Download Renal blood flow (RBF)

Formation and Excretion of Urine
outline
I.
Functional renal anatomy
II.
Renal blood flow
III.
Glomerular filtration
IV.
Transport in the renal tubule and collecting duct
V.
Urinary concentration and dilution
VI.
Regulation of urine formation
VII. Clearance
VIII.Renal regulation of acid-base balance
IX.
Micturition
Excretion pathway
Respiratory system
Large intestine
Skin
Kidney
Excretory Approach
Urinary System
General principles
Kidney Functions**
• Kidneys regulate water and electrolyte levels.
• Kidneys regulate acid-base balance.
• Kidneys excrete metabolic waste products and foreign
substances.
• Hormones produced are angiotensin Ⅱ,1, 25dihydroxyvitamin D3, aldosterone and
erythropoietin(EPO).
Body water homeostasis (balance)
I.
Functional renal anatomy
• The nephron is the basic subunit of the kidney. It is
composed of two components: the glomerulus and the renal
tubule.
• Renal arterioles lead to glomerular capillary tufts, which are
the site of blood filtration.
• Bowman’s capsule receives this filtrate, which is modified
as it passes along the kidney tubules.
• A single kidney is divided into four major sequential
sections:
Proximal tubule, loop of Henle, distal tubule, and collecting
duct, each with unique characteristics.
• Capillaries surround kidney tubules enabling exchange
between blood and tubular fluid.
1.Basic kidney structure
2. Nephron structure
Renal Tubules
Nephron is composed of two components: the glomerulus and the renal tubule.
Nephron structure
Nephron is composed of two components:
the glomerulus and the renal tubule.
Nephrons can reach to
renal medulla
• Cortical nephron
• The nephrons have their glomeruli located in the
outer and middle portion of the renal cortex are
called cortical nephrons.
• Juxtamedullary nephron
• The nephrons have glomeruli that lie deep in the
renal cortex near the medulla and have long loops
of Henle that are deep into the medulla are called
juxtamedullary nephron.
3. Glomerulus
— Called Capillary Tufts
Under the Electronic
Microscope
Glomerulus
Blood Out
Blood In
Relationship visualized as a fist
(Glomerulus, in) and a balloon
(Bowman`s capsule, out)
juxtaglomerular apparatus
• The juxtaglomerular apparatus consists of
the juxtaglomerular cells, the macula densa
and the extraglomerular mesangial.
juxtaglomerular cell
• The juxtaglomerular cells are specialized
myoepithelial cells in the media of afferent
arteriole close to the glomerulus.
Juxtaglomerular apparatus
– JG cells can secrete Renin.
– JG cells serve as baroreceptor in afferent arteriole.
4. Glomerular filtration membrane
The epithelial cells
of Bowman`s
capsule called
Space
porous
• Glomerular filtration membrane
• The barrier between the capillary blood and
the fluid inside the Bowmen's capsule is
called glomerular filtration membrane.
Glomerular filtration membrane
Glomerular filtration membrane is
impermeable to blood cell and plasma
protein.
Pores
5. Renal tubule
The renal tubule is divided into
four sections: proximal tubule,
loop of Henle, distal tubule and
collecting duct.
（Glomerulus ）
renal
corpuscle
(Bowman capsule)
proximal
convoluted
tubule
proximal
tubule
Nephron
renal tubule
henle loop
distal tubule
Collecting
duct
distal
convoluted
tubule
II. Renal blood flow (RBF)
Renal blood flow distribution
95%
Renal blood flow (RBF)
Renal blood flow distribution
1. A second capillary networks called
the peritubular capillaries
a first capillary
network
a second capillary
network
These capillaries surround specific
segments of the tubule, and they return
water and substances reabsorbed by
the tubule to the general circulation, as
well as deliver needed nutrients to the
tubule.
Peritubular capillaries
Under the electronic microscope
Higher plasma colloid osmotic pressure in the peritubular
capillaries is in favor of tubular reabsorption.
2. vasa recta
3. Characteristics of renal blood flow **
! Large blood flow：400 ml/min·100g
Renal blood volume
! Maldistribution of blood flow ：
renal papilla (1%) ＜renal medulla (5%)＜renal cortex (94%)
! Primary and secondary capillary networks
# glomerular capillary network (primary network)
(between afferent glomerular arteriole and efferent glomerular arteriole,
high blood pressure，in favour of glomerular filtration)
#peritubular capillary network (secondary network)
(made by branch of efferent glomerular arteriole, low blood pressure, in
favour of tubular reabsorption)
Autoregulation of renal blood flow
Tubuloglomerular feedback
Nervous and humoral regulation
4. Determinants and regulation of RBF
• RBF is determined by systemic arterial blood
pressure and renal vascular resistance (renal
sympathetic vasoconstrictor nerve control).
• RBF demonstrates autoregulation.
• Autoregulation involves afferent not efferent
arterioles.
• Autoregulation is explained either by the myogenic
hypothesis or tubuloglomerular feedback.
