8/8/2019 Physiology, Lecture 6, Urinary System
1/74
Urinary systemUrinary system
IntroductionIntroduction
GFGF
Tubular reabsorptionTubular reabsorption Tubular secretionTubular secretion
Urine excretion & plasma clearanceUrine excretion & plasma clearance
8/8/2019 Physiology, Lecture 6, Urinary System
2/74
functionsfunctions11-- maintaining ECF stabilitymaintaining ECF stability volume &volume &
compsoitioncompsoition
22-- main route for eliminating potentiallymain route for eliminating potentially
toxic wastes & foreign compounds fromtoxic wastes & foreign compounds from
the bodythe body
33-- acidacid--base balancebase balance
44-- producing erythropoitenproducing erythropoiten
55-- producing renin which triggers a chainproducing renin which triggers a chainreaction important in salt conservationreaction important in salt conservation
by kidneysby kidneys
66-- converting vitamin D into its activeconverting vitamin D into its active
formform
8/8/2019 Physiology, Lecture 6, Urinary System
3/74
Kidneys: urine forming organs, beanKidneys: urine forming organs, bean--shaped, located in the back of theshaped, located in the back of theabdominal wallabdominal wall
Renal pelvis: central collecting cavityRenal pelvis: central collecting cavitythat leads to the ureter which is athat leads to the ureter which is a
smooth muscle walled ductsmooth muscle walled duct Urinary bladder: smooth muscleUrinary bladder: smooth muscle
walled sac that stores urinewalled sac that stores urine
Urethra: straight and short inUrethra: straight and short infemale, long and curving course infemale, long and curving course inmales passing through the prostatemales passing through the prostate
gland and the penisgland and the penis
8/8/2019 Physiology, Lecture 6, Urinary System
4/74
Nephron: the functional unit, 2 million inNephron: the functional unit, 2 million inboth kidneys: aboth kidneys: a-- medullary bmedullary b-- corticalcortical
vascular components of the nephron :vascular components of the nephron :
11-- Glomerulus : ball like tuft of capillariesGlomerulus : ball like tuft of capillaries
22--afferent arteriole to the glomerulusafferent arteriole to the glomerulus
33--efferent arteriole out of the glomerulusefferent arteriole out of the glomerulus
44--peritubular capillaries then venulesperitubular capillaries then venules
8/8/2019 Physiology, Lecture 6, Urinary System
5/74
8/8/2019 Physiology, Lecture 6, Urinary System
6/74
Tubular components of the nephron:Tubular components of the nephron:
--hallow fluid filled tube, single layer ofhallow fluid filled tube, single layer ofepitheliumepithelium
11--Bowman's capsule around theBowman's capsule around the
glomerulusglomerulus
22--proximal tubule convolutedproximal tubule convoluted
33--loop of Henle: uloop of Henle: u--shaped, dips into theshaped, dips into the
medulla:medulla:
aa--ascending bascending b--descendingdescending
passes between the afferent & efferentpasses between the afferent & efferentarteriolesarterioles
44--distal tubule: lies in the cortexdistal tubule: lies in the cortex
55--collecting duct: 8 nephrons drain in onecollecting duct: 8 nephrons drain in one
8/8/2019 Physiology, Lecture 6, Urinary System
7/74
Fig. 13-2, p. 408
Proximal tubule Distal
tubule Collecting
duct
Bowmans
capsule
Glomerulus
Cortex
Medulla
Loop of
Henle
To renalpelvisOverview of Functions of Parts of a Nephron
Peritubular
capillaries
Vein
Artery
Afferent
arteriole
Efferentarteriole
Juxtaglomerular
apparatus
8/8/2019 Physiology, Lecture 6, Urinary System
8/74
GlomerularfiltrationGlomerularfiltration Plasma free from protein filters in b. capsulePlasma free from protein filters in b. capsule 20% of plasma that enters the glomerulus is filtered20% of plasma that enters the glomerulus is filtered 125mL of glomerular filtrate is formed each minute (125mL of glomerular filtrate is formed each minute (
180L/day)180L/day) kidneys filter the entire plasma volume 65 times/daykidneys filter the entire plasma volume 65 times/day Glom. Membrane:Glom. Membrane:
aa--wall of glom. Capillaries is 100x more permeablewall of glom. Capillaries is 100x more permeablebb--basement membrane: acellular gelatinous layerbasement membrane: acellular gelatinous layercc--inner layer ofB. capsule is made of podocytes which areinner layer ofB. capsule is made of podocytes which areoctopus like cells between filtration slitsoctopus like cells between filtration slits
8/8/2019 Physiology, Lecture 6, Urinary System
9/74
Fig. 13-5c, p. 410
Podocyte
foot process
Filtration
slit
Basement
membrane
Capillary
pore
Endothelial
cell
Lumen of glomerular
capillary
Lumen of
Bowmans capsule
8/8/2019 Physiology, Lecture 6, Urinary System
10/74
Fig. 13-4, p. 409
Afferent
arteriole
Efferent
arteriole
80% of the plasma
that enters theglomerulus is
not filtered
and leaves through
the efferent arteriole.
