Renal Physiology

Xiaohong Xia
夏晓红
Department of Physiology
Hebei Medical University
E-mail: xiaunmc@hotmail.com)
 About this Chapter

• Anatomy of the excretory system

• How the kidney is organized
• How the nephron works to filter blood,
recycle, secrete, and excrete
• How filtration is regulated
• Urination reflex
 Kidney Function
1. Regulation of water and inorganic ions
balance
2. Excretion of metabolic waste products
3. Removing of foreign chemicals
by producing﹠excreting urine
to maintain the internal homeostasis
of the body
 Kidney Function
4. Secretion of hormones
a. Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary.),
which controls erythrocyte production
b. Renin, ( is produced by juxtaglomerular cell)
which controls formation of angiotensin
c. 1,25-dihydroxyvitamin D3 ,
which influences calcium balance
 Outline:
• 􀂋 Functional Anatomy of Kidneys and
Renal
Circulation
• 􀂋 Glomerular Filtration
• 􀂋 Tubular Processing of Urine Formation
• 􀂋 Urine Concentration and Dilution
• 􀂋 Regulation of Water and Sodium
Excretion
• 􀂋 Renal Clearance
• 􀂋 Urine Volume and Micturition
 SECTION 1:
Functional Anatomy of Kidneys and
Renal Circulation

Urinary system :

 paired kidneys
 paired ureters
 a bladder
 a urethra
Anatomical Characteristics of the Kidney

The kidney: renal cortex

renal medulla
renal pelvis
 Anatomical Characteristics of the Kidney

1. Nephrons: functional unit of kidneys

(1). Consist of nephron
• Nephron is the basic smallest functional unit
of kidney.
• Nephron consists of renal corpuscle and renal
tubule.
• Each kidney is composed of about 1 million
microscopic functional unit.
 Consist of Nephron
glomerulus
renal corpuscle
Bowman’s capsule

Nephron proximal convoluted tubule

proximal tubule
thick descending limb
thin descending limb
renal tubule thin segment loop of Henley
thin ascending limb

thick ascending limb

distal tubule
distal convoluted tubule
 Anatomical Characteristics of the Kidney

Functional unit -nephron:

Corpuscle:
Bowman’s capsule
Glomerulus capillaries
Tubule:
PCT
Loop of Henley
DCT
Collecting duct
 Two Types of Nephron
• Cortical nephrons
• ~85% of all nephrons
• Located in the cortex
• Juxtamedullary
nephrons
• Closer to renal
medulla
• Loops of Henle extend
deep into renal
pyramids
Tab. 8-1. Differences between a cortical and a Juxtamedullary nephron
Cortical nephron Juxtamedullary nephron
Location Outer part of the cortex Inner part of the cortex
next to the medulla
Glomerulus Small Big

Loop of Henle Short, next to outer cortex Longer, into inner part of
cortex
Diameter of AA* AA > EA AA = EA
Diameter of EA** 2 1
EA To form Peritubular capillary To form Vasa recta

Sympathetic Rich Poor

nerve innervation
Concentration of renin High Almost no

Ratio 90% 10%

Function Reabsorption and secretion Concentrate and dilute
urine
* AA = afferent glomerular arteriole
** EA = efferent glomerular arteriole
Cortical and Juxtamedullary Nephrons
2. Collecting duct
Function: As same as distal tubular
3. Juxaglomerular apparatus (JGA)
 macula densa --- in initial portion of DCT
Function : sense change of volume and NaCl
concentration of tubular fluid , and transfer
information to JGC
 mesangial cell
 juxtaglomerular cell (JGC) --- in walls of the afferent
arterioles)
Function: secrete renin
 Juxaglomerular apparatus

JA locate in cortical nephron, consist of juxtaglomerular

cell、 mesangial cell and macula densa.
 Tubulo-glomerular Feedback

• Macula densa can detects Na+, K+ and Cl-

of tubular fluid, and then sent some
information to glomerule, regulation
releasing of renin and glomerular filtration
rate. This process is called Tubulo-
glomerullar feedback.
 Renal circulation
1.Characteristics of renal blood circulation
• Huge volumes blood：
1200ml/min，1/5 – 1/4 of the cardiac output.
• Distribution：
Cortex 94%, outer medulla 5 - 6%, inner medulla <1%.
• Two capillary beds:
Renal artery→interlobar arteries →arcuate arteries
→afferent arterioles →glomerular capillaries →efferent
arteriole →peritubular capillaries →arcuate vein
→interlobar vein →renal vein.
 Renal circulation