Autoregulation of RBF and GFR
Autoregulation means simply regulation of blood flow by
Rena the tissue itself. Whenever on excessive amount of blood
l
flows through a tissue., the local vasculture constricts and
Bloo
decreases the blood flow forward to normal.
d
Flow
or
Glo
meru
lar
Filtra
tion
Rate
Glomerular Filtration Rate
Renal Blood Flow (RBF)
80
150
Systemic Arterial Pressure (mm Hg)
The kidney maintains a constant blood flow (autoregulation) and
glomerular filtration rate over the physiological range of systemic
arterial pressure.
Autoregulation of RBF and GFR
Mechanism
of autoregulation
Two hypotheses describe autoregulation:
myogenic and tubuloglomerular feedback.
•1.The myogenic hypothesis: When systemic arterial pressure increases RBF,
the afferent arterioles are stretched. This stretch stimulates them to contract
increasing their resistance and maintaining a constant RBF. If RBF
decreased, then the opposite would occur.
•2. Tubuloglomerular feedback involves an interaction between the distal
tubules and the afferent arterioles. The beginning portion of the distal tubule
passes close to the afferent arteriole, and together they form a specialized
structure called the juxtaglomerular apparatus. Specialized epithelial cells in
this portion of the distal tubule, called macula densa cells, sense the amount
of NaCl (sodium chloride) in the tubular fluid. With an increase in RBF there
will be an increase in GFR, an increase in filtration, and an increase in the
amount of NaCl passing by the macula densa cells. In response to this
increased NaCl, a yet unidentified substance is released that causes afferent
arteriolar constriction. This constriction reduces RBF, GFR, and the amount
of NaCl delivered to the macula densa cells. If RBF were to decrease, then
the opposite would occur.
Tubuloglomerular feedback
NaCl
NaCl
5. Nerve innervation of kidney
Renal sympathetic vasoconstrictor nerve
control the smooth muscle of afferent glomerular arteriole
and efferent glomerular arteriole, renal tubule and
juxtaglomerular cell.
– Vasoconstriction and RBF regulation
– Increased reabsorption of Na+、Cl-, etc., in the renal
tubular epithelial cell
–control juxtaglomerular cell to release renin
Kidney have no vagus nerve fibers innervation
Renal afferent nerve fibers act on mechanical and
chemical stimulation toward central nervous system.
Process of urine formation
Three steps:
Glomerular filtration
Renal tubule/collecting duct
reabsorption
Renal tubule/collecting duct
secretion and excretion
Material transport of renal
tubule/collecting duct
III. Glomerular filtration
Glomerular filtration rate (GFR)
Effective filtration pressure (EFP)
Factors affecting glomerular filtration rate
Regulation of GFR
Interaction between renal blood flow (RBF)
and GFR
Basic renal terminology *
• Glomerular filtration rate (GFR) is the amount of fluid
moving into Bowman’s capsule per unit time (min).
• Renal blood flow (RBF) is the amount of blood flowing
through the kidney per unit of time (min).
• Filtration is the process by which substances enter
Bowman’s capsule.
• Reabsorption is the process by which substances move
from inside to outside the tubule.
• Secretion is the process by which substances move from
outside to inside the tubule.
• Excretion refers to substances that pass from the kidney
into the bladder.
• it is the ability of the kidney to selectively move specific
substances into and out of the tubule in a very controlled
and coordinated manner that makes normal kidney function
so critical to life.
Explanation for some terms
1. Glomerular filtration rate (GFR)
•Glomerular filtration*
Filtration is the process by which substances enter
Bowman’s capsule.
•Glomerular filtration rate, GFR*
It is the amount of fluid moving into Bowman’s capsule per
unit time (min).
•glomerular filtration fraction, GFF*
The glomerular filtration fraction is the filtration rate as
percentage of the total renal plasma flow that passes
through both kidneys.
2. Factors affecting glomerular filtration rate
•
Effective filtration pressure
•
Filtration coefficient，Kf
(1) Glomerular effective filtration pressure
•The effective filtration pressure of glomerulus
represents the sum of the hydrostatic and
colloid osmotic forces that either favor or
oppose filtration across the glomerular
capillaries.
Formula*:
Effective
filtration pressure
＝
Glomerular
capillary pressure
－（
Plasma colloid
osmotic pressure
＋
intracapsular
pressure
）
(2) Filtration coefficient，Kf
•Under the effective filtration pressure (EFP) driving force,
liquid volume passing through filtration membranes per
unit time.
•Two determinants of Kf：
filtration membranes area (s)
permeability coefficient of filtration membranes (K)
Kf = k× s
3. Factors affecting glomerular filtration**
 Change
of effective filtration pressure
 Change of filtration coefficient
GFR＝ Kf × S × （PGC－πGC－PBC）
EFP
GFR: glomerular filtration rate
S:
Kf :
PGC: glomerular capillary pressure
permeability coefficient
glomerular filtration membrane area
πGC: plasma colloid osmotic pressure PBC: hydrostatic pressure in bowman

Changes in renal blood flow
Determinants and regulation of GFR and RBF
• GFR is determined by the balance of forces acting across the
filtration membrane. The forces that drive fluid out of the glomerulus
are the capillary blood pressure (PGC) and the osmotic pressure (∏BC)
of the fluid in Bowman’s capsule. The forces driving fluid into the
glomerulus are the hydrostatic pressure (PBC) of the fluid in
Bowman’s capsule and the osmotic pressure (∏GC) of the blood
within the glomerulus. The difference between these four forces
determines the net filtration pressure, which is approximately 15 mm
Hg.
