RENAL PHYSIOLOGY REVIEWED
DANIL HAMMOUDI.MD
Capillary Beds
Figure 25.5a
Afferent
arteriole
Glomerular
capsule
10
mm
H
Hg
Net
filtration
pressure
Glomerular (blood) hydrostatic pressure
(HPg = 55 mm Hg)
Blood colloid osmotic pressure
(Opg = 30 mm Hg)
Capsular hydrostatic pressure
(HPc = 15 mm Hg)
Figure 25.11
C ill
Capillary
Filtration membrane
• Capillary endothelium
• Basement membrane
• Foot processes of podocyte
of glomerular
glomer lar capsule
caps le
Filtration slit
Plasma
as a
Fenestration
(pore)
Slit diaphragm
Filtrate in
capsular
space
Foot processes
of podocyte
(c) Three parts of the filtration membrane
Figure 25.9c
Cortical
radiate
artery
Afferent arteriole
Glomerular capillaries
Efferent arteriole
Glomerular capsule
Rest of renal tubule
containing filtrate
Peritubular
capillary
Three major
renal processes:
Glomerular filtration
Tubular reabsorption
Tubular secretion
To cortical radiate vein
Urine
Figure 25.10
Body Fluid Compartments
27-8
formation of
hyperosmotic urine
Functions of the Nephron
–
Secretion
–
Reabsorption
•
Material added to
lumen of kidney from
blood
Active transport
p
(usually) of toxins and
foreign substances
» Saccharine
» Penicillin
Normally glucose is
totally reabsorbed
Excretion
Filtration
–First step in urine formation
–Bulk transport of fluid from blood to kidney tubule
–Result of hydraulic pressure
–GFR = 180 L/day
–
Excretion:
–
Loss of fluid from body in form of urine
Amount = Amount + Amount
of Solute
Filtered
Secreted
Excreted
--
Amount
Reabsorbed
Functions
Regulating blood ionic composition
Regulating blood pH
Regulating blood volume
Regulating blood pressure
Produce calcitrol and erythropoietin
Regulating blood glucose
Excreting
c e g wastes
as es
Major Functions of the Kidneys
1. Regulation of:
•
body fluid osmolarity and volume
•
electrolyte balance
•
acid-base balance
•
blood pressure
2. Excretion of
•
metabolic products
•
foreign substances (pesticides, chemicals etc.)
•
excess substance (water, etc)
3. Secretion of
•
erythropoitin
•
1,25-dihydroxy vitamin D3 (vitamin D activation)
•
renin
•
prostaglandin
The three basic renal processes
Glomerular filtration
Tubular reabsorption
Tubular secretion
GFR is very high: ~180l/day. Lots
of opportunity to precisely regulate
ECF composition and get rid of
unwanted substances.
N.B.
N
B it is the ECF that is being
regulated, NOT the urine.
Mechanisms of Urine Formation
The kidneys filter the body
body’ss entire plasma volume 60
times each day
The filtrate:
Contains all plasma components except protein
† Loses water,
water nutrients,
nutrients and essential ions to become urine
†
The urine contains metabolic wastes and unneeded
substances
bt
Net Filtration Pressure (NFP)
The pressure responsible for filtrate formation
NFP equals the glomerular hydrostatic pressure (HPg)
minus the
h oncotic pressure off glomerular
l
l blood
bl d (OPg)
combined with the capsular hydrostatic pressure (HPc)
NFP = HPg – (OPg + HPc)
Glomerular Filtration Rate (GFR)
The total amount of filtrate formed p
per minute byy
the kidneys
Factors governing filtration rate at the capillary
bed are:
† Total
oa
surface
su ace area
a ea available
ava ab e for
o filtration
a o
† Filtration membrane permeability
† Net filtration pressure
Glomerular Filtration Rate (GFR)
GFR is directly proportional to the NFP
Changes in GFR normally result from changes in
glomerular blood pressure
Extracellular Fluid Osmolality
Osmolality
†
Adding or removing
water from a solution
changes
h
this
hi
D
Decreased
d osmolality
l lit
† Inhibits
thirst and ADH
secretion
i
Increased osmolality
†
Triggers thirst and ADH
secretion
27-25
Antidiuretic
Hormone: ADH
ADH is also known as arginine
vasopressin (AVP= ADH) because
off its
i vasopressive
i activity,
i i but
b its
i
major effect is on the kidney in
preventing water loss.
