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Transcript
Renal Physiology
肾动脉
肾静脉
肾盂
输尿管
最新WHO
泌尿系统疾病发病率(%)
发展中国家
泌尿系统疾病
发达国家
19.7
7.8
泌尿系感染
9.6
2.0
肾炎
8.6
2.9
结石
1.3
2.0
肿瘤
0.4
0.4
多囊肾
0.4
0.1
结核
0.3
< 0.1
糖尿病肾病
0.2
0.2
慢性肾功能不全
0.3
0.1
发
展
中
国
家
发
达
国
家
慢性肾功能不全
糖尿病肾病
结核
多囊肾
肿瘤
结石
肾炎
泌尿系感染
泌尿系统疾病
0.0% 5.0% 10.0 15.0 20.0 25.0
%
%
%
%
• 评价:
发展中国家泌尿系统疾病发病率高,主要是高发
的泌尿系感染、急性肾炎、间质性肾炎、结核等,
其主要原因包括:
1. 感染性疾病未得到足够控制,导致泌尿系感染、
急性肾炎、间质性肾炎和结核的发病率高
2. 严重的环境污染和生活毒素未得到控制,导
致肾小球和肾间质炎症的发病率高,也与高
发的肾肿瘤有关
3. 对遗传性疾病缺乏生育控制,与多囊肾
等先天性疾病的多发有关
4. 社会医疗服务经费的缺乏,使得较多患
者的疾病发展到慢性肾功能衰竭
5. 透析和移植治疗的缺乏,使得慢性肾功
能衰竭不能得到纠正,引起更多的感染
和肿瘤发生
Overview of kidney function
• Excretion - the body substances of metabolic end
products and do not need to or surplus material
excreted process
• The kidneys process the plasma portion of blood by
removing waste materials that are either ingested or
produced by metabolism.
• In so doing, they perform a variety of functions.
Overview of kidney function
Urine:
color: pallideflavens
Specific gravity: 1.015~1.025
Osmotic pressure: higher than the plasma
pH:5.0~7.0
urine volume :1000-2000ml/24h,
Average :1500ml /24h
Polyuria :>2500ml
oliguresis :<100~500ml
anuresis : < 100ml
Major organ of the excretion
oxygen intake
food, water intake
Respiratory
System
Digestive System
nutrients,
water,
salts
elimination
of carbon
dioxide
oxygen
carbon
dioxide
Urinary
System
Circulatory System
water
solutes
elimination
of food
residues
rapid transport
to and from all
living cells
elimination of
excess water
salts, wastes
Excretion
Separating wastes & eliminating from body
 Organ systems –
Respiratory – CO2, H2O
Skin – H2O, inorganic salts, lactic acid, urea – sweat
Digestive – H2O, CO2, salts, lipids, bile pigments,
cholesterol,
Urinary – metabolic wastes, toxins, drugs,
hormones, salts, H+, H2O.

Kidney Function

Excretion of metabolic waste products and
foreign chemicals






Primary function
Regulation of water and electrolyte
balances
Regulation of body fluid osmolality and
electrolyte concentrations
Regulation of acid-base balance
Regulation of arterial pressure
Secretion
Kidney Function (continued)

Secretion
Renin
prostaglandin
1,25-dihydroxy vitamin D3
(calcitriol)
erythropoietin
Urine formation
• Three steps:
1. filtration of glomerulus ultrafiltrate formation
↓
2.Selective reabsorption of renal tubule and collecting duct
↓
3. Excretion of renal tubule and collecting duct
Introduction to the Urinary System
Structure of the Kidney
Nephron


