DR.SREEJITH.H
Kidneys
Kidneys are a pair of excretory organs situated on the
posterior abdominal wall, extending from upper border of
T...
Functions of the Kidney:nce
Regulation of body fluid volume and osmolality
Regulation of electrolyte balance
Regulation...
Renal cortexRenal cortex
 Cortical lobules - whichCortical lobules - which
form caps over theform caps over the
bases of ...
 Histologically, each kidney is composed 1-3 millionHistologically, each kidney is composed 1-3 million
uriniferous tubul...
Circulation of renal blood flowCirculation of renal blood flow
Renal artery divides serially into – interlobar arteryRenal...
Two types of nephrons are presentTwo types of nephrons are present
 Cortical nephronsCortical nephrons with short loop of...
Juxtaglomerular apparatusJuxtaglomerular apparatus
 Macula densaMacula densa – modified portion of thick ascending limb– ...
The Nephron
Functional unit of the kidney (1,000,000)
Responsible for urine formation:
Filtration
Secretion
Reabsorpt...
Proximal
Tubule
Distal
Tubule
Thin descending
Thin ascending
Loop of Henle
Thick ascending
(diluting segment)
Early
Late
C...
FunctionsFunctions
Nephron regulatesNephron regulates
 Intravascular volume, osmolality, acid base balance,Intravascular ...
Basic Theory of Urine Formation
Filtration
Reabsorption
Secretion
Excretion
Glomerulus -Glomerulus - Five componentsFive components
 Capillary endotheliumCapillary endothelium – 70-100– 70-100
nm f...
Filtration barrier - Size and charge selective
Charge: all 3 layers contain negatively charged
glycoproteins  restricts ...
Glomerular Filtration Rate (GFR)Glomerular Filtration Rate (GFR)
 Normal GFR: in men = 125 ml/min, 10% lower in femalesNo...
Regulation of GFR
Changes in Kf (Permeability or
Surface area):
Mesangial Cell Contraction or
Relaxation
+ ANP, NO
- AII, ...
A volume of plasma from which a substance is
completely removed by the kidneys per unit time.
Clearance
Where UF = urine f...
Freely Filtered Not Metabolized
Not Reabsorbed Does Not Change GFR
Not Secreted Not Produced
Measurement of GFR
(Inulin M....
Reabsorption
and secretion
Reabsorption
Active Transport –requires ATP
Na+, K+ ATP pumps
Passive Transport-
Na+ symporters (glucose, a.a., etc)
...
Factors influencing Reabsorption
Saturation: Transporters can get saturated
by high concentrations of a substance - failu...
Proximal tubule - reabsorbs 65 % of filtered Na+ as
well as Cl-
, Ca2+
, PO4, HCO3
-
. 75-90% of H20. Glucose,
carbohydrat...
Secretion
Proximal tubule – uric acid, bile salts, metabolites,
some drugs, some creatinine
Distal tubule – Most active ...
TubuleTubule
Proximal Tubule (PCT)Proximal Tubule (PCT)
 60-75% ultrafiltrate60-75% ultrafiltrate  reabsorb isotonicall...
Pump mechanisms of tubulePump mechanisms of tubule
Sodium reabsorption in PCT (65-75% of filtered NaSodium reabsorption in PCT (65-75% of filtered Na++
loadload
reabsorbed)r...
 WaterWater  specialised channels composed of membranespecialised channels composed of membrane
protein aquaporin-1 (ap...
FunctionsFunctions
ReabsorptionReabsorption
 NaClNaCl
 WaterWater
 BicarbonateBicarbonate
 GlucoseGlucose
 ProteinsPr...
Proximal Tubule Reabsorption
Early
Late
Na+Na+
K
+
K
+
LumenCapillary
Na+
K+
↑π
↓Pc
Na+Na+
K
+
K
+
Na+
K+
Na+
Na+
Cl-
Cl-
...
Proximal Tubule Reabsorption
PROXIMAL TUBULE SUMMARY
• 2/3 of salts and water reabsorbed
•All glucose and a.a. reabsorbed
•Reabsorption is isotonic:
PT...
CONCENTRATION & DILUTION
•permeability aspects of the Loop of Henle, DT & CD.
•the importance of the high medullary inters...
Loop of HenleLoop of Henle
 25-30% ultrafiltrate reaches loop of Henle25-30% ultrafiltrate reaches loop of Henle
↓↓
 15-...
Sodium and chloride reabsorption in thick ascending loopSodium and chloride reabsorption in thick ascending loop
Countercurrent exchange
The structure and transport
properties of the loop of
Henle in the nephron create
the Countercurr...
Loop of Henle
Goal= make isotonic filtrate
into hypertonic urine (don’t
waste H20!!)
Counter-current multiplier:
 Desce...
 Tubular fluid enters the distal PCT iso-osmotic with plasma (300Tubular fluid enters the distal PCT iso-osmotic with pla...
 Fluid entering distal tubule is quite hypo-osmotic (100 mOsm/kg)Fluid entering distal tubule is quite hypo-osmotic (100 ...
Counter current multiplierCounter current multiplier
Counter current exchange by vasa rectaCounter current exchange by vasa recta
Distal tubuleDistal tubule
 Very tight junctions between tubular cellsVery tight junctions between tubular cells
relative...
Collecting tubuleCollecting tubule
5-7% of filtered Na5-7% of filtered Na++
load is reabsorbedload is reabsorbed
Cortica...
Secretion of hydrogen and reabsorption of bicarbonateSecretion of hydrogen and reabsorption of bicarbonate
and potassium i...
AldosteroneAldosterone
 Enhances NaEnhances Na++
KK++
ATPase activity byATPase activity by ↑↑ number of open Nanumber of ...
K+ sparing diureticsK+ sparing diuretics
CompetitiveCompetitive
 Spironolactone – aldosterone receptor antagonistSpironol...
Medullary collecting tubuleMedullary collecting tubule
 Site of actiion of ADH or AVP (arginine vasopressin)Site of actii...
300
300
300
300
300
300
1200 1200 1200
900 900 900
400 400 400
500 500 500
600 600 600
700 700 700
800 800 800
1100 1100 1...
300
300
300
300
300
300
1200
Low permeability to solutes
High permeability to water
H2O
H2O
1200 1200 1200
Thin descending...
300
300
300
300
300
300
1200
permeable to solutes
H2O
H2O
Thin ascending
limb of the loop
of Henle low permeability to H2O...
300
300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2 Cl-
150
Thick Ascending
limb of the loop
of Henle (TAL)
...
300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2 Cl-
150Distal Tubule
Na+
K+
2 Cl-
Na+
K+
2 Cl-
Impermeable t...