• Net filtration pressure* = (PGC +∏BC) － (PBC +∏GC)
= (55+0)－(15+25) = 15 mm Hg
∏BC is zero. Explanation
• Filtration coefficient (Kf), a factor reflects permeability of filtration
membrane.
Net filtration pressure
4. Regulation of GFR
•Changes in systemic arterial pressure, the radius of the renal
arterioles, and the filtration coefficient normally regulate
GFR.
1. If systemic arterial pressure increases, then the pressure
in the glomerular capillaries will increase and GFR will
increase. The opposite will happen if systemic arterial
pressure decreases.
2. Renal arteriolar resistance. (see next illustration)
3. Filtration coefficient—The filtration coefficient can be
altered by the contractile activity of an additional set of cells
located among the podocytes. These cells are called
mesangial cells. These cells can be stimulated to contract,
and when this occurs they decrease the area available for
filtration and thus decrease the filtration coefficient and GFR.
4. Clinic diseases:
Starvation / Burn → GFR↑,Renal Stones → GFR↓
5. Interaction between RBF and GFR
As discussed above, an increase in efferent arteriolar
resistance produces opposite effects on RBF and GFR.
RBF decreases and GFR increases. Under normal
situations, blood leaving the glomerular capillary bed is at
a higher osmotic pressure (∏GC) than the blood entering
because of the fluid lost as ultrafiltrate. This rise in ∏GC is
not sufficient to significantly limit GFR.
However, with a large increase in efferent resistance,
RBF is reduced enabling ∏GC to increase to such an
extent that GFR is reduced. Therefore, GFR does not
increase as much as expected with an increase in efferent
arteriolar resistance because of the relationship between
GFR, RBF, and ∏GC.
Regulation of GFR with different arteriolar
diameters
PGC
Decreased Afferent
Arteriolar Diameter
GFR
Glomerular Capillary
PGC
Decreased Efferent
Arteriolar Diameter
GFR
Changes in arteriolar resistance before (afferent) and after (efferent) the
glomerular capillary bed have different effects on capillary hydrostatic
pressure (PGC) and therefore on glomerular filtration rate (GFR).
Effects of different arteriolar resistance
on GFR
Effects of different arteriolar resistance
on GFR
Effects of different arteriolar resistance
on GFR
Effects of different arteriolar resistance
on GFR
Nervous and humoral regulation of RBF and GFR
Nervous regulation：
Renal sympathetic nerve:
Hypovolemia, noxious stimulation or agitation, etc.→sympathetic
nervous activity↑→ afferent glomerular arteriole contraction→
RBF
and GFR↓;
Hypervolaemia→sympathetic nervous activity ↓ → afferent glomerular
arteriole dilatation → RBF and GFR↑.
Humoral regulation：
epinephrine, norepinephrine, vasopressin, angiotensinⅡ
— Renal vasoconstriction decreases RBF.
prostaglandin, NO, ANP, bradykinin, endothelin
— Renal vasodilatation increases RBF.
Summary
• Urine formation starts with the filtration of plasma in the
kidney.
• Glomerular filtration is favored by the high hydrostatic
pressure of the blood in the glomerular capillaries and is
opposed by the hydrostatic pressure in the urinary space of
Bowman’s capsule and by the glomerular capillary colloid
osmotic pressure.
• Glomerular filtration is rather nonselective; proteins are
mostly retained in the plasma by the glomerular barrier, but
all low-molecular-weight substances are freely filtered.
• Key terms: GFR, EFP, FF, Autoregulation
IV.
•
•
•
•
•
Transport in the renal tubule and collecting duct
1. Overview of tubule properties
Permeability properties of the luminal and basolateral
membranes of the epithelial cells lining renal tubules are
different, enabling directional movement of salt and water.
Proximal tubule reabsorbs isotonically a constant 60% of
the GFR.
Loop of Henle reabsorbs more salt than water.
Distal tubule continues to reabsorb more salt than water.
Permeability of the collecting duct to salt and water is
hormonally controlled by antidiuretic hormone (ADH) and
aldosterone. [dilute urine / concentrated urine]
Reabsorption and secretion in the renal tubule and
collecting duct
Definition
•Transport
• ! Renal tubular reabsorption*
Tubular reabsorption denotes the transport of substances
from the tubular fluid through the tubular epithelium into
peritubular capillary blood.
• ! Secretion of the renal tubule and collecting duct
Product made by epithelial cells itself or blood substance
are transported into renal tubular lumen.