Functional unit
of the kidney.
Consists of:
 Renal
corpuscle
 Renal
tubules:
 PCT.
 LH.
 DCT.
 CD.
Descending limb
Ascending limb
Nephron
glomerulus-------------------------
nephron
renal
Bowman capsule-------------------corpuscle
filtration
proximal
proximal convoluted limb
tubule
thick descending limb
thin segment
renal
thin descending limb loop of
tubule distal tubule thin ascending limb Renle
reabsorption
secretion
excretion
thick ascending limb
distal convoluted tubule
collecting duct --------------------------------
肾小球
(毛细血管球)
肾 小 体
肾小囊 (脏层、囊腔、壁层)
近曲小管
近端小管
肾 单 位
髓袢降支粗段
髓袢降支细段
肾小管
髓袢细段
肾
髓袢升支细段
髓袢升支粗段
脏
远端小管
弓形集合管
集合管
直集合管
乳头管
远曲小管
髓 袢
Types of Nephron

Cortical nephron:




Originates in outer
2/3 of cortex.
85% of all nephrons
Involved in solute
reabsorption.
Juxta medullary
nephron:



Originates in inner
1/3 cortex.
Important in the
ability to produce a
concentrated urine.
Has longer LH and
vasa recta.
Insert fig. 17.6
Cortical and Juxta medullary Nephron
皮质肾单位和近髓肾单位
项
目
皮质肾单位
近髓肾单位
肾单位数量
80-90%
10-15%
肾小球分布
皮质外1/3-2/3
皮质内1/3
肾小球体积
小
大
血管口径
入球〉出球小动脉2:1
入球〈出球小动脉
出球小动脉特点
为一支分布近、远段肾
小管周围
分两支分布近、远段肾
小管周围,另一支形成
U型直小血管
髓袢长度
短
长
近球小体
有
无
肾素颗粒
多
少
交感神经支配
分布入球小动脉
分布出球小动脉
血流量
多(〉90%)
少(〈10%)
功能特点
尿生成和肾素分泌
尿浓缩和稀释
Juxtaglomerular apparatus
•Juxtaglomerular cells smooth muscle on afferent and
efferent arterioles - dilate
and constrict arterioles;
renin secreted in response to
< BP
•Macula densa – patch of
dense epithelial cells in DCT
- monitor salinity of tubular
fluids
•
Juxtaglomerular Apparatus
• 主要分布在皮质肾单位,由近球细胞、系膜细胞和致密斑
组成
细
胞
位
置
功
能
接近肾小球的一段入球小动
脉中膜内
分泌肾素
致密斑细胞
远曲小管起始部(入、出球
小动脉)
Na+感受器,能感受小管液中
Na+量的变化,调节近球细胞
释放肾素
间质细胞
入、出球小动脉和致密斑细
胞之间的细胞
可能与传递信息有关
近球细胞
肾脏的神经支配
•T12-L2发出
•经腹腔神经丛支配肾动脉、肾
小管和颗粒细胞。
•肾交感神经末梢释放去甲肾上
腺素,调节肾血流量、肾小球滤
过率、肾小管重吸收和肾素释放。
•肾的各种感受器可经肾神经传
入纤维进入脊髓,并从脊髓投射
到中枢的不同部位。
The Blood Supply to the Kidneys
Blood flow to kidneys
is normally about 22%
of the cardiac output,
or 1200 ml/min.
Renal Blood Vessels
(continued)
Afferent arteriole:
Delivers blood into the glomeruli.
Glomerulus:
Capillary network that produces filtrate that enters the
urinary tubules.
Efferent arteriole:
Delivers blood from glomeruli to peritubular capillaries.
Peritubular capillaries:
Deliver blood to vasa recta.
Two Capillary Beds

Glomerular capillaries :
High hydrostatic pressure
--rapid fluid filtration


Peritubular capillaries:
Low hydrostatic pressure
 High plasma colloid osmotic pressure
--rapid fluid reabsorption