300
300
300
300
300
1200
1200 1200 1200
Na+
K+
2 Cl-
Na+
K+
2 Cl-
150
Na+
K+
2 Cl-
Na+
K+
2 Cl-
60Na Cl Na Cl
Cortical
Col...
Renal Regulation of Special Substances
Urea, Glucose, Phosphate, Sulfate, Water,
Sodium, Potassium & Calcium
John R. Dietz...
Renal Regulation of Special Substances
(Urea, Glucose, Phosphate & Sulfate)
•How urea is reabsorbed.
•Principles of second...
Reabsorption of Urea
50% of Filtered
Urea Reabsorbed
4
5
30
100500600
600
Tubular Concentrations of Urea are in mmoles/L
M...
Reabsorption of Glucose
in the Proximal Tubule
LumenBasal Membrane
Na+
K+
Glucose
Glucose
Na+
SGL
T1
GL
UT2
Glu
Sodium Powered Secondary Active
Transport
Na+
Na+
LumenCell Membrane
Stanley J. Nazian,
Ph..D.,
This slide was stolen
...
Reabsorption of Glucose
in the Proximal Tubule
LumenCapillary
Na+
K+
Glucose
Glucose
Na+
SGL
T1
GL
UT2
Facilitated Diffusion
Interstitium CellMembrane
Glu
Glu
Glu
Glu
Glu
GluGlu
Secondary Active Transport
Henderson-Hasselbalch Equation:
pH = pK + log HCO3
-
CO2
pH =
  H+
exchanged for Na+
H+
ATPase
H+
- K+
ATPase
Various Mechanisms of H+ Secretion
H+
H+
H+
H+
H+
H+
H+
H+
H+
CO2 + H2O
H2CO3
HCO3
-
+ H+
HCO3
-
Cl-
HCO3
-
Na+
Na+
H+
ATPase
H+
C.A.
Blood Cell Lumen
ATPase
H+
K+
Renal Transport of H...
CO2 + H2O
H2CO3
HCO3
-
+ H+
Bicarbonate Reabsorption
C.A.
Filtered
H2CO3
CO2 + H2O
C.A.
Primarily in Proximal Tubule - 0 %...
CO2 + H2O
H2CO3
HCO3
-
+ H+
Bicarbonate Reabsorption
C.A.
Filtered
H2CO3
CO2 + H2O
C.A.
Primarily in Proximal Tubule - 0 %...
CO2 + H2O
H2CO3
HCO3
-
+ H+
Titratable Acid Excretion
C.A.
Na+
Filtered
H+
+ HPO4
2-
Primarily in Distal Tubule & CD - 33 ...
CO2 + H2O
H2CO3
HCO3
-
+ H+
Ammonium Excretion
C.A.
H+
+ NH3
Primarily in Distal Tubule & CD - 66 % of Acid Excretion
NH4
...
H+ Secretion in the Nephron
Factors that Stimulate H+ Secretion
• Acidosis
Metabolic or
Respiratory
• Hypokalemia
• Aldosterone
Regulation of H+ Excretion
CO2 + H2O
H2CO3
HCO3
-
+ H+
HCO3
-
Na+
H+
C.A.
Blood Cell Lumen
ATPase
Renal Responses to a Metabolic Acidosis
• Decreased filtered bicarbonate
• Increased H+
secretion
• Increased NH3 producti...
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
Increased Renal Acid Secretion in Acidosis
Hormones Produced by the Kidney
Renin:
Released from juxtaglomerular apparatus when low
blood flow or low Na+. Renin lea...
Renin-Angiotensin system
Regulation of Blood Pressure and Sodium Output
The American Heritage® Dictionary
of the English L...
Stimulation of Renin Secretion
 Blood pressure activates renal vascular
receptor (baroreceptor) and  renin.
 Blood pres...
Renin-Angiotensin-Aldosterone System
↓ Blood Pressure
↑ Renin (Kidney)
↑ Angiotensin I
↑ Angiotensin II
Angiotensinogen
(Liver)
Angiotensin Converting
Enzyme (...
Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance
Renin/AII and Regulation of GFR
GFR = Kf(PGC - PBS - COPGC)
• “flight or fright”
∀⇑ sympathetic tone
• afferent arteriolar...
Renin/AII and Regulation of GFR
GFR = Kf(PGC - PBS - COPGC)
•Low BP sensed in afferent arteriole or low Na in
distal tubul...
Aldosterone
Secreted by the adrenal glands in response
to angiotensin II or high potassium
Acts in distal nephron to inc...
Anti-Diuretic Hormone (ADH)
Osmoreceptors in the brain (hypothalamus)
sense Na+ concentration of blood.
High Na+ (blood ...
Summary of ADH Actions on the Kidneys
• Increases permeability of entire Collecting Duct to Water.
• Increases permeabilit...
RENAL BLOOD FLOW (RBF)
NORMAL = 1200-1300ml/min.
(both kidneys)
= 20-25% of C. O.
RENAL PLASMA FLOW (RPF)
= RBF (1-hematoc...
Distribution of Blood Flow
Cortex - 1000 ml/min (75%)
Outer Medulla - 240 ml/min (20%)
Inner Medulla - 60 ml/min (5%)
Renal autoregulationRenal autoregulation
 Enables the kidney to maintain solute and water regulationEnables the kidney to...
• Blood Pressure
• Intrinsic:
autoregulation
1. Myogenic
2. Tubuloglomerular feedback
prostaglandins
• Extrinsic:
nerves
h...
Afferent and efferent control mechanism (myogenic)Afferent and efferent control mechanism (myogenic)
Renal vascular resist...
GFP = 60 mmHg (N), i.e. 60% of MAP
Afferent and efferent control mechanism (myogenic)Afferent and efferent control mechani...
Tubuloglomerular feedbackTubuloglomerular feedback
↑↑ GFRGFR
↓↓
↑↑ delivery of NaCl to distal tubuledelivery of NaCl to di...
 Normally, a balance is present between systems promotingNormally, a balance is present between systems promoting
renal v...
Epinephrine & norepinephrineEpinephrine & norepinephrine
↓↓
↑↑ Afferent arterial tone (directly & preferentially)Afferent ...
Renin angiotensin and Atrial natriuretic peptide (ANP)Renin angiotensin and Atrial natriuretic peptide (ANP)
 Hypotension...
ProstaglandinsProstaglandins
Systemic hypotension and renal ischemiaSystemic hypotension and renal ischemia
↓↓
Angiotensin...
Neuronal RegulationSympathetic outflow from spinal cord
↓
Celiac & renal plexus
↓
α1 receptors ↑ sodium reabsorption
in PC...