• Glomerular capillaries:
Higher pressure, benefit for filtration
• Peritubular capillaries:
Lower pressure, benefit for reabsorption
• Vasa recta
Concentrate and dilute urine
Renal circulation
Glomerular Peritubular
capillary capillary

cortex

medulla

vasa recta
 Regulation of renal blood flow

 Autoregulation
When arterial pressure is in range of 80 to 180 mmHg, renal
blood flow (RBF) is relatively constant in denervated, isolated
or intact kidney.
Flow autoregulation is a major factor that controls RBF
 Mechanism of autoregulation: myogenic theory of
autoregulation
 Physiological significance:
To maintain a relatively constant glomerular filtration rate
(GFR).
Autoregulation of renal blood flow
 Neural regulation
Renal efferent nerve from brain to kidney
• Renal sympathetic nerve
Renal afferent nerve from kidney to brain
• Renal afferent nerve fiber can be stimulated
mechanical and chemical factors.
renorenal reflex:
One side renal efferent nerve activity can effect other
side renal nerve activity.

Activity of sympathetic nerves is low, but can increase

during hemorrhage, stress and exercise.
 Hormonal regulation
Vasoconstriction RBF
• Angiotensin II
• Epinephrine
• Norepinephrine
Vasodilation RBF
• Prostaglandin
• nitrous oxide
• Bradykinin
 Basic processes for urine formation
Glomerular filtration:
Most substances in blood, except for protein and cells, are
freely filtrated into Bowman's space.
Reabsorption:
Water and specific solutes are reabsorbed from tubular fluid
back into blood (peritubular capillaries).
Secretion:
Some substances (waste products, etc.) are secreted from
peritubular capillaries or tubular cell interior into tubules.
Amount Excreted = Amount filtered – Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine.
Basic processes for urine formation
Section 2 Glomerular Filtration

Only water and small solutes can be filtrated----selective.

1. Composition of the glomerular filtrates

Except for proteins, the composition of glomerular filtrates is

same as that of plasma. ?
 2. Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowman’s
space.
Composition: three layers
• Capillary endothelium ---
fenestrations(70-90nm)
• Basement membrane ---
meshwork
• Epithelial cells (podocyte) -
--slit pores

Figure 26.10a, b
Showing the filtration membran. To be filtered, a substance must pass
through 1. the pores between the endothelial cells of the glomerullar capillary,
2. an cellular basement membrane, and 3. the filtration slits between the foot
processes of the podocytes of the inner layer of Bowman’s capsule.
Selective permeability of filtration
membrane

Structure Characteristics:
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
 Selective permeability of filtration
membrane

Size selection :
impermeable to substances
with molecule weight (MW)
more than 69, 000 or EMR 4.2 nm. (albumin)
Charge selection :
Repel negative charged substances.
 Filtrate Composition
• Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
• Neutral solutes:
• Solutes smaller than 180 nanometers in radius are freely
filtered
• Solutes greater than 360 nanometers do not
• Solutes between 180 and 360 nm are filtered to various
degrees
• Serum albumin is anionic and has a 355 nm radius,
only ~7 g is filtered per day (out of ~70 kg/day passing
through glomeruli)
• In a number of glomerular diseases, the negative
charge on various barriers for filtration is lost due to
immunologic damage and inflammation, resulting in
proteinuria (i.e. increased filtration of serum proteins
that are mostly negatively charged).
• Glomerular filtration rate (GFR)：
The minute volume of plasma filtered through
the filtration membrane of the kidneys is called
the glomerular filtration rate.
(Normally is 125ml/min)
• Filtration fraction (FF)：
The ratio of GFR and renal plasma flow
 Factors affecting glomerular filtration

• Effective filtration pressure (EFP)