肾血流量及其调节
(一)肾脏的血液供应特点
血液供应量大:1200ml/min,占心输出量的1/5 - 1/4
分布不均匀:皮质 94% 外髓质5 - 6%
内髓质<1%
毛细血管两次分布:
肾动脉分支入球小动脉肾小球毛细血管
出球小动脉肾小管旁毛细血管
肾小球毛细血管内压较高,利于滤过
肾小管旁毛细血管血压较低,有利于重吸收
直小血管有利于维持髓质的高渗梯度
肾血流量的调节
• 自身调节: 动脉血压变动于80~180mmHg范围内
时,肾血流量保持相对恒定,肌原学说
• 意义:使肾血流量相对稳定,保证泌尿正常进行
神经调节:
a、交感神经在皮质肾单位的入球小动脉和近髓
肾单位的出球小动脉上分布密度大
b、兴奋时,肾血管收缩,血流量减少;冲动减
小时,肾血管舒张,肾血流量增加
体液调节:
E、NE、ADH、血管紧张素能使肾血管收缩,
肾血流量减少
PGI2、PGE2、NO和缓激肽等血管舒张
Urine formation
1.Glomerular filtration
2.Tubular reabsorption
3.Tubular secretion
Urine Formation by the Kidneys:
Glomerular Filtration
Urinary excretion
= Filtration – Reabsorption+Secretion
Renal handling of different substances
(creatinine)
(amino acids
glucose )
(electrolytes)
(Phenolphthalein,
penicillin, ammonia )
Glomerular filtration
-the first step in urine formation
Mechanism of producing ultrafiltrate
under hydrostatic pressure of the blood.

Process similar to the formation of
tissue fluid by other capillary beds.

Glomerular Filtration Membrane
Glomerular Filtration Membrane
(continued)
capillary endothelium:
 Endothelial capillary pores are large
fenestrate.
 Negative charge.
 Pores are small enough to prevent RBCs,
platelets, and WBCs from passing through
the pores.
Glomerular Filtration Membrane

Filtrate must pass through the
basement membrane:




(continued)
Thin glycoprotein layer.
Strong negative charges.
Can filter water and small solutes.
Podocytes:


Foot pedicels form small filtration
slits.
Passageway through which filtered
molecules must pass.
Except proteins and blood cells, other constituents, including
most salts and organic molecules, can through the filtration
membrane enter the glomerular capsule. So the filtered fluid
is essentially protein-free and devoid of cellular elements,
including red blood cells. The concentration of other
constituents are similar to the concentrations in the plasma.
Glomerular Filtration
Glomerular Filtration
Whether the substances can though
glomerular filtration membrane:
•
size
•
type of electric charge
Filterability of substances
Substance
Molecular Weight
Filterability
Water
18
1.0
Sodium
23
1.0
Glucose
180
1.0
5500
1.0
Myoglobin
17000
0.75
Albumin
69000
0.005
Inulin
Glomerular Ultrafiltrate

Fluid that enters glomerular capsule is
called ultrafiltrate.


Composition:



Water & some solutes from blood electrolytes, glucose, amino acids,
nitrogenous wastes, vitamins
no protein(Plasma proteins are excluded by
size and charge)
no RBC’s
Glomerular filtration rate(GFR)
GFR: Volume of filtrate produced by both
kidneys each minute.
 Averages 115 ml/min. in women;
125 ml/min. in men.
 180 L/day
 99% filtrate is reabsorbed
– 1-2 L excreted /day
Filtration fraction
FF: filtration rate as percentage of the
total renal plasma flow that pass
through the both kidneys.
Filtration fraction
=GFR / Renal plasma flow
=125 / (1200 x 55%)
=0.2
Formation of Interstitial Fluid
Net
filtration
pressure
=
Glomerular
hydrostatic
pressure
_
Bowman’s
capsule
pressure
_
Glomerular
colloid osmotic
pressure
Filtration balance
colloid osmotic pressure
capillary pressure
blood pressure(kPa)
Filtration
pressure
capsule pressure
afferent
arteriole
capillary length
efferent
arteriole
Factors controlling the GFR





Increased glomerular filtration
membranous pores increases GFR
Increased blood hydrostatic pressure
increases GFR
Increased Bowman’s capsule hydrostatic
pressure decreases GFR
Increased glomerular capillary colloid
osmotic pressure decreases GFR
Regulation of GFR

Vasoconstriction or dilation of the
afferent arterioles affects the rate
of blood flow to the glomerulus.