Autoregulation impaired inAutoregulation impaired in
 Severe sepsisSevere sepsis
 ARFARF
 During cardiopulmonary bypass...
ReferencesReferences
 Miller’s Anaesthesia, 6th ed. Functional anatomy and renalMiller’s Anaesthesia, 6th ed. Functional ...
Renal system
Renal system
Renal system
Renal system
Upcoming SlideShare
Loading in …5
×

Renal system

1,483 views

Published on

Published in: Health & Medicine
  • Be the first to comment

Renal system

  1. 1. DR.SREEJITH.H
  2. 2. Kidneys Kidneys are a pair of excretory organs situated on the posterior abdominal wall, extending from upper border of T12 to L3 vertebra Right kidney is slightly lower than the left Each kidney is 11 cm long, 6 cm broad and 3 cm thick, weight 150 g in males and 135 g in females Capsules or coverings of kidneys - Fibrous capsule, Peri- renal fat, Renal fascia and Para-renal fat Coronal segment – cortex; medulla; renal sinus
  3. 3. Functions of the Kidney:nce Regulation of body fluid volume and osmolality Regulation of electrolyte balance Regulation of acid-base balance Excretion of waste products (urea, ammonia, drugs, toxins) Production and secretion of hormones Regulation of blood pressure
  4. 4. Renal cortexRenal cortex  Cortical lobules - whichCortical lobules - which form caps over theform caps over the bases of the pyramidsbases of the pyramids  Renal columns - whichRenal columns - which dip in between thedip in between the pyramidspyramids Renal medullaRenal medulla  has 10 conical masseshas 10 conical masses called renal pyramids,called renal pyramids, their apices form renaltheir apices form renal papillaepapillae Renal sinusRenal sinus  Space that extends into kidney from hilusSpace that extends into kidney from hilus  Contains branches of renal artery and renal veinContains branches of renal artery and renal vein  Renal pelvis divides into 2-3 major calices and these in turn divide into 7-Renal pelvis divides into 2-3 major calices and these in turn divide into 7- 13 minor calices, each minor calyx (cup of flower) ends in an expansion13 minor calices, each minor calyx (cup of flower) ends in an expansion which is indented by 1-3 renal papillaewhich is indented by 1-3 renal papillae
  5. 5.  Histologically, each kidney is composed 1-3 millionHistologically, each kidney is composed 1-3 million uriniferous tubules. Each consists ofuriniferous tubules. Each consists of  Secretory part - which forms urine is called nephron, functionalSecretory part - which forms urine is called nephron, functional unit of kidneyunit of kidney  Nephrons open in to collecting tubules. Many such tubules uniteNephrons open in to collecting tubules. Many such tubules unite to form the ducts of Bellini which open into minor calicesto form the ducts of Bellini which open into minor calices Arterial SupplyArterial Supply  One renal artery on each side arising from abdominal aortaOne renal artery on each side arising from abdominal aorta  At or near hilus, renal artery divides into anterior andAt or near hilus, renal artery divides into anterior and posterior branches giving rise to segmental arteriesposterior branches giving rise to segmental arteries LymphaticsLymphatics  Lateral aortic nodesLateral aortic nodes Nerve SupplyNerve Supply  Renal plexus (an off shoot of coeliac plexus, T10-L1)Renal plexus (an off shoot of coeliac plexus, T10-L1)
  6. 6. Circulation of renal blood flowCirculation of renal blood flow Renal artery divides serially into – interlobar arteryRenal artery divides serially into – interlobar artery  arcuatearcuate  interlobular arteriesinterlobular arteries  afferent arteriolesafferent arterioles  capillary tufts of renal glomeruli into outer cortexcapillary tufts of renal glomeruli into outer cortex  efferent arteriolesefferent arterioles  in juxtamedullary zonein juxtamedullary zone  arterioles become vasa recta (closely applied to loop of henle)arterioles become vasa recta (closely applied to loop of henle) Venous drainage:Venous drainage: Stelate veinsStelate veins  interlobular veinsinterlobular veins  arcuate veinsarcuate veins  interlobar veinsinterlobar veins
  7. 7. Two types of nephrons are presentTwo types of nephrons are present  Cortical nephronsCortical nephrons with short loop of Henlewith short loop of Henle  Juxtamedullary nephronsJuxtamedullary nephrons with long loops of Henlewith long loops of Henle
  8. 8. Juxtaglomerular apparatusJuxtaglomerular apparatus  Macula densaMacula densa – modified portion of thick ascending limb– modified portion of thick ascending limb which is applied to glomerulus at the vascular pole betweenwhich is applied to glomerulus at the vascular pole between the afferent and efferent arterioles containingthe afferent and efferent arterioles containing chemoreceptor cells which sense tubular concentration ofchemoreceptor cells which sense tubular concentration of NaClNaCl  Granular cellsGranular cells – Produce renin, which catalyses the– Produce renin, which catalyses the formation of angiotensinformation of angiotensin  modulates efferent and afferentmodulates efferent and afferent arterial tone and GFRarterial tone and GFR
  9. 9. The Nephron Functional unit of the kidney (1,000,000) Responsible for urine formation: Filtration Secretion Reabsorption
  10. 10. Proximal Tubule Distal Tubule Thin descending Thin ascending Loop of Henle Thick ascending (diluting segment) Early Late Collecting Duct Cortical Medullary
  11. 11. FunctionsFunctions Nephron regulatesNephron regulates  Intravascular volume, osmolality, acid base balance,Intravascular volume, osmolality, acid base balance, excrete the end product of metabolism and drugsexcrete the end product of metabolism and drugs  Urine is formed by combination of glomerularUrine is formed by combination of glomerular ultrafiltration + tubular reabsorption and secretionultrafiltration + tubular reabsorption and secretion Nephron produces hormonesNephron produces hormones  Fluid homeostasis (renin, prostaglandins, kinins)Fluid homeostasis (renin, prostaglandins, kinins)  Bone metabolism (1,25-dihydroxycholecalciferol)Bone metabolism (1,25-dihydroxycholecalciferol)  Hematopoiesis (erythropoietin) – produced by interstitialHematopoiesis (erythropoietin) – produced by interstitial cells in peritubular capillary bed (85%cells in peritubular capillary bed (85% →→ stimulusstimulus hypoxiahypoxia
  12. 12. Basic Theory of Urine Formation Filtration Reabsorption Secretion Excretion
  13. 13. Glomerulus -Glomerulus - Five componentsFive components  Capillary endotheliumCapillary endothelium – 70-100– 70-100 nm fenestrations – restrictsnm fenestrations – restricts passage of cellspassage of cells  Glomerular basement membraneGlomerular basement membrane – filters plasma proteins– filters plasma proteins  Visceral epitheliumVisceral epithelium – podocytes– podocytes with s foot processes with 25-60with s foot processes with 25-60 nm gaps, permeability altered bynm gaps, permeability altered by contraction of foot processescontraction of foot processes  Parietal epitheliumParietal epithelium (Bowman’s(Bowman’s capsule)capsule)  MesangiumMesangium (interstitial cells) –(interstitial cells) – pericytes, structural support,pericytes, structural support, phagocytosis, restricts bld flow inphagocytosis, restricts bld flow in response to angiotensin-IIresponse to angiotensin-II FiltrationbarrierFiltrationbarrier