•It is primarily regulated by osmotic
and volume stimuli.
stimuli
•Water
deprivation
increases
osmolality
of
plasma
which
activates hypothalmic
yp
osmoreceptors
p
to stimulate ADH release.
Regulation of ECF Volume
Increased ECF results in
Mechanisms
†
Neural
† Renin-angiotensinaldosterone
† Atrial natriuretic
h
hormone
(ANH)
† Antidiuretic hormone
(ADH)
†
†
27-27
†
†
Decreased aldosterone secretion
Increased ANH secretion
Decreased ADH secretion
Decreased sympathetic stimulation
Decreased ECF results in
†
†
†
†
Increased aldosterone secretion
D
Decreased
d ANH secretion
ti
Increased ADH secretion
Increased sympathetic stimulation
Hormonal Regulation of Blood Volume
27-28
Hormonal Regulation of
Blood Osmolality
27-29
Overview: the 3 p
phases of urine formation
Explain why the functional unit of the kidney is best described as more than just the nephron.
FFor eachh phase,
h
describe
d
ib the
th 1) location
l ti along
l
the
th nephron,
h
2) th
the mechanism(s)
h i ( ) off ttransport,t
and 3) the net direction of movement.
Filtration: the first phase in urine
formation
Briefly compare the composition of blood plasma and of urinary filtrate as it enters
the proximal convoluted tubule.
Tubular Reabsorption: the second phase
in urine formation
Describe the features of cells in the
proximal convoluted tubule that make
them well suited for selective transport.
What solute is
excreted by this
mechanism?
What is obligatory water reabsorption?
Wh
Where
and
d why
h d
does this
hi occur??
Tubular Reabsorption
p
of Glucose
In which direction does Na+ leave the cell?
Why?
In which direction does Na+ enter the cell?
Why?
In which direction does glucose enter the cell?
Why?
In which direction does glucose leave the cell?
Why?
What other solutes are selectively
reabsorbed by similar means?
Tubular Secretion: the third
(and last) phase in urine
formation
What is the normal p
pH range
g of
urine?
What is the advantage of using
this enzyme-catalyzed
enzyme catalyzed reaction
to generate H+?
What is the net direction for the movement of materials
by tubular secretion? Is this the same direction as in
filtration at the renal corpuscle?
Wh other
What
h solutes
l
are secreted
d this
hi way?? Why?
Wh ?
Homeostatic
M h i
Mechanism
involving
g ADH to
Regulate Water
B l
Balance
Is this obligatory or facultative water
reabsorption?
What two types of changes result in increased
osmolarity
l i off b
body
d fluids,
fl id and
d so would
ld
stimulate ADH release?