•Transport patterns：
! Passive transport：
diffusion, permeation, facilitate diffusion, solvent daggling
! Active transport：
sodium pump, hydrogen pump, calcium pump (symport
or antiport)
•Transport pathway:
– Paracellular pathway
– transcellular pathway
2. Reabsorption of the renal tubule and collecting duct
General situation
• Proximal tubule reabsorbs 67%of the filtered Na+, Cl- and
H2O
• Proximal tubule is the only site for glucose reabsorption
• Loop of Henle reabsorbs 20% of the filtered Na+ and Cl-
• The luminal cell membrane of the thick ascending limb
contains a Na+-k+-2Cl- cotransporter
• The distal tubule and collecting duct reabsorb 12% of the
filtered Na+ and Cl-
Renal tubule reabsorption of
salt and water
3. Proximal tubule reabsorption of
salt and water
• NaCl reabsorption is dependent upon the coordinated
action of the Na-K-ATPase on basolateral membrane of
the epithelial cell and several facilitated transport
systems on the luminal membrane of the epithelial cell.
• Water reabsorption follows and is dependent upon Na
ion reabsorption.
• Water reabsorption is assisted by the elevated
osmolarity of the peritubular capillary blood.
Proximal tubule reabsorption of salt and
water
Proximal Tubular Cell
Na+
B
L
O
O
D
Glucose & amino acids
Na+
ATP
K+
Cell 1
H+
Cell 2
Basal lateral
membrane
Na+
T
U
B
U
Water L
A
R
FL
UI
Luminal membrane
D
The major mechanisms by which molecules move across the epithelium of
the proximal tubule are diagramed in this figure.
Proximal tubule reabsorption of
+
Na
Proximal tubule reabsorption
of salt and water
4. Proximal tubule reabsorption of
glucose and amino acids
• Reabsorption of glucose and amino acids is
coupled to the reabsorption of Na ions.
• Glucose reabsorption is overwhelmed when
blood glucose is very high (diabetes).
[daiebi:ti:z, -ti:s]
Proximal tubule reabsorption
of glucose
Proximal tubule reabsorption
of glucose
Relationship between plasma glucose
and filtration rate of glucose
Relationship between plasma glucose
and reabsorption rate of glucose
Relationship between Plasma Glucose
and Excretion Rate of Glucose
renal glucose threshold*
When the plasma glucose concentration increases
up to a value about 180 to 200 mg per deciliter,
glucose can first be detected in the urine, this value
is called the renal glucose threshold.
Summary about Glucose
Graph Questions
5. Proximal tubule reabsorption
of bicarbonate ions
• Bicarbonate reabsorption requires Nadependent H ion secretion.
• Bicarbonate reabsorption occurs indirectly
through the formation of CO2 and H2O.
Proximal tubule reabsorption
of bicarbonate ions
B
L
O
O
D
Na+ + HCO3-
Na+
HCO3- + H+
H+ + HCO3-
H2CO3
CA
H2O + CO2
H2CO3
CA
CO2 + H2O
T
U
B
U
L
A
R
FL
UI
D
Reabsorption of bicarbonate ions in proximal tubule requires the formation and
breakdown of carbonic acid (H2CO3) within the tubular fluid and epithelial cells.
The enzyme carbonic anhydrase (CA) is essential for this process to occur.
Some diuretics work by inhibiting the carbonic anhydrase enzyme.
Proximal tubule reabsorption
of bicarbonate ions
6. Loop of Henle reabsorption of
salt and water
• Descending limb of the loop of Henle is
permeable to water but not to salt.
• Ascending limb of the loop of Henle is
permeable to salt, because of a Na-K-Cl ion
tritransporter, but not to water.
• Reabsorption of water from the descending limb
results from the reabsorption of salt by the
tritransporter in the ascending limb.
Loop of Henle reabsorption of
salt and water
Ascending limb of the loop of Henle: a Na-K-Cl ion
tritransporter for reabsorption of salt
Tubular
Lumen
Fluid
Blood
Na+-2Cl--K+
tritransporter
Tubule epithelial Cell
CELL
Place is the ascending limb of the loop of Henle
Counter-current multiplication
• An osmotic gradient is established in the interstitial
space surrounding the loop of Henle that increases
from the top to the bottom of the loop.
• The action of the tritransporter of the epithelial cells
of the ascending limb, the water permeability of the
descending limb, and the shape of the loop
contribute to the development of this osmotic
gradient.
• The process by which this occurs is called countercurrent multiplication.
Counter-current dissipation
Counter-current exchange
Counter-current multiplication
Assuming that initially all fluid within the loop
has the same osmolarity (panel A) the
tritransporter will reabsorb Na, K, and Cl from
the tubular fluid creating an osmotic gradient
of 200 mOsm between the interstitial space
and the tubular fluid. The ascending limb is
not permeable to water so water cannot
follow. The descending limb is not permeable
to salt so it cannot enter from the interstitial
space. However, the descending limb is
permeable to water so water is reabsorbed
into the interstitial space. A new steady state
is established (panel B). At this point new
fluid enters from the proximal tubule
displacing the fluid within the loop. This
disrupts the steady state (panel C).Through
the reabsorption of salt by the ascending
limb and water by the descending limb, a new
steady state is established (panel D). Notice
that an osmotic gradient is being established
in the interstitial space from the top to the
bottom of the loop. It is the result of the loop
structure and the different permeabilities of
the two limbs of the loop. Fluid leaving the
ascending limb is hypotonic compared to the
fluid entering because more salt than water is
reabsorbed. We will see in a later section that
the interstitial osmotic gradient is critical for
water reabsorption.