  14. 14. Filtration barrier - Size and charge selective Charge: all 3 layers contain negatively charged glycoproteins  restricts passage of other negatively charge proteins Size: Molecules with radius <1.8 nm  water, sodium, urea, glucose, inulin  freely filtered >3.6 nm  hemoglobin and albumin  not filtered Between 1.8-3.6  cations filtered, anions not Glomerulonephritis  negatively charged glycoproteins destroyed polyanionic proteins filtered  proteinuria
  15. 15. Glomerular Filtration Rate (GFR)Glomerular Filtration Rate (GFR)  Normal GFR: in men = 125 ml/min, 10% lower in femalesNormal GFR: in men = 125 ml/min, 10% lower in females  Depends on permeability of filtration barrierDepends on permeability of filtration barrier  Difference between hydrostatic processDifference between hydrostatic process pushing fluid intopushing fluid into Bowman’s spaceBowman’s space andand osmotic forces keeping fluid inosmotic forces keeping fluid in plasmaplasma GFR = Kuf [(Pgc – Pbs) – (GFR = Kuf [(Pgc – Pbs) – (ΠΠgc –gc – ΠΠbs)bs) Pgc & Pbs = Hydrostatic pressure in glomerular capillaryPgc & Pbs = Hydrostatic pressure in glomerular capillary and basement membraneand basement membrane ΠΠgc &gc & ΠΠbs = plasma oncotic pressure in glomerularbs = plasma oncotic pressure in glomerular capillary and basement membranecapillary and basement membrane Kuf = Ultrafiltration coefficient reflects capillary permeabilityKuf = Ultrafiltration coefficient reflects capillary permeability and glomerular surface areaand glomerular surface area
  16. 16. Regulation of GFR Changes in Kf (Permeability or Surface area): Mesangial Cell Contraction or Relaxation + ANP, NO - AII, Endothelin, Norepi, Epi, ADH
  17. 17. A volume of plasma from which a substance is completely removed by the kidneys per unit time. Clearance Where UF = urine flow; Ux = urine concentration of X; Px = plasma concentration of X; Cx = clearance of X Cx = UF • Ux = Volume/Time eg. ml/min or L/day Px
  18. 18. Freely Filtered Not Metabolized Not Reabsorbed Does Not Change GFR Not Secreted Not Produced Measurement of GFR (Inulin M.W. = 5,000) Amount Filtered = Amount Excreted GFR · PIN = UF ·UIN GFR = UF ·UIN = CIN PIN (Filtered Inulin = Excreted Inulin) Excreted Inulin Plasma Inulin(volume/time)
  19. 19. Reabsorption and secretion
  20. 20. Reabsorption Active Transport –requires ATP Na+, K+ ATP pumps Passive Transport- Na+ symporters (glucose, a.a., etc) Na+ antiporters (H+) Ion channels Osmosis
  21. 21. Factors influencing Reabsorption Saturation: Transporters can get saturated by high concentrations of a substance - failure to resorb all of it results in its loss in the urine (eg, renal threshold for glucose is about 180mg/dl). Rate of flow of the filtrate: affects the time available for the transporters to reabsorb molecules.
  22. 22. Proximal tubule - reabsorbs 65 % of filtered Na+ as well as Cl- , Ca2+ , PO4, HCO3 - . 75-90% of H20. Glucose, carbohydrates, amino acids, and small proteins are also reabsorbed here. Loop of Henle - reabsorbs 25% of filtered Na+. Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs HCO3-. Collecting duct - reabsorbs the remaining 2% of Na+ only if the hormone aldosterone is present. H20 depending on hormone ADH.
  23. 23. Secretion Proximal tubule – uric acid, bile salts, metabolites, some drugs, some creatinine Distal tubule – Most active secretion takes place here including organic acids, K+, H+, drugs, Tamm- Horsfall protein (main component of hyaline casts).
  24. 24. TubuleTubule Proximal Tubule (PCT)Proximal Tubule (PCT)  60-75% ultrafiltrate60-75% ultrafiltrate  reabsorb isotonically in PCTreabsorb isotonically in PCT  To be reabsorbed most substances have to pass throughTo be reabsorbed most substances have to pass through apical side of cell membraneapical side of cell membrane  basolateral cell membranebasolateral cell membrane  renal interstitiumrenal interstitium  peritubular capillariesperitubular capillaries  Carbonic anhydrase inhibitors (acetazolamide) interfereCarbonic anhydrase inhibitors (acetazolamide) interfere with Nawith Na++ reabsorption and Hreabsorption and H++ secretion in PCTsecretion in PCT
  25. 25. Pump mechanisms of tubulePump mechanisms of tubule
  26. 26. Sodium reabsorption in PCT (65-75% of filtered NaSodium reabsorption in PCT (65-75% of filtered Na++ loadload reabsorbed)reabsorbed)  Na+ is actively transported out of PCT cells at their capillaryNa+ is actively transported out of PCT cells at their capillary sides by membrane bound Nasides by membrane bound Na++ KK++ ATPaseATPase ↓↓  Resulting low intracellular concentration of NaResulting low intracellular concentration of Na++ ↓↓  Passive movement of KPassive movement of K++ down its gradient from tubular fluid intodown its gradient from tubular fluid into epithelial cellsepithelial cells ↓↓  NaNa++ reabsorption is coupled with reabsorption of other solutesreabsorption is coupled with reabsorption of other solutes  and secretion of Hand secretion of H++  reabsorption of 90% of filtered HCOreabsorption of 90% of filtered HCO33 ionsions  Chloride absorptionChloride absorption  passivepassive  follows concentrationfollows concentration gradientgradient  transverse tight junctions between adjacent tubulartransverse tight junctions between adjacent tubular epitheliumepithelium
  27. 27.  WaterWater  specialised channels composed of membranespecialised channels composed of membrane protein aquaporin-1 (apical membrane)protein aquaporin-1 (apical membrane)  facilitate waterfacilitate water movement passively along osmotic gradientsmovement passively along osmotic gradients Secretion :Secretion :  Cations (Cations ( Creatinine, cimetidine, quinidine,) :Creatinine, cimetidine, quinidine,) : share sameshare same pump mechanism and interfere in excretion of one anotherpump mechanism and interfere in excretion of one another  Anions includeAnions include Urate, ketoacids, penicillins,Urate, ketoacids, penicillins, cephalosposins, diuretics, salicyclatescephalosposins, diuretics, salicyclates andand most x-ray dyesmost x-ray dyes
  28. 28. FunctionsFunctions ReabsorptionReabsorption  NaClNaCl  WaterWater  BicarbonateBicarbonate  GlucoseGlucose  ProteinsProteins  AminoacidsAminoacids  KK++ , Mg, PO, Mg, PO44 ++ , uric acid,, uric acid, ureaurea SecretionSecretion  Organic anionsOrganic anions  Organic cationsOrganic cations  Ammonia productsAmmonia products Reabsorption of solutes in PCTReabsorption of solutes in PCT
  29. 29. Proximal Tubule Reabsorption Early Late Na+Na+ K + K + LumenCapillary Na+ K+ ↑π ↓Pc Na+Na+ K + K + Na+ K+ Na+ Na+ Cl- Cl- Cl-Cl- & H2O H2O H2O & H2O
  30. 30. Proximal Tubule Reabsorption
  31. 31. PROXIMAL TUBULE SUMMARY • 2/3 of salts and water reabsorbed •All glucose and a.a. reabsorbed •Reabsorption is isotonic: PT Osmolality is isotonic at the beginning & the end
  32. 32. CONCENTRATION & DILUTION •permeability aspects of the Loop of Henle, DT & CD. •the importance of the high medullary interstitial osmolality. •the reabsorption of Na+, Cl-, urea and water in the Loop, DT and CD. •changes in osmolality along the tubule and actions of ADH on the CD.