Glomerulus
Bowmans
capsule
20% of the
plasma that
enters the
glomerulus
is filtered.
Kidney
tubule
(entire
length,
uncoiled)
Urine excretion
(eliminatedfrom the body)
To venous system
(conserved
for the body)
Peritubular
capillary
GF
TR
TS
8/8/2019 Physiology, Lecture 6, Urinary System
11/74
Fig. 13-5a, p. 410
Afferent arteriole Efferent arteriole
Glomerulus
Bowmans
capsule
Lumen of
Bowmans
capsule
Outer layer of
Bowmans capsule
Inner layer
of Bowmans capsule
(podocytes)
Proximal convoluted tubule
Lumen of
glomerular
capillary
Endothelial
cell
Basement
membrane
Podocyte
foot process
(see
nextslide)
8/8/2019 Physiology, Lecture 6, Urinary System
12/74
Forces involved in GFForces involved in GF
Like forces starling capillary circulation with 2 exceptions:Like forces starling capillary circulation with 2 exceptions:aa-- permeability is much higherpermeability is much higherbb-- filtration occurs through out the whole glomerulus capillaryfiltration occurs through out the whole glomerulus capillary
11-- glomerulus blood pressure ~55mmHg larger than any otherglomerulus blood pressure ~55mmHg larger than any othercapillary because the afferent arteriole are wide and thecapillary because the afferent arteriole are wide and theefferent are narrowefferent are narrow
22--plasma colloid osmotic pressure ~30mmHg, opposesplasma colloid osmotic pressure ~30mmHg, opposesfiltrationfiltration
33--Bomans capsule hydrostatic pressure ~15mmHg exerted byBomans capsule hydrostatic pressure ~15mmHg exerted bythe fluid in the initial part of the tubule, opposes filtrationthe fluid in the initial part of the tubule, opposes filtration
8/8/2019 Physiology, Lecture 6, Urinary System
13/74
Table 13-1, p. 412
8/8/2019 Physiology, Lecture 6, Urinary System
14/74
GFRGFR
Net filtrating pr. = 55Net filtrating pr. = 55-- (30+15)= 10mmHg(30+15)= 10mmHg
Changes in GFR occurs mainly due to changes inChanges in GFR occurs mainly due to changes inthe glom. capillary pr. By the sympathetic effectthe glom. capillary pr. By the sympathetic effectmainly on the afferent arteriole not the efferentmainly on the afferent arteriole not the efferent
oneone decreased BPdecreased BP carotid & aortic baroreceptorscarotid & aortic baroreceptorsincrease symp.increase symp. vasoconstrictionvasoconstriction afferentafferentspasmspasm decrease bl. Flowdecrease bl. Flow decrease glom. Cap.decrease glom. Cap.Pr.Pr. decrease GFRdecrease GFR decrease urinedecrease urine conserveconserve
body fluid & saltsbody fluid & salts
increaseBP
increaseBP
8/8/2019 Physiology, Lecture 6, Urinary System
15/74
GFRGFR
increased BPincreased BP carotid & aortic baroreceptorscarotid & aortic baroreceptorsdecrease symp.decrease symp. vasodilatationvasodilatation afferentafferentdilatationdilatation increase bl. Flowincrease bl. Flow increase glom. Cap.increase glom. Cap.P
r.P
r.