A
B
Equilibrium State
300
300 300
400 400
200
Water
300
Reabsorption
300 300
400 400
200
400 400
200
300
300 300
400 400
200
300
300 300
Na-K-Cl 400 400
Reabsorption
200
C
D
Equilibrium State
300 400
200
350 350
150
300 400
200
350 350
150
350 350
150
400 400
400
400
400
500 500
300
400
500 500
300
400
400
Increasing
Osmotic Gradient
The shape and permeability properties of the loop of Henle enable an osmotic gradient to be established
within the kidney. Diagrams A through D show in a step-wise manner how the gradient is established.
Counter-current exchange
of vasa recta
7. Distal tubule reabsorption of
salt and water
• More salt than water is reabsorbed.
• Na and Cl ions reabsorbed together.
The distal tubule retains some of the properties of
the ascending limb of the loop of Henle in that it is
not very permeable to water and reabsorbs Na and
Cl ions. The reabsorption of Na and Cl ions occurs
through a co-transport carrier protein on the luminal
side of the epithelial cell that combines the
movement of one Na and Cl ion into the cell. This
reabsorption is driven by the Na ion concentration
gradient established by the Na-K-ATPase on the
basal lateral side of the epithelial cell.
Distal tubule reabsorption of
salt and water
Tubular
Fluid
Tubule epithelial Cell
Lumen
Tubule epithelial Cell
Symporter
Tubule epithelial Cell
Blood
8. Collecting duct reabsorption
of salt and water
• The permeability of the collecting duct to Na
ions and water is variable.
• Antidiuretic hormone (ADH or Vasopressin,
VP) increases the permeability of the collecting
duct to water.
• Aldosterone increases the reabsorption of Na
ions by the collecting duct.
Collecting duct reabsorption
+
of Na
Tubular
Lumen
Fluid
Blood
Epithelial Cell of the Collecting Duct
Epithelial Cell of the Collecting Duct
Effect of antidiuretic hormone (ADH) on the
permeability of the collecting duct to water
ADH release
Epit
heli
al
Cell
of
the
Coll
ecti
ng
Duc
t
Concentrated Urine
Effect of antidiuretic hormone (ADH) on the
permeability of the collecting duct to water
ADH not release
Epit
heli
al
Cell
of
the
Coll
ecti
ng
Duc
t
Dilute Urine
Antidiuretic Hormone
(ADH or vasopressin, VP)
Mechanism of ADH or VP in the
collecting duct for water reabsorption
Antidiuretic hormone, also known as vasopressin, a posterior pituitary
hormone, increases the number of aquaporin channels in the membrane of
the epithelial cells increasing water reabsorption. In the presence of ADH,
water can leave the collecting duct in response to the osmotic gradient.
Relationship between plasma osmolarity
and plasma vasopressin
Mechanism of aldosterone in the
+
collecting duct for Na reabsorption
Epithelial Cell of the Collecting Duct
Epithelial Cell of the Collecting Duct
Aldosterone,a hormone secreted by the adrenal cortex, acts on collecting duct
in several ways to increase Na reabsorption.
9. Collecting duct secretion of K
and H ions
•The collecting duct secretes both K and H ions.
•K and H ion secretion is sensitive to aldosterone.
K ions are secreted through channels located in the luminal
membrane of specialized epithelial cells of the collecting
duct called principle cells. This secretion is down a
concentration gradient established by the Na-K-ATPase
located on the basolateral membrane. In the presence of
aldosterone, more channels are opened and secretion is
increased.
Specialized cells of the collecting duct, called intercalated
cells, are responsible for H ion secretion. This secretion is
due to an active transport process that moves H ions from
the inside of epithelial cell to the tubular fluid. The activity of
this transporter is increased by aldosterone.
Collecting duct secretion of K
and H ions
Tubular
Lumen
Fluid
Epithelium of the Collecting Duct
principle cell
Channels
+ aldosterone
Cl-
intercalated cell
+
aldosterone
Epithelium of the Collecting Duct
Blood
10. NH3 secretion is related to H+and HCO3transport
• 60% of NH3 secretion
from glutaminate ,
40%from glycine
• NH3 secretion promotes
H+ secretion and HCO3reabsorption, in favor of
renal acids excretion and
alkaline reabsorption.
NH3
NH4
NH3
V.
Urinary concentration and dilution
• Urinary dilution
• Urinary concentration
• The loops of Henle are countercurrent
multipliers
• The vasa recta are countercurrent exchangers
• Urea plays a special role in the concentrating
mechanism
1. Overview
• urinary concentration
• The basic requirements for forming a concentrated urine
are a high level of ADH and a high osmolarity of the renal
medullary interstitial fluid.
