Proximal tubulus
Anions
Cations
Endogenous
bile salts
oxalate
adrenaline
histamine
Exogenous
diuretics
penicillin
morphine
atropine
Figure X
Acid/base homeostasis
Metabolic source of acids/bases
Volatile acids
CO2 (potential acid)
carbonic anhydrase
CO2 + H2O
H2CO3
HCO3- + H+
Nonvolatile acids H+, phosphate, sulphate, uric acid,
oxalic acid, lactic acid, keto-acids,
acetate
Kidney: must reabsorb all HCO3- and secrete nonvolatile acids
therefore, kidney acidifies urine
Acid/base homeostasis
Metabolism
15 000 mmol CO2/day
CO2
Diet
20 mmol H+/day
ECF
pH 7.4
GI system
Vomitus loss of H+
Diarrhea loss of HCO3-
Feces
10 mmol OH-/day
Reabsorb
4320
mmol HCO3-/day
Kidneys
Filter 4320
mmol HCO3-/day
Urine
70 mmol/day
40 mmol NH4+/day
30 mmol titratable
Acid/day
Table 14-7 like
Absorption of HCO3100% HCO3-
4% HCO3-
20% HCO3-
10% HCO3-
<0.01% HCO3-
Figure X
Reabsorption of bicarbonate
in proximal tubulus
lumen
interstitium
filtered
HCO3-
Na+
Na+
HCO3-
+
H+
H+
+
HCO3-
HCO3-
H2CO3
H2CO3
CA
CO2 + H2O
H2O + CO2
AQP1
Figure 14-33 like
Formation of titratable acid and generation of
new bicarbonate in proximal tubulus
lumen
lumen
Na+
Na+
interstitium
filtered
glutamine
+
HPO42-
NH4+
H+
H+
glutamine
NH4+
+
ATP
HCO3-
H2PO4-
HCO3-
NH4+
Figure 14-34 and 14-35 like
Acid/base disorders
renal comp.
Respiratory acidosis
CO2
H+
HCO3-
renal comp.
Respiratory alkalosis
CO2
H+
HCO3-
resp. comp.
Metabolic acidosis
H+
HCO3-
CO2
resp. comp.
Metabolic alkalosis
H+
HCO3-
CO2
Table 14-9 like
Excretion of Nitrogen compounds
Figure X
Kidney diseases
Various defects:
Regulation defects:
Obstruction of ureter/urethra
Impaired response to vasopressin
(diabetes insipidus)
hypoaldosteroidism
Kidney stones
Too much renin - renal hypertension
Toxic chemicals (e.g. ochratoxin)
infections
glomerulonephritis
tumors
Genetic defects:
Defect in Na-K-Cl cotransporter – Barter syndrome
Defect in Na channels – Liddle´s disease
Defect in AQP2 channels – nephrogenic diabetes insipidus
Polycystic kidney disease – defects in primary cilia
Kidney and cardiovascular system
Diuretics
What do they do?
Increase volume of urine
Why?
To treat high blood pressure, fluid retension
in body e.g. congestive heart failure
Where do they act? Mostly on luminal transporters in
different nephron segments
How do diuretics get in? They are secreted