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Lu Ning 卢 宁
Associate professorDepartment of Physiology and
Pathophysiology
Buiding 7, Rm 219 Tel:[email protected]
intenet classroom: ID -Ning
Medical education between Medical education between China and USAChina and USA
High school High school
medicine (5-8y) Biology (4y)
Resident medical college (4y)Exam
Resident Doctor Doctor
ReunionReunion
flower showflower showShanghai plant gardenShanghai plant garden
Painting ExhibitionPainting Exhibition(2010.3.10(2010.3.10--6.6)6.6)
Shanghai MuseumShanghai Museum
82 pieces works
during the 15-20thcentury
saved by Italy Museum
2010.4.102010.4.10--5.95.9
“陈逸飞 Art Exhibition”Shanghai Art galleryShanghai Art gallery
Kidney
Urine formation and excretion
Urinary SystemUrinary System
Renal failureRenal failure
Overview Overview –– Functions of the KidneyFunctions of the Kidney
Regulation of body fluid osmolality and volumes
Regulation of electrolyte and water Excretion of waste products Regulation of acid- base balance
filtrationSelective reabsorptionsecretion
Urine formation
Functions of the KidneyFunctions of the KidneyRegulation of body fluid osmolality and volumes
maintain cell volumenormal function of the cardiovascular system
Regulation of electrolyte and water Na+ , K + ,Cl -, HCO3
-, H +, Ca + (excretion=intake)
Excretion of waste products (Urea, Uric acids, creatine)
Regulation of acid- base balance
Functions of the KidneyFunctions of the Kidney
Production of hormoneserythropoietin: stimulate red blood cell
formation by bone marroweg: Anemia
renin: renin-angiotensin-addsterone system
Calcitriol : a metabolite of Vit D3
Renal failureRenal failure
Urine FormationUrine Formation
Structure of the KidneyStructure of the Kidney
一、nephron1~ 1.2 million each
glomerulusBowman’s capsule
Renal corpuscle
Renal tuble
proximal tubule
loop of henle
distal tuble
nephronnephron
Nervous System
Urinary SystemUrinary System
Cortical Cortical nephronnephron and and JuxtamedullaryJuxtamedullarynephronnephron
Cortical Cortical JuxtamedullaryJuxtamedullary
location
sizeA./A.E (efferent)
ratioin diameter
A.E
function
85%
short
2:1
Peritubularcapillaries
Filtration and reabsorbtion of salt
15%
loog
1:1
Vasa recta, peritubularcapillaries
Concentration and diluting
NephronNephron
Cortical Cortical nephronnephron and and JuxtamedullaryJuxtamedullarynephronnephron
Cortical Cortical JuxtamedullaryJuxtamedullary
location
sizeA./A.E ratioin diameter
A.E
function
85%
short
2:1
Peritubularcapillaries
Filtration and reabsorbtion
15%
loog
1:1
Vasa recta
Concentration and diluting
球旁器 juxtaglomerularjuxtaglomerular apparatusapparatus
Juxtaglomerular apparatus
1) The juxtaglomerular cells: renin-producing granular
cells
2) Macula densa
3) Extraglomerular mesangial cells (Mesangial cell)
1. juxtaglomerular cell
granular cells:
modified smooth muscle cells
Produce ,store and release renin
juxtaglomerularjuxtaglomerular apparatusapparatus
juxtaglomerularjuxtaglomerular apparatusapparatus
2. macula densa:
detecting change of NaCl content → send a signal to the renal arterial system
juxtaglomerularjuxtaglomerular apparatusapparatus
3. extraglomerularmesangial cell:
phagocytic
Blood Blood Supply (main filtration: Supply (main filtration: in cortex of in cortex of nephronnephron))