• urinary dilution
• The mechanism for forming a dilute urine is continuously
reabsorbing solutes from the distal segments of the
tabular system while failing to reabsorb water.
Urinary concentration and dilution
2. Definition
• Plasma osmotic pressure (POP)：300 mmol/L（
300mOsm/kg H2O）
• Urine osmotic pressure＞POP, hypertonic urine
—Concentrated urine, 1200 mmol/L
• Urine osmotic pressure ＜POP, hypotonic urine
—Diluted urine, 50 mmol/L
• Urine osmotic pressure =POP, isosthenuria
—Urinary concentration and dilution of kidney is
damaged.
3. Mechanism of urinary concentration and dilution
• Urinary concentration
Forming mechanisms of hypertonicity in the medulla
Countercurrent multiplication of Henle's loop
Countercurrent exchange of vasa recta
Counter-current theory
vasa recta
• Countercurrent multiplication
• Countercurrent multiplication is the process
where by a small gradient established at
any level of the loop of Henle is increased
(multiplied) into a much larger gradient
along the axis of the loop.
Process of urinary concentration and dilution
VI. Regulation of urine formation
•
•
•
•
•
•
Autoregulation of urinary formation
Glomerulotubular banlance
Effect of renal sympathetic nerve
Effect of antidiuretic hormone
Renin-angiotensin-aldosterone system
Effect of atrial natriuretic peptide
1. Regulatory patterns and Significance
•Regulatory patterns:
Autoregulation
Nervous regulation
Humoral regulation
•Significance：
Maintenance of internal environment
homeostasis.
2. Autoregulation in kidney
• osmotic diuresis
– Solute concentration of renal tubular fluid
– Mannitol
（clinic use）
– Different from water diuresis *
The volume of urine increases when water intake
exceeds body needs, it is resulted from suppression of
ADH secretion.
• Glomerulotubular balance
• One of the most basic mechanisms for controlling tubular
reabsorption is the intrinsic ability of the tubules to increase
their reabsorption rate in response to increased tubular
inflow. This phenomenon is referred to as glomerular-tubular
balance.
3. Nervous regulation
• Renal sympathetic nerve
– αreceptor activation contracts afferent and efferent
glomerular arteriole inducing decreased RBF and GFR .
– αreceptor activation increases proximal convoluted tubule
reabsorbing Na+ and other solutes;
– β receptor activation promotes juxtaglomerular cell releasing
renin;
• Homeostasis of Na+and water maintained.
• Renal sympathetic nerve involved in reflex:
– cardiopulmonary receptor reflex;
– Kidney – Kidney reflex.
4. Humoral regulation
• Renin-angiotensin-aldosterone system，RAAS
• Renal kallikrein-kinin system
• Atrial natriuretic peptide，ANP
• Endothelin，ET
• Nitric oxide，NO
• Vasopressin，VP
Antidiuretic hormone，ADH
• Catecholamine, CA
• Prostaglandin, PG
Renal regulation of salt and water
balance
Sensing alterations in salt balance
• Salt balance, principally NaCl concentration, is
assessed by monitoring osmolarity.
• Salt levels are changed by adjusting water
reabsorption through the action of antidiuretic
hormone (ADH).
• ADH* increases the number of open aquaporin
channels in the collecting duct thereby
increasing water reabsorption.
Renal regulation of salt and water balance
[NaCl]o↑
Cells shrink
Signal to
Sensing alterations in water balance
• Water balance is assessed by monitoring blood volume
through changes in blood pressure.
• Water levels are changed by adjusting salt reabsorption
through the renin-angiotensin-Ⅱ-aldosterone system.
• Increased sympathetic nerve stimulation directly
increases renal secretion of renin.
• Decreased distal tubule Na-load directly stimulates renal
renin secretion.
• Increased volume stimulates the secretion of atrial
natriuretic peptide form the atria.
Sensing alterations in water balance
Sensing alterations in water balance
Renin-Angiotensin-Ⅱ-Aldosterone
system (R-A-A-S).
+
Increased sympathetic nerve stimulation directly increases
renal secretion of renin.
Angiotensin-Ⅱalso directly stimulates Na+
reabsorption by cells of the proximal tubule.
-
Effects of ANP on kidney
• Dilatation of afferent glomerular arteriole increases GFR and
Na+ in tubular fluid;
• Inhibiting Na+ channel on the collecting duct epithelium with
help of cGMP decreases Na+ and water reabsorption at the
collecting duct;
• Inhibiting renin release reduces ANGⅡ and aldosterone
secretion, then indirectly inhibits Na+ reabsorption
• Inhibiting ADH secretion induces kidney water drain
increasingly.
Sensing alterations in water balance
Renal regulation of salt and water balance
── Relationship of osmolarity and volume
5. Reflex response to dehydration*
Dehydration results from an imbalance between water
intake and water loss
• Dehydration initiates reflexes to conserve both salt
and water .
• Dehydration reduces blood pressure , which
reduces GFR and RBF independent of other factors.
• Baroreceptor-regulated increased sympathetic
nerve activity activates the renin-angiotensin- Ⅱaldosterone system and decreases GFR and RBF.