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.
• EFP is promotion of filtration.
• Formation and calculate of EPF
Formation of EPF depends on three pressures:
Glomerular capillary pressure (Pcap)
Plasma colloid osmotic pressure (Pcol)
Intracapsular pressure (Picap)
• Calculate of EPF
EFP = Pcap – (Pcol + Picap)
• Part of afferent arterial
EFP = Pcap – (Pcol + Picap) = 55 – (30 + 15) = 10
• Part of efferent arterial
EFP = Pcap – (Pcol + Picap) = 55 – (40 + 15) = 0
Effective filtraton pressure
 Filtration Coefficient ( Kf )

• Filtration coefficient is a minute volume of

plasma filtered through the filtration
membrane by unit effective filtration pressure
drive. Kf =K×S
• GFR is dependent on the filtration coefficient
as well as on the net filtration pressure.
GFR=P× Kf
• The surface area the permeability of the
glomerular membrane can affect Kf.
 Factors Affecting Glomerular Filtration
What kind of factors can affect filtration rate?
1.Effective filtration pressure
2.Glomerular capillary pressure
3.Plasma colloid osmotic pressure
4.Intracapsular pressure
5.Renal plasma flow
6.Kf =K×S Kf : filtration coefficient
K: permeability coefficient
S: surface area the permeability
 Regulation of Glomerular Filtration
• If the GFR is too high, needed substances cannot
be reabsorbed quickly enough and are lost in the
urine
• If the GFR is too low - everything is reabsorbed,
including wastes that are normally disposed of
• Control of GFR normally result from adjusting
glomerular capillary blood pressure
• Three mechanisms control the GFR
• Renal autoregulation (intrinsic system)
• Neural controls
• Hormonal mechanism (the renin-angiotensin system)
 Autoregulation of GFR
• Under normal conditions (MAP =80-180mmHg) renal autoregulation
maintains a nearly constant glomerular filtration rate
• Two mechanisms are in operation for autoregulation:
• Myogenic mechanism
• Tubuloglomerular feedback
• Myogenic mechanism:
• Arterial pressure rises, afferent arteriole stretches
• Vascular smooth muscles contract
• Arteriole resistance offsets pressure increase; RBF (& hence GFR)
remain constant.
• Tubuloglomerular feed back mechanism for autoregulation:
• Feedback loop consists of a flow rate (increased NaCl) sensing
mechanism in macula densa of juxtaglomerular apparatus (JGA)
• Increased GFR (& RBF) triggers release of vasoactive signals
• Constricts afferent arteriole leading to a decreased GFR (& RBF)
 Extrinsic Controls
• When the sympathetic nervous system is at rest:
• Renal blood vessels are maximally dilated
• Autoregulation mechanisms prevail
• Under stress:
• Norepinephrine is released by the sympathetic nervous system
• Epinephrine is released by the adrenal medulla
• Afferent arterioles constrict and filtration is inhibited
• The sympathetic nervous system also stimulates the
renin-angiotensin mechanism
• A drop in filtration pressure stimulates the
Juxtaglomerular apparatus (JGA) to release renin and
erythropoietin
Response to a Reduction in the GFR
 Renin-Angiotensin Mechanism
• Renin release is triggered by:
• Reduced stretch of the granular JG cells
• Stimulation of the JG cells by activated macula densa cells
• Direct stimulation of the JG cells via 1-adrenergic receptors by
renal nerves
• Renin acts on angiotensinogen to release angiotensin I
which is converted to angiotensin II
• Angiotensin II:
• Causes mean arterial pressure to rise
• Stimulates the adrenal cortex to release aldosterone
• As a result, both systemic and glomerular hydrostatic
pressure rise
Figure 25.10
 Other Factors Affecting Glomerular Filtration

• Prostaglandins (PGE2 and PGI2)

