Renal physiology

Renal phys iology
Dr R ma n M med A
. a da oha hmed.

Esl m.a
a nes@yahoo.com

C hief Func tions of Renal S ys tem
• Regulation of water & electrolyte balance
• Regulation of ac id & bas e balance
• E xc retion of was te products of protein metabolis m, e.g.,
 Urea from protein breakdown
 Uric ac id from nucleic acid breakdown
 C reatinine from mus cle creatine breakdown
 E nd produc ts of hemoglobin breakdown
• E xc retion of foreign chemic als , e.g., drugs , food additives ,
pes tic ides , …etc .
• E ndocrine func tion: erythropoietin, renin, 1,25-dihydoxy-
vitamin D.

2

FUNC TIONA L A NA TOMY OF KIDNE YS &
URINA RY TRA C T
• The kidneys lie high on the pos terior abdominal wall below
the diaphragm & on either s ide of the vertebral column.
• In adults eac h kidney is the s ize of a clenched fis t &
weighs ~ 150 g.
• Urine produced by the kidneys is delivered to the urinary
bladder by 2 ureters .

• The bladder continuous ly
acc umulates urine and periodically
empties its c ontents via urethra
under the control of an external
urethral s phincter – a proces s
known as micturition. 3

FUNC TIONA L A NA TOMY: kid
• E ac h kidney is formed of 2
dis tinct parts :
A n outer cortex
A n inner medulla.
• The medulla c ontains 5-10 renal
pyramids . Their tips projec t into
the renal pelv is & the dilated
upper part of the ureter.
• The nephron is the func tional unit
of the kidney. E ac h kidney
contains ~ 1 million nephrons .
• The nephron is c ompos ed of 2
main components :
A . The renal corpus cle 4
B . The renal tubule

THE NE PHRON
A . Renal C orpus cle: (S ite of filtration of blood)
1. The G lomerulus :
- It is pres ent in the cortex.
- E ac h glomerulus is formed of a tuft of capillaries that are
invaginated into the B owman’s caps ule.
- B lood enters the capillaries through the afferent arteriole
and leaves
through the s lightly narrower efferent arteriole.
- G lomerular capillaries are unique in that they are
interpos ed between 2 arterioles . This arrangement
s erves to maintain a high hydros tatic pres s ure in the
c apillaries , whic h is nec es s ary for filtration.
- The capillaries in the glomerulus have large pores c alled
6
fenes trae,

THE NE PHRON
A . Renal C orpus cle:
2. The B owman’s C aps ule:
It is the proximal expanded portion of the renal tubule
forming a
double-walled c up:
a. The inner layer (vis ceral layer) is formed of s pec ialized
epithelium
made up of podocytes :
 Thes e cells have an oc topus -like s tructure.
 They have foot proces s es that interdigitate and
s urround the glomerular capillaries .
 The foot proces s es do not form a continuous layer, but
leave gaps that provide filtration s lits .
b. The outer layer (parietal layer) is c ontinuous with the
7
epithelium of

The Renal
C orpus cle

8

THE GLOME RULA R ME MB RA NE
• It s eparates the plas ma in glomerular capillaries from the
fluid in B owman’s c aps ule. It is formed of 3 layers :
1. E ndothelium of c apillary with large fenes trae.
2. B as ement membrane: It contains large s paces , allowing
the filtration of large amounts of water & s mall s olutes .
Yet, the bas ement membrane is formed of negatively
charged glyc oproteins &, thus , oppos es the filtration of
the negatively charged plas ma proteins .
3. Foot proc es s es of podocytes with large filtration s lits .
• Due to its s pecial s tructure, the glomerular membrane
filters s everal hundred times as much water & s olutes as a
us ual c apillary membrane.
• The filtrate is called an ultrafiltrate as it is formed of plas ma
minus plas ma proteins . 9

Glomerular Membrane
Thus , the filtrability of s olutes is
determined by:
1. The s ize of molecules : The
filtrability is invers ely related
to the molec ular s ize of
s olute.
⇒ E lec trolytes (as Na+) &
s mall organic s olutes (as
glucos e) pas s freely, while
large molecules (as proteins )
do not pas s through the
membrane pores .
2. C harges of molec ules :
Negatively c harged large
10
molecules are les s filterable
than pos itively charged

THE NE PHRON
B . Renal Tubule:
1. Proximal convoluted tubule (PC T)
2. Loop of Henle: It is further s ubdivided into:
► Thin des c ending limb
► Thin as cending limb
► Thic k as cending limb
3. Dis tal c onvoluted tubule (DC T)
- Many DC Ts open into a collecting duc t (C D). C Ds pas s from
the
c ortex (c ortic al C D) to the medulla (medullary C D) and finally
drain
urine into the renal pelvis .
- PC T & DC T are pres ent in the c ortex, while the des cending
11
limb of

THE NE PHRON

J uxtaglomerular A pparatus :
 E ach DC T pas s es between the afferent & efferent arterioles
of its own nephron. A t this point there is a patch of c ells
with crowded nuc lei in the wall of the DC T c alled the
macula dens a. They s ens e the conc entration of NaC l in
this portion of the tubule.
 The wall of the afferent arteriole oppos ite the macula
dens a contains s pecialized cells known as the
juxtag lomerular cells (J G cells ). They s ec rete renin.

Together, the mac ula dens a & J G cells are called the
juxtag lomerular 12

apparatus (J GA).

Juxtaglomerular apparatus
* It is a structure formed when the distal convoluted
tubule bends around to contact the afferent arteriole
at the place where it enters the glomerulus.

* It is composed of specialized tubular epithelial cells
of distal convoluted tubule and the granular cells of
the adjacent of the afferent arteriolar wall.
* The granular cells secrete an enzyme called renin.
This enzyme is responsible for the production of
angiotensins, of which angiotensin II.
Angiotensin II stimulates the secretion of aldosterone
hormone.

The J uxta-
glomerular
A pparatus

15

THE NE PHRON (cont.)
N.B .
- There are 2 types of nephrons in the kidney:
1. C ortical Nephrons : (80% of nephrons )
 Their glomeruli lie in the outer layers of the cortex.
 Their tubular s ys tem is relatively s hort.
 Their loops of Henle penetrate only for a s hort dis tanc e
into the outer portion of renal medulla.

2. J uxtamedullary Nephrons : (20% of nephrons )
 Their glomeruli lie at the boundary between cortex &
medulla.
 They have long loops of Henle, whic h dip deeply down
into the medulla toward the tips of the pyramids .
16
 They play a major role in the proc es s of urine
conc entration.

Types of nephrons
I tem s Cor ti ca l n eph r on s J u x ta m ed u l l a r y n eph r on s

% Of total 85 % 15%
Glomeruli Out part of cortex Inner part of cortex .
Loop of Hnle Short i.e. dips to the junction Long i.e. dips deeply into the
between inner and outer medullary pyramids to the
medulla. inner medulla
Blood supply Peritubular capillaries Vasa recta and peritubular
No Vasa Recta capillaries
Special function Na reabsorption Urine concentration
Afferent arteriole Thick muscular wall Thin muscular wall
Very sensitive to symp Less sensitive to symp
Stimulation. Stimulation.
Have JG apparatus Have no JG apparatus
Exhibit autoregulation Do not exhibit autoreg
Low resistance to blood flow at High resistance to blood flow at
rest rest
Efferent arteriole Thin muscular wall Thick muscular wall
Less sensitive to symp Very sensitive to symp
Stimulation & vasopressin. Stimulation & vasopressin.
Tone decreased by
Prostaglandins (PGs).
JG apparatus Present Absent
Autoregulation Present Absent

Renal corpuscle
Renal corpuscle
Proximal
Nephrons convoluted tubule
Afferent
arteriole
Efferent
arteriole
They are the
structural & Distal convoluted
tubule
Peritubular
functional capillaries

units of the Renal arteriole

kidney

There are 2 structural classes of nephrons
which are:
1- Cortical nephrons: representing 85% of
nephrons where almost all the length of which
lies within the renal cortex.
2- Juxtamedullary nephrons: representing
15% where their loops of Henle dip deeply
into the renal medulla.

Juxtamedullary Nephron Cortical Nephron

The efferent vessels of juxtamedullary glomeruli form long looped vessels,
called vasa recta which is important for urine concentration.

S o,why is the loop of Henle
us eful?
• T l
he ongert l t mor concent aed
he oop, he e rt
t filr t a t medulayIFbecome
he t ae nd he lr

• Impora t colect t e r
t nce: he l ing ubul uns
t ough t hyper ic medula
hr he osmot l
mor a it t r bsor H2O
e bil y o ea b

Desert animals have long nephron
Loop  More H2O is reabsorbed

B LOOD VE S S E LS in the NE PHRONS
• E ach kidney receives its blood s upply from a renal artery,
which aris es directly from the abdominal aorta.
• In the kidney, the renal artery progres s ively s ubdivides into
s maller branc hes until they form afferent arterioles , whic h
break up into a tuft of capillaries , the g lomerulus . Then the
c apillaries form the efferent arteriole.
• The efferent arteriole again s ubdivides to form peritubular
capillaries , whic h s urround the various s egments of the
renal tubules .
N.B . There are 2 s ets of c apillaries & 2 s ets of arterioles !!

• The efferent arterioles of juxtamedullary nephrons form a
s pecial type of peritubular capillaries c alled v as a recta.
 They are s traight & long c apillaries that form hairpin
loops along s ide the loops of Henle.
22
 They play an important role in the proces s of urine
c onc entration.