RBF:1200 ml/min, 20-25 % of the cardiac output 94 % through the cortex; 5-6 % through the outer medulla; < 1 % through the inner medulla
nephronnephron
CapillaryCapillary
Regulation of Renal CirculationRegulation of Renal Circulation
1.Autoregulation of Renal CirculationRelatively constant of RBF and GFR,when the range
of arterial blood pressure: 80 to 180mmHg
Mechanisms of autoregulation: 1) Myogenic mechanism 2) Flow dependent mechanism
(tubuloglomerular feedback)
Regulation of Renal CirculationRegulation of Renal Circulation
1. Autoregulation1) Myogenic mechanism:
an increased arterial blood pressure →→contraction of the vascular smooth muscle →→constriction of the blood vessel →→ the blood flow is maintained relatively constant
Regulation of Renal CirculationRegulation of Renal Circulation
2) Tubuloglomerular feedback:an increased in renal blood flow →→
change in glomerular filtration →→
change in Na+ content in the renal filtrate →→ detected by the macula densa →→send a signal to the renal arterial system →→restore RBF and glomerular filtration rate (GFR) to normal
TubuloglomerularTubuloglomerular feedback:feedback:
2. Neural and Hormonal Regulation2. Neural and Hormonal Regulation
1) Neural Regulationstrong activation of the renal
sympathetic nerves →→ constrict the renal arterioles →→ ↓renal blood flow and GRF
2. Neural and Hormonal Regulation2. Neural and Hormonal Regulation
2) Hormonal RegulationNorepinephrine, Epinephrine, and Endothelinconstrict renal blood vessel and ↓GFRAngiotensin IIconstricts efferent arteriolesNitric Oxide↓renal vascular resistance and ↑GFRProstaglandins and Bradykinintend to increase GRF
GlomerularGlomerular FiltrationFiltration
GlomerularGlomerular Filtration Rate Filtration Rate
Definition:When blood passes through glomerular
capillaries, part of blood plasma free of proteins is filtered into Bowman’s space.
the volume of fluid filtered from the glomeruli into Bowman’s space per unit time is termed the GFR.
GlomerularGlomerular FiltrationFiltration
substance plasma(g/L)
ultrafiltred(g/L)
Excreted(g/L)
Excreted/plasma
Na+
K+
Cl-
UreaNH3
Glucoseprotein
3.30.23.70.3
0.0011.0
70~90
3.30.23.70.30.001.00.3
3.51.56.0
20.00.400
1.17.51.660.0
400.000
GlomerularGlomerular FiltrationFiltration
GlomerularGlomerular filtration barrierfiltration barrier
Structure of the filtration membrane:2-4nm1) Capillary endothelium:
fenestration: 70~90 nm2) Basement membrane:
meshwork of collagen and proteoglycan fibrillae: 2~8 nm3) Epithelial cells of the renal capsule: nephrin
slit pore: 4~11 nm
GlomerularGlomerular filtration barrierfiltration barrierthe filtration membranethe filtration membrane
GlomerularGlomerular filtration barrierfiltration barrierinfluence of size and electrical charge of dextran on its filterability
GlycoproteinsImmunolgical
damage and inflammation
dextrandextran
Cationnic molecules are more readily filted than are anionic molecules.The reduced filtration of anionic
molecules is explained by the presence of negively charged glycoprotein on the surface of all component of the glomerular filtration barrier.
AlportAlport syndromsyndrom
Nephrin is a transmembrane protein(slit diaphragm)
Alport syndrom is characterrized by hematuriaand progressive glumerulonephritis and account for 1%-2% of causes of end-stage failure.
