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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?
2012 4-16 renal physiology

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2012 4-16 renal physiology

  • 1. Renal Physiology Xiaohong Xia 夏晓红 Department of Physiology Hebei Medical University E-mail: xiaunmc@hotmail.com)
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. 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
  • 6. SECTION 1: Functional Anatomy of Kidneys and Renal Circulation Urinary system :  paired kidneys  paired ureters  a bladder  a urethra
  • 7. Anatomical Characteristics of the Kidney The kidney: renal cortex renal medulla renal pelvis
  • 8. 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.
  • 9. 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
  • 10. Anatomical Characteristics of the Kidney Functional unit -nephron: Corpuscle: Bowman’s capsule Glomerulus capillaries Tubule: PCT Loop of Henley DCT Collecting duct
  • 11. 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
  • 12. 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
  • 14. 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
  • 15. Juxaglomerular apparatus JA locate in cortical nephron, consist of juxtaglomerular cell、 mesangial cell and macula densa.
  • 16. 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.
  • 17. 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.
  • 18. Renal circulation • Glomerular capillaries: Higher pressure, benefit for filtration • Peritubular capillaries: Lower pressure, benefit for reabsorption • Vasa recta Concentrate and dilute urine
  • 19. Renal circulation Glomerular Peritubular capillary capillary cortex medulla vasa recta
  • 20. 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).
  • 22. 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.
  • 23. Hormonal regulation Vasoconstriction RBF • Angiotensin II • Epinephrine • Norepinephrine Vasodilation RBF • Prostaglandin • nitrous oxide • Bradykinin
  • 24. 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
  • 25. Three basic processes of the formation of urine.
  • 26. Basic processes for urine formation
  • 27. Section 2 Glomerular Filtration Only water and small solutes can be filtrated----selective.
  • 28. 1. Composition of the glomerular filtrates Except for proteins, the composition of glomerular filtrates is same as that of plasma. ?
  • 29. 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
  • 30. 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.
  • 31. Selective permeability of filtration membrane Structure Characteristics: There are many micropores in each layer Each layer contains negatively charged glycoproteins
  • 32. 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.
  • 33. 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).
  • 34. • 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
  • 35. 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.
  • 36. • 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
  • 38. 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.
  • 39. 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
  • 40. 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)
  • 41. 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)
  • 42. 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
  • 43. Response to a Reduction in the GFR
  • 44. 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
  • 46. 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
  • 47. 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
  • 48.
  • 49. 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
  • 50. 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
  • 52. 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.
  • 53. (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
  • 54. Na+ active transport in PT epithelium
  • 55. • 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
  • 56. Fig.8-23. The pathway of reabsorption
  • 57. Reabsorption of transcellular and paracellular pathway
  • 58. Na+ and Cl - paracellular reabsorption in PT epithelium
  • 59. Location of reabsorption  Proximal tubule Brush border can increase the area of reabsorption  Henle's loop  Distal tubule  Collecting duct
  • 60. (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).
  • 61. 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-.
  • 62. • Cl- reabsorption: Passive reabsorption with Na+ • water reabsorption: Passive reabsorption with Na+ and Cl-
  • 63. Na+ transcellular transportation in early part of PT epithelium
  • 64. Cl- passive reabsorption in later part of PT epithelium
  • 66. 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
  • 67. 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
  • 69. 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)
  • 70. Glucose secondary active transport in early part of PT
  • 71. 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
  • 72. Glucose secondary active transport in early part of PT
  • 73. Co-transport of amino acids via Na+ symport mechanism.
  • 74. 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+
  • 75. • 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.
  • 76. 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
  • 77. K+ and H+ secretion in distal tubule and collecting duct
  • 78. Co-transport of amino acids via Na+ symport mechanism.
  • 79. 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.
  • 80. 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.
  • 81. formation of dilute and concentrated urine.
  • 82. 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
  • 83.  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
  • 85. • 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.
  • 86. 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
  • 87.  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.
  • 88. • 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.
  • 89. 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
  • 90.  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.
  • 91. 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
  • 92. Countercurrent Multiplier and Exchange • Medullary osmotic gradient • H2OECFvasa recta vessels
  • 93. 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
  • 94. 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)
  • 95. : 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
  • 96. Water Balance Reflex: Regulators of Vasopressin Release Figure 20-7: Factors affecting vasopressin release
  • 97. 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
  • 98. Nervous regulation  Role of Renal Sympathetic Nerve  Reflex of renal sympathetic nerve Reflex of cardiopumonary receptor renorenal reflex  Renin-angiotention-aldosterone system
  • 100. 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.
  • 101. 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
  • 103. Effects of ADH on the DCT and Collecting Ducts Figure 26.15a, b
  • 104. Regulation of ADH release: over hydration
  • 105. Regulation of release: hypertonicity
  • 106. 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
  • 107.  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.
  • 108. A Summary of Renal Function Figure 26.16a
  • 109. 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
  • 110. 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
  • 111. 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
  • 112. 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.
  • 113. 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
  • 114. 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
  • 115. 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
  • 116. 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.
  • 117. 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.
  • 118. 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.
  • 119. 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.
  • 120. 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)
  • 121. 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
  • 123. Urination: Micturation reflex Figure 19-18: The micturition reflex
  • 124. Micturition (Voiding or Urination) Figure 25.20a, b
  • 125. 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
  • 126. 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 ?
  • 127. 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?