• Vasodilators produced in response to sympathetic
stimulation and angiotensin II
• Are thought to prevent renal damage when peripheral
resistance is increased
• Nitric oxide – vasodilator produced by the
vascular endothelium
• Adenosine – vasoconstrictor of renal vasculature
• Endothelin – a powerful vasoconstrictor secreted
by tubule cells
 Control of Kf
• Mesangial cells have contractile properties, influence
capillary filtration by closing some of the capillaries –
effects surface area
• Podocytes change size of filtration slits
 Process of Urine Formation
• Glomerular filtration
• Tubular reabsorption of
the substance from the
tubular fluid into blood
• Tubular secretion of the
substance from the blood
into the tubular fluid
• Mass Balance
• Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
 Tubular Secretion
• Essentially reabsorption in reverse, where
substances move from peritubular capillaries or
tubule cells into filtrate
• Tubular secretion is important for:
• Disposing of substances not already in the filtrate
• Eliminating undesirable substances such as urea and
uric acid
• Ridding the body of excess potassium ions
• Controlling blood pH
Tubular reabsorption and secretion
SECTION 3: Tubular processing of urine formation

Characteristics and mechanism of reabsorption and

secretion
Characteristics of reabsorption:
quantitatively large
More than 99% volume of filtered fluid are reabsorbed
(> 178L).
selective
100% glucose, 99% sodium and chloride, 85%
bicarbonate are reabsorbed

Urea and creatinine are partly reabsorbed.

 (1). Type of transportation in renal tubule and
colllecting duct

• Reabsorption and secretion are divided two types

• Passive reabsorption (needless energy)
Diffusion, osmosis, facilitated diffusion
• Active reabsorption (need energy)
• Saldium pump (Na+-K+ ATPase), proton pump (H+-
ATPase), calcium pump (Ca2+-ATPase).
• Cotransport (coupled transport):
One transportor can transport two or more substances.
• Symport transport: like Na+ and glucose, Na+ and amine acids
Antiport transport: like Na+-H+ and Na+-K+
• Secondary active transport : like H+ secretion
Na+ active transport in PT epithelium
• Passway of transport
Apical membrane, tight juction, brush border,
basolateral membrane
• Transcellular pathway
Na+ apical membrane epithelium Na+ pump peritubular
capillary
• Paracellular transport
Water, Cl- and Na+ tight juction peritubular capillary
K+ and Ca2+ are reabsorpted with water by solvent drag
Fig.8-23. The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Na+ and Cl - paracellular reabsorption in PT epithelium
Location of reabsorption

 Proximal tubule
Brush border can increase the area of
reabsorption
 Henle's loop

 Distal tubule

 Collecting duct
 (2). Reabsorption and secretion in different part of
renal tubule

• Proximal tubule (PT)

67% Na+, Cl-, K+ and water; 85% HCO3- and 100%
glucose and amine acids are reabsorption
secretion H+
2/3 Transcellular pathway
1/3 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule).
1. Na+、Cl- and water reabsorption
Na+ and Cl- reabsorption：
• About 65 - 70% in proximal tubule, 10% in
distal tubule, 20% loop of Henle.
• Valume of filtration: 500g/day，
Valume of excretion 3 – 5g，99% are
reabsorption.
• Front part of PT: Na+ reabsorption with HCO3-、
Glucose and Amine acids；
Behind part of PT: Na+ reabsorption with Cl-.
• Cl- reabsorption:
Passive reabsorption with Na+
• water reabsorption:
Passive reabsorption with Na+ and Cl-
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
Water passive reabsorption
K+ reabsorption
 Most of in PT (70%)，20% in loop of Henle

 Active reabsorption

Ca2+ reabsorption
 70% in PT, 20% in loop of Henle, 9% in DCT

 20% is transcellular pathway

80% is paracellular transport
HCO -3 reabsorption and H+ secretion

• About 80% in PT, 15% in ascending thick limb, 5% in

DCT and CD
• H2CO3 CO2 + H2O, CO2 is easy reabsorption
• HCO3– reabsorption is priority than Cl-

H+ secretion
• CO2 + H2O H2CO3 HCO3–+ H+
• H+ secretion into lumen
Bicarbonate reabsorption
 Glucose and amino acid reabsorption
Glucose reabsorption:
99% glucose are reabsorption, no glucose in urine
• Location:
early part of PT
• Type of reabsorption:
secondary active transport
• Renal glucose threshold
When the plasma glucose concentration increases up to a
value about 160 to 180 mg per deciliter, glucose can first
be detected in the urine, this value is called the renal
glucose threshold.
9-10.1 mmol/L (160-180mg/dl)
Glucose secondary active transport in early part of PT
Transport maximum (Tm) 转运极限
Transport maximum is the maximum rate at which
the kidney active transport mechanisms can
transfer a particular solute into or out of the
tubules.