• Osmoreceptors stimulate the release of ADH.
• Sense of thirst is stimulated.
Reflex response to dehydration *
With sweating (running) induced dehydration→water volume↓and
osmolarity↑→blood pressure↓→GFR,RBF↓→water and salt excretion↓
Blood pressure↓→baroreceptor –mediated reflex response→
sympathetic nerve activity↑→R-A-A-S↑→water and salt
reabsorption↑→diminish dehydration
Sympathetic nerve activity↑→afferent arteriolar constriction→
GFR,RBF↓→ diminish dehydration
Blood pressure↓→GFR and the distal tubule Na﹢load↓→The distal
tubular epithelial cells stimulate→renin↑→R-A-A-S↑
Extracellular osmolarity↑→ADH release↑→water reabsorption↑
Water volume↓and osmolarity↑→thirst occurs→drink water
VII. Renal clearance
Research method of kidney function
Renal clearance **
•The volume of plasma per unit time needed
to supply its quantity of substance excreted
in the urine per unit time.
Clearance*
•
•
•
•
Clearance used to measure GFR and RBF
Clearance is based on the principle of conservation
of mass.
Clearance is the volume of blood per unit of time
that had all of a particular substance removed by
the kidney.
The clearance formula is Cx = (VU×[X]U) / [X]p
The clearance of substances with specific
properties enables one to determine GFR and RBF.
Clearance for use
1 g/mL
Glomerular Capillary
Efferent Arteriole
Afferent Arteriole
Bowman`s
Capsule
125 mL/min
125 g/min
Proximal Tubule
Peritubular
Capillary
1 mL/min
125 g/mL
125 g/min
Urine
×
This figure illustrates the principle of
clearance and how it can be used to
determine glomerular filtration rate.
Clearance = GFR
• Creatinine, that is normally present in the blood
and is not reabsorbed and minimally secreted
by the kidney. By measuring urine flow rate and
the concentration of creatinine in the blood and
urine, the GFR can be calculated. Because of
the characteristics of creatinine, you can say
that the clearance of creatinine is the GFR.
• The clearance equation: Cx = (VU×[X]U) / [X]p
Urea clearance
Glucose clearance
Penicillin clearance
Clearance for use
• The clearance equation can also be used to
calculate renal plasma flow (RPF) if a substance
with an additional property is used. This
additional property is that all of it needs to be
removed from the blood by the kidney through a
combination of filtration and secretion.
• Para-aminohippuric acid (PAH) clearance equals
the RPF.
• RBF = RPF / (1 - Hct). (hematocrit, Hct)
Significance of renal clearance
•Estimate renal function;
•Determine glomerular filtration rate (GFR )
•Determine renal blood flow (RBF)
•Presume renal tubular transport effect
•Free-water clearance
Afferent arteriole
•微穿刺和微
灌流技术
Bowman
capsule
Distal convoluted tubule
Efferent arteriole
Glomerulus
•（micropuncture）
VIII. Renal regulation of acid-base
balance
General considerations
• Metabolism of food generates acid.
• Acid in the body is in two forms: fixed and
volatile.
• Kidneys remove excess fixed acid; lungs
remove excess volatile acid.
• Acidemia is excess H ions in the blood;
alkalemia is excess bicarbonate ions in the
blood.
Renal regulation of acid-base balance
• Normal Blood pH Value 7.35－7.45
• CO2 + H2O
H2CO3
H+ + HCO3-, H+ is volatile acid
• Increasing ventilation will blow off more CO2 driving the reaction to
the left and lowering the H+ concentration.
• Decreasing ventilation will allow CO2 to accumulate driving the
reaction to the right and increasing the H+ concentration.
• Other acids named fixed acids. (such as sulfuric and phosphoric
acids ).
• Kidneys role (keeps appropriate level of bicarbonate ions / excretes
the fixed acids produced by the body / secretes hydrogen ions).
• Lungs role (ventilation controls CO2 adjusting [H+] ).
• When the blood contains excess H ions the condition is called
acidemia (acidosis ). Diarrhea
• When the blood contains excess bicarbonate ion, the condition is
called alkalemia (alkalosis). Vomiting
Renal regulation of acid-base balance
Renal production of bicarbonate ions
• The kidney produces bicarbonate through the
formation of titratable acid.
• The kidney produces bicarbonate through the
metabolism of glutamine.
Renal production of bicarbonate ions
(Disodium salts) Na2HPO4
T
Renal Tubular
Na++NaHPO4- U
Epithelial Cell
Glutamine →NH3
B
NH3+H+
Na+
U
L
+
+
+
H
HCO3 + H
H
H + NaHPO4
A
Carbonic acid
R
(Monosodium
salts)
NaH
PO
2
4
(H2CO3)
FL
UI
Urine
Formation of titratable acid in the proximal tubule is one way by whichD
the kidney
B
L
O
O
D
generates new bicarbonate ions in response to acidemia. The H+ ion secreted by the
epithelium is excreted as NaH2PO4 (titratable acid) leaving a bicarbonate ion behind.