increase GFRincrease GFR
increase urineincrease urine
decrease bodydecrease bodyfluidfluid decrease BPdecrease BP
8/8/2019 Physiology, Lecture 6, Urinary System
16/74
Fig. 13-8a, p. 413
Vasoconstriction
(decreases blood flow
into the glomerulus)
Afferent arteriole
Glomerulus
Efferent arteriole
Glomerular
capillary
blood pressure
Net filtration
pressure
GFR
8/8/2019 Physiology, Lecture 6, Urinary System
17/74
Fig. 13-8b, p. 413
Afferent arteriole
Glomerulus
Efferent arteriole
Glomerular
capillary
blood pressure
Net filtration
pressure
GFR
Vasodilation
(increases blood flow
into the glomerulus)
8/8/2019 Physiology, Lecture 6, Urinary System
18/74
Fig. 13-7, p. 413
Short-termadjustmentfor
Arterial bloodpressure
Long-term
adjustment for
Arterialbloodpressure
Detection by aorticarch and carotid sinusbaroreceptors
Cardiac
output
Total
peripheral
resistance
Sympathetic activity
Generalized
arteriolar vasoconstriction
Afferent arteriolarvasoconstriction
Glomerular capillary
blood pressure
GFR
Urine volume
Conservation of fluid and salt
Arterial blood pressure
8/8/2019 Physiology, Lecture 6, Urinary System
19/74
2222--25% of the cardiac output goes25% of the cardiac output goesto the kidneys ( 1140mL/min) andto the kidneys ( 1140mL/min) andHtc. accounts for 45% so the kidneyHtc. accounts for 45% so the kidneyreceives 625mL plasma/min andreceives 625mL plasma/min and20% of those are filtrated20% of those are filtrated
(125mL)(125mL)(GFR)(GFR)
8/8/2019 Physiology, Lecture 6, Urinary System
20/74
Tubular reabsorptionTubular reabsorption
Tremendously & highly selective & has aTremendously & highly selective & has ahigh reabsorptive capacity for neededhigh reabsorptive capacity for neededmaterialsmaterials
Little capacity for wastes & no capacity forLittle capacity for wastes & no capacity fortoxicstoxics
125mL/min GFR125mL/min GFR 124 ml is reabsorbed124 ml is reabsorbed(99% H(99% H22O, 100% glucose, 99.5% salts)O, 100% glucose, 99.5% salts)
Steps of transepithelial transport:Steps of transepithelial transport:
11--luminal membrane 2luminal membrane 2--cytosolcytosol33--basolateral mem. 4basolateral mem. 4--interstitialinterstitial55--capillary wallcapillary wall
8/8/2019 Physiology, Lecture 6, Urinary System
21/74
Passive transport and active transport :Passive transport and active transport :active if one step is activeactive if one step is active
--glucose, AA, organic nutrients, Na, POglucose, AA, organic nutrients, Na, PO44
Na reabsorption: NaNa reabsorption: Na--K pump at basolateralK pump at basolateral
membrane is essential forN
amembrane is essential forN
areabsorption(99.5%):reabsorption(99.5%):
--67% in proximal tubules67% in proximal tubules
--25% in loop of henle25% in loop of henle
--8% in collecting & distal tubules8% in collecting & distal tubules
--in proximal tubules Na reabsorption helps inin proximal tubules Na reabsorption helps inglucose, AA, Hglucose, AA, H22O, Cl, and urea reabsorption.O, Cl, and urea reabsorption.
+ -3
8/8/2019 Physiology, Lecture 6, Urinary System
22/74
in the ascending limb of the loop of henle Nain the ascending limb of the loop of henle Nareabsorption along with Cl play a critical role inreabsorption along with Cl play a critical role inproducing urine of varying concentration andproducing urine of varying concentration andvolumevolume
Theres noN
a reabsorption in the descendingTheres noN
a reabsorption in the descendinglimb of loop of henlelimb of loop of henle In the distal & collecting tubules Na reabsorptionIn the distal & collecting tubules Na reabsorption
is variable & subject to hormonal control, and itis variable & subject to hormonal control, and itplays a role in regulating ECF volume and linksplays a role in regulating ECF volume and linkswith K & H secretionwith K & H secretion
Na is firstly absorbed by the NaNa is firstly absorbed by the Na--K pump in theK pump in thebasolateral wall then from the lumen in cells bybasolateral wall then from the lumen in cells bypassive transportpassive transport
Na reabsorptionNa reabsorption
8/8/2019 Physiology, Lecture 6, Urinary System
23/74
Fig. 13-10, p. 416
Lumen Tubular cell Interstitial fluid
Peritubular
capillary
Diffusion
Na+
channelActive transport
Basolateral
Na+ K+ ATPase
carrier
Lateral space Diffusion
8/8/2019 Physiology, Lecture 6, Urinary System
24/74
Glucose reabsorptionGlucose reabsorption
Proximal tubules with glucose cotransportProximal tubules with glucose cotransportand AA almost 100%, then by facilitatedand AA almost 100%, then by facilitatedpassive transport in the basolateral wall, Napassive transport in the basolateral wall, Na--
glucose carriers as well as Naglucose carriers as well as Na--AA areAA arespecificspecific
--those carriers has a maximum transportthose carriers has a maximum transportcapacity called tubular maximum (Tcapacity called tubular maximum (Tmm))
--any quantity beyond Tany quantity beyond Tmm will escape intowill escape intourineurine
--filtered load= plasma con. x GFRfiltered load= plasma con. x GFR
for glucose= 100mg/100mL x 125mL/min =for glucose= 100mg/100mL x 125mL/min =
8/8/2019 Physiology, Lecture 6, Urinary System
25/74
Glucose reabsorptionGlucose reabsorption
--TTmm for glucose averages 375mg/minfor glucose averages 375mg/min
--the plasma con. Of glucose at whichthe plasma con. Of glucose at whichglucose reaches its Tm is called renalglucose reaches its Tm is called renalthreshold (300mg/100mL)threshold (300mg/100mL)
--if glucose plasma con. Increasesif glucose plasma con. Increases ititwill leave the filtratewill leave the filtrate
--if glucose plasma con. decreasesif glucose plasma con. decreases ititwill be completely reabsorbedwill be completely reabsorbed
--kidneys do not regulate glucose andkidneys do not regulate glucose andAAAA
8/8/2019 Physiology, Lecture 6, Urinary System
26/74
Fig. 13-12, p. 420
8/8/2019 Physiology, Lecture 6, Urinary System
27/74
Phosphate & calcium reabsorptionPhosphate & calcium reabsorption
Both are actively absorbed and regulatedBoth are actively absorbed and regulatedby the kidneysby the kidneys
The renal threshold for both of theseThe renal threshold for both of thesesubstances equals to their plasma con.substances equals to their plasma con.--the tubules will reabsorb the samethe tubules will reabsorb the samenormal plasma con. And any excess that isnormal plasma con. And any excess that isingested will be spilled out in the urineingested will be spilled out in the urinerestoring the normal plasma con.restoring the normal plasma con.