Renin-Angiotensin-Aldosterone System
in the Regulation of Water Balance
Normal Blood Volume/ Normal BP
Na
+
, Water
K
+
, Na
+
BP
KIDNEY
KIDNEY
Aldosterone
( plasma)
(
Renin
plasma)
ADRENAL CORTEX
( Zona
Glomerulosa)
ACE
Angiotensin II
Angiotensin I
( lungs)
Vasoconstriction
Stimulates ADH release
Thirst
( BP, and venous return)
Angiotensinogen
Rennin-Angiotensin-Aldosterone System
Stimulates Sodium Reabsorption in distal and
collecting tubules
Naturetic peptide inhibits
In absence of Aldosterone, 20mg of sodium/day
may be excreted
Aldosterone can cause 99.5% retention
12/6/2009
Rennin-Angiotensin-Aldosterone System
Fall in NaCl, extracellular fluid volume, arterial blood pressure
Adrenal
Cortex
Juxtaglomerular
Apparatus
Liver
Lungs
Renin
+
Angiotensin
Helps
Correct
Angiotensin
Converting
Enzyme
Angiotensin
Increased
Sodium
12/6/2009
Reabsorption
Ald t
Aldosterone
Glomerular Filtration
First step in urine formation
180 liters/day filtered
Entire plasma volume filtered
f
65
6 times/day
/
Proteins not filtered
Forces Involved in
Glomerular Filtration
Glomerular Capillary
Blood Pressure
Plasma Colloid
Osmotic Pressure
Bowman’s Capsule
Hydrostatic Pressure
+
-
55
30
15
Net Filtration Pressure
+
10
12/6/2009
Tubular Reabsorption
Water: 99% reabsorbed
Sodium: 99.5% reabsorbed
Urea: 50% reabsobed
Ph l 0% reabsorbed
Phenol:
b b d
12/6/2009
Tubular Reabsorption
By passive diffusion
By primary active transport: Sodium
S
By secondary active transport: Sugars and Amino
Acids
12/6/2009
DUAL CONTROL OF ALDOSTERONE SECRETION
Increased
Plasma
Potassium
Fall in sodium
ECF Volume
Blood Pressure
Increased Aldosterone secretion
IIncreased
dT
Tubular
b l
Potassium Secretion
Increased Urinary
Potassium Secretion
IIncreased
dT
Tubular
b l
Sodium Reabsorption
Fall
ll in
i Urinary
i
Sodium Excretion
12/6/2009
ReninAngiotensin
System
COUNTERCURRENT MAKES
THE OSMOTIC GRADIENT
From
Proximal
Tubule
Active
Sodium
Transport
Passive
Water
Transport
300
300
100
450
450
250
600
600
400
750
750
550
900
900
700
1050
1050
850
1200
1200
Long Loop
1200
1200
of Henle
To Distal
Tubule
Cortex
Medulla
1000
1000
12/6/2009
THE OSMOTIC GRADIENT CONCENTRATES THE URINE WHEN
VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS PRESENT
Interstitial Fluid
300
300
450
600
Collecting
Duct
1050
1200
P i Water
Passive
W t Flow
Fl
1200
550
700
750
900
400
From
Distal
sta
Tubule
Pores
Open
850
1000
1100
1200
12/6/2009
Cortex
Medulla
WHEN VASOPRESSIN (ANTI DIURETIC HORMONE [ADH]) IS
ABSENT A DILUTE URINE IS PRODUCE
Interstitial Fluid
100
300
450
600
Collecting
Duct
1050
1200
N W
No
Water
t Flow
Fl
Out1200
of Duct
100
100
750
900
100
From
Distal
sta
Tubule
Pores
Closed
100
100
100
100
12/6/2009
Cortex
Medulla
Secretion of Aldosterone regulated by:
•Angiotensin II (+)
•Plasma K (+)
•ACTH (+)
•Plasma Na (-)
()
•ANF (-)
Total filtered Na/day = GFR x PNa
= 180
8 L/
L/day
ay x 145
5 mmol/L
mmo /L = 26,100
6,
mmol/day
mmo / ay
= ~ 15 g NaCl!
GLOMERULAR FILTRATION RATE (GFR): The rate, in mL/min, at which blood is filtered through the glomerulus: GFR = Kf (Pgc
- Pt - PIb) = (Kf)x(Pf)
Kf = FILTRATION COEFFICIENT: A constant representing the permeability of the glomerular filter.
†
You can calculate a value for Kf by measuring GFR and Pf.
REGULATION OF GFR and RBF: In general, GFR changes in the same direction as RBF, RBF usually changes more profoundly.
†
Lower Kf (less permeability) ------> lower GFR
„
†
This is somewhat compensated by a slower rate of rise of oncotic pressure which is a direct consequence of the lower
GFR. That leads to a slightly higher Pf, which balances off the GFR a little.
ARTERIOLAR CHANGES:
„
„
„
„
Efferent Arteriolar Vasoconstriction ------>
„
LOWER RBF
„
HIGHER GFR, because of higher Pgc
Afferent Arteriolar Vasoconstriction ------>
„
LOWER RBF
„
LOWER GFR, because of lower RBF
Afferent Arteriolar Vasodilation ------>
„
HIGHER RBF
„
HIGHER GFR, because of higher RBF
COMBINED CHANGES: When two or more factors both change, RBF is generally affected more than GFR. GFR
remains relatively stable.