  33. 33. Loop of HenleLoop of Henle  25-30% ultrafiltrate reaches loop of Henle25-30% ultrafiltrate reaches loop of Henle ↓↓  15-20% filtered Na15-20% filtered Na++ load reabsorbedload reabsorbed  Solute and water reabsorption is passive and followsSolute and water reabsorption is passive and follows concentration and osmotic gradientsconcentration and osmotic gradients (except thick(except thick ascending loop)ascending loop) Ascending thick segmentAscending thick segment  Sodium reabsorption is coupled to both KSodium reabsorption is coupled to both K++ and Cland Cl-- reabsorptionreabsorption  ClCl-- in tubular fluid is rate limiting factorin tubular fluid is rate limiting factor  Important site for calcium and magnesium reabsorptionImportant site for calcium and magnesium reabsorption  Parathyroid hormoneParathyroid hormone ↑↑ calcium reabsorption at this sitecalcium reabsorption at this site  Loop diuretics inhibit Na and Cl reabsorption in TALLoop diuretics inhibit Na and Cl reabsorption in TAL compete with Cl- for its binding site on carrier proteincompete with Cl- for its binding site on carrier protein
  34. 34. Sodium and chloride reabsorption in thick ascending loopSodium and chloride reabsorption in thick ascending loop
  35. 35. Countercurrent exchange The structure and transport properties of the loop of Henle in the nephron create the Countercurrent multiplier effect. A substance to be exchanged moves across a permeable barrier in the direction from greater to lesser concentration. Image from http://en.wikipedia.org/wiki/Countercurrent_exchange
  36. 36. Loop of Henle Goal= make isotonic filtrate into hypertonic urine (don’t waste H20!!) Counter-current multiplier:  Descending loop is permeable to Na+, Cl-, H20  Ascending loop is impermeable to H20- active NaCl transport  Creates concentration gradient in interstitium  Urine actually leaves hypotonic but CD takes adv in making hypertonic
  37. 37.  Tubular fluid enters the distal PCT iso-osmotic with plasma (300Tubular fluid enters the distal PCT iso-osmotic with plasma (300 mOsm/kg)mOsm/kg) (1)(1)..  Descending limb of HenleDescending limb of Henle (2)(2)  water rapidly diffuses out into thewater rapidly diffuses out into the increasingly hypertonic medulla and is removed by the vasa rectaincreasingly hypertonic medulla and is removed by the vasa recta  Tubular fluid becomes hypertonic, largely because of conc. of NaCl.Tubular fluid becomes hypertonic, largely because of conc. of NaCl.  Urea diffuses in from the hypertonic interstitium, further increasingUrea diffuses in from the hypertonic interstitium, further increasing tubular fluid osmolality (1200 mOsm/kg).tubular fluid osmolality (1200 mOsm/kg).  Thin ascending loop of HenleThin ascending loop of Henle (3)(3), NaCl passively diffuses into the, NaCl passively diffuses into the interstitium along its concentration gradientinterstitium along its concentration gradient  But water is trapped in the water-impermeable tubule, whichBut water is trapped in the water-impermeable tubule, which progressively decreases tubular fluid osmolality.progressively decreases tubular fluid osmolality.  Urea passively diffuses into the tubular fluid (urea recycling).Urea passively diffuses into the tubular fluid (urea recycling).  Tubular dilution is accelerated by active reabsorption of NaCl in theTubular dilution is accelerated by active reabsorption of NaCl in the thick ascending loop and proximal distal tubulethick ascending loop and proximal distal tubule (4)(4)..
  38. 38.  Fluid entering distal tubule is quite hypo-osmotic (100 mOsm/kg)Fluid entering distal tubule is quite hypo-osmotic (100 mOsm/kg)  In the collecting segmentIn the collecting segment (5)(5), the osmolality of the tubular fluid, the osmolality of the tubular fluid returns to that of plasma (300 mOsm/kg)returns to that of plasma (300 mOsm/kg)  But contents of the proximal tubule, the solute component consistsBut contents of the proximal tubule, the solute component consists largely of urea, creatinine, and other excreted compounds.largely of urea, creatinine, and other excreted compounds.  Increased plasma antidiuretic hormone (ADH) renders the corticalIncreased plasma antidiuretic hormone (ADH) renders the cortical and medullary collecting ductsand medullary collecting ducts (6)(6) permeable to water, whichpermeable to water, which passively diffuses into the hypertonic medullary interstitium.passively diffuses into the hypertonic medullary interstitium.  Some urea diffuses out into the medulla, the maximal osmolality ofSome urea diffuses out into the medulla, the maximal osmolality of concentrated urineconcentrated urine (7)(7) approaches that of the hypertonic medullaryapproaches that of the hypertonic medullary interstitium, about 1200 mOsm/kginterstitium, about 1200 mOsm/kg  In the absence of ADH, the collecting ducts remain impermeable toIn the absence of ADH, the collecting ducts remain impermeable to water, and the urine is diluted.water, and the urine is diluted.