NephroticNephrotic syndromesyndrome
An increase in the permeability of the glomerular capilaries to proteins
proteinuria
edema, hypoalbuminemia
GlomerularGlomerular FiltrationFiltration
1) The Glomerular filtration rate (GFR)Defined as the quantity of the glomerularultrafiltrate formed each minute in all nephrons of the both kidneys The normal value of GFR: 125 ml / min
Department of Physiology, Zhejiang University School of Medicine
GlomerularGlomerular FiltrationFiltration
Factors Affecting Filtration1) The glomerular hydrostatic pressure 2) The colloid osmotic pressure of plasma3) The Bowman’s capsule pressure4) The renal plasma flow5) Filtration area6) Permeability of the filtration membrane
Factors that alter filtration pressure Factors that alter filtration pressure change GFRchange GFR
1. Glomerular hydrostatic pressure (PGC)systemic blood pressure
afferent and efferent arteriolar diameters
Blood lose, shock→ PGC ↓→NFP ↓→GFR↓
2. 2. Capsular hydrostatic pressureCapsular hydrostatic pressure(P(PBSBS))
Renal calculus, tumor,
→PBS↑→NFP↓→GFR↓
3. The colloid osmotic pressure of plasma (πGC)
Ponderosus transfusion→ πGC ↓→NFP↑→GFR
↑
GlomerularGlomerular FiltrationFiltration
4. The renal plasma flow
a decrease in the rate of the oncotic pressure
the distance along the capillary in which filtration was taking place
filtration
Factors governing GFRFactors governing GFR
Factors at the capillary bed are:
Total surface area available for filtration
Filtration membrane permeability
Net filtration pressure (NFP)
Consequences of loss of protein in the urine:
decrease in osmotic pressure
edema
low circulatory volume and possibly shock.
Loss of blood clotting proteins : uncontrolled bleeding.Loss of globulins and complement proteins make the
individual prone to infection.
GlomerularGlomerular FiltrationFiltration
The Glomerular Capillary Filtration Coefficient, Kf
The product of the hydraulic conductivity and surface area of the glomerular capillaries
Kf = GRF/Net filtration pressure
Filtration fraction :125/660=19 %
2) Filtration fraction (FF)The percentage of GFR in the renal plasma flow
GlomerularGlomerular filtration rate (GFR)filtration rate (GFR)
Regulation of Regulation of GlomerularGlomerularFiltrationFiltration
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
GFRGFR is used to evaluate the kidneysis used to evaluate the kidneys’’ ability to ability to remove waste products from the bodyremove waste products from the body
GFR is used to screen for:GFR is used to screen for:
Early signs of kidney damageEarly signs of kidney damage
A coffee maker
Presence of protein in the urine is called proteinuria.
• Presence of blood cells in the urine is called hematuria.
AlbuminuriaThe presence of significant amounts of albumin in the urine.
The The UremicUremic SyndromeSyndrome
Homeostatic Disorder of water,Electrolyte and Acid-alkali Balance:
Volume OverloadMetabolic AcidosisHyperkalemiaHyponatremiaHypocalcemiaHyperphosphatemia
Factors regulated by three mechanisms
renin-angiotensin-aldosterone system
ReabsorptionReabsorption and Secretion by the Renal and Secretion by the Renal Tubules (Tubules (bukubuku yang yang dikshdiksh halhal 643)643)
ReabsorptionReabsorption and Secretion by the and Secretion by the Renal TubulesRenal Tubules
reabsorption (cat, buku yang diksh paragraf pertama hal643)
180L/d 1.5L/d,
Normal urine volume: 1.5 L, >99% reabsorbed , (<1% excreted)
secretion:Urine volume:
1.5L/d normal(contains no RBC, no glucose bcs 100%glucose are reabsorbed)
> 2.5 L polyuria< 400 ml oliguria< 100 ml anuria
(cannot be 0)
Renal handing of various plasma Renal handing of various plasma constituents in a normal adult humanconstituents in a normal adult human
ReabsorptionReabsorption and Secretion by the Renal and Secretion by the Renal TubulesTubules
Mechanisms of tubular transport
1) Passive transport(down their chemical or electrical gradient)
Simple diffusionosmosisfacilitated diffusionsolvent drag:the solutes dissolved in the water are also carried
along with the water.