Affects GFR.
Mechanisms to regulate GFR:


Sympathetic nervous system.
Autoregulation.
Sympathetic activation



Produces powerful vasoconstriction of afferent
arterioles
 Decreases GFR and slows production of filtrate
Changes the regional pattern of blood flow
 Alters GFR
Stimulates release of renin by JGA
Sympathetic Regulation of GFR

Stimulates
vasoconstriction of
afferent arterioles.


Preserves blood volume
to muscles and heart.
Cardiovascular shock:


Decreases glomerular
capillary hydrostatic
pressure.
Decreases urine output
(UO).
Renal Autoregulation of GFR

Ability of kidney to maintain a constant
GFR under systemic changes.



Achieved through effects of locally produced
chemicals on the afferent arterioles.
When MAP drops, afferent arteriole
dilates.
When MAP increases, vasoconstrict
afferent arterioles.
Autoregulation of renal plasma flow
and glomerular filtration rate
Autoregulation of renal blood flow

Ability of kidneys to maintain a stable GFR in
spite of changes in BP

Juxtaglomerular cells ––– renin secreted
from cells in response to drop of

BP
Macula densa ––– monitor salinity of tubular
fluids

High GFR
= high NaCl  macula densa causes
constriction of afferent arteriole
 GFR decrease
Tubulo-glomerular feedback:
Increased flow of filtrate sensed
by macula densa cells in thick
ascending LH.

Signals afferent arterioles to
constrict.

The Response to a Reduction in the GFR
Urine Formation by the Kidneys:
Tubular Processing of the
Glomerular Filtrate
Functions of Tubule
•Tubular reabsorption
highly selective
quantitatively large
•Tubular secretion
Tubular reabsorption
Manner:
•Active transport
primary active transport: Na+, K+, Clsecondary active transport:
glucose, amino acid
•Passive transport:
H2O, Cl-, HCO3-
Filtrate
side
Tubular cells
Capillary
Tight
junction
Direction of
reabsorption
Apical
membrane
Active
transport
Proximal Tubular Reabsorption



About 65% -70% of the filtered load of sodium
and water and a slightly lower percentage of
filtered chloride are reabsorbed.
 Passive water reabsorption by osmosis is
coupled mainly to sodium reabsorption.
 Reabsorption of chloride, urea, and other
solutes by passive diffusion
Essentially all the filtered glucose and amino
acids are reabsorbed.
Isosmotic reabsorption
Salt and Water Reabsorption in
Proximal Tubule
Reabsorption of Proximal
Tubule
Active Transport of Sodium
Due to low
permeability of
plasma membrane to
Na+.
Active transport
of Na+ out of the
cell by Na+/K+
pumps

-----Favors [Na+]
gradient
-----Na+ diffusion
into cell.
Ascending Limb LH



NaCl is actively
extruded from the
ascending limb into
surrounding
interstitial fluid.
Na+ diffuses into
tubular cell with the
secondary active
transport of K+ and Cl-.
Occurs at a ratio of 1
Na+ and 1 K+ to 2 Cl-.
Insert fig. 17.15
Reabsorption
of Limb LH
Reabsorption of Limb LH
Early distal tubule
Na+, Cl-, Ca2+, Mg2+
Reabsorption
of distal tubule
Late distal tubule
H2O
K+
Reabsorption of Collecting Duct


H20 is drawn
out of the CD
by osmosis.
Permeable to
H20 depends
upon the
presence of ADH.
Reabsorption of HCO3