  39. 39. Counter current multiplierCounter current multiplier
  40. 40. Counter current exchange by vasa rectaCounter current exchange by vasa recta
  41. 41. Distal tubuleDistal tubule  Very tight junctions between tubular cellsVery tight junctions between tubular cells relatively impermeable to water and Narelatively impermeable to water and Na++  5% of filtered Na5% of filtered Na++ loadload  reabsorbedreabsorbed  Major site of parathyroid hormone and vit DMajor site of parathyroid hormone and vit D mediated calcium reabsorptionmediated calcium reabsorption  The late distal segment (collecting segment)The late distal segment (collecting segment)  Hormone mediated CaHormone mediated Ca++ reabsorptionreabsorption  Aldosterone mediated NaAldosterone mediated Na++ reabsorptionreabsorption
  42. 42. Collecting tubuleCollecting tubule 5-7% of filtered Na5-7% of filtered Na++ load is reabsorbedload is reabsorbed Cortical collecting tubule – two types ofCortical collecting tubule – two types of cells:cells: Principal cellsPrincipal cells  secrete Ksecrete K++ aldosteronealdosterone mediated Namediated Na++ reabsorptionreabsorption Intercalated cellsIntercalated cells  acid base regulationacid base regulation
  43. 43. Secretion of hydrogen and reabsorption of bicarbonateSecretion of hydrogen and reabsorption of bicarbonate and potassium in cortical collecting tubuleand potassium in cortical collecting tubule
  44. 44. AldosteroneAldosterone  Enhances NaEnhances Na++ KK++ ATPase activity byATPase activity by ↑↑ number of open Nanumber of open Na++ & K& K++ channels in luminal membranechannels in luminal membrane  Enhances HEnhances H++ secreting ATPase on the luminal border odsecreting ATPase on the luminal border od intercalated cellsintercalated cells  Because principal cells reabsorb NaBecause principal cells reabsorb Na++ via an electrogenicvia an electrogenic pumppump  Either ClEither Cl-- must be reabsorbedmust be reabsorbed  KK++ must be secreted to maintain electroneutralitymust be secreted to maintain electroneutrality  ↑↑ intracellular Kintracellular K++ favours Kfavours K++ secretionsecretion
  45. 45. K+ sparing diureticsK+ sparing diuretics CompetitiveCompetitive  Spironolactone – aldosterone receptor antagonistSpironolactone – aldosterone receptor antagonist  Inhibits aldosterone mediated sodium reabsorption andInhibits aldosterone mediated sodium reabsorption and potassium secretion in collecting tubulepotassium secretion in collecting tubule Non-competitiveNon-competitive  Triamterene and amiloride inhibits sodium reabsorption andTriamterene and amiloride inhibits sodium reabsorption and potassium secretion by decreasing number of openpotassium secretion by decreasing number of open channels in luminal membrane of collecting tubulechannels in luminal membrane of collecting tubule
  46. 46. Medullary collecting tubuleMedullary collecting tubule  Site of actiion of ADH or AVP (arginine vasopressin)Site of actiion of ADH or AVP (arginine vasopressin)  activates adenylate cyclaseactivates adenylate cyclase  DehydrationDehydration  ↑↑ ADH secretionADH secretion  luminal membraneluminal membrane becomes permeable to waterbecomes permeable to water  water is osmotically drawnwater is osmotically drawn out of tubular fluid passing through the medullaout of tubular fluid passing through the medulla  concentrated urine (upto 1400 mos)concentrated urine (upto 1400 mos)  Adequate hydration – suppressed ADH secretionAdequate hydration – suppressed ADH secretion  fluid influid in collecting tubule passes through medulla unchanged andcollecting tubule passes through medulla unchanged and remains hypotonic (100-200 msom/l)remains hypotonic (100-200 msom/l)  Hydrogen ion secreted are excreted in the form of titrableHydrogen ion secreted are excreted in the form of titrable acids (phosphates) and ammonium ionsacids (phosphates) and ammonium ions
  47. 47. 300 300 300 300 300 300 1200 1200 1200 900 900 900 400 400 400 500 500 500 600 600 600 700 700 700 800 800 800 1100 1100 1100 1000 1000 1000
  48. 48. 300 300 300 300 300 300 1200 Low permeability to solutes High permeability to water H2O H2O 1200 1200 1200 Thin descending limb of the loop of Henle
  49. 49. 300 300 300 300 300 300 1200 permeable to solutes H2O H2O Thin ascending limb of the loop of Henle low permeability to H2O NaCl Urea
  50. 50. 300 300 300 300 300 300 1200 1200 1200 1200 Na+ K+ 2 Cl- Na+ K+ 2 Cl- 150 Thick Ascending limb of the loop of Henle (TAL) Diluting segment impermeable to H2O Special carriers co-transport ions from tubule to interstitium Na+ K+ 2 Cl- Na+ K+ 2 Cl-
  51. 51. 300 300 300 300 300 1200 1200 1200 1200 Na+ K+ 2 Cl- Na+ K+ 2 Cl- 150Distal Tubule Na+ K+ 2 Cl- Na+ K+ 2 Cl- Impermeable to H2O Special carriers co-transport ions from tubule to interstitium 60Na Cl Na Cl
  52. 52. 300 300 300 300 300 1200 1200 1200 1200 Na+ K+ 2 Cl- Na+ K+ 2 Cl- 150 Na+ K+ 2 Cl- Na+ K+ 2 Cl- 60Na Cl Na Cl Cortical Collecting Duct 1200 H2O H2O H2O H2O Medullary Collecting Duct Variable permeability to H2O Regulated by Antidiuretic Hormone (ADH)
  53. 53. Renal Regulation of Special Substances Urea, Glucose, Phosphate, Sulfate, Water, Sodium, Potassium & Calcium John R. Dietz Physiology & Biophysics University of South Florida College of Medicine
  54. 54. Renal Regulation of Special Substances (Urea, Glucose, Phosphate & Sulfate) •How urea is reabsorbed. •Principles of secondary active transport and how it applies to carrier mediated secretion and reabsorption. •Transport maximum and how it is calculated. •Renal handling of glucose in diabetes.