B LOOD S UPPLY
• Renal artery fr a t ; ent s hil div
om ora er um; ides
• Interlobar arteries – r lcol div
ena umn; ide
• A rcuate arteries – a boundayofcorex &medula div
t r t l ; ide
• Interlobular arteries – int corex; div int sev a
o t ide o er l
• A fferent arterioles : suppl one nephr end in cl erofca l r –
y on; ust pilaies
G LOME RULUS (ca l r filr t
pilay taion)–
• Dr ined by
a
• E fferent arterioles – w for pl – PE RITUB ULA R
hich m exus
C A PILLA RIE S - suround r lt e
r ena ubul
• Fom ca l r bl fl s
r pilaies ood ow
• Interlobular veins
• A rcuate veins
• Interlobar veins
• Renal vein
• Infer v ca a
ior ena v
• Nephr w h t deep in medula– E entat iol giv r t VA S A RE C TA
ons it ubes l ffer rer es e ise o
(ca l r
pilaies).

Portal system (capillary beds in series), paralleling the nephron
Renal ==> afferent ==> glomerular ==> efferent ==> peritubular
arteries ==> arterioles ==> capillaries ==> arterioles ==> capillaries.

Major renal capillaries
Glomerular capillary Peritubular capillary
bed bed

1. Receives bl from afferent Receives bl from efferent
art. art.
2. High presure bed 55 Low pressure bed 13 mmHg
mmHg
3.Represents arterial end of Represents venous end of
cap. cap.
4. allows fluid filtration. Allows fluid reabsorption.

B lood S upply
of C ortical &
J uxtamedullar
y Nephrons

27

RENAL BLOOD FLOW (RBF)
Renal blood flow is about 20% of the cardiac output
This is a very large flow relative to the weight of the kidneys
(≈350 g)
RBF determines GFR
RBF also modifies solute and water reabsorption and delivers
nutrients to nephron cells.
Renal blood flow is autoregulated between 70 and 170 mm
Hg by varying renal vascular resistance (RVR).

i.e. the resistances of the interlobular artery, afferent arteriole
and efferent arteriole

Factors affecting RB F
1) Autoreg ulation:
– RBF is kept relatively cons tant between A B P;
70-170 mmHg, It is pres ent in denervated,
is olated kidney, this proving that this property
is intrins ic property.

2) S ympathetic s timulation:
– VC of afferent arteriole of cortical nephrons →
dec reas ed cortical blood flow.
– Les s effect on juxtamedullary nephrons →
remains well perfus ed.
– VC of vas a recta → decreas e medullary blood
flow → more urine concentration.

A utoregulation of RB F & GFR
• Note:
A utoregulation is
important to
prevent large
changes in G FR
that would greatly
affect urinary
output.

A utoregulation (Myogenic
mechanis m)
• Response t cha in pr e w hin t nephr v scul r
o nges essur it he on’s a a
component
• At iol conta inher l in r
rer es r ct enty esponse t t stet
o he r ch
accompa ↑ pr e. V a omaical const ict w
nying essur essel ut t ly r s, hich
hel l bl fl int gl ul despit incr sed syst
ps imit ood ow o omer us e ea emic
pr e
essur
• Opposit r ct occur w smoot muscl sense adr in
e ea ion s hen h es op
pr e
essur

AUTOREGULATION

AUTOREGULATORY
1.5 RANGE
RBF (L/min)

1.0

0.5

40 80 120 160 200 240
BP (mmHg)

EFFECT OF ARTERIAL PRESSURE CHANGES
ON GFR, RBF AND URINE OUTPUT
RBF or GRF (% of normal)

150
RBF

100 GFR

Urine Output
50

50 100 150 200
Arterial Pressure (mmHg)

Tubuloglomerular feedback
• J a omer a a r t
uxt gl ul r ppaaus
– t combinaion oft a a v scul rcels w e t t e pa t ough
he t ubul r nd a a l her he ubul sses hr
t a e for byt a enta effer at iol a t j t
he ngl med he ffer nd ent rer es s hey oin he
gl ul
omer us
• Smoot muscl cels w hin t a entat iol for gr nul rcels
h e l it he ffer rer e m a a l
• Speciaized t a cels in t r know a ma adensa sense
l ubul r l his egion n s cul -
cha in satl eloft a fl
nges l ev ubul r uid

• M cul Densa
a a
↓ Arterial pressure ↑ Arterial pressure

↑ Fluid reabsorption ↑ GFR
↓ GFR in proximal tubule
↑ Tubular flow rate
↓ Tubular flow rate ↑ Na+ and Cl- delivery
↓ Na+ and Cl- delivery to Macula Densa
to Macula Densa
↑ Na+ and Cl- reabsortion
↓ Na+ and Cl- reabsorption in Macula Densa
in Macula Densa

↑ Renin release ↓ Renin release

A utoregulation of High Filtration
Pres s ure

Importance of Autoreg ulation
• T myogenic a t ogl ul rfeedba mecha w k
he nd ubul omer a ck nisms or
in t ndem t a or ae G Rw hin aM Pr nge of8 - 0
a o ut egul t F it A a 018
mmHg
• A or aion gr tybl s t dir effectt tcha in
ut egul t eal unt he ect ha nges
at ia pr e mightot w ha e on G Ra pr v
rer l essur her ise v F nd eser es
w t a sol e homeost sis a al s w st excr ion t
aer nd ut a nd low a e et o
car on a usua
ry s l

Impact of autoregulation
• A utoregulation:
– G FR=180L/day and tubular
reabs orption=178.5L/day
– Res ults in 1.5L/day in urine

• Without autoregulation:
– S mall ↑ in BP 100 to 125mm Hg, ↑ GFR by 25%
(180 to 225L/day)
– If tubular reabs orption cons tant, urine flow of
46.5 L/day
• What would happen to plas ma volume?

ME A S URE ME NT OF RE NA L B LOOD FLOW
• Renal blood flow (RB F) is determined by meas uring firs t
the renal plas ma flow (RPF) and then c alculating the RB F.

• We meas ure RPF us ing paraaminohippuric ac id (PA H) .
• PA H is a s ubs tanc e that is :
 freely filtered by the glomeruli,
s ecreted in the tubules ,
but not reabs orbed.
If PA H is given by intravenous (IV) infus ion s o that its
conc entration is kept low in plas ma (e.g., 2 mg%), it is
almos t c ompletely removed with a s ingle c irculation of
plas ma in the kidneys .

10% of PA H remain in blood, bec aus e 10% of the blood that
goes to
40
the kidneys does not reach the nephrons , but s upplies other
renal

ME A S URE ME NT OF RE NA L B LOOD FLOW
• If we apply Fic k’s principle, we can c alculate RPF:
Amount of PAH Amount of PAH
=
filtered & secreted/min excreted in urine/min

• A mount of PA H filtered & s ec reted = P x E RPF
• A mount of PA H exc reted in urine/min. = U x V

w e, P = conc. ofPA in pl sma
her H a
E RPF = effect e R (90 ofpl smaonl i.e., t king int a
iv PF % a y, a o ccount t t10
ha %
bypa t nephr
sses he ons).
U = conc. ofPA in ur
H ine
V = v ume ofur min.
ol ine/

P x E RPF = U x V
UxV
E RPF 41
=
P

ME A S URE ME NT OF RE NA L BLOOD
FLOW
E xample: In a patient, if PA H is infus ed s o that its conc . in
plas ma (P) is
2 mg% (= 0.02 mg/ml) and the urine vol. (V) is 1.3 ml/min. &
PA H
c onc . in urine (U) is l0 mg/ml, then
E RPF = 10 mg/ml x 1.3 ml/min. / 0.02 mg/ml
= 650 ml/min.

S ince E PRF is 90% of actual RPF,
RPF = 650 x 100 / 90 = 720 ml/min.

If the hematocrit value is 45%, then plas ma cons titutes 55%
RB F = 720 x 100 / 55 = 1300 ml/min.

S ince c ardiac output is 5 L/min, RB F (1300 / 5000 x100) is

Ur F maion
ine or t
• Glomerular Filtration
• substances move from blood to glomerular capsule

• Tubular Reabsorption
• substances move from renal tubules into blood of
peritubular capillaries
• glucose, water, urea, proteins, creatine
• amino, lactic, citric, and uric acids
• phosphate, sulfate, calcium, potassium, and sodium ions

• Tubular Secretion
• substances move from blood of peritubular capillaries into renal
tubules
• drugs and ions

Overall fluid mov ement in the kidneys

Glomerular filtration.
It takes place between glomerular capillaries endothelium
(characterized by the presence of numerous small pores (fenestrations)
and Bowman’s capsule (characterized by the presence of podocytes).
Podocytes are modified squamous epithelial cells with numerous
elongated branches called foot processes which are separated by narrow
gaps called filtration slits (slit pores).

Fluid and small solutes dissolved in the plasma such as glucose, amino
acids, Na, K, Cl, HCO3- , other salts, and urea pass through the
membrane and become part of the filtrate.
The glomerular membrane hold back blood cells, platelets and most
plasma proteins.
The filtrate is about 10% of the plasma.
The volume of fluid filtered per unite time is called the glomerular
filtration rate (GFR). The GFR is about 180 L/day (=125 ml/min.).