The Response to a Reduction in the GFR
Figure 26.11b
The Response to a Reduction in the GFR
Figure 26.11a
GFR depends on diameters of afferent and efferent arterioles
Glomerulus
Afferent arteriole
×GFR
Aff. Art. dilatation
Prostaglandins,
Kinins, Dopamine
(low dose), ANP,
NO
Efferent arteriole
Glomerular filtrate
Eff. Art. constriction
Angiotensin II (low
dose)
ØGFR
Aff. Art.
constriction
t i ti
Ang II (high dose), Noradrenaline
(Symp nerves), Endothelin, ADH,
Prost. Blockade)
Eff. Art. dilatation
Angiotensin II
blockade
E ti i C
Extrinsic
Controls:
t l Renin-Angiotensin
R i A i t i Mechanism
M h i
Triggered
gg
when the granular
g
cells of the JGA release
renin
angiotensinogen (a plasma globulin)
resin →
angiotensin I
angiotensin converting
enzyme (ACE) →
angiotensin II
Effects of Angiotensin II
Constricts arteriolar smooth muscle,, causing
g MAP
to rise
Stimulates the reabsorption of Na+
1.
2.
†
†
3.
Acts directly on the renal tubules
Triggers adrenal cortex to release aldosterone
Stimulates the hypothalamus to release ADH and
activates the thirst center
Effects of Angiotensin II
4
4.
5.
Constricts efferent arterioles, decreasing
peritubular capillary hydrostatic pressure and
increasing fluid reabsorption
Causes glomerular mesangial cells to contract,
d
decreasing
i the
th surface
f
area available
il bl for
f
filtration
Extrinsic Controls: Renin-Angiotensin
Mechanism
Triggers for renin release by granular cells
† Reduced
stretch of granular cells (MAP below
80 mm Hg)
† Stimulation of the granular cells by activated macula
densa cells
† Direct stimulation of granular cells via β1-adrenergic
receptors by renal nerves
SYSTEMIC BLOOD PRESSURE
Blood pressure in
afferent arterioles; GFR
Stretch of smooth
muscle in walls of
afferent arterioles
Granular cells of
juxtaglomerular
apparatus of kidney
Release
GFR
Filtrate flow and
NaCl in ascending
limb of Henle’s loop
Targets
Vasodilation of
afferent arterioles
(+)
Catalyzes cascade
resulting in conversion
Angiotensinogen
Macula densa cells
of JG apparatus
of kidney
Release of vasoactive
chemical inhibited
(+)
Renin
(+)
Adrenal cortex
((–))
Baroreceptors in
blood vessels of
systemic circulation
(+)
Sympathetic
nervous system
Angiotensin II
(+)
Systemic arterioles
(+)
Releases
Aldosterone
Targets
Vasoconstriction;
peripheral resistance
Kidney tubules
Vasodilation of
afferent arterioles
GFR
Na+ reabsorption;
water follows
(+) Stimulates
((–)) Inhibits
Increase
Decrease
Blood volume
Systemic
blood pressure
Myogenic mechanism
of autoregulation
Tubuloglomerular
mechanism of
autoregulation
Intrinsic mechanisms directly regulate GFR despite
moderate changes in blood pressure (between 80
and 180 mm Hg mean arterial pressure).
Hormonal (renin-angiotensin)
mechanism
Neural controls
Extrinsic mechanisms indirectly regulate GFR
by maintaining systemic blood pressure, which
drives filtration in the kidneys.