Amino acid reabsorption:

Location and type of reabsorption as same as
glucose
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism.
Loop of Henle:
Ascending thick limb of loop of Henle
Na+, Cl- and K+ cotransport
Transportation rate: Na+ : 2Cl- : K+

Distal tubule and collecting duct:

Principal cell: Reabsorption Na+ 、water and
secretion K+
Intercalated cell: Secretion H+
• 12% Na+, Cl- and water are reabsorbed in distal tubule and
collecting duct.
• Water reabsorption: depends on whether lack of
water of body. ADH (discuss later)
• Na+ and K+ reabsorption: Aldosteron (discuss later)
• K+ secretion: Na+ - K+ - ATPase,
• H+ secretion: Na+ -H+ antiport transport
• NH3 secretion: Related to H+ secretion
NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+
NH4Cl excretion with urine, Na+ reabsorption into blood.
 Secretion at the DCT

• DCT performs final adjustment of urine

• Active secretion or absorption
• Absorption of Na+ and Cl-
• Secretion of K+ and H+ based on blood pH
• Water is regulated by ADH (vasopressin)
• Na+, K+ regulated by aldosterone
K+ and H+ secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism.
Table. 8-2. Summary of transport across PT, DT and collecting duct
Proximal tubule
Reabsorption Secretion
67% of filtered Na+ actively Variable H+ secretion,
reabsorbed, not subject to control; depending on acid-base
Cl- follows passively. status of body.
All filtered glucose and amino acids
reabsorbed by secondary active
transport, not subject to control.
65% of filtered H2O osmotically
reabsorbed, not subject to control.
Almost all filtered K+ reabsorbed,
not subject to control.
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed by Variable H+ secretion,
Aldosterone; depending on acid-base
Cl- follows passively. status of body.
Variable H2O reabsorption, Variable K+ secretion,
controlled by vasopressin (ADH) controlled by aldosterone.
 Urinary Concentration and Dilution
• Hypertonic urine:
Lack of water in body can forms concentrated urine
(1200 mOsm/L).
• Hypotonic urine:
More water in body can forms dilute urine (50 mOsm/L).
• Isotonic urine：Injury of renal function
• 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:
The basic requirements for forming a concentrated urine are a high
level of ADH and a high osmolarity of the renal medullary interstitial
fluid.
formation of dilute and concentrated urine.
Control of Urine Volume and Concentration

• Urine volume and osmotic concentration are regulated

by controlling water and sodium reabsorption
• Precise control allowed via facultative water reabsorption
• Osmolality
• The number of solute particles dissolved in 1L of water
• Reflects the solution’s ability to cause osmosis
• Body fluids are measured in milliosmols (mOsm)
• The kidneys keep the solute load of body fluids constant
at about 300 mOsm
• This is accomplished by the countercurrent mechanism
 Formation of concentrated and diluted urine
Drink more water ADH water reabsorption
in DCT and CD diluted urine.
Lack of water ADH water reabsorption
in DCT and CD concentrated urine.
 Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid.
Role of countercurrent exchanger
Urinary concentrating environment.
• Basic structure：
“U”type of loop of Henle
Vasa recta’s cliper type (发卡样排列)
Collecting duct from cortex to medulla
• Basic function：
Different permeability of solutes and water in
DCT, CD and loop of Henle.
• Osmotic gradient exit from cortex to medulla.
Tab.8-2. Permeabilities of different segments of the renal tubule

Segments of Permeability to Permeability to Permeability to

renal tubule water Na+ urea
Thick ascending Almost not Active transport of Almost not
limb Na+, Secondary
active Transport of Cl-