C OMPOS ITION OF GFR
a- Contents: -w t aer
-ions: Na , K+ , Cl
+ -
-fr yfiler subst nces e.g. gl
eel t ed a ucose, a a
mino cids.
-0 3 abumin (mol a w 690 ).
.0 % l ecul r eight 0
b - O sm olality: 3 0mosmolL isot (sa osmol l ya pl sma
0 /, onic me ait s a ).
C- Sp ecific gravity: 10 10
D - p H : dr t 6in ur due t a
ops o ine o cidificaion byt kidney.
t he

GFR
–In an av erag e man: 125 ml/minute. In
women 10% les s .
:
–High r lbl fl (2025% ofcadia out )needed forhigh G R
ena ood ow - r c put F.
–GF R equals about 180 L/day so pl smav ume (3 )
a ol L
filer a 60t da y, M e t n 99% ofG Ris nor ly
t ed bout imes il or ha F mal
r bsor
ea bed.
–Nor lvolume of urine is a 1.5 litre/day.
ma bout

Filtration fraction

It is the fraction of the renal plasma flow
(RPF) that becomes glomerular filtrate. the
average filtration fraction about 16-20%.
It is calculated as (GFR/RPF X100).

Glomerular membrane
Capillary endothelium;
It has small holes (70-90 nm). It does not act as a barrier
against plasma protein filtration.
Basement membrane; (BM)
filamentous layer attached to glomerular endothelium &
podocytes, carry strong-ve charges which prevent the
filtration of plasma proteins, but filters large amount of
H2O and solutes.
Podocytes;
Epithelial cells that line the outer surface of the glomeruli.
They have numerous foot processes that attach to the BM,
forming filtration slits (25 nm wide).

Permeability of the glomerular
membrane
S ize of the molecules
• S ubs tanc es having diameters les s than 4
millmicrons (molecular weight 5500) are freely
filtered while thos e having diameters more than
8 millimicrons (molecular weight more than
7000) are not filtered.

C harges of the molecules
• -ve charged molecules are filtered Les s eas ily
than neutral molecules of equal s ize. (pos s ibly
due to neg ative charg es in the bas ement
membrane).

Filterability of the Membrane
• Filterability is a term us ed to des cribe
membrane s electivity bas ed on the molecular
s ize and charge

• Pore s ize would favor plas ma protein (albumin)
pas s age, but negative charge on protein is
repelled by the (-) charged bas ement membrane
(proteoglyc an filaments & podocytes )

• Los s of this (-) charge caus es proteinuria
condition called minimal chang e nephropathy

What Drives Filtration?
Howdoes fl mov fr t pl smaa oss t gl ul r
uid e om he a cr he omer a
membr ne int Bow n’s ca e?
a o ma psul
• No a iv ta tmecha
ct e r nspor nisms
• No l lener expendit e
oca gy ur
Simpl pa e physica for a
e ssiv l ces ccompl filr t
ish taion
-F taion occur t oughoutt l h oft ca l r
ilr t s hr he engt he pilaies

F orces involved in F iltration
• Gomer a ca l r bl pr e (fa or filr t
l ul r pilay ood essur v s t aion)
• Pl smacoloid osmot pr e (opposes filr t
a - l ic essur t aion)
• Bow n’s ca e hydr aic pr e (opposes filr t
ma psul ost t essur taion)

Forces affecting the GFR:
A) Forces helping filtration:
1- Hydrostatic pressure of the blood inside glomerular capillaries (HPG) (= 50 mmHg)
due to:
i- The afferent arteriole is 3 times wider than the efferent arteriole
ii- The diameter of the renal artery is large in relation to the relelatively small size of
the kidney.
iii- The renal artery comes directly from the aorta.
2- Colloidal osmotic pressure of the fluid inside the Bowman’s capsule (COPBC).
Where the filtrate is free of proteins, so this force normally equals to zero mmHg.

B) Forces opposing filtration:
1- Colloidal osmotic pressure of the glomerular capillary blood (COPG).
This pressure is due to plasma proteins and equals 30 mmHg.
2- 1- Hydrostatic pressure of the fluid inside the Bowman’s capsule (HPBC) (= 10
mmHg).
Accordingly,
The net filtering force= The forces helping filtration - The forces opposing filtration
= (HPG + COPBC) - (COPG + HPBC)
= (50 + 0) - (30 + 10) = 10 mmHg.

Forces affec ting filtration
Favoring Filtration Opposing Filtration
Glomerular hydrostatic Glomerular capillary colloid osmotic
pressure pressure
60 mm Hg 32 mm Hg

Bowman’s capsule colloid Bowman’s capsule hydrostatic
osmotic pressure pressure
0 mm Hg 18 mm Hg

Net = +10 mm Hg

Determinants of GFR
GFR=Kf x Net filtration pressure
Kf = Capillary filtration coeficient

F iltration coefficient (Kf)
• It is the GFR / mmHg of net filtration
pres s ure, it is normally
12.5ml/min/mmHg. It is cons tant
(normally).
• Glomerular filtration rate = Net filtration
pres s ure X Filtration coefficient
• GFR = NFP (l0) X Kf (12.5) = 125ml/min.
-Kf is determined by 2 factors :
1-T per bil yoft ca l r bed.
he mea it he pilay
2-T sur ce aeaoft ca l r bed.
he fa r he pilay

Glomerular Filtration Rate
• Depends on
– T netfilr t pr e
he t aion essur
– Howmuch gl ul rsur ce aeais a a a e forpenet aion
omer a fa r v il bl rt
– Howper bl t gl ul rmembr ne is
mea e he omer a a

GFR = K f x net filtration pres s ure

W e (Kf)= filr t coefficient(apr oft a e t o
her t aion oduct he bov w
gl ul rpr t
omer a operies)
-Roug hly 125 ml/min in males

Regulation of Filtration
(1) Chang es in g lomerular hydros tatic pres s ure.
(1) Diameter of the afferent arterioles .
– VD of afferent arterioles → ++ Hydros tatic pr. in glomerular
capillary → ++ GFR.
– VC of afferent arterioles e.g ++ s ympathetic activity → --
Hydros tatic pr. in glomerular capillary (HPGC ) → -- GFR.
(2) Diameter of the efferent arterioles .
– Moderate VC → ++ HPG C → s light ++ of G FR.
– S evere VC → -- RB F → -- G FR.
(3) ABP;
B etween 70 & 170 mmHg: GFR and RB F are kept relatively
cons tant by autoreg ulatory mechanis ms .
(4) Renal blood flow: direct relation
(5) S ympathetic s timulation: VC of aff. A rteriole.

C hanges in GFR by cons triction or dilation of
afferent (A A ) or efferent (E A ) arterioles

65

Regulation of Filtration
(2) Chang es in Bowman’s Caps ule hydros tatic pres s ure
+ + Hydr aicprin Bow n’s ca e e.g. st in
ost t ma psul one
ur er→ - G R.
et -F
(4) Chang e in g lomerular colloidal os motic pres s ure
Incr sed Coloida osmot pr e in gl ul rca l r
ea l l ic essur omer a pilay
• e.g in dehydr t → decr sed G R
aion ea F .
Decr sed Coloida osmot pr e in gl ul rca l r
ea l l ic essur omer a pilay
• e.g in hypopr einemia→ incr sed G R
ot ea F .
• F unctioning kidney mas s
• Glomerular s urface area
a ding t t st t ofmesa lcels.
ccor o he ae ngia l
Contracted: A &a II.
DH ng
Relaxed: A NP.

Lis t fiv e conditions in which g lomerular
filtration rate (GF R) decreas es .

1- g lomerular hydros tatic pres s ure is reduced (i.e.
hypotens ive s hock)
2-Bowman's s pace hydros tatic pres s ure are
increas e ureteric obs truction.
3- plas ma oncotic pres s ure ris es to unus ually hig h
lev els in dehydration.
4- decreas ed rates of renal blood and plas ma flow
(e.g . heart failure).
5- Reduced permeability and / or total filtering
s urface area.

Meas urement of GFR:
(1) Inulin c learance; Inulin has the following
characteris tics :
• F eel filer i.e. pl smaconc.= filr t concent aion.
r y t ed a tae rt
– notr bsor orsecr ed byr lt es i.e. a
ea bed et ena ubul mountfiler permin.= a
t ed mountexcr ed in ur min.
et ine/
– Notmet bol
a ized.
– Notst ed in t kidney.
or he
– Does nota filr t r t &it conc. is ea ymea ed.
ffect taion ae s sil sur

(2) C reatinine clearance
• F eel filer
r y t ed
• Notr bsor
ea bed
• pat lysecr ed byr lt es.
rial et ena ubul
• E ndogenous so used ea ybutina ae.
sil ccur t

Renal C learance
Definition: Volume of the plas ma cleared
from the s ubs tance per minute.
R = UVP
C /

R = r lcl r nce r t
C ena eaa ae
U = concentaion (mg/ )oft subst nce in ur
rt ml he a ine
V= fl r t ofur for t (mlmin)
ow ae ine maion /
P= concentaion oft sa subst nce in pl sma
rt he me a a

Free Water C learance (C H20)
Qua ifies r aiv l orga ofw t in t ur
nt el t e oss in aer he ine

• Cl r nce ofosmol (Cosm)is t v ume ofw t necessayt secr e t osmot
eaa es he ol aer r o et he ic
l d in aur isot w h pl sma
oa ine onic it a
– Differ bet een ur fl a t cl r nce ofosmol (Cosm)
ence w ine ow nd he eaa es
• CH20 = Ṽ – UosmṼ
Posm
– Negaiv w ur concentaed (hyperonic)
t e hen ine rt t
– Posit e w ur dil e (hypot
iv hen ine ut onic)

TUB ULA R FUNC TION
• T glomerular filtrate
he
is for a ar t of125 ml/
med t ae
min. or 180 L/day. It
pa t t r lt es.
sses o he ena ubul
• In t t es, t tubular
he ubul he
fluid is subj ed t t 2 ma
ect o he in
t a funct
ubul r ions,
reabs orption &
s ecretion.
• Itis final excr ed a urine a a
ly et s t
r t ofa 1-2 ml/min. or
ae bout
c a. 1.5 L/day.