Figure 25.12
•FACTORS AFFECTING ARTERIOLES: oResting tone in the arterioles, maintained by intrinsic myogenic activity. oSYMPATHETICS
o innervate both afferent and efferent arterioles to cause vasoconstriction. ƒEpinephrine and Norepinephrine both cause vasoconstriction in the kidneys, ƒModerate sympathetic increase ‐‐‐‐‐‐> decrease RBF with little change in GFR. ƒLarge increase in sympathetics ‐‐‐‐‐‐> stop glomerular filtration entirely. g
y
p
ƒATRIAL STRETCH RECEPTORS have a more significant effect on the kidneys than the baroreceptors. oRENIN / ANGIOTENSIN II RENIN / ANGIOTENSIN II leads to vasoconstriction. ƒBiosynthetic Pathway: JGA Cells secrete Renin in response to low tubular osmolarity. ƒRenin converts Angiotensinogen ‐‐‐‐‐‐> Angiotensin I in the kidney. ƒACE converts Angiotensin
converts Angiotensin I ‐‐‐‐‐‐> Angiotensin
I ‐‐‐‐‐‐> Angiotensin II in the lungs. in the lungs
ƒANGIOTENSIN II: It causes water retention (reabsorption) by two mechanisms: ƒDirect action on tubules to promote Na+ and water reabsorption
ƒIndirect action on kidneys by stimulating Aldosterone secretion in adrenal cortex. oPROSTAGLANDIN E2 (PGE2): Vasodilator. Its release is stimulated by Angiotensin II, and it acts primarily on the afferent arteriole. oENDOTHELIN is released locally and causes vasoconstriction of primarily the efferent arteriole ‐‐‐‐‐‐> reduce RBF •RENAL AUTOREGULATION: The intrinsic response of the kidney to changes in blood pressure
changes in blood pressure, independent of innervation. oSmooth Muscle Smooth Muscle Myogenic
Myogenic Response: The smooth muscle response to pressure accounts for some of this autoregulation. oTUBULO‐GLOMERULAR
oTUBULO
GLOMERULAR FEEDBACK:
FEEDBACK: Macula Densa
Macula Densa senses changes in the tubular fluid flow rate
senses changes in the tubular fluid flow rate
and modifies the arterioles accordingly. ƒA higher arterial blood pressure will lead to higher tubular fluid flow: MABP ‐‐‐‐‐‐> Capillary Pressure ‐‐‐‐‐‐> Tubular Flow ‐‐‐‐‐‐> Macula Densa senses the higher tubular flow ‐‐‐‐‐‐> Resistance in Afferent Arteriole ‐‐‐‐‐‐>Blood pressure ff
l
l d
ƒThis feedback is on a per‐nephron basis. Macula Densa cells will affect the resistance only in the afferent arteriole of that local nephron. Macula Densa
Densa may sense Na
may sense Na+ or Cl
or Cl‐ concentration. We don
concentration. We don'tt know for sure what it senses know for sure what it senses
ƒMacula
Role of urea in concentrating urine
Urea very useful in concentrating urine.
High protein diet = more urea = more concentrated
urine.
urine
Kidneys filter, reabsorb and secrete urea.
Urea excretion rises with increasing urinary flow.
Urea recycling
Urea toxic at high levels,
but can be useful in
small amounts.
Urea recycling causes
buildup of high [urea] in
inner medulla.
medulla
This helps create the
osmotic gradient at loop
of Henle so H2O can be
reabsorbed.
A Summary
S
of Renal
Function
Figure 26.16a
Regulation--Mineralocorticoids
Regulation
Sti li ffor RRenin
Stimuli
i SSecretion
ti
1.. Ø b
blood
ood pressure
p essu e
2. Ø serum Na
3. Ø blood volume
4 ANS stimulation
4.
i l i
Regulation-Mineralocorticoids
Regulation-Mineralocorticoids
Actions of Angiotensin II
1. Direct arteriolar vasoconstrictor
2 Stimulus to aldosterone secretion
2.
Figure 26.1
Figure 26.2
Figure 26.3
Figure 26.4
Figure 26.5
Figure 26.6
Figure 26.7
Figure 26.8
Figure 26.9
Figure 26.10
Figure 26.11
Figure 26.12
Figure 26.13
Figure 26.14
Table 23.1.1
Table 26.1.2
Table 26.2.1
Table 26.2.2
Normal Constituents of Urine
Urea – from metabolism of amino acids
Creatinine – from creatine metabolism
Uric acid – from
f
catabolism off nucleic acids
Urobilinogen – breakdown of hemoglobin
Hippuric acid, indican, and ketone bodies
Other substances and inorganic molecules
Inulin clearance