Thin ascending Almost not Yes Moderate

limb

Thin descending Yes Almost not Almost not

limb

Distal convoluted Permeable Secretion of K+ Almost not

tubule Under ADH K+-Na+ exchange
action

Collecting Permeable Yes Cortex and outer

duct Under ADH Medulla almost not
action Inner medulla Yes
 Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
 Formation of osmotic gradient is related to
physiological characters of each part of renal tubule.
 Outer medulla：
Water are permeated in descending thin limb, but not NaCl
and urea.
NaCl and urea are permeated in ascending thin limb, but
not water.
NaCl is active reabsorbed in ascending thick limb, but not
Urea and water.
 Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla.
• Inner medulla：
• High concentration urea exit in tubular fluid.
• Urea is permeated in CD of inner medulla but not
in cortex and outer medulla
• NaCl is not permeated in descending thin limb
• NaCl is permeated in ascending thin limb
• Urea recycling：
• Urea is permeated in ascending thin limb, part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again.
• Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla.
 Countercurrent Mechanism
• Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
• The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
 Countercurrent exchange
Countercurrent exchange is a common process in
the vascular system. Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta, and solutes and water
are Exchanged between these capillary blood vessels.

 Countercurrent multiplication
Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop.
 Loop of Henle: Countercurrent Multiplication
• Vasa Recta prevents loss of medullary osmotic gradient equilibrates with
the interstitial fluid
• Maintains the osmotic gradient
• Delivers blood to the cells in the area
• The descending loop: relatively impermeable to solutes, highly permeable to
water
• The ascending loop: permeable to solutes, impermeable to water
• Collecting ducts in the deep medullary regions are permeable to urea
 Countercurrent Multiplier and Exchange

• Medullary osmotic
gradient
• H2OECFvasa recta
vessels
 Formation of Concentrated Urine
• ADH (ADH) is the
signal to produce
concentrated urine it
inhibits diuresis
• This equalizes the
osmolality of the
filtrate and the
interstitial fluid
• In the presence of
ADH, 99% of the
water in filtrate is
reabsorbed
 Formation of Dilute Urine

• Filtrate is diluted in the ascending

loop of Henle if the antidiuretic
hormone (ADH) or vasopressin is not
secreted
• Dilute urine is created by allowing this
filtrate to continue into the renal pelvis
• Collecting ducts remain impermeable
to water; no further water
reabsorption occurs
• Sodium and selected ions can be
removed by active and passive
mechanisms
• Urine osmolality can be as low as 50
mOsm (one-sixth that of plasma)
 :
Mechanism of ADH (Vasopressin) Action:
Formation of Water Pores
• ADH-dependent water reabsorption is called facultative
water reabsorption

Figure 20-6: The mechanism of action of vasopressin

 Water Balance Reflex:
Regulators of Vasopressin Release

Figure 20-7: Factors affecting vasopressin release

Regulation of Urine Formation in the Kidney

• Way of regulation for urine formation：

Filtration, Reabsorption and Secretion
• Autoregulation
• Solute concentration of tubular fluid
Osmotic diuresis -- diabatic、mannitol
• Glomerulotubular balance
 Nervous regulation
 Role of Renal Sympathetic Nerve
 Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
 Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
 Regulation by ADH

• Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality.
• Dehydration or excess
salt intake:
• Produces sensation
of thirst.
• Stimulates H20
reabsorption from
urine.
 The regulation of ADH secretion

 Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei

The change of crystal osmotic

pressure

Effective stimuli

The change of effective blood

volume
Source of ADH
Effects of ADH on the DCT and Collecting Ducts

Figure 26.15a, b
Regulation of ADH release: over hydration
Regulation of release: hypertonicity
 Atrial Natriuretic Peptide Activity

 Increase GFR , reducing water reabsorption

 Decrease the osmotic gradient of renal medulla
and promotes Na+ excretion
 Acting directly on collecting ducts to inhibit Na+
and water reabsorption, promotes Na+ and
water excretion in the urine by the kidney
 Inhibition renin release and decrease
angiotensin II and aldosterone, promotes Na+
excretion
 Endothelin (ET)
Constriction blood vessels, decrease GFR
 Nitic Oxide (NO)
Dilation blood vessels, increase GFR
 Epinephrine (EP), Norepinephrine (NE)
promote Na+ and water reabsorption
 Prostaglandin E2 ,I2
Dilation blood vessels, excretion Na+ and water.
A Summary of Renal Function

Figure 26.16a
 Renal clearance

1. Concept:
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance by
the kidneys per unit time (min)
2. Calculate
concentration of it in urine ×urine volume
C=
concentration of it in plasma
 Renal Clearance

RC = UV/P

RC = renal clearance rate

U = concentration (mg/ml) of the substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance in plasma
• Renal clearance tests are used to:
• Determine the GFR

• Detect glomerular damage

• Follow the progress of diagnosed renal disease
Theoretical significance of clearance
3.1 Measure GFR
• A substance---freely filtered, non reabsorbed,
non secreted--its renal clearance = GFR
• Clearance of inulin or creatinine can be used to
estimate GFR
3.2 Calculate RPF and RBF

A substance--freely filtered, non reabsorbed, secreted

completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous.