Apical membranes of tubule cells are impermeable
to HCO3-.
 Reabsorption is indirect.
When urine is acidic, HCO3- combines with H+ to
form H2C03-, which is catalyzed by CA located in
the apical cell membrane of PCT.
 As [C02] increases in the filtrate, C02
diffuses into tubule cell and forms H2C03.
- and H+.
 H2C03 dissociates to HCO3
HCO3- generated within tubule cell diffuses into
peritubular capillary.
Reabsorption of Bicarbonate
Reabsorption of chloride and H2O
Proximal Tubular Reabsorption
Reabsorption of
glucose and amino acids
• secondary active
transport
• Co-transport with
Na+
•Filtered glucose and
amino acids are
completely reabsorbed
in the proximal
convoluted tubule
under normal
conditions.
Reabsorption of glucose


Transport maximum is the maximum rate at
which glucose can be reasorbed from the
tubules, 320mg/min.
Renal glucose threshold refers to the
filtered load of glucose at which
glucose first begins to be excreted in
the urine, 220mg/min.
Glycosuria
•Glucose in urine
•More glucose in filtrate than can
be reabsorbed by tubule = glucose
in urine = diabetes mellitus
Significance of PCT Reabsorption





65% Na+, Cl-, and H20 reabsorbed across the PCT
into the vascular system.
90% K+ reabsorbed.
Essentially all the filtered glucose and amino
acids are reabsorbed in the PCT.
Reabsorption occurs constantly regardless of
hydration state.
 Not subject to hormonal regulation.
Energy expenditure is 6% of calories consumed
at rest.
Tubular Secretion


Chemicals from capillaries secreted into
tubular fluid.
Mainly secret H+, K+, NH3(ammonia)
Secretion of H+
Countertransport
Secretion of H+
Regulation of
extracellular pH
through renal
secretion of H+
and absorption
of HCO3-.
Tubular
secretion of H+
leads to
reabsorption of
filtered HCO3-.
Secretion of H+
Secreted H+
can
protonate
filtered
phosphates.
Secretion of H+ and NH3
Secreted H+
can
protonate
filtered
ammonia.
Reabsorption and Secretion of K+



Freely filtered;
Reabsorbed in
the proximal
convoluted
tubule;
Secreted in the
cortical
portion of
collecting duct.
K+ Secretion

Secretion of K+ occurs in CD.
+ secreted depends upon:
 Amount of K
+ delivered to the region.
 Amount of Na
 Amount of aldosterone secreted.
+ is reabsorbed, lumen of tubule becomes
 As Na
charged.
+ into
 Potential difference drives secretion of K
tubule.
+
 Transport carriers for Na separate from
transporters for K+.
Functions of Secretion

1. Waste removal – urea, uric acid,
bile salts, ammonia, catecholamines,
creatinine, penicillin secreted


2. Acid-base balance – hydrogen ions
& bicarbonate ions – regulate pH of
body fluids
Na+, K+, and H+ Relationship




Na+ reabsorption in CD
creates electrical
gradient for K+
secretion.
Plasma [K+] indirectly
affects [H+].
When extracellular [H+]
increases, H+ moves
into the cell, causing
K+ to diffuse into the
ECF.
In severe acidosis, H+
is secreted at the
expense of K+.
Insert fig. 17.27
Regulation of Tubular Reabsorption

Glomerulotubular balance
-the ability of the tubules to increase
reabsorption rate in response to increased
tubular load (increased tubular inflow).
the percentage of GFR reabsorbed in the
proximal tubular remains relatively constant at
about 65 per cent. 肾小管
Regulation of Tubular Reabsorption

Glomerulotubular balance
(reabsorbed 65%).

