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. 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. 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. 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. 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. 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. 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. The Nephron
Functional unit of the kidney (1,000,000)
Responsible for urine formation:
Filtration
Secretion
Reabsorption
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. Basic Theory of Urine Formation
Filtration
Reabsorption
Secretion
Excretion
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. 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.
16. 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
17.
18. Regulation of GFR
Changes in Kf (Permeability or
Surface area):
Mesangial Cell Contraction or
Relaxation
+ ANP, NO
- AII, Endothelin, Norepi,
Epi, ADH
19. 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
20. 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)
22. Reabsorption
Active Transport –requires ATP
Na+, K+ ATP pumps
Passive Transport-
Na+ symporters (glucose, a.a., etc)
Na+ antiporters (H+)
Ion channels
Osmosis
23. 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.
24. 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.
25. 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).
26.
27. 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
29. 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
30. 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
34. 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
35. 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.
36. 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
37. Sodium and chloride reabsorption in thick ascending loopSodium and chloride reabsorption in thick ascending loop
38. 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
39. 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
40. 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)..
41. 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.
44. 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
45. 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
46. Secretion of hydrogen and reabsorption of bicarbonateSecretion of hydrogen and reabsorption of bicarbonate
and potassium in cortical collecting tubuleand potassium in cortical collecting tubule
47. 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
48. 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
49. 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
56. 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
57. 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.
58. 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
59. Reabsorption of Glucose
in the Proximal Tubule
LumenBasal Membrane
Na+
K+
Glucose
Glucose
Na+
SGL
T1
GL
UT2
60. 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
68. 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+
69. 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+
70. 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
71. 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
77. 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.
79. 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
83. 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
84. 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
85. 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
86. 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
87. 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.
88. 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
90. 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
92. 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
93. GFP = 60 mmHg (N), i.e. 60% of MAP
Afferent and efferent control mechanism (myogenic)Afferent and efferent control mechanism (myogenic)
94. 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
95. 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
96. 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
97. 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
100. 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
101. 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.