78

TUB ULA R RE A B S ORPTION
• R lt es ta tsubst nces a oss t membr nes t int st ia fl a t t ough t
ena ubul r nspor a cr heir a o er it l uid nd hen hr he
per ubul rca l r membr ne ba t bl
it a pilay a ck o ood.

• Subst nces ca be ta t by:
a n r nspored
1. Trans cellular Route:
-Subst nces pa t ough t cel membr nes:
a ss hr he l a
–crossing t l lmembr ne &t t ba aer lmembr ne.
he umina a hen he sol t a a
-T ta tbyt r e ma be ac tive bymea ofapr ein
he r nspor his out y ns ot
car orpas s ive bydiffusion.
rier

2. Parac ellular Route:
-Subst nces pa a oss t j ions bet een t a cels.
a ss cr ight unct w ubul r l
-Ta tbyt r e occur pas s ively bydiffusion.
r nspor his out s
79

Tubular Reabs orption is a Function of the
E pithelial C ells Making up the Tubule

Lumen

Cells

Plasma

Tubular Reabs orption
A) Active transport; against electrochemical gradient.
(1) Primary active transport
Requires energy directly from ATP.
►Example; Na+ reabsorption in PCT
(2) Secondary active transport
-It does not require energy direct from ATP.
a) Co-transport
two substances bind to a specific carrier are cotransported in one direction.
b) Counter-transport
two substances bind to a specific carrier are
transported in two directions.
B) Passive reabsorption;
(1) Simple diffusion
Passive reabsorption of chloride & Osmosis of water
(2) Facilitated diffusion
Need carrier.
C) Pinocytosis
It is an active transport mechanism for reabsorption of proteins and
peptides in the proximal convoluted tubules.

Primary ac tive trans port of s odium
through the tubular epithelial c ell

82

Proximal C onvoluted Tubule

• 65% of t nephr funct occur in
he on ion s
PCT .
• T PCT ha a singl l yer of cuboida
he s ea l
cels w h milions ofmicr ili.
l it l ov l
– Incr sed sur ce aeaforr bsor ion.
ea fa r ea pt
• PCT ma funct is r bsor ion.
's in ion ea pt
• T PCTis ful ofmit
he l ochondria

Reabs orption in Proximal Tubule

• 10 % Gucose, pr ein a A A
0 l ot nd mino cids
• 60 Sodium, Cl a H2O.
% , nd
• 8 % PH, HCO3 K.
0 ,
• 60 Ca
% .
• 50 ofF t ed Ur .
% iler ea

Nar bsor ion
ea pt
 A ba aer lside oft t a epit ia cel t e is a ext e Na - + APa syst (=
t sol t a he ubul r hel l l her n ensiv + K T se em
Na - + pump).
+
K
 Itpumps 3Na a iv youtoft cel int t int st ium, a a t sa t car 2 K+
+
ct el he l o he er it nd t he me ime ries
int t cel.
o he l
 ButK+ w ldiffuse immediael ba int t int st ium due t
il t y ck o he er it o:
(1)high concentaion gr dient&
rt a
(2)high per bil yofepit ia cels t K+ .
mea it hel l l o
 A ar toft t e is:
s esul his her
-↓ inta l a Na concentaion
r celul r + rt
-↑ inta l a negaiv y(- mV
r celul r t it 70 )

 A l lmembr ne t e w lt efor be pa e diffusion ofNa int t cel aongbot
t umina a her il her e ssiv +
o he l l h
concentaion a el r gr dient cr t byt Na - + APa pump. T diffusion is
r t nd ectic a s eaed he + K T se his
fa it t byapr ein car .
cil aed ot rier

G lucose reab sorp tion
• The trans porter for glucos e on the bas olateral
membrane has a limited capacity to carry glucos e
bac k into the blood. If blood glucos e ris es above
180 mg/dl, s ome of the glucos e fails to be
reabs orbed and remains in the urine  glucos uria.

Tubular maximum for glucos e (TmG):

• The maximum amount of glucos e (in mg ) that
can be reabs orbed per min.
• It equals the s um of TmG of all nephrons .
• TmG not the s ame in all nephrons
• It is an indication of the reabs orptive capacity of
the kidney.
• It is determined by the number of glucos e
carriers in PC T.
• The maximum reabs orption rate is reached when
all the carriers are fully s aturated s o they can
not handle any additional amounts at that time.
• Value; 300 mg/min in ♀ , 375 mg/ min in ♂.

Renal Thres hold for Glucos e

• Is a oximael 18 mg/
ppr t y 0 dl
• Ifpl smagl
a ucose is gr t t n 18 mg/ :
eaer ha 0 dl
– T oft a cels is exceeded
m ubul r l
– gl a r in ur
ucose ppeas ine

GLUC OS E RE A B S ORPTION HA S A
TUB ULA R MA XIMUM

Glucose Filtered Excreted
Reabsorbed
mg/min

Reabsorbed

Plasma Concentration of Glucose

Glucos uria
pres ence of glucos e in urine
1. Diabetes mellitus
–blood gluc os e level > renal thres hold.
2. Renal g lucos uria
–It is c aus ed by the defect in the glucos e trans port
mec hanis m.
3. Phlorhizin
–A plant gluc os ide whic h c ompetes with gluc os e for the
c arrier and res ults in gluc os uria (phloridzin diabetes ).
4 Preg nancy
.
–due to altered gluc os e handling in dis tal nephrons .

17-59

S ecretion in Proximal Tubule
• Hydr secr ion fora ba r aion.
ogen et cid/ se egul t
• Ammoniasecr ion fora ba r aion.
et cid/ se egul t
• PA H.
• Cr t
eainine.
• Ur a
ic cid.
• Penicilin.
l

S PE C IFIC FUNC TIONS OF DIFFE RE NT
TUB ULA R S E GME NTS (cont.)

II. Loop of Henle:
• T l ofHenl w h it 3segment (t tdifferstuct al &funct ly)contibut t cr t agr dual incr sing
he oop e it s s ha r ur ly ional r es o eaing a ly ea
hyper ait (3 0→120 mosmolL)in t r lmedulayint st ium.
osmol l y 0 0 / he ena l r er it
A . Thin des cending limb:
- highly permeable to w t . 20% ofH2Ois r bsor her
aer ea bed e.
-onl moder t yper bl t sol es.
y ael mea e o ut
⇒ Osmol l yoft a fl ↑ gr dual a l dips deep int t medulaypyr mid (r ches 120 mosmol
ait ubul r uid a ly s oop o he l r a ea 0 ).
B. Thin as cending limb:
-impermeable to w t aer
-l a pt e pow forsol es.
ow bsor iv er ut
C . Thick as cending limb:
-impermeable to w t aer
-high r bsor iv pow forsol es: Ita iv yr bsor 25% offiler
ea pt e er ut ct el ea bs t ed
+ + - + - +
Na , K , &Cl (by1 Na , 2 Cl, 1 K cota t t medulayint st ium.
r nspor) o l r er it
⇒ Osmol l yoft a fl ↓ gr dual a itr ches DCT(becomes hypoosmot Itis cal t diluting s egment.
ait ubul r uid a ly s ea ic). led he

97

SPE F IONSOFDIF . T A SE M NT
C. UNCT F UBUL R G E S
III. Dis tal C onvoluted Tubule (DC T) & C ollecting Duct (C D):
A . E arly DC T:
 T patoft r lt es is in effecta ext
his r he ena ubul n ension oft t a
he hick scending l ofl ofHenl
imb oop e:
- Itis impermeable to w t . aer
-T e is cont r a ofNa , K+ , Cl &ot ions w houtH2O.
her inued emov l + -
her it
⇒ T e is furherdil ion oft a fl a it osmol l y↓ ev mor (10 mosmol
her t ut ubul r uid nd s ait en e 0 ).
⇒ T patis cal t cortical diluting s egment.
his r led he
B. Late DC T & C ortical C D:
 T ae impermeable to ur .
hey r ea
 T ha e 2 cel t
hey v l ypes:
(1) Principal C ells :
a. T a iv yr bsor Na in excha forK+ secr ion. T a ion is incr sed byaldos terone.
hey ct el ea b + nge et his ct ea
b. A ntidiuretic hormone (A DH) ca t inserion ofH2Ocha s (aquaporins ) in l l
uses he t nnel umina
membr ne oft cels → al s r bs. ofH2O.
a hese l low ea
In t a
he bsence ofA t pr lcels ae imper bl t H2O.
DH, he incipa l r mea e o

99

SPE ICF IONSOFDIF E E T A SE M NT (cont
CIF UNCT F R NT UBUL R G E S .)

B . Late DC T & C ortical C D: (cont.)
(2) α-Intercalated C ells :
-T cels secr e H+ byH+ - T se independentofNa
hese l et APa +

r bsor ion. T a ion is incr sed byaldos terone.
ea pt his ct ea
C . Medullary C D:
• In t l stporion oft nephr t e is final adjus tment of volume & concentration of
his a t he on her
urine.
 T per bil y oft segmentt w t , sa a t toft l t DCT&corica CD, is v r bl &depends on t l el
he mea it his o aer me s ha he ae t l aia e he ev
ofcir aingA (= facultative water reabs orption).
cul t DH
 W h high bl l el ofA t e is ↑ r bsor ion ofH2O byosmosis, a t a fl in CD is subj ed t
it ood ev s DH, her ea pt s ubul r uid ect o
gr dual incr sing hyper ait oft medulayint st ium.
a ly ea osmol l y he l r er it
 T patis aso permeable t ur , t tdiffuses int t int st ium w it concentaion in t a fl ↑ due
his r l o ea ha o he er it hen s rt ubul r uid
t H2Or bsor ion.
o ea pt
T ur contibut t t hyper ait ofmedulayint st ium.
hus, ea r es o he osmol l y l r er it
⇒ In t pr
he esence ofA ur excr ed is concentaed &smalin v ume.
DH: ine et rt l ol
⇒ In t a
he bsence ofA ur excr ed is dil e ur &l r in v ume.
DH: ine et ut ine age ol

101

Medullary C ollecting Duct

• r bsor < 10 offiler Na a w t
ea bs % t ed + nd aer
• fina sit forpr
l e ocessingofurine
functional characteris tics :
5. per bil yt w t is contoled byA l el
mea it o aer rl DH ev
-↑A DH ↑ w t r bsor ion
aer ea pt
2. per bl t ur
mea e o ea
-ur is r bsor int t medulay
ea ea bed o he lr
int st ium w e ithel incr se t
er it her p ea he
osmol l yoft int st ium a t efor hel t concentae ur
ait he er it nd her e p o r t ine.