Mechanisms of tubular transportMechanisms of tubular transport
2) Active transportPrimary active transport
against an electrochemical gradientdirectly requires metabolic energy (i.e. hydrolysis of ATP)
Examples: Na+-K+ ATPase, H+ ATPase, H+-K+ ATPase Ca+2 ATPase
ReabsorptionReabsorption and Secretion by the Renal and Secretion by the Renal TubulesTubules
Secondary active transport Symport (Co-transport) Transported substances move in the same direction across the membraneNa+-glucose, Na+- amino acid
Antiport (Counter-transport) Transported substances move in opposite directions across the membrane
Na+-H+ antiport
Reapportion and Secretion by the Reapportion and Secretion by the Renal TubulesRenal Tubules
The pathway of reabsorption1) Paracellular transport
5-10% of water transferPassive diffusion onlyRequires favorable electrochemical gradientPassive diffusion of ions and large non-polar solutes
2) Transcellular pathway90-95% of water transferPassive transportAll active transport
the pathway of the pathway of reabsorptionreabsorption
Apical
mem
brane
Basolateralmembrane
Basolateral
mem
brane
Transcelluar pathway
Paracelluar pathway
ReabsorptionReabsorption and Secretion by the and Secretion by the Renal TubulesRenal Tubules
3) endocytosisUptake by cells of particles too large to diffuse through
the cell membraneExample: Reabsorption of filtered proteins in the proximal
tubules
ReabsorptionReabsorption by the Renal Tubulesby the Renal Tubules
(一)Na+、Cl- Reabsorption
1. Proximal tubule 70%
(1) Na+ and Cl-
first half:active mechanisms
Na+: 65 ~ 70% absorbedco-transport: Na+– glucose and amino acids counter-transport: Na+– H+
Cl–: 55% absorbed passively
co-transport: Na+– glucose and amino acids counter-transport: Na+– H+
Proximal tubule first half
Second half:Proximal tubule
Transcellular and paracellularpathway
TranscellularNa+ and Cl- co-transport ,Na+-H+
Cl-/HCO3 counter-transport
Paracellular:NaCl (Cl- by chamical gradient)
Waterhydrostatic pressure
(2)WaterPassive diffusionPassive diffusionosmoticTranscellular and
paracellular
water channels:aquaporin(AQP-1)
(2003 Nobel prize)
blood
Tubular Tubular ReabsorptionReabsorption of Solutes and Waterof Solutes and Water
Cl- goes up because Na+ is reabsorbed with glucose, amino acids, Pi and HCO3
-
Glucose, amino acids, Pi and HCO3
- go down due to reabsorptionwith Na+
Unchanged due to isosmoticreabsorption
2. Loop of henle
the thick ascending limb: Na+、Cl-:
Na+:2Cl-:K+ co-transportNa+-H+ counter-transport
Na+、 Cl-、 K+:Transcellular and paracellular
the thick ascending limb: N
a+
、Cl-
:
2、Loop of Loop of henlehenle
Clinic
furosemide (速尿) inhibit cotransporter →NaCl reabsorbtion
osmolarity of the interstitial
water excretion
3、 Distal tubule and collecting ductsDistal tubule and collecting ducts
Distal tubule:Na+-Cl- symporter
↑
Thiazide diuretics
Distal tubule and collecting ductsDistal tubule and collecting ducts
pricipal cell (主细胞)
Na+ and water: amiloride
secretion:K+
intercalated cell (闰细胞)
reabsorbtion:HCO3-
secretion :H+
Distal tubule Distal tubule and collecting and collecting ductsducts
CA:cabonicCA:cabonic anhydraseanhydrase
amilorideInhibiteInhibite Na+ Channels
Distal tubule and collecting ductsDistal tubule and collecting ducts
Water:1) Isosmotic trasporting mechanism
a small amount in the early distal tubule 2) Counter-current mechanism
in the late distal tubule and collecting ductcontrolled by ADH
Distal tubule and collecting ductsDistal tubule and collecting ducts
Water:AQP-2:apical membrane,VP(ADH)AQP-3
AQP-4Basolateral membrane
Acid-base balance
Acid-base balance
Acid-base balance
HCO3- and H+ transport
Acid-base balance
1、HCO3- reabsorbtion and H+ serection
(1)proximal:>80% HCO3- reabsorbtion
HCO3- : by CO2 reabsorbtion
Na+-H+ antiport
proton pump (H+-ATPase)
Na+-HCO3-
Cl--HCO3-
H+分泌
HCO3-
1、HCO3- and H+