  55. 55. Reabsorption of Urea 50% of Filtered Urea Reabsorbed 4 5 30 100500600 600 Tubular Concentrations of Urea are in mmoles/L Maximal ADH H2O H2O H2O H2O
  56. 56. Reabsorption of Glucose in the Proximal Tubule LumenBasal Membrane Na+ K+ Glucose Glucose Na+ SGL T1 GL UT2
  57. 57. Glu Sodium Powered Secondary Active Transport Na+ Na+ LumenCell Membrane Stanley J. Nazian, Ph..D., This slide was stolen without remorse from Na+ Na+ Na+ Na+ Na+ Glu
  58. 58. Reabsorption of Glucose in the Proximal Tubule LumenCapillary Na+ K+ Glucose Glucose Na+ SGL T1 GL UT2
  59. 59. Facilitated Diffusion Interstitium CellMembrane Glu Glu Glu Glu Glu GluGlu
  60. 60. Secondary Active Transport
  61. 61. Henderson-Hasselbalch Equation: pH = pK + log HCO3 - CO2 pH =
  62. 62.   H+ exchanged for Na+ H+ ATPase H+ - K+ ATPase Various Mechanisms of H+ Secretion
  63. 63. H+ H+ H+ H+ H+ H+ H+ H+ H+
  64. 64. CO2 + H2O H2CO3 HCO3 - + H+ HCO3 - Cl- HCO3 - Na+ Na+ H+ ATPase H+ C.A. Blood Cell Lumen ATPase H+ K+ Renal Transport of HCO3 - & H+
  65. 65. CO2 + H2O H2CO3 HCO3 - + H+ Bicarbonate Reabsorption C.A. Filtered H2CO3 CO2 + H2O C.A. Primarily in Proximal Tubule - 0 % of Acid Excretion Blood Cell Lumen HCO3 - Na+ Na+ HCO3 - Na+ H+ H+
  66. 66. CO2 + H2O H2CO3 HCO3 - + H+ Bicarbonate Reabsorption C.A. Filtered H2CO3 CO2 + H2O C.A. Primarily in Proximal Tubule - 0 % of Acid Excretion Blood Cell Lumen HCO3 - Na+ Na+ HCO3 - Na+ H+ H+
  67. 67. CO2 + H2O H2CO3 HCO3 - + H+ Titratable Acid Excretion C.A. Na+ Filtered H+ + HPO4 2- Primarily in Distal Tubule & CD - 33 % of Acid Excretion Na+ + H2PO4 - or H SO4 - + HPO4 2- or SO4 2- H+ Blood Cell Lumen HCO3 - Cl- ATPase
  68. 68. CO2 + H2O H2CO3 HCO3 - + H+ Ammonium Excretion C.A. H+ + NH3 Primarily in Distal Tubule & CD - 66 % of Acid Excretion NH4 + H+ NH3 produced in the cortex from glutamine NH3 NH3 [H+] is 1000 X greater in the lumen than the cell HCO3 - Cl- ATPase
  69. 69. H+ Secretion in the Nephron
  70. 70. Factors that Stimulate H+ Secretion • Acidosis Metabolic or Respiratory • Hypokalemia • Aldosterone
  71. 71. Regulation of H+ Excretion CO2 + H2O H2CO3 HCO3 - + H+ HCO3 - Na+ H+ C.A. Blood Cell Lumen ATPase
  72. 72. Renal Responses to a Metabolic Acidosis • Decreased filtered bicarbonate • Increased H+ secretion • Increased NH3 production
  73. 73. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ Increased Renal Acid Secretion in Acidosis
  74. 74. Hormones Produced by the Kidney Renin: Released from juxtaglomerular apparatus when low blood flow or low Na+. Renin leads to production of angiotensin II, which in turn ultimately leads to retention of salt and water. Erythropoietin: Stimulates red blood cell development in bone marrow. Will increase when blood oxygen low and anemia (low hemoglobin). Vitamin D3: Enzyme converts Vit D to active form 1,25(OH)2VitD. Involved in calcium homeostasis.
  75. 75. Renin-Angiotensin system Regulation of Blood Pressure and Sodium Output The American Heritage® Dictionary of the English Language
  76. 76. Stimulation of Renin Secretion  Blood pressure activates renal vascular receptor (baroreceptor) and  renin.  Blood pressure also  GFR and delivery of Cl- to Macula Densa in the distal tubule which  renin.  Blood pressure causes a reflex activation of renal sympathetic nerves which  renin. Juxtaglomerular Apparatus
  77. 77. Renin-Angiotensin-Aldosterone System
  78. 78. ↓ Blood Pressure ↑ Renin (Kidney) ↑ Angiotensin I ↑ Angiotensin II Angiotensinogen (Liver) Angiotensin Converting Enzyme (ACE) ↑ Aldosterone ↑ Na+ Reabsorption ↑ FF↑ ADH & Thirst (water reabsorption) Vasoconstriction +
  79. 79. Renin, Angiotensin, Aldosterone: Regulation of Salt/Water Balance
  80. 80. Renin/AII and Regulation of GFR GFR = Kf(PGC - PBS - COPGC) • “flight or fright” ∀⇑ sympathetic tone • afferent arteriolar constriction (divert cardiac output to other organs) ∀⇓PGC ∀⇓GFR and renal blood flow
  81. 81. Renin/AII and Regulation of GFR GFR = Kf(PGC - PBS - COPGC) •Low BP sensed in afferent arteriole or low Na in distal tubule •renin released •renin converts angiotensinogen to Angiotensin I •ACE converts AI to AII •efferent > afferent arteriolar constriction ∀⇑ PGC ⇒ ⇑ GFR (this is AUTOREGULATION of GFR) PGC⇑ constricts
  82. 82. Aldosterone Secreted by the adrenal glands in response to angiotensin II or high potassium Acts in distal nephron to increase resorption of Na+ and Cl- and the secretion of K+ and H+ NaCl resorption causes passive retention of H2O
  83. 83. Anti-Diuretic Hormone (ADH) Osmoreceptors in the brain (hypothalamus) sense Na+ concentration of blood. High Na+ (blood is highly concentrated) stimulates posterior pituitary to secrete ADH. ADH upregulates water channels on the collecting ducts of the nephrons in the kidneys. This leads to increased water resorption and decrease in Na concentration by dilution
  84. 84. Summary of ADH Actions on the Kidneys • Increases permeability of entire Collecting Duct to Water. • Increases permeability of Medullary CD to Urea. • Decreases Vasa Recta blood flow. • Increases expression of the Na/K/2Cl transporter in the TAL.