S ummary For Tubular Functions

S ummary of c hanges in os molality of tubular fluid
in various parts of the nephron

RE GULA TION OF TUB ULA R
RE A B S ORPTION

1. Glomerulotubular B alance
• intinsic a it oft t es t incr se t r bsor ion r t in
r bil y he ubul o ea heir ea pt ae
response t a incr se in gl ul rfilr t
o n ea omer a taion
• cha in G Rinduces apr t lcha in t a r bsor ion
nges F oporiona nge ubul r ea pt
• t a r t ofr bsor ion incr ses a filer l d incr ses butt
ot l ae ea pt ea s t ed oa ea he
per a ofG Rr bsor r ins r aiv yconst nt
cent ge F ea bed ema el t el a
• second l ofdefense forpr ent cha in r l hemodyna
ine ev ing nges ena mics
fr ca l r cha in sodium orfl excr ion
om using age nges uid et
• bl s sodium excr ion r
unt et esponse t cha in G Rinduced bycha in
o nges F nges
at ia pr e
rer l essur

2. Peritubular C apillary and
Renal
Inters titial Fluid S tarling’s
Forces
A . Peritubular C apillary Hydros tatic
Pres s ure:
↑ PPC ↓ r bsor ion
ea pt
Syst at ia pr e (PA):
emic rer l essur
↑ PA ↑ PPC ↓ r bsor ion
ea pt
B. PTC Os motic Pres s ure (Π PC ):
↑ ΠPC ↑ r bsor ion
ea pt
C . Renal inters itial fluid hydros tatic
pres s ure:
-Decr sed r bsor ion in t per ubul rca l r w lr tin:
ea ea pt he it a pilaies il esul
1. ↑ PIF due t a
o ccumul t offl in t int st ia compat
aion uid he er it l rment
2. ↓ ΠIF due t dil ion ofint st ia fl pr eins
o ut er it l uid ot

3. A rterial Pres s ure
• smalincr ses in at ia pr e oft ca maked incr ses
l ea rer l essur en use r ea
in ur r excr ion ofw t a sodium (pr e diur a
inay et aer nd essur esis nd
pr e nar esis)
essur tiur

mec hanis m:
1. sl incr se in G R
ight ea F.
2. incr sed PPC ↓ r bsor ion fr int st ia spa
ea ea pt om er it l ce ↑ PIF ↓
r bsor ion ofw t a
ea pt aer nd
sodium fr t a l
om ubul r umen
3 decr sed A ensin II
. ea ngiot ↓ Na r bs
+
ea

4. Hormonal C ontrol
Hormone Site of Action Effects
Aldosterone Collecting tubule and duct ↑ NaCl, H2O
reabsorption, ↑K+
secretion
Angiotensin II Proximal tubule, thick ↑ NaCl, H2O
ascending loop of reabsorption, ↑H+
Henle/distal tubule, secretion
collecting tubule

Antidiuretic Distal tubule/ collecting ↑ H2O reabsorption
hormone tubule and duct

Atrial natriuretic Distal tubule/ collecting ↓ NaCl reabsorption
peptide tubule and duct

Parathyroid Proximal tubule, thick ↓ PO4--- reabsorption, ↑
hormone ascending loop of Ca- reabsorption
Hental/distal tubule

5. S ympathetic S timulation
• w ldecr se sodium a w t excr ion (incr se sodium a w t
il ea nd aer et ea nd aer
r bsor ion)bythe following mechanis ms :
ea pt

1. v soconstict ofbot a enta effer
a r ion h ffer nd ent
at iol t ebydecr singG R
rer e her ea F .
2. incr se sodium r bsor ion in t pr l
ea ea pt he oxima
t ea t a
ubul nd hick scendingl imb.
3 incr se r r ea
. ea enin el se incr sed A IIea ng incr sed sodium
ea
r bsor ion.
ea pt

Hormones ac ting on the kidney
1. A ldos terone:
• S timulus for its s ecretion:
↓ Bl v ume (v r a ent syst
ood ol ia enin- ngiot in em).
• A ctions & their s ite:
Itst aes Na r bsor ion in DC T & cortical C D t ough:
imul t + ea pt hr
1) In principal cells : ↑ Na r bsor ion in excha w h K+ .
+
ea pt nge it
2) In α -intercalated cells : ↑ Na r bsor ion in excha w h H+ .
+
ea pt nge it
2. A ngiotens in II: Itis t mostpow fulNa r a hor
he er + et ining mone.
↓ at ia bl pr e &bl v ume, e.g., hemorha (v r
rer l . essur ood ol r ge ia enin).
1. It↑ Na r bsor ion bysev a mecha
+
ea pt er l nisms:
a Byst aing adost one secr ion.
. imul t l er et
b. In PC T: -Bydir l st aing Na - + APa a ba aer lbor .
ecty imul t +
K T se t sol t a der
-Bydir l st aing Na - + count ta a l lbor .
ecty imul t +
H err nsp. t umina der
2. Itconstict effer at iol
r s ent rer es.
112

Hormones acting on the kidney
3. A trial Natriuretic Peptide (A NP): Itfa it t Na &H2Oexcr ion.
cil aes Cl et
• S timulus for its s ec retion:
↑ Ar lpr e (r ea fr specific ar lfiber w bl v ume is ↑)
tia essur el sed om tia s hen ood ol
• A c tions & their s ite:
1. It↑ G byV ofa ent&V ofeffer at iol
FR D ffer C ent rer e.
2. It↓ Na r bsor ion from DC T & cortical C D .
+
ea pt
4. A DH:
↑ Pl smaosmol r y&↓ bl v ume.
a ait ood ol
↑ w t r bsor ion in late DC T, cortical & medullary C D: byinseringa por w t
aer ea pt t qua in aer
cha s int t l lmembr nes.
nnel o heir umina a
5. Parathormone (PTH):
↓ Pl smaCa concentaion.
a 2+
rt
• A ctions & their s ite: 114
1. ↑ Ca r bsor ion from DC T.
2+
ea pt 2. ↓ Phosphae r bsor ion from PC T.
t ea pt

H A N D L IN G O F
C E R T A IN
IM P O R T A N T
S O L U TE S
B Y RENAL
TU B U L E S
116

I. GLUC OS E :
A nor lbl gl l el (~10 mg%), gl is fr yfiler a ar t of125 mg/ (= pl smaconc. XG R
t ma ood ucose ev s 0 ucose eel t ed t ae min. a F
= 10 mg% x 125 mlmin.).
0 /
+
T a
he mountfiler is compl el r bsor fr t upperhafofPCTbyNa - ucose cota t(mecha see
t ed et y ea bed om he l gl r nspor nism:
before).

+
T e is, how er al ed numberofNa - ucose car s:
her ev , imit gl rier
a- A t a blood glucos e level of les s than 180 mg%, alt filer gl
l he t ed ucose ca be
n
r bsor beca pl yofcar s ae a a a e.
ea bed use ent rier r v il bl

b- A t a blood glucos e level of 180 mg%, gl st rs t a rin ur
ucose at o ppea ine.
T l elofbl gl is cal t renal thres hold forgl
his ev ood ucose led he ucose. It coresponds t arenal
r o
tubular load of 220 mg/min.

c- A t a renal tubular load of glucos e of 320 mg/min, alt car s ae saur t
l he rier r t aed,
i.e., t trans port maximum forgl
he ucose, T G, is r ched.
m ea
A furher↑ in filer gl
ny t t ed ucose is notr bsor &is117et in ur
ea bed excr ed ine.

G luc os e Titration C urves

119

I. GLUC OS E : (cont.)

I. G LUC OS E : (cont.)
S play:
-Itis t r ofgl cur es bet een r lt eshol &T G.
he egion ucose v w ena hr d m
-Itoccur bet een r lt a gl l ds of220 - 320 mg/min..
s w ena ubul r ucose oa
-Itr esent t excr ion ofgl in ur befor ful saur t of
epr s he et ucose ine e l t aion
t gl car s forr bsor ion (T G)is a ed.
he ucose rier ea pt m chiev
-Itis expl ined byt het ogeneit ofnephr
a he er y ons:
Notalnephr ha e exa l t sa T G. Some nephr
l ons v cty he me m ons
r ch saur t a l erpl smaconcentaions t n ot s, a
ea t aion t ow a r t ha her nd
gl w lbe excr ed in ur befor t a er ge T G is r ched.
ucose il et ine e he v a m ea

120

GLUC OS URIA :
• Definition:
Itis t pr
he esence ofgl in ur Itis usual a
ucose ine. ly ccompa bypol iadue t osmot diur
nied yur o ic esis.
• C aus es :
1. Diabetes Mellitus :
-T bl gl l elis high, exceeding t nor lr lgl
he ood ucose ev he ma ena ucose t eshol of18 mg%.
hr d 0
-In t condit t pl smacl r nce ofgl is a e zer &t mor a a t condit of
his ion, he a eaa ucose bov o, he e dv nced he ion
dia es, t highert gl cl r nce.
bet he he ucose eaa
2. Renal G lucos uria:
-In t condit t bl gl l elis nor l
his ion he ood ucose ev ma.
-T defectl in t r lt es t
he ies he ena ubul hemsel es. T e is adecr sed r lgl t eshol bel it
v her ea ena ucose hr d ow s
nor lv l due t acongenit ldefectin t gl ta tmecha so t tt e is l ofgl
ma aue o a he ucose r nspor nism, ha her oss ucose
in ur a nor lbl gl l el
ine t ma ood ucose ev s.