(1)proximal tubules:80%(2)loop of henle:15%,(3)distal tuble and collecting tuble:5%
proton pumpH+-K+–ATP ase
HCO3- CO2+H2O
HPO42- H2PO4-
NH3 NH4+
H+
HCO3- and H+ transport
NHNH33
glutaminase
Glutamine glutamate +NH4+
glutamic dehydrogense
∂-ketoglutarate +NH4+
(2H+, 2HCO3- )
NH4+ NH3 + H+
Acid-base balance
PotasPotasssiumiumthe proximal tubule (65-70%)
Loop of henle(25-30%)(key element)
in the distal tubule tubule and collecting duct. (both secretion and reabsorbtion)
dependent on reabsroption of sodium, under the control of aldosterone. in competition with secretion of H+
PotasPotasssiumium
Tubular Tubular ReabsorptionReabsorption of Solutes and Waterof Solutes and Water
4. Calcium99% of filtered Ca+2 is reabsorbed
Proximal tubule (60-65%), thick ascending loop of Henle (25-30%):
passive and paracellular (favorable electrochemical gradient)
4. Calcium4. Calcium
Distal tubule & collecting duct (4-9%): active and transcellularCa+2 diffuses down electrochemical gradient at luminal membraneTransported across basolateral membrane by Na+-Ca+2 antiporter and Ca+2 ATPaseRegulation: parathyroid hormone,calcitriol
Tubular Tubular ReabsorptionReabsorption of Solutes and Waterof Solutes and Water
5. Glucose totally in the proximal
tubule, mainly the early portions
Sodium-dependent glucose transporter
GlucoseGlucose
Tm-G:(the tubular transport maximum for glucose)
Renal threshold for glucosethe critical value of the plasma glucose concentration when the kidney begins to excrete glucose 180 mg/dL
GlucoseGlucose
Renal threshold for glucosethe critical value of the plasma glucose concentration at
which the glucose first appears in the urine180 mg/dL
Maximal rate of transport of glucose (TmG)plasma glucose concentration:300mg/100ml
375 mg/min (men), 300mg/min(women)
GlucoseGlucose
Tubular Tubular ReabsorptionReabsorption of Solutes and Waterof Solutes and Water
6. Amino acidsIn a similar way as glucose but by different carrier
Urinary Dilution and ConcentrationUrinary Dilution and Concentration
Urine volume: 1.5L/d normal> 2.5 L /d polyuria< 400 ml /d oliguria< 100 ml/d anuria
osmolality : 50-1200 mOsm/(kg.H2O)
> plasma hyperosmolality urine= plasma < plasma hypoosmolality urine
location:Loop of henle
Urinary concentrating mechanismUrinary concentrating mechanism
Corticomedullaryconcentration gradientA gradient of increasing osmolality
Urinary concentrating mechanismUrinary concentrating mechanism
The countercurrent exchanger in the kidney
Urinary Dilution and ConcentrationUrinary Dilution and Concentration
Urinary concentrating mechanism—the countercurrent theory
The countercurrent multiplication
Urinary concentrating mechanismUrinary concentrating mechanism
The countercurrent exchanger in the kidney Permeability properties of the tubular system
Portions of the tubular system
Water Sodium Urea
Thick ascending limb of Henle’s loop
impermeable Actively transport impermeable
thin ascending limb of Henle’s loop
impermeable Highly permeable mid permeable
thin descending limb of Henle’s loop
highly permeable impermeable impermeable
the distal tubule highly permeable in the presence of ADH
secretion of H+ in the presence of aldosterone in exchange for Na+
impermeable
the collecting duct in the cortical and outer medulla
highly permeable in the presence of ADH
highly permeable impermeable
the collecting duct in the inner medulla
highly permeable in the presence of ADH
highly permeable highly permeable
Urinary concentrating mechanismUrinary concentrating mechanism
The countercurrent exchanger in the kidney
Urinary concentrating mechanismUrinary concentrating mechanism
Establishing of osmotic gradient of the renal medulla
Urinary concentrating mechanismUrinary concentrating mechanism
Maintenance of the osmotic gradient in the medulla
Urinary concentrating mechanismUrinary concentrating mechanism
The countercurrent exchange