GFR
proximal tubular loading of
distal tubule(change)
reabsorption
100
65
35
(- 8.75)
125
81.25
43.75
(0)
150
97.5
52.5
(+8.75)
Prevent overloading of distal tubule when GFR
increases.
Regulation of Tubular Reabsorption

Tubular solute concentration increase, tubular
reasorption decrease.
Glycosuria
Blood sugar exceed renal glucose threshold---more glucose in filtrate than can be
reabsorbed by tubule ---- glucose in urine --- tubular solute concentration increase ---inhibit H2O reasorption ---- urine increase ---diuresis(osmotic diuresis)
Regulation of Tubular Reabsorption


Peritubular
capillary
hydrostatic pressure
increase, tubular
reabsorption
decrease;
Peritubular
capillary colloid
osmotic pressure
increase, tubular
reabsorption
increase.
Renal Clearance
Renal Clearance

The volume of plasma which would be
completely cleared must be the volume o
plasma containing the relevant amount
of solute.
Renal Clearance
Determine the clearance for substance X(C):
Collect urine over a known period of time;
 Measure urinary volume(V);
 Measure the urinary concentration of the
relevant solute(U)
 The plasma concentration of the solute(P)
The total amount of solute in the urine = U•V

∴ C=Plasma volume containing(U•V) of solute
∴ C=
Volume=Amount/Concentration
U•V
(ml/min)
P
Renal Clearance
V • U
P
 V = urine volume per min.
 U = concentration of substance in urine
 P = concentration of substance in plasma
Compare renal “handling” of various substances
in terms of reabsorption or secretion.
Renal clearance(C) =

Renal Clearance


Substance is filtered, but not reabsorbed:
 All filtered will be excreted.
Substance filtered, but also secreted and
excreted will be:
 > GFR (GFR = 125 ml/ min.).
Measurement of GFR

A substance obeys the required criteria for
renal handing:
 It must be freely filtered in the glomerulus;
 It must not be reabsorbed from the nephron;
 It must not be secreted into the nephron;
 It must not be metabolized in the nephron.
Excretion(U•V)=Filtration – Reabsorption +
Secretion
=Filtration – 0 + 0
= GFR • P
∴GFR =
U•V
= C
P
(Inulin, Creatinine)
Measurement of GFR
•
Ability of the kidneys to remove molecules from plasma and excrete those
molecules in the urine.
If a substance is not reabsorbed or secreted, then the amount excreted = amount
filtered.
Quantity excreted = V x U
Quantity excreted = mg/min.
V = rate of urine formation.
U = inulin concentration in urine.
If a substance is neither reabsorbed nor secreted by tubule:
The amount excreted in urine/min. will be equal to the amount filtered out of
the glomeruli/min.
Rate at which a substance is filtered by the glomeruli can be calculated:
Quantity filtered = GFR x P
P = inulin concentration in plasma.
Amount filtered = amount excreted
GFR = V x U
P
The polysaccharide inulin is one such material which may be injected into the
subject, allowing plasma concentration and urinary excretion to be measured. In
clinical practice, however, creatinine clearance is usually measured. Creatinine is
a metabolic of muscle creatine and, as a naturally occurring substance, does not
have to introduced into the circulation artificially. Urine is collected over 24 hours
and a plasma sample taken during this period is used to determine the circulating
creatinine concentration. This represent total filtration in both kidneys.
Renal Clearance of Inulin
Insert fig. 17.22
Measurement of Renal Blood Flow

Be completely removed
from the plasma in a
single circuit
through the kidneys,
i.e. its
concentration reduced
to zero (filtration,
secretion, no
reabsorption) before
the plasma reaches
the renal venous
system.
(para-aminohippuric acid, PAH)
Measurement of Renal Blood Flow
(continued)
Delivery in the arterial blood = Urinary excretion
Delivery = Renal plasma flow • Plasma
concentration(P)
Excretion = Urine concentration(U) • volume(V)
∴ Renal plasma flow • P = U • V
Renal plasma flow =


U•V
P
= C
PAH clearance actually measures renal plasma
flow.
Averages 625 ml/min.
Measurement of Renal Blood Flow
Total Renal Blood Flow