121

S odium Handling
- + is fr y filer a oss gl ul rca l r T it concentaion in gl ul rfilr t equas t tin
Na eel t ed cr omer a pilaies. hus, s rt omer a tae l ha
pl sma
a .
+
- ofNa ae r bsor aong alsegment oft r lt e, exceptt t descending l oft l
99% r ea bed l l s he ena ubul he hin imb he oop
ofHenle.

Na+ reabs orption along the nephron:
1. Proximal c onvoluted tubule:
ea bs 3 t ed +
R bsor 2/ (67%)offiler Na &H2O. T pr is isoosmot
his ocess ic.
a. E arly PC T:
+
-Na is r bsor bycota tw h gl
ea bed r nspor it ucose, a a phosphae &l ct t
mino cids, t a ae.
-Na is aso r bsor bycount ta tv Na - + excha
+
l ea bed err nspor ia + H nge.
b. Late PC T:
Na is r bsor (1 ry a iv ta t w h Cl (pa e diffusion).
+
ea bed ct e r nspor) it - ssiv

122

S odium Handling
2. Thic k as cending limb of loop of Henle:
R bsor 25% offiler Na byt Na - + - - cota t in t l l
ea bs t ed + he + K 2Cl r nsporer he umina
membr ne.
a
3. Dis tal convoluted tubule & collecting duct:
oget hey ea b % he t ed +
T hert r bsor 8 oft filer Na .
a. E arly DC T:
Cont ins aNa - + - - cot a t in l lmembr ne simil rt
a +
K 2Cl r nsporer umina a ao
t tin t a
ha hick scending l ofl ofHenl
imb oop e.
b. Late DC T & C D: (T effectis incr sed byaldos terone).
his ea
i. Principal cells : r bsor Na in excha forK+ .
ea b + nge
ii. α -Intercalated cells : r bsor Na in excha forH+ .
ea b + nge
123

Na+ handling along the nephron

124

Factors affecting Na+
reabs orption:
1. Rate of tubular flow:
Sl r t offl ↑ r bsor ion ofNa in l ofHenl e.g., in ↓ G R
ow ae ow ea pt +
oop e, F.
2. Glomerulotubular balanc e in PC T:
- Itr esent t a it oft PCTt r bsor aconst ntfr ct (2/ or67%)oft filer
epr s he bil y he o ea b a a ion 3 he t ed
+
l d ofNa &w t .
oa aer
- IfG R↑ fora r son, t filer l d ofNa aso ↑. T w ll d t a incr se in t
F ny ea he t ed oa +
l his il ea o n ea he
+ +
amountofNa r bsor in PCT so t tt a
ea bed , ha he mountofNa excr ed incr ses onl sl l
et ea y ighty.
- Imporat nce:
Itis a intinsic mecha t tca be seen in dener aed kidneys. Ithel pr entov l ding
n r nism ha n vt ps ev eroa
ofdist lt a segment w G R↑.
a ubul r s hen F

125

Factors affecting Na+
reabs orption
2. G lomerulotubular balanc e in PC T:
- M nism:
echa
Gomer ot a baa is ba on
l ul ubul r l nce sed
St ring for in per ubul rca l r
al ces it a pilaies,
hich ler +
w at Na &H2Or bsor ion:
ea pt
↑ in G Rr t in ↑ in pr ein conc. &
F esuls ot
oncot pr e (πC), a w la a↓ hydr
ic essur s el s o-
st t pr e (PC)ofper ubul rca l r
aic essur it a pilaies.
T in t n, ca a ↑ in w t r bsor ion fr PCT
his, ur uses n aer ea pt om .
+
Since w t r bsor ion is a
aer ea pt ccompa byNa r bsor ion, t e is maching filr t &r bsor ion,
nied ea pt her t taion ea pt
orgl ul ubul rbaa
omer ot a l nce.

3. Hormones : (s ee before)
126
1. A ldos terone, 2. A ngiotens in II, 3. A NP

Potas s ium Handling
1. G lomerular c apillaries :
F t aion ofK+ occur fr ya oss t gl ul rca l r
ilr t s eel cr he omer a pilaies.
2. PC T:
Itr bsor 67% oft filer K+ aong w h Na &w t .
ea bs he t ed l it + aer
3. Thick as c ending limb of loop of Henle & early DC T:
Itr bsor 20 oft filer K+ byt Na - + - - cota t in t l lmembr ne.
ea bs % he t ed he + K 2Cl r nsporer he umina a
4. Late DC T & c ollec ting duc t:
T eit r bsor orsecr e K+ .
hey her ea b et
a. Reabs orption of K +:
- It occur onl in K+ depl ion (= l K+ diet Under t condit K+ excr ion ca be a l a 1% of
s y et ow ). hese ions et n s ow s
+
filer l d beca t kidney conser es a much K a possibl
t ed oa use he v s s e.
-Itinv v aK+ - + excha a l lmembr ne ofα- er l t cels.
ol es H nge t umina a int caaed l
b. S ec retion of K +:
-Itoccur in pr lcels byNa - + excha
s incipa l +
K nge.
-Itis v r bl Itdepends on diet r K+ , adost one &a ba st t
aia e. ay l er cid- se aus.

127

K + handling along the nephron

128

Mechanis m of dis tal K + s ecretion in principal
cells
- A t bas olateral membrane: K+ is a iv yta t int t cel byt Na -
ct el r nspored o he l he +
K+ APa → T mecha ma a ahigh I.C. K+ conc.
T se his nism int ins
- A t luminal membrane: K+ is pa el secr ed int t l t ough K+
ssiv y et o he umen hr
cha s.
nnel

he mount of t pa e secr ion is det mined by t concentaion gr dient a ing on K+
T a his ssiv et er he rt a ct
a oss t l lmembr ne:
cr he umina a
In condit t t↑ I.C. K+ conc. or↓ t l lK+ conc.
ions ha he umina
→ ↑ t dr ingfor forsecr ion.
he iv ce et
In condit t t↓ I.C. K+ conc. or↑ t l lK+ conc.
ions ha he umina
→ ↓ t dr ingfor forsecr ion.
he iv ce et

129

Mechanis m of K + s ecretion in the principal
cell of the DC T

2

1
3

130

HA NDLING OF C E RTA IN IMPORTA NT
S OLUTE S B Y RE NA L TUB ULE S
Fac tors affecting dis tal K + s ec retion:
1. Dietary K +:
High K+ diet→ ↑ I.C. K+ → ↑ dr ing for → ↑ K+ secr ion.
iv ce et
LowK+ diet → ↓ I.C. K+ → ↓ dr ing for → ↓ K+ secr ion.
iv ce et
2. A ldos terone:
-A t ba aer lmembr ne: Itst aes Na - + APa → ↑ K+
t he sol t a a imul t + K T se
upt ke bypr lcels → ↑ I.C. K+ concentaion → ↑ dr ing for for
a incipa l rt iv ce
K+ secr ion.
et
-A t l lmembr ne: It↑ t numberofK+ cha s.
t he umina a he nnel
3. A c id-bas e s tatus :
A Na ions ae r bsor in excha fort secr ion ofK+ orH+ ions, t e is compet ion forNa ions in t
s + r ea bed nge he et her it +
he
t a fl
ubul r uid:
In a cidosis: M e H+ t n K+ ent s t a epit ia cel a oss t ba aer lmembr ne → ↓ I.C. K+ → ↓
or ha er ubul r hel l l cr he sol t a a
dr ingfor forK+ secr ion.
iv ce et
In akaosis: L H+ t n K+ ent s t a epit ia cel a oss t ba aer lmembr ne → ↑ I.C. K+ → ↑
l l ess ha er ubul r hel l l cr he sol t a a
dr ingfor forK+ secr ion.
iv ce et 131


V. Phos phate:
5% t ed t ea bed r nspor it + nd he est
- 8 offiler phosphae is r bsor in PCTbycota tw h Na a t r is excr ed in
et
urine.

- Paahyr hor (PT inhibit phosphae r bsor ion in PCT&ca phos phaturia.
r t oid mone H) s t ea pt uses

- Phosphae is aur r bufferforH+ .
t inay

132


VI. C alc ium:
- Nor ly, 99% offiler cacium ae r bsor byr lt es.
mal t ed l r ea bed ena ubul
- Itshoul be not how er t tonl 50 ofpl smacacium, w is ionized cacium, is filer a oss
d ed, ev , ha y % a l hich l t ed cr
t gl ul rca l r w e t ot 50 ofpl smacacium ae bound t pl smapr eins a
he omer a pilaies, hil he her % a l r o a ot nd
ca be filer
nnot t ed.
 67% ae r bsor in PCT
r ea bed .
 25- 0 ae r bsor in t l ofHenl
3 %% r ea bed he oop e.
 5- % ae r bsor in DCT&CD. PT st aes Ca r bsor t fr DCT
10 r ea bed H imul t 2+ ea p-ion om .

Urea Handling
(1) PC T
A bout 50% of the filtered urea is pas s ively reabs orbed
The wall of PC T is partially permeable to urea but highly permeable to water s o water
reabs orption from PC T → increas es urea concentration in tubular lumen. This
creates concentration gradient → Urea reabs orption.
(2) Thick as cending limb of loop of Henle, DC T and cortical
collecting tubules
A ll are relatively impermeable to urea.
H2O reabs orbed in DC T and cortical collecting tubule (in pres ence
of A DH) → increas ed urea concentration in tubular fluid.
(3) Inner medullary portion of the collecting duct
Urea diffus es into the medullary inters titium to increas e its os molality.
Diffus ion of urea is facilitated by A DH.
40 - 60% of the tubular load of urea is exc reted in urine.
► Urea cycle
• Urea moves from the medullary inters titium into the thin loop of
• the Henle and back down into the medullary collecting
• duct and again to medullary inters titium
• s everal times before urea is excreted.

Handling of Hydrog en
1. PC T 85%
2. Thic k as cending loop of Henle 10%
3. DC T and collec ting tubule 5%.
Mechanis m of H+ s ecretion
A) In PCT, LH and initial part of DCT:
M ofH+ is secr ed bys econdary active trans port.
ost et
Itis Na dependent.
A ipor car a l lbor bind Naa H.
nt t rier t umina der nd

B) In late part of DCT and CD:
Hydr is secr ed byprimary activ e trans port ByInterc alated cells ,
ogen et
hydr secr ion is st aed byadost one a bot
ogen et imul t l er nd h
hydr a pot ssium compet forsecr ion.
ogen nd a e et

B icarbonate Handling
Plas ma HCO3 plays an important
role in the reg ulation of pH of
plas ma.
Mos t of the filtered bicarbonate (99
% or more) is reabs orbed.
1) A bout 80 to 90 % of the
bicarbonate reabs orption
occurs in the PC T.
2) In the thick as cending loop of
Henle, 10 % of the filtered
bicarbonate is reabs orbed,
3) the remainder of the
reabs orption takes place in

A mino acid handling

• S econdary
active
trans port
coupled with
s odium

Subs Description Proximal tubule Loop of Henle Distal tubule Collecting duct

If glucose is not reabsorbed by reabsorption (almost
the kidney, it appears in the 100%) via
glucose urine, in a condition known as sodium-glucose transport proteins- - -
glucosuria. This is associated (apical)
with diabetes mellitus.. and GLUT(basolateral
).
amino acids Almost completely conserved. Reabsorption (active) - - -

urea Regulation of osmolality. Varies reabsorption (50%) via secretion - reabsorption in
with ADH passive transport medullary ducts
reabsorption reabsorption reabsorption (5%,
Uses Na-H antiport, Na-glucose reabsorption (65%, (25%, thick (5%, principal cells),
sodium symport, sodium ion channels isosmotic) ascending, sodium-chloride symporter by
stimulated
Na-K-2Cl symporter ) aldosterone
)
Usually follows sodium. Active reabsorption reabsorption
chloride (transcellular) and passive ( reabsorption (thin ascending, (sodium- -
paracellular) thick ascending, chlorid symp
Na-K-2Cl
reabsorption
water Uses aquaporin. - reabsorption - (with ADH, via
(descending) vasopressin recepto
)
Helps maintain acid-base reabsorption (80-90%) reabsorption reabsorption
HCO3 balance. [8] [9] (thick ascending) - (intercalated
[10]
cells,
secretion
H Uses [[vacuolar H+ATPase]] - - - (intercalated
cells)
reabsorption
(20%, thick secretion increased by
K Varies upon dietary needs. reabsorption (80%) ascending, aldosterone)
Na-K-2Cl symporter
)
reabsorption (thick reabsorption
calcium reabsorption ascending) via stimulated -
passive transport by PTH
reabsorption (80%)
phosp Excreted as titratable acid. Inhibited by - - -
parathyroid hormone.

Table 41-3 NaCl transport along the nephron
Segment Percentage filtered Mechanism of Na+ Major regulatory
reabsorbed entry across the hormones
apical membrane
Proximal tubule 67% Na+-H+exchange, Angiotensin II
Na+-cotransport with
amino acids and Norepinephrine
organic solutes, Na+/
H+-Cl-/anion Epinephrine
exchange
Dopamine
Paracellular
Loop of Henle 25% 1 Na+-1K+-2Cl- Aldosterone
symport
Distal tubule ~4% NaCl symport Aldosterone

Late distal tubule ~3% Na+ channels Aldosterone
and collecting duct
Atrial natriuretic
peptide
Urodilatin

Table 41-4 Water transport along the nephron

Segment Percentage of Mechanism of Hormones
filtered load water that regulate
reabsorbed reabsorption water
permeability
Proximal tubule 67% Passive None

Loop of Henle 15% DTL only; None
passive

Distal tubule 0% No water None
reabsorption

Late distal ~8%-17% Passive ADH, ANP
tubule and

Mechanis ms to C oncentrate
Urine
creation of
• Countercurrent Multiplication--
osmot gr dient
ic a
– L ofHenl
oop e
– G aes aur t tis concentaed a high a 60 mosm/
ener t ine ha rt s s 0 L
• Urea recycling
– M l r Colect Duct
edulay l ing
– Needed t incr se t osmol rgr dientfr 60 t 120 mosm/
o ea he a a om 0 o 0 L
– Kidneys use ur t do osmot w k w in st t ofa idiur
ea o ic or hen ae nt esis
• Countercurrent exchang e-- asarectam aintains the
v
medulayinst st ia osmot gr dientsetup byt count curentmulipl
l r er it l ic a he er r t ier

PRODUC TION OF C ONC E NTRA TE D URINE
• Concentaed ur is aso cal hyperos motic urine (ur osmol r y> bl osmol r y).
r t ine l led ine ait ood ait
• T kidneyexcr es excess sol es, butdoes notexcr e excess a s ofw t .
he et ut et mount aer
• The bas ic requirements for forming a c onc entrated urine
are:
1. a high level of A DH, e.g., in w t depr aion orhemorha
aer iv t r ge
→ ↑ per bil yofl t DCT&CDs t w t , al ing t segment
mea it ae o aer low hese s
t r bsor al r a
o ea b age mountofw t . aer
2. a high os molarity of the renal medullary inters titial fluid
→ pr ides t osmot gr dientnecessayforw t r bsor ion t
ov he ic a r aer ea pt o
occurin t pr
he esence ofhigh l el ofA
ev s DH.
• A erpa t t int st ium, w t is car byt v sar aba int t bl
ft ssing o he er it aer ried he a ect ck o he ood.

146

PRODUC TION OF C ONC E NTRA TE D URINE
Reabs orption of Water in Pres ence of ADH:
In PC T, loop of Henle & early DC T:
-Sa a in for t ofdil e ur (see befor
me s maion ut ine e).
-T t a fl r ching t l t DCTis hyposmot (10 mOsm/).
he ubul r uid ea he ae ic 0 L
Late DC T:
-A ↑ t w t per bil yoft pr lcels oft l t DCT
DH he aer mea it he incipa l he ae .
⇒ Wt is r bsor unt t osmol r yoft DCTequas t tofsurounding int st ia fl in r l
aer ea bed il he ait he l ha r er it l uid ena
corex (3 0mOsm/).
t 0 L
C Ds :
-A ↑ t w t per bil yofpr lcels ofCDs.
DH he aer mea it incipa l
-A t t a fl fl s t ough t CDs, itpa t ough r
s he ubul r uid ow hr he sses hr egions ofincr sing hyper ait t ad
ea osmol r y ow r
t innermedula
he l.
-Wt is r bsor fr t CDs unt t osmol r yoft t a fl equas t toft surounding
aer ea bed om he il he ait he ubul r uid l ha he r
int st ia fl
er it l uid.
⇒ T osmol r yoft fina ur r ches 120 mOsm/.
he ait he l ine ea 0
147 L

II. PRODUC TION OF C ONC E NTRA TE D URINE (cont.)

148

II. PRODUC TION OF C ONC E NTRA TE D URINE (cont.)

149

The C ounterc urrent S ys tem
• T count curentsyst is r
he er r em esponsibl fort cr t &ma ena ofagr dual incr sing
e he eaion int nce a ly ea
hyper ait in t r lmedulayint st ium, w is essent lforena ing t kidneyt
osmol r y he ena l r er it hich ia bl he o
concentae ur in t pr
r t ine he esence ofenough cir aing A
cul t DH.
• T osmot gr dientis due t a
his ic a o ccumul t ofsol es (pr r yNa &ur )in gr texcess ofw t in
aion ut imail Cl ea ea aer
t medulayint st ium.
he l r er it
• Once t high sol e concentaion in medulaha been a ed, itis ma a byabaa out owof
he ut rt l s chiev int ined l nced fl
sol es &w t in t medula
ut aer he l.
• T osmot gr dientis
his ic a
1. est bl byt l ofHenl w a s a ac ounterc urrent multiplier.
a ished he oop e, hich ct s
2. pot iaed byt colect duct w al s urea recycling t occur
ent t he l ing , hich low o .
3 ma a byt v sar a w a a counterc urrent exchangers .
. int ined he a ect , hich ct s

150

THE C OUNTE RC URRE NT S YS TE M
Loop of Henle A cting as C ounter C urrent Multiplier
How does the renal medulla become
hyperos motic?
1. Befor t osmot gr dientoft medulais est bl
e he ic a he l a ished, t osmol r yis t sa t oughoutt
he ait he me hr he
nephr (3 0mOsm/).
on 0 L
2. T a iv pumping ofNa outoft thick as c ending limb occur w houtconcomit nt
he ct e Cl he s it a
movementofw t → ↓ in osmol r yoft a fl inside a
aer ait ubul r uid scending l (20 mOsm/)&↑ in
imb 0 L
osmol r yofmedulayint st ia fl (4 0mOsm/).
ait l r er it l uid 0 L

3 A fl pa dow t des c ending limb, itr ches osmot equil ium w h medulay
. s uid sses n he ea ic ibr it lr
int st ium due t osmosis ofw t outofdescending l [Int st ia osmol r yis ma a a 4 0
er it o aer imb. er it l ait int ined t 0
mOsm/ due t cont ta tofions outoft a
L o inued r nspor imb.] T t e is agr dua ↑ in
hick scending l hus, her a l
t a fl osmol r ya itfl s t ads t ha pin bend.
ubul r uid ait s ow ow r he ir
4 A mor fl ent s descending l fr PCT hyper ic fl pr iousl pr in descending
. s e uid er imb om , osmot uid ev y esent
l nowfl s int t a
imb ow o hick scending l imb.

151

Loop of Henle A cting as C ounter C urrent
Multiplier
5. M e Na is pumped fr t a
or Cl om hick scending l int int st ium, but w t r ins in t e. T
imb o er it aer ema ubul his
cont unt a20 mOsm/ osmot gr dientis est bl
inues il 0 L ic a a ished. Nowosmol r yin medulayint st ium ha
ait l r er it s
r furhert 50 mOsm/.
isen t o 0 L
6. Once a in t fl in descending l equil aes w h hyper ic medulay int st ia fl now
ga he uid imb ibr t it osmot l r er it l uid,
r ching 50 mOsm/ a t t
ea 0 L t he ip.
7. T st ae r t ov & ov , a
hese eps r epeaed er er dding mor & mor sol e t t medulain excess ofw t . T
e e ut o he l aer his
pr ocess gr dual ta sol es in t medula ev ual r ising t int st ia osmol r y t 120
a ly r ps ut he l , ent ly a he er it l ait o 0
mOsm/. L
• Ov al t pr essiv ta t of Na fr t t a fl int t int st ium r t in t
er l, he ogr e r nspor Cl om he ubul r uid o he er it esuls he
est bl
a ishmentofal udina osmot gr dientin t medula
ongit l ic a he l.
⇒ Thus , the countercurrent arrangement of the loop of Henle
multiplies a relatively s mall trans epithelial os motic gradient into a
large longitudinal gradient.

152

C OUNTE RC URRE NT MULTIPLIE R S YS TE M IN
LOOP OF HE NLE

153

Role of DC T & C Ds in Urine C oncentration
• T a fl fl ing fr l ofHenl int DCTis dil e.
ubul r uid ow om oop e o ut
• T eal DCTfurherdil es t fl beca t segment l t a
he ry t ut he uid, use his , ike he scending l ofl ofHenl
imb oop e,
a iv yta t Na outoft e, butis imper bl t w t .
ct el r nspors Cl ubul mea e o aer
• W h high A concentaions, l t DCT&corica CD become highl per bl t w t → large
it DH r t ae t l y mea e o aer
amounts of water are reabs orbed from the tubule into the
c ortical inters titium, w e itis sw a a byt per ubul rca l r
her ept w y he it a pilaies.
• W h high A l el t e is furherw t r bsor ion fr medulayCDs t int st ium. How er t
it DH ev s, her t aer ea pt om lr o er it ev , he
amountofw t is r aiv ysmalcompaed w h t ta t t corica int st ium. R bsor w t
aer el t el l r it ha dded o he t l er it ea bed aer
is quickl car a a byv sar aint v
y ried w y a ect o enous bl ood.
N.B . T fa t tl r a s ofw t ae r bsor int t corex, r t t n int t medula hel
he ct ha age mount aer r ea bed o he t aher ha o he l , ps
t pr v t high medulayint st ia fl osmol r y.
o eser e he l r er it l uid ait
• T in t pr
hus, he esence ofA t fl a t end ofCDs ha t sa osmol r ya t medulay
DH, he uid t he s he me ait s he lr
int st ium (120 mOsm/).
er it 0 L
⇒ Byr bsor a much w t a possibl t kidneys for ahighl concentaed ur w e a
ea bing s aer s e, he m y r t ine hil dding
w t ba t E &compensaing fordeficitofbodyw t .
aer ck o CF t aer

154

Urea Rec ycling
• he esence ofA urea c ontibutes 40% t t medulayint st ia osmol r y(=
In t pr DH, o he l r er it l ait
50 mOsm/)bypa e ur r bsor ion fr t innermedulayCDs int t int st ium.
0 L ssiv ea ea pt om he lr o he er it
Mec hanis m:
-Ascending l ofl ofHenl DCT corica CDs &out medulayCDs ae imper bl t ur .
imb oop e, , t l er lr r mea e o ea
-A w t is r bsor fr l t DCT corica &out medulayCDs, ur concent aion ↑ r pidl
s aer ea bed om ae , t l er lr ea rt a y.
-In innermedulayCDs, furherw t r bsor ion t kes pl ce, so t tur concentaion r ev mor
lr t aer ea pt a a ha ea r t ises en e.
T ur diffuses outoft t e int r lint st ium beca t segmentis highl per bl t
hus, ea he ubul o ena er it use his y mea e o
ur , a A incr ses t per bil yev mor
ea nd DH ea his mea it en e.
-Amoder t shae oft ur t tmov int medulayint st ium diffuses int t descending l of
ae r he ea ha es o l r er it o hin imb
l ofHenl so t titpa a in in t a fl Itr cul t sev a t befor itis excr ed.
oop e, ha sses ga ubul r uid. ecir aes er l imes e et
E ch t aound itcontibut t ahigherconcentaion ofur in int st ium.
a ime r r es o rt ea er it
⇒ Ur r cul t pr ides a a iona mecha forfor ahyper icmedula
ea ecir aion ov n ddit l nism ming osmot l.

155

URE A RE C YC LING

156

Vas a Recta as C ountercurrent E xchanger
• Bl mustbe pr ided t r lmedulat suppl it met bol needs, butw houtaspecia bl fl syst
ood ov o ena l o y s a ic it l ood ow em,
sol es pumped int t medulabycount curentmulipl w d r pidl getl .
ut o he l er r t ier oul a y ost
• T e ae 2 specia feaur in medulay bl fl t t contibut t t pr v t of t high sol e
her r l t es l r ood ow ha r e o he eser aion he ut
concentaions:
rt
1. The medullary blood flow is low (onl 1- of t a R → sufficient for met bol
y 2% ot l BF) a ic
needs oftissues, butminimizes sol e l
ut oss.
2. The vas a rec ta s erve as countercurrent exchangers .
C ountercurrent E xchange Mechanis m:
• A bl des c ends into medulla, itbecomes mor &mor concentaed, byga sat&l
s ood e e rt ining l osing
w t . A t t ofv sar abl ha aconcentaion of1200 mOs m/L.
aer t he ips a ect ood s rt
• A bl a
s ood scends ba t ad corex, t r er sequence occur a bl l v v sar ais onl sl l
ck ow r t he ev se s, nd ood ea ing a ect y ighty
hyperos motic to normal plas ma.
⇒ Dur it pa ge t ough medula bl ha r ed t excess sat& w t t tha e been a by t
ing s ssa hr l , ood s emov he l aer ha v dded he
ta tpr
r nspor ocesses occuring in t deeperr
r he egions oft medula
he l.
⇒ T t U- pe ofv sar amaintains the concentration of s olutes est bl
hus, he sha a ect a ished
bycount curentsyst
er r em.

157

Vas a Rec ta as C ounterc urrent E xc hanger

158

Diures is and diuretics
Diures is is an increas e in the rate of urine output.
(A ) H2O diures is
Increas e H2O intake → decreas e Os motic. Pr → decreas e A DH →
decreas e facultative H2O reabs orption i.e. Urine large volume and
hypotonic.

(B ) Os motic diures is
Unreabs orbable s olute in PC T→ decreas e obligatory H2O
reabs orption → decreas e Na+ concentration in tubular fluid →
decreas e os molarity of medullary inters titium → decreas e
facultative H2O reabs orption.
-Urine: large volume and is otonic or hypertonic.

(C ) Pres s ure diures is
Increas e in arterial blood pres s ure leads to:
• ↑G FR.
• Inhibition of rennin angiotens in s ys tem → ↓ renin and
angiotens in II production.

(4) Diuretic drugs
(A)Thiazides : inhibitNar bsor ion in DCT
ea pt .

(B) Aldos terone inhibitors : (Potas s ium-s paring
diuretics ) e.g. alldactone:
inhibitNaKexcha in DCTa colect t es → decr se ser
- nge nd l ing ubul ea um
Naa incr se ser K+ .
nd ea um

(C) Carbonic anhydras e inhibitors e.g. acetazolamide
(Diamox).
Itinhibit cabonic a a enzyme → decr se Hsecr ion → decr se Na
s r nhydr se ea et ea
a HCO3-r bsor ion in PCTa incr se Ksecr ion in DCT
nd ea pt nd ea et
→ incr se Na HCO3 &Kexcr ion in ur
ea , et ine.
M yl d t acidos is .
a ea o

(D) Loop diuretics e.g. frus emide (las ix):
inhibitNaK- cota t s in t t a
- 2Cl r nsporer he hick scending l
imb
ofl ofHenl
oop e.

Micturition Reflex
• A s bladder fills s ens ory s tretch receptors
s end s ignals via pelvic nerves to s acral
s egments of s pinal c ord.

• Paras ympathetic s timulation of