  85. 85. RENAL BLOOD FLOW (RBF) NORMAL = 1200-1300ml/min. (both kidneys) = 20-25% of C. O. RENAL PLASMA FLOW (RPF) = RBF (1-hematocrit) = 600-700 ml/min. (both kidneys) FILTRATION FRACTION (FF) = GFR/RPF = 125ml/min/650 ml/min = 20 % Regulation of Blood Flow (review of CV) Clearance (again?) John R. Dietz, Ph.D. Molecular Pharmacology & Physiology University of South Florida College of Medicine
  86. 86. Distribution of Blood Flow Cortex - 1000 ml/min (75%) Outer Medulla - 240 ml/min (20%) Inner Medulla - 60 ml/min (5%)
  87. 87. Renal autoregulationRenal autoregulation  Enables the kidney to maintain solute and water regulationEnables the kidney to maintain solute and water regulation independently of fluctuations in arterial blood pressureindependently of fluctuations in arterial blood pressure  Kidney maintains a constant renal blood flow and GFRKidney maintains a constant renal blood flow and GFR through renal arterial range of 80-180 mmHgthrough renal arterial range of 80-180 mmHg
  88. 88. • Blood Pressure • Intrinsic: autoregulation 1. Myogenic 2. Tubuloglomerular feedback prostaglandins • Extrinsic: nerves hormones Control of Renal Blood Flow
  89. 89. Afferent and efferent control mechanism (myogenic)Afferent and efferent control mechanism (myogenic) Renal vascular resistanceRenal vascular resistance ↓↓ Mediated by variable resistance of afferent arteriolesMediated by variable resistance of afferent arterioles ↓↓ ↓↓ mean arterial pressuremean arterial pressure ↓↓ ↓↓ renal vascular resistancerenal vascular resistance ((↓↓ tone, dilatation of afferent arterioles)tone, dilatation of afferent arterioles) ↓↓ Myogenic responseMyogenic response ↓↓ Renal blood flow and GFR maintainedRenal blood flow and GFR maintained ↓↓ Vice versa, afferent arterioles constrict in response toVice versa, afferent arterioles constrict in response to ↑↑ MAPMAP
  90. 90. GFP = 60 mmHg (N), i.e. 60% of MAP Afferent and efferent control mechanism (myogenic)Afferent and efferent control mechanism (myogenic)
  91. 91. Tubuloglomerular feedbackTubuloglomerular feedback ↑↑ GFRGFR ↓↓ ↑↑ delivery of NaCl to distal tubuledelivery of NaCl to distal tubule ↓↓ ↑↑ Cl- sensed by macular Densa cellsCl- sensed by macular Densa cells ↓↓ Release of renin (from afferent arterioles)Release of renin (from afferent arterioles) ↓↓ AngiotensinAngiotensin ↓↓ Arteriolar constrictionArteriolar constriction ↓↓ GFR and RBFGFR and RBF
  92. 92.  Normally, a balance is present between systems promotingNormally, a balance is present between systems promoting renal vasoconstriction and sodium retention versus systemsrenal vasoconstriction and sodium retention versus systems promoting renal vasodilation and sodium excretion.promoting renal vasodilation and sodium excretion.  Surgical stress, ischemia, and sepsis tip the balance in favor ofSurgical stress, ischemia, and sepsis tip the balance in favor of vasoconstriction and sodium retention.vasoconstriction and sodium retention.  On the other hand, hypervolemia (or induction of atrial stretch)On the other hand, hypervolemia (or induction of atrial stretch) tips the balance in favor of vasodilation and sodium excretion.tips the balance in favor of vasodilation and sodium excretion. Hormonal RegulationHormonal Regulation
  93. 93. Epinephrine & norepinephrineEpinephrine & norepinephrine ↓↓ ↑↑ Afferent arterial tone (directly & preferentially)Afferent arterial tone (directly & preferentially) ↓↓ MarkedMarked ↓↓ in GFR prevented indirectly by release of renin andin GFR prevented indirectly by release of renin and angiotensin-IIangiotensin-II
  94. 94. Renin angiotensin and Atrial natriuretic peptide (ANP)Renin angiotensin and Atrial natriuretic peptide (ANP)  Hypotension or hypovolemiaHypotension or hypovolemia  reninrenin  afferent arterioleafferent arteriole  angiotensin IIangiotensin II  release of aldosterone from the adrenal cortexrelease of aldosterone from the adrenal cortex  Volume reexpansion causes atrial distentionVolume reexpansion causes atrial distention  release of ANPrelease of ANP  ANP inhibits the release of renin, renin's action onANP inhibits the release of renin, renin's action on angiotensinogen to form angiotensin II, angiotensin-inducedangiotensinogen to form angiotensin II, angiotensin-induced vasoconstriction, stimulation of aldosterone secretion byvasoconstriction, stimulation of aldosterone secretion by angiotensin II, and action of aldosterone on collecting ductangiotensin II, and action of aldosterone on collecting duct
  95. 95. ProstaglandinsProstaglandins Systemic hypotension and renal ischemiaSystemic hypotension and renal ischemia ↓↓ Angiotensin induced prostaglandin synthesis (PGDAngiotensin induced prostaglandin synthesis (PGD22, PGE, PGE22 & PGI& PGI22)) ↓↓ Vasodilation (protective mechanism)Vasodilation (protective mechanism)
  96. 96. Neuronal RegulationSympathetic outflow from spinal cord ↓ Celiac & renal plexus ↓ α1 receptors ↑ sodium reabsorption in PCT ↓ α2 receptors ↓ Na+ reabsorption and ↑ water excretion Dopamine dilates afferent andDopamine dilates afferent and efferent arteriolesefferent arterioles (via D1 receptor activation)(via D1 receptor activation) ↓↓ Low dose dopamine partiallyLow dose dopamine partially reverses norepinephrine inducedreverses norepinephrine induced renal vasoconstrictionrenal vasoconstriction ↓↓ DopamineDopamine ↓↓ PCT NaPCT Na++ reabsorptionreabsorption
  97. 97. Autoregulation impaired inAutoregulation impaired in  Severe sepsisSevere sepsis  ARFARF  During cardiopulmonary bypassDuring cardiopulmonary bypass  Autoregulation is not abolished by most anaesthetic agentsAutoregulation is not abolished by most anaesthetic agents
  98. 98. ReferencesReferences  Miller’s Anaesthesia, 6th ed. Functional anatomy and renalMiller’s Anaesthesia, 6th ed. Functional anatomy and renal physiology.physiology.  Wylie and Churchill Davidson’s. Functional anatomy and renalWylie and Churchill Davidson’s. Functional anatomy and renal physiology, 7th ed.physiology, 7th ed.  Barash Clinical Anaesthesia, Functional anatomy and renalBarash Clinical Anaesthesia, Functional anatomy and renal physiology, 5th ed.physiology, 5th ed.  Morgan. Clinical Anaesthesiology, 4Morgan. Clinical Anaesthesiology, 4thth ed.ed.  Ganong WF. Review of Medical Physiology, 20Ganong WF. Review of Medical Physiology, 20thth ed.ed.

×