-- POPO44 & Ca renal threshold can be& Ca renal threshold can beregulated by the parathyroid hormoneregulated by the parathyroid hormonedepending on the body needsdepending on the body needs
-3 +2
8/8/2019 Physiology, Lecture 6, Urinary System
28/74
aldosteronealdosterone
Aldosterone stimulates Na reabsorption in the distalAldosterone stimulates Na reabsorption in the distaland collecting tubulesand collecting tubules
--ifNa con. In plasma is highifNa con. In plasma is high no regulationno regulation Na outNa out
--ifNa con. In plasma is lowifNa con. In plasma is low aldosterone releasealdosterone releasemore reabsorptionmore reabsorption conserve Naconserve Na
ReninRenin--angeotensinangeotensin--aldosterone system (RAAS):aldosterone system (RAAS):
--renin is secreted from the juxtaglomerulusrenin is secreted from the juxtaglomerulusapparatus which activates the angiotensin in theapparatus which activates the angiotensin in the
plasma into angiotensin Iplasma into angiotensin I--angiotensin I under the effect of ACE in theangiotensin I under the effect of ACE in thepulmonary circulation is converted to angiotensin IIpulmonary circulation is converted to angiotensin IIwhich stimulates aldosterone releasewhich stimulates aldosterone release
8/8/2019 Physiology, Lecture 6, Urinary System
29/74
Fig. 13-11, p. 417
NaCl / ECF volume /
Arterial blood pressure
Liver Kidney LungsAdrenal
cortexKidney
H2O
conserved
Na+ (and CI)osmotically holdmore H2O in ECF
Na+ (and CI)
conserved
Na+ reabsorption
by kidney tubules
( CI
reabsorption
follows passively)
Vasopressin Thirst Arteriolarvasoconstriction
H2O reabsorption
by kidney tubulesFluid intake
Renin
Angiotensin-
convertingenzyme
Angiotensinogen Angiotensin I Angiotensin II Aldosterone
8/8/2019 Physiology, Lecture 6, Urinary System
30/74
aldosterone effects:aldosterone effects:--promotes insertion of new Na channels intopromotes insertion of new Na channels into
the luminal membranethe luminal membrane--additional Naadditional Na--K carriers in the basolateralK carriers in the basolateralmembranemembrane
--these effects are seen in the distal &these effects are seen in the distal &collecting tubulescollecting tubules
When Na load, ECF/plasma volume, and BPWhen Na load, ECF/plasma volume, and BPare above normalare above normal renin release is inhibitedrenin release is inhibitedno aldosteroneno aldosterone Na portion in the distalNa portion in the distaltubules and the collecting ducts is excertedtubules and the collecting ducts is excerted
8% is not a small amount considering the8% is not a small amount considering thefact that per day plasma will be filtered 65fact that per day plasma will be filtered 65times so 20g of salt is lost per daytimes so 20g of salt is lost per day
8/8/2019 Physiology, Lecture 6, Urinary System
31/74
Fig. 13-15, p. 423
Na+ / ECF volume/
arterial pressure
Renin
Angiotensin I
Angiotensin IIPlasma K+
Aldosterone
Tubular K+ secretion Tubular Na+ reabsorption
Urinary K+ excretion Urinary Na+ excretion
8/8/2019 Physiology, Lecture 6, Urinary System
32/74
ANPANP
(atrial natriuretic peptide)(atrial natriuretic peptide)
ANP is released from the atria whenANP is released from the atria whenthe heart is stretched by expansionthe heart is stretched by expansionof the ECF volume as a result ofNa &of the ECF volume as a result ofNa &HH22O retentionO retention
--increased BPincreased BP ANP releaseANP release inhibitinhibitNa reabsorptionNa reabsorption more Na & Hmore Na & H22O areO are
released into the urinereleased into the urine less ECFless ECFvolumevolume decrease BPdecrease BP
8/8/2019 Physiology, Lecture 6, Urinary System
33/74
Table 13-3, p. 424
8/8/2019 Physiology, Lecture 6, Urinary System
34/74
Cl reabsorptionCl reabsorption
Passively absorbed down thePassively absorbed down theelectrical gradient which is createdelectrical gradient which is createdby active Na reabsorptionby active Na reabsorption
-
8/8/2019 Physiology, Lecture 6, Urinary System
35/74