Operation of the Operation of the vasavasa recta as recta as countcurrentcountcurrent exchangers in the kidneyexchangers in the kidney
NaCl and urea diffuse out of the ascending limb of the vessel and into the descending limb,whereas water diffuses and into the ascending limb of the vascular loop
Urinary concentrating mechanismUrinary concentrating mechanism
Corticomedullaryconcentration gradient
Urinary Dilution and ConcentrationUrinary Dilution and Concentration
Formation of concentrated or dilute urine
In the presence of ADH, which increases the permeability of the collect duct to water, water is drawn from the lumen into the interstitial fluid, that results in the excretion of a concentrated urine
In the absence of ADH, the dilute renal fluid is excreted
Urinary Dilution and ConcentrationUrinary Dilution and Concentration
Factors that affect the concentration and dilution of the urine
1) Damage of renal medullaresult in an impairment of the concentrating ability
2) Loop diuretics such as frusemide, inhibit the active transport of NaCl at the thick asending portion of Henle’ loop, interfere with the establishiment of the osmotic gradient in the medulla of the kidney
Urinary Dilution and ConcentrationUrinary Dilution and Concentration
3) Lack of urea in the body such as malnutrition, reduce the osmotic gradient established in the renal medulla
4) Increased velocity of blood flow in the vasa rectaupset the osmotic gradient in the medulla by carrying away amount of NaCl, thus reducing the osmotic gradient
Control of Renal FControl of Renal Functionsunctions
Autoregulationosmotic diuresisglomerulotubular balance
Nervous Control of Renal Functionsrenal sympathetic Hormonal Control of Renal Functions
Renin-angiotensin systemvasopressin
osmotic diuresisosmotic diuresis
The presence of large quanties of unreabsorbed solutes in the renal tubules causes an increase in urine volume called __Solutes that are not reabsorbed in the proximal tubules exert an appreciable osmotic effect
osmotic diuresisosmotic diuresis
the concentration of unreabsorbed solutes in the tubules↑→isotonic fluid→
water reabsorption ↓→ Na+ reabsorption↓→
urine volume↑,
excretion of NaCl ↑
diabetes(glucose)
mannitol→ isotonic fluid →diuresis
glomerulotubular balance1. Conceptor:GFR ↑→
an increased reabsorption of solutes and water in theproximal tubule
2. Mechanism: in general the percentage of the solutereabsorbed is held constant despite variations in GFR
constant fraction reabsorption (65-70% of GFR )
glomerulotubular balance
The protein in the glomerular capillary plasamathe oncotic pressure in the peritubular capillaries↑
↓solute and fluid into peritubular capillaries
Na+ reabsorption ↑
GFR↑
GG--T balanceT balance
3. Meaning: the percentage of the solute in urine is held constant
G-T balance is to reduce the impact of GFR changes on the amount of Na+ and water excreted in the urine
Nervous Nervous Control of Renal FControl of Renal Functionsunctions
Renal sympathetic nerve
1. α-R→arterioles contracts→ RBF↓→GFR↓
2. Proximal tubule α-R→Na+、water reabsorption↑
3. juxtaglomerular cellsβ-R→Renin↑→
Na+、water reabsorption↑
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
vasopressin, VPRenin-angiotensin systematrial natriretic peptide, ANPKallirein and kinin systemendothelin ETnitric oxide
catecholamineProstaglandin E
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
Antidiuretic hormone (ADH) acts on the kidneys to regulate the volume and
osmolarity of the urine
Peptide hormone, increasing water permeability of collecting duct
ADH diuresisADH antiduresis
Insertion of aquaporins in apical membrane
Antidiuretic hormone (ADH)Antidiuretic hormone (ADH)
Paraventricular
Supraoptic nucleusPosterior pituitury
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
There are two effective stimuli that change ADH release.