45% blood is
RBCs
55% plasma
Total renal
blood flow =
PAH clearance
0.55
Insert fig. 17.23
Regulation of Extracellular
Fluid Osmolarity and Sodium
Concentration
Formation of Hyperosmotic
Renal Medullary Interstitium
Osmolality of Different Regions of
the Kidney
Insert fig. 17.19
Countercurrent Multiplier System
Outer medulla



Different parts of the
loop are permeable to
different molecules.
Multiplies the
[interstitial fluid]
and [descending limb
fluid].
Flow in opposite
directions in the
ascending and
descending limbs.
Inner medulla

Ascending limb LH
and terminal CD are
permeable to urea;
Urea diffuses out
CD and into
ascending limb LH.


NaCl
Recycle urea.
Thin ascending limb
LH passively
reabsorption NaCl.
Urea
Countercurrent Multiplier




Function of juxta-medullary nephron loops
Descending limb – permeable to water , not
salt; water leaves, salt stays;
concentration 1200 mOsm/L
Ascending limb – impermeable to water; Na, K,
CL out of tubule; tubular fluid more dilute
= 100 mOsm/L at top of loop
The loop acts to continually recapture salt
& return it to deep medulla; multiplies
salinity in deep medulla
Countercurrent exchange system




Vasa recta.
Recycles NaCl in
medulla.
Transports H20 from
interstitial fluid.
Descending limb:



Urea transporters.
Aquaporin proteins
(H20 channels).
Ascending limb:

Fenestrated
capillaries.
Insert fig. 17.17
Countercurrent exchange




Vasa recta – blood supply
Blood exchanges water for salt when surrounding
descending limb
Exchanges salt for water when surrounding the
ascending limb of the loop
This maintains the osmolarity of the medulla
 Removes solutes and water
 Balances solute reabsorption and osmosis in
the medulla
Mechanism of Concentrated Urine




Concentrated urine (hypertonic)
 Urinary osmolality > Plasma
osmolality
Isosmotic urine
 Urinary osmolality = Plasma
osmolality
Dilute urine (hypotonic)
 Urinary osmolality < Plasma
osmolality
Mechanism of Concentrated Urine
• Countercurrent
multiplier of Henle’s
loop produces a
hyperosmotic renal
medullary interstitium;
• Countercurrent
exchange of vasa recta
maintains the
osmolarity of the
medulla.
Mechanism of Concentrated Urine
Medullary area
impermeable to high
[NaCl] that surrounds
it.

The walls of the
collecting duct (CD)
are permeable to H20.

H20 is drawn out of
the CD by osmosis.

Permeable to H20
depends upon the
presence of ADH.

Regulation of Extracellular
Fluid Volume and Osmolality
Regulation of Renal Na+ and Water
Reabsorption


Nervous regulation
 Renal sympathetic nerve
 Strong activation constrict the renal
arterioles and decrease renal blood flow
and GFR;
 Moderate or mild activation has little
influence on renal blood flow and GFR.
Humoral regulation
 Antidiuretic hormone (ADH)
 Aldosterone
 Atrial natriuretic hormone
Antidiuretic Hormone (ADH)


Is manufactured
by cells in the
supraoptic
nucleus of the
hypothalamus;
Is stored and
released from
the posterior
pituitary.
ADH secretion is stimulated by:
Increased osmolality in the extracellular fluid,
which is detected by osmoreceptors within the
hypothalamus; these also stimulate drinking.
 Decreased circulating blood volume, as detected
by cardiovascular volume receptors.
 Decreased arterial pressure as detected by
cardiovascular baroreceptors.
Function of ADH