H22O reabsorptionO reabsorption Passive by osmosis following NaPassive by osmosis following Na
reabsorptionreabsorption
-- 65% (117L/day) by the end of65% (117L/day) by the end of
the proximal tubulesthe proximal tubules-- 15% of filtered H2O is obligatorily15% of filtered H2O is obligatorily
reabsorbed from loop of henlereabsorbed from loop of henle
-- 20% remaining is reabsorbed in distal20% remaining is reabsorbed in distal
tubulestubules
Hormonal regulation:Hormonal regulation:
--water channels in the aquaporins partwater channels in the aquaporins part
is regulated by vasopressinis regulated by vasopressin
8/8/2019 Physiology, Lecture 6, Urinary System
36/74
Urea reabsorptionUrea reabsorption
Passive linked to active NaPassive linked to active Nareabsorptionreabsorption
In the proximal tubules [urea] isIn the proximal tubules [urea] isincreased three time because ofNa &increased three time because ofNa &HH22O reabsorptionO reabsorption
Urea is passively absorbed but itUrea is passively absorbed but itdoes not have good permeabilitydoes not have good permeability
only 50% of urea is reabsorbedonly 50% of urea is reabsorbed
8/8/2019 Physiology, Lecture 6, Urinary System
37/74
Fig. 13-13, p. 421
Glomerulus
Bowmanscapsule
Beginning of
proximaltubule
Peritubular
capillary
Na+ (active)
H2O (osmosis)
Na+ (active)
H2O (osmosis)
Passive diffusion
of urea down itsconcentration gradient
44 ml
of
filtrate
125 ml
of
filtrate
End of
proximal
tubule
= Urea molecules
8/8/2019 Physiology, Lecture 6, Urinary System
38/74
wasteswastes
Waste products are not reabsorbedWaste products are not reabsorbedbecause the permeability of thebecause the permeability of thetubules to these products is almosttubules to these products is almostzero :zero :
--phenolphenol
--creatininecreatinine
--other toxicsother toxics
8/8/2019 Physiology, Lecture 6, Urinary System
39/74
Tubular secretionTubular secretion
Supplemental mechanisms that hastenSupplemental mechanisms that hastenelimination of substances from the bodyelimination of substances from the body
11-- hydrogen:hydrogen:
-- important for acidimportant for acid--base balancebase balance
-- secreted by proximal, distal, &secreted by proximal, distal, &
collecting tubulescollecting tubules
8/8/2019 Physiology, Lecture 6, Urinary System
40/74
22-- potassium:potassium:
--actively reabsorbed in proximalactively reabsorbed in proximal
tubulestubules
--actively secreted in distal &actively secreted in distal &
collecting tubulescollecting tubules
--when plasma [K] increases,when plasma [K] increases,
secretion is adjusted to eliminate Ksecretion is adjusted to eliminate Koutout
8/8/2019 Physiology, Lecture 6, Urinary System
41/74
--mechanism of secretion:mechanism of secretion:
coupled with Nacoupled with Na--K pump whichK pump which
reduces [K]reduces [K]interstitialinterstitial plasma Kplasma K
leaves peritubular capillaryleaves peritubular capillary thethe
pump get K inside the tubular cellspump get K inside the tubular cells
which has many K channels towhich has many K channels tohelp K to get out to the tubularhelp K to get out to the tubular
lumin passivelylumin passively
--K channels in the proximal tubulesK channels in the proximal tubules
are located at the basolateral sideare located at the basolateral side
8/8/2019 Physiology, Lecture 6, Urinary System
42/74
--control ofK secretion:control ofK secretion:
increased [K]increased [K]plasmaplasma stimulation ofstimulation of
adrenal cortexadrenal cortex increaseincrease
aldosteronealdosterone increase in Kincrease in K
secretion &Na reabsorptionsecretion &Na reabsorption
8/8/2019 Physiology, Lecture 6, Urinary System
43/74
Fig. 13-14, p. 423
Lumen Tubular cellPeritubularcapillaryInterstitial fluid
K+
channel
Active
transport
Diffusion
Diffusion
8/8/2019 Physiology, Lecture 6, Urinary System
44/74
33-- organic anions & cations:organic anions & cations:
--two types of carriers one fortwo types of carriers one foranions & the other for cations:anions & the other for cations:
--prostaglandinsprostaglandins
--food additivesfood additives--histamine & norhistamine & nor--epinephrineepinephrine
--environmental pollutantsenvironmental pollutants
(pesticides), drugs(pesticides), drugs
8/8/2019 Physiology, Lecture 6, Urinary System
45/74
urine excretionurine excretion
125mL/min is filtered, 124mL/min is125mL/min is filtered, 124mL/min isreabsorbed, so 1mL/min is excretedreabsorbed, so 1mL/min is excreted
If125mL/min is filtered, and weIf
125mL/min is filtered, and wehave a slightly reduced reabsorptionhave a slightly reduced reabsorption
(123mL/min) then urine excretion is(123mL/min) then urine excretion isdoubled (2mL/min)doubled (2mL/min)
By excreting substances in the urine,By excreting substances in the urine,kidneys clear the plasma flowingkidneys clear the plasma flowingthrough them of these substancesthrough them of these substances
8/8/2019 Physiology, Lecture 6, Urinary System
46/74
Plasma clearancePlasma clearance
Plasma clearance of any substance isPlasma clearance of any substance is
the volume of plasma completelythe volume of plasma completelycleared of that substance by thecleared of that substance by thekidneys per minutekidneys per minute
8/8/2019 Physiology, Lecture 6, Urinary System
47/74
--a substance (X) that is filtered but nota substance (X) that is filtered but notreabsorbed or secreted has a plasmareabsorbed or secreted has a plasma
clearance= GFRclearance= GFR 125mL/min of plasma is filtered125mL/min of plasma is filtered
containing an amount of X, thiscontaining an amount of X, this
amount of X is left behind andamount of X is left behind andis excreted with urine thus eachis excreted with urine thus each
minute 125mL of plasma will beminute 125mL of plasma will be
cleared from Xcleared from X exampleexample inulininulinproduced chemicallyproduced chemically
8/8/2019 Physiology, Lecture 6, Urinary System
48/74
Fig. 13-16a, p. 426
Glomerulus
Tubule
Peritubular
capillary
Inurine
For a substance filtered and not reabsorbed
or secreted, such as inulin, all of the filteredplasma is cleared of the substance.
8/8/2019 Physiology, Lecture 6, Urinary System
49/74
--a substance (Y) is filtered anda substance (Y) is filtered andreabsorbed but not secreted has areabsorbed but not secreted has aplasma clearance that is less thanplasma clearance that is less thanGFRGFR
examples:examples:
aa-- glucose pl. cl. = 0glucose pl. cl. = 0
bb-- urea pl. cl. =62.5mL/minurea pl. cl. =62.5mL/min
8/8/2019 Physiology, Lecture 6, Urinary System
50/74
Fig. 13-16b, p. 426
For a substance filtered,
not secreted, and completelyreabsorbed, such as glucose,
none of the filtered plasma
is cleared of the substance.
8/8/2019 Physiology, Lecture 6, Urinary System
51/74
Fig. 13-16c, p. 426
For a substance filtered,
not secreted, and partially
reabsorbed, such as urea, only
a portion of the filtered plasma
is cleared of the substance.
8/8/2019 Physiology, Lecture 6, Urinary System
52/74
-- a substance (Z) is filtered and secreteda substance (Z) is filtered and secretedbut not reabsorbed has a plasmabut not reabsorbed has a plasma
clearance that is larger than GFRclearance that is larger than GFR H+ is an example which is cleared byH+ is an example which is cleared by
the following rates: 125mL/min bythe following rates: 125mL/min by
filtration & 25mL/min by secretion so itfiltration & 25mL/min by secretion so ithas a pl. cl =150mL/minhas a pl. cl =150mL/min
paraaminohippuric acid (PAH), 20% ofparaaminohippuric acid (PAH), 20% of
this chemical is filtered, and thethis chemical is filtered, and the
remaining 80% will be secreted so it aremaining 80% will be secreted so it a
has a pl. cl =plasma flow ratehas a pl. cl =plasma flow rate (625mL/min)(625mL/min)
8/8/2019 Physiology, Lecture 6, Urinary System
53/74
Fig. 13-16d, p. 426
For a substance filtered and secreted
but not reabsorbed, such as hydrogen
ion, all of the filtered plasma is
cleared of the substance, and the
peritubular plasma from which the
substance is secreted is also cleared.