Clearance of para-aminohippuric acid (PAH) or diodrast

can be used to calculate RPF.
3.3 Estimate of tubular handling for a substance

If the clearance of substance>125ml/min?

---it must be secreted
If it <125ml/min? --- it must be reabsorbed
 Physical Characteristics of Urine

 Color and transparency

• Clear, pale to deep yellow (due to urochrome)
• Concentrated urine has a deeper yellow color
• Drugs, vitamin supplements, and diet can change the color of
urine
• Cloudy urine may indicate infection of the urinary tract
 pH
• Slightly acidic (pH 6) with a range of 4.5 to 8.0
• Diet can alter pH
 Specific gravity
• Ranges from 1.001 to 1.035
• Is dependent on solute concentration
 Chemical Composition of Urine

• Urine is 95% water and 5% solutes

• Nitrogenous wastes include urea, uric acid, and
creatinine
• Other normal solutes include:
• Sodium, potassium, phosphate, and sulfate ions
• Calcium, magnesium, and bicarbonate ions
• Abnormally high concentrations of any urinary
constituents may indicate pathology
 Urine Volume and Micturition

1. Urine volume
 Normal volume : 1.0~2.0L/day
 Obligatory urine volume ~400ml/day
Minimum needed to excrete metabolic wastes of
waste products in body.
 Oliguria--- urine volume < 400ml/day
 Anuria---urine volume < 100ml/day
Accumulation of waste products in body.
 Polyuria--- urine volume > 2500ml/day long time
Abnormal urine volume: Losing water and electrolytes.
 Micturition
Functions of ureters and bladder:
Urine flow through ureters to bladder is
propelled by contractions of ureter-wall
smooth muscle.
Urine is stored in bladder and intermittently
ejected during urination, or micturition.
 Micturition
• Micturition is process of emptying the
urinary bladder
• Two steps are involved:
• (1) bladder is filled progressively until its
pressure rises
• above a threshold level (400~500ml);
• (2) a nervous reflex called micturition
reflex occurs that empties bladder.
 Micturition

• Pressure-Volume curve of the bladder has

a characteristic shape.
• There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered.
 Pressure-volume graph for normal human
bladder
1.25

1.00
Pressure (kPa)

Discomfort
Sense of
0.75 1st desire urgency
to empty
bladder
0.50

0.25

100 200 300 400

Volume (ml)
 Micturition (Voiding or Urination)

• Bladder can hold 250 - 400ml

• Greater volumes stretch bladder walls initiates
micturation reflex:
• Spinal reflex
• Parasympathetic stimulation causes bladder to
contract
• Internal sphincter opens
• External sphincter relaxes due to inhibition
Innervation of bladder
Urination: Micturation reflex

Figure 19-18: The micturition reflex

Micturition (Voiding or Urination)

Figure 25.20a, b
 Review Questions
Explain concepts
1.Glomerular filtration rate
2. Effective filtration pressure
3. Filtration fraction
4.Renal glucose threshold
5.Osmotic diuresis
6.Renal clearance
 Review Questions
1. What are the functions of the kidneys?
2. Describe autoregulation of renal plasma
flow.
3. What are three basic processes for urine
formation?
4. Describe the forces affecting glomerular
filtration.
5. Describe the factors affecting GFR.
6. What is the mechanism of sodium
reabsorption in the proximal tubules ?
 Review Questions
7. What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption?
8. What is the mechanism of formation of
concentrated and diluted urine?
9. After drinking large amount of water, what does
the amount of urine change? Why?
10. Why a patient with diabetes has glucosuria and
polyuria?