Increase the
water
permeability in
the distal
convoluted
tubule and
collecting duct.
• This promotes reabsorption of water under the influence of the
high medullary osmolality and so helps expand the extracellular
fluid volume while reducing its osmolality. ADH can help to
elevate arterial blood pressure by direct vasoconstriction,
leading to its alternative name of vasopressin.
COLLECTING DUCTS – begin in cortex, enter medulla; reabsorb
water , concentrate urine
Produce concentrated urine because osmolarity of medulla is 4X
greater than that of cortex
CD is permeable to water not salt
As urine passes down CD water leaves tubule by osmosis and
becomes more concentrated
Control by state of hydration & ADH
ADH released - dehydration – more water reabsorbed, urine
output <
Collecting duct can adjust water reabsorption to produce urine
– hypotonic = 50 mOsm/L
Or Hypertonic = 1200mOsm/L
Depending on the water needs of the body
ADH – makes the CD permeable to water and reabsorbed water =
concentrated urine
The Effects of ADH on the DCT and
Collecting Ducts
ADH

Secretion regulated by
negative feedback


Hypothalamic osmoreceptors
regulate secretion of ADH
in response to changes in
blood osmolarity
ADH regulates
facultative water
reabsorption in last
part of DCT and
collecting ducts

Stimulates insertion of
water channel into apical
membranes of principal
cells
Sweat
vomiting
diarrhea
Extracellular volume
and osmolarity
comeback
What effects would drinking 500
ml of water have on fluid
handling in the kidney?
What difference would there be if
you drank 500 ml of an isotonic
sports drink instead?
Aldosterone




Release from the adrenal cortex
Stimulated as Na+ levels decrease and K+
levels increase
Reabsorb more Na+ and water; secrete
more K+ from DCT and Collecting duct
Salt and water help maintain blood
volume and pressure, control of
electrolyte and acid-base balance
The Renin-angiotensin-aldosterone
system
E
Blood Na+↓, K+ ↑
Na+ Reabsorption




90% filtered Na+
reabsorbed in PCT.
In the absence of
aldosterone, 80% of
the remaining Na+ is
reabsorbed in DCT.
Final [Na+] controlled
in CD by aldosterone.
When aldosterone is
secreted in maximal
amounts, all Na+ in
DCT is reabsorbed.
Insert fig. 17.26
K+ Secretion



Final [K+]
controlled in CD by
aldosterone.
 When aldosterone
is absent, no K+
is excreted in
the urine.
High [K+] or low
[Na+] stimulates
the secretion of
aldosterone.
Only means by which
K+ is secreted.
Insert fig. 17.24
Atrial natriuretic hormone





Produced by atria due to stretching of
walls.
Antagonist to aldosterone.
Increases Na+ and H20 excretion.
Acts as an endogenous diuretic.
Urine production

Homeostasis of body fluid volume depends
in large part on the ability of the
kidneys to regulate the rate of water
loss in urine

ADH controls whether dilute or
concentrated urine is formed
Micturition Reflex

Actions of the internal urethral sphincter and
the external urethral sphincter are regulated
by reflex control center located in the spinal
cord.

Filling of the urinary bladder activates the stretch
receptors, that send impulses to the micturition
center.



Activates parasympathetic neurons, causing rhythmic
contraction of the detrusor muscle and relaxation of the
internal urethral sphincter.
Voluntary control over the external urethral
sphincter.
When urination occurs, descending motor tracts
to the micturition center inhibit somatic motor
fibers of the external urethral sphincter.
Clinical note – Edema

In some kidney diseases
glomerular capillaries
are damaged
 Plasma proteins enter
glomerular filtrate
 Reduces blood colloid
osmotic pressure
 More fluid moves into
tissues
 Causes edema
Clinical note - diuretics

Diuretics slow renal reabsorption of water
+ transporters
 Most act by blocking Na
+ reabsorbed
 Less Na
 Less water reabsorbed by obligatory
reabsorption
 Cause diuresis (increased urine production)
 Reduces plasma volume
 Reduces edema
A Representative Nephron
An Overview of Urine Formation
A Summary of Renal Function