8/8/2019 Physiology, Lecture 6, Urinary System
54/74
Urine excretion ofvaryingUrine excretion ofvarying
concentrationsconcentrations
Interstitial fluid of the medulla build upInterstitial fluid of the medulla build upa large osmotic gradienta large osmotic gradient
The concentration of fluid progressivelyThe concentration of fluid progressivelyincreases from the cortex downincreases from the cortex downthrough the depth of the medulla up tothrough the depth of the medulla up to
1200mOsmole/L1200mOsmole/L
M d ll
8/8/2019 Physiology, Lecture 6, Urinary System
55/74
Fig. 13-17, p. 427
Medulla
Cortex
All values in milliosmols (mosm)/liter.
8/8/2019 Physiology, Lecture 6, Urinary System
56/74
Urine is excreted in the range of100Urine is excreted in the range of100--12001200mOsmole/L depending on body fluid status:mOsmole/L depending on body fluid status:
11-- ideallyideally 1mL/min, isotonic1mL/min, isotonic22-- overhydrationoverhydration up to 25mL/min,up to 25mL/min,
hypotonic, 100mhypotonic, 100mOOsmole/Lsmole/L
33--dehydrationdehydration
0.3mL/min0.3mL/minhypertonic, up to 1200mOsm/Lhypertonic, up to 1200mOsm/L
1, 2, 3 represent the medullary countercurrent1, 2, 3 represent the medullary countercurrent
systemsystem
8/8/2019 Physiology, Lecture 6, Urinary System
57/74
Countercurrent multiplicationCountercurrent multiplication
(c.c.m)(c.c.m)
In the proximal tubules, 65% reabsorbedIn the proximal tubules, 65% reabsorbed(water & salts) so solvent & solute are equally(water & salts) so solvent & solute are equallyabsorbed, so the tonicity will remain isotonicabsorbed, so the tonicity will remain isotonic
In the loop of henle:In the loop of henle:
11--descending limb:descending limb: --high water permeabilityhigh water permeability
--no sodium reabsorptionno sodium reabsorption22--ascending limb:ascending limb: --actively reabsorbed NaClactively reabsorbed NaCl
--impermeable for waterimpermeable for water
Gl l
8/8/2019 Physiology, Lecture 6, Urinary System
58/74
Fig. 13-19a, p. 430
Glomerulus
Bowmans capsule
Proximal tubule
Distal tubule
Cortex
Medulla
Long loop
of Henle
Collecting
tubule
8/8/2019 Physiology, Lecture 6, Urinary System
59/74
Mechanism ofc.c.mMechanism ofc.c.m
Initial scene: interstitial fluid is 300mOsm/LInitial scene: interstitial fluid is 300mOsm/L
Step1:Step1: --NaCl actively pumped fromNaCl actively pumped from
ascending with the force ofascending with the force of
200mOsm/L dif.200mOsm/L dif.
--water will be reabsorbed from thewater will be reabsorbed from the
descending to equilibrate with thedescending to equilibrate with the
outside until both have 400mOsm/Loutside until both have 400mOsm/L
8/8/2019 Physiology, Lecture 6, Urinary System
60/74
Fig. 13-19b, p. 431Step 1
8/8/2019 Physiology, Lecture 6, Urinary System
61/74
Step2:Step2: --movement of luminal filtrate somovement of luminal filtrate so
from ascending 200mOsm/L fluidfrom ascending 200mOsm/L fluid
to the distal tubules, &to the distal tubules, &
300mOsm/L fluid from proximal300mOsm/L fluid from proximal
tubules gets in the descendingtubules gets in the descending
limb & in between 400mOsm/L islimb & in between 400mOsm/L is
moved around the tipmoved around the tip
8/8/2019 Physiology, Lecture 6, Urinary System
62/74
Fig. 13-19c, p. 431Step 2
To
distal
tubule
From
proximal
tubule
8/8/2019 Physiology, Lecture 6, Urinary System
63/74
Step3:Step3: --ascending limb pumps NaClascending limb pumps NaCl
while water is reabsorbedwhile water is reabsorbed
from the descending limb untilfrom the descending limb until
200mOsm/L dif. Is established200mOsm/L dif. Is established
between the ascending, thebetween the ascending, the
interstitial fluid & theinterstitial fluid & the
descendingdescending
8/8/2019 Physiology, Lecture 6, Urinary System
64/74
8/8/2019 Physiology, Lecture 6, Urinary System
65/74
Step4:Step4: --movement of filtrate willmovement of filtrate will
again disrupt the 200mOsm/Lagain disrupt the 200mOsm/L
gradient at the horizontal levelgradient at the horizontal level
Step5:Step5: --active NaCl pump in theactive NaCl pump in the
ascending limb with waterascending limb with water
diffusion in the descending onediffusion in the descending one--the 200mOsm/L is reestablishedthe 200mOsm/L is reestablished
8/8/2019 Physiology, Lecture 6, Urinary System
66/74
Step4 Step5Step4 Step5
From
proximal