One is plasma osmolalityplasma osmolality↑ →→hypothalamic osmoreceptors →→ production and release of ADH ↑
the other is blood volume
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
the other is blood volume
blood volume ↓→→ baroreceptor reflex & atrial
stretch receptors→→ vagus nerve→→ brainstem(NTS)→→ ADH release ↑
Water diuresisWater diuresis
Water diuresisWater diuresis
plasma osmolality →→hypothalamic osmoreceptors →→production and release of ADH
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
Aldosterone
secreted by the glomerulosa of the adrenal cortex Increases the reabsorption sodium in the distal tubule and early collecting duct
Increases number of Na+ channelsIncreases number activity of Na+ pumps
The reabsrption of sodium is coupled to secretion of potassium.
Hormonal Control of Renal FHormonal Control of Renal Functionsunctions
Regulation of Aldosterone secretiona. Renin-angiotensin system b. Plasma concentrations of sodium and potassiumc. Extracellular fluid volumed. Adrenocorticotrophin (ACTH)
ReninRenin--angiotensin systemangiotensin system
ReninRenin--angiotensin systemangiotensin system
ReninRenin--angiotensin systemangiotensin system
Atrial natriuretic peptides (ANP) Atrial natriuretic peptides (ANP)
Involved in control of both salt and water balanceStretch-sensitive cells in wall of atriumStimulated by stretch to secrete ANPANP
Atrial natriuretic peptide (ANP)
•Produces natriuresis and
diuresis
•Decreases renin release
•Reduces total peripheral
resistance via
vasodilatation
•Decreases heart rate,
cardiac output
•Vasodilator factors
PGI2--prostacyclin
EDRF, NO--endothelium-derived
relaxing factor, nitric oxide
EDHF--endothelium-dependent
hyperpolarizing factor
Endothelium-derived vasoactive substances
The 1998 Nobel Prize in Physiology or Medicine
Nitric oxide as a signaling molecule in the cardiovascular system
Louis J Ignarro Ferid Murad Robert F Furchgott
NO, a signaling molecule with potent cardiovascular, immunomodulatory
& neuromediatory activities (Bredt, 1994)
•Vasoconstrictor factors
Endothelin
Kinin & histamine
Bradykinin, Kallidin--PlasmaHistamine--Mast cells in response to injury, inflammation, and allergic responses
Similar effects:causes vasodilatationincreases capillary permeability
Prostaglandins
Hormonal Control of Renal Hormonal Control of Renal FFunctionsunctions
Epinephrine and norepinephrineProstaglandin AdrenomedullinParathyroid hormone, PTH
Renal ClearanceRenal Clearance
Renal ClearanceRenal Clearance
Defined as the volume of plasma required to supply the amount of a substance X to be excreted in urine per unit time
PxVUxCx *
=Px
VUxCx *=
MicturitionMicturition
Micturition reflexMicturition occurs when the intravesicular pressure reaches 70 cmH2O via a reflex action
50
0
Pdet, cm H2O
0 volume 300 ml
detrusor
MicturitionMicturition
Higher control of micturition
There are inhibitory and facilitatory centers in the cerebral cortex and pons
MicturitionMicturition
Micturition reflex.swf
Micturition mechanism.swf
Abnormality of micturition
Injureaffrent nerve →overflow incontinence
effrent nerve→ urine retention
spinal cord spastic neurogenic bladder