Renal production of bicarbonate ions
Renal production of bicarbonate ions
Tubular
Lumen Fluid
Epithelium of the Collecting Duct
Blood
(New HCO3- )
Epithelium of the Collecting Duct
Renal production of bicarbonate ions
Renal secretion of H ions
Tubular
Lumen
Fluid
Epithelium of the Collecting Duct
principle cell
Blood
[H+]=4×10-8 M
pH=7.4
Channels
+ aldosterone
Cl-
Pump
[H+]=3×10-5 M
intercalated cell
+
aldosterone
pH=4.5
Epithelium of the Collecting Duct
• H ion secretion in the collecting duct leads to acidification of the urine.
• Collecting duct H ion secretion is stimulated by aldosterone.
Renal compensation for alkalemia
When the blood contains excess base, the kidney
excretes bicarbonate and does not generate
additional
bicarbonate.
Increase
bicarbonate
excretion occurs because there are insufficient H
ions to be secreted by the proximal tubules to
reabsorb all the filtered bicarbonate. The excess
bicarbonate is excreted. Also, the low level of H ions
means that filtered sulfuric and phosphoric acids will
not be titrated and so no additional bicarbonate will
be generated. In these ways, the kidney attempts to
lower
the
blood
bicarbonate
concentration
compensating for the alkalemia.
Renal compensation for alkalemia
Renal compensation for acidemia
When the blood contains excess H ions, the kidney
excretes H ions and generates additional bicarbonate. In the
presence of excess H ions, there are plenty of H ions to
reabsorb all the filtered bicarbonate. In addition, the filtered
fixed acid will be titrated generating additional bicarbonate
ions. Also, the excess H ions stimulate the metabolism of
glutamine by the kidney and the production of even more
bicarbonate. Finally, the collecting duct increases its
secretion of H ions. The combined effects of complete
bicarbonate reabsorption , new bicarbonate generation, and
the secretion of H ions helps the body compensate for the
acidosis.
Renal compensation for acidemia
concentration
Relationship Between plasma K Ion
Concentration and Acid-base Status
• Increase in plasma
levels can lead
to acidemia.
• Increase in plasma H+ levels can lead
to hyperkalemia.
• Plasma K+ levels can compromise the
+
ability of the kidney to regulate H
excretion.
+
K
A relationship exists between the K and
the H ion levels of the blood
• [ K+]o↑(hyperkalemia) → [ K+] into cells↑→H+ leaves cells to
blood for countering K+ into the cell→ [plasma H+]↑→ acidemia.
• In an opposite manner, [ K+]o↓ (hypokalemia) →alkalemia.
• [plasma H+]↑(acidemia)→K+ leave cells into blood→ [ plasma
K+]↑(hyperkalemia).
• In an opposite manner, [plasma H+]↓(alkalemia) → hypokalemia.
• Plasma K+ levels at the time of onset of either acidemia or
alkalemia affect the ability of the kidney to compensate for the
acid-base disturbance.
Renal handling of calcium and phosphate
Renal handing of calcium
• All segments of the nephron reabsorb calcium except the
descending limb of the loop of Henle.
• Calcium moves from the tubular fluid into the epithelial cells
by passive diffusion down a concentration gradient. On the
basal lateral side of the cells, it leaves either in exchange for
Na ions or by means of an ATP-requiring calcium efflux
pump.
• Reabsorption is influenced by parathyroid hormone (PTH)
and calcium levels.
• An increase in plasma calcium levels reduces Ca++
reabsorption , while an increase in PTH results in an
increase in Ca++ reabsorption.
Renal handling of calcium and
phosphate
Renal Handling of Phosphate
• Phosphate is reabsobed in the proximal tubule coupled with
sodium reabsorption.
• Phosphate reabsorption exhibits saturation.
• The maximum capacity of this reabsorptive system is close
to the amount of phosphate normally filtered.
• Parathyroid hormone (PTH) inhibits renal phosphate
reabsorption. PTH lowers the transport maximum of the Naphosphate co-transporter, reducing phosphate reabsorption
and increasing phosphate excretion.
IX. Micturition
Urinary excretion
Urinary excretion is the renal important
function for maintaining normal metabolism
and homeostasis of internal environment in
the human body.
Urinary excretion
Pr
es
su
re
in
th
e
Bl
ad
de
r(
c
m
H2
O
)
Bladder
Contractive Wave
Volume (mL)
Volume and Pressure Relationship Curve in the Bladder
Urinary excretion
Pr
es
su
re
in
th
e
Bl
ad
de
r(
c
m
H2
O
)
Volume (mL)
Volume and Pressure Relationship Curve in the Bladder
Reflex of urinary excretion
Reflex of urinary excretion
Clinic Problem is related to Reflex of Urinary excretion
Summary on renal physiology
Consideration after class
1. Please describe the uropoietic elementary process .
2. What are the influential factors of glomerular filtration？
3. Please describe main position , patterns and mechanism of
Na+ reabsorption.
4. Please describe physiological function and secretion
regulation of ADH.
5. Please describe physiological function and secretion
regulation of aldosterone.
6. What is the mechanism of water diuresis？