tubule
to
distal
tubule
8/8/2019 Physiology, Lecture 6, Urinary System
67/74
Step6:Step6: --filtrate movement again will changefiltrate movement again will changethe gradient so that it will lead to athe gradient so that it will lead to a
progressive increment in theprogressive increment in the
tonicity of the fluid in thetonicity of the fluid in thedescending limb & decrement in thedescending limb & decrement in the
ascending oneascending one
From
8/8/2019 Physiology, Lecture 6, Urinary System
68/74
Fig. 13-19g, p. 431Step 6 and on
From
proximal
tubule
To
distal
tubule
8/8/2019 Physiology, Lecture 6, Urinary System
69/74
Vasopressin effectsVasopressin effects
180L/day is filtered, 65% is reabsorbed180L/day is filtered, 65% is reabsorbedin the prox. tubules, 15% is reabsorbedin the prox. tubules, 15% is reabsorbedin the L.H, & the remaining 20% isin the L.H, & the remaining 20% is
reabsorbed in the distal tubulesreabsorbed in the distal tubules~36L/day~36L/day
This 36L filtrate is very hypotonicThis 36L filtrate is very hypotonic(100mOsm/L), whereas the interstitial(100mOsm/L), whereas the interstitialfluid is isotonic in the cortex and up tofluid is isotonic in the cortex and up to1200mOsm/L in the collecting ducts1200mOsm/L in the collecting ducts
through the medullathrough the medulla
8/8/2019 Physiology, Lecture 6, Urinary System
70/74
Vasopressin will make the distal & collectingVasopressin will make the distal & collectingducts permeable to waterducts permeable to water
Vasopressin is produced in the hypothalamus,Vasopressin is produced in the hypothalamus,stored in the posterior pituitary gland, &stored in the posterior pituitary gland, &stimulated by hypertonicity of the ECFstimulated by hypertonicity of the ECF
Vasopressin binds receptors in the distal &Vasopressin binds receptors in the distal &collecting tubulescollecting tubules activates cAMPactivates cAMP promotespromotesinsertion of aquaporins in the luminalinsertion of aquaporins in the luminal
membranemembrane
Vasopressin effectsVasopressin effects
8/8/2019 Physiology, Lecture 6, Urinary System
71/74
The previous process is reversible byThe previous process is reversible bydecreasing vasopressindecreasing vasopressin
Maximum effect of vasopressin:Maximum effect of vasopressin:
--everyday 600 mOsm of waste iseveryday 600 mOsm of waste is
produced, this should be dissolvedproduced, this should be dissolved
in water, the normal ability of thein water, the normal ability of thekidneys to concentrate a sln. iskidneys to concentrate a sln. is
1200mOsm/L, so these 600mOsm1200mOsm/L, so these 600mOsm
will be dissolved in 0.5Lwill be dissolved in 0.5L
Vasopressin effectsVasopressin effects
8/8/2019 Physiology, Lecture 6, Urinary System
72/74
Vasopressin effectsVasopressin effects
--these 0.5L of urine is the minimum volumethese 0.5L of urine is the minimum volumeof urine that is required to excrete dailyof urine that is required to excrete dailywaste (obligatory water loss)waste (obligatory water loss)
--if there is no vasopressin, the distal &if there is no vasopressin, the distal &collecting tubules are impermeable tocollecting tubules are impermeable towater, so 20% of filtrate cannot bewater, so 20% of filtrate cannot be
reabsorbed completely, so 25mL/min willreabsorbed completely, so 25mL/min willbe excreted & the fluid will be hypotonicbe excreted & the fluid will be hypotonic
From Filtrate has concentration
of 100 mosm/liter as it
8/8/2019 Physiology, Lecture 6, Urinary System
73/74
Fig. 13-20a, p. 433
proximal
tubule
of 100 mosm/liter as it
enters distal and
collecting tubules
In the
face
of a
water
deficit
Collecting
tubule
Loop of
HenleMedulla
Cortex
Distal tubule
Concentration of
urine may be up
to 1,200 mosm/literas it leaves
collecting tubule
= permeability to H2O
increased by vasopressin
= passive diffusion of
H2O
= active transport of NaCl
= portions of tubule
impermeable to H2O
*
From
proximal Filt t h t ti
8/8/2019 Physiology, Lecture 6, Urinary System
74/74
proximal
tubuleFiltrate has concentration
of 100 mosm/liter as it
enters distal and
collecting tubules
In the
face
of a
water
excess
Collecting
tubule
Loop of
HenleMedulla
Cortex
Distal tubule
Concentration of
urine may be as low
as 100 mosm/liter
as it leaves
collecting tubule
= passive diffusion of
H2O
= portions of tubule
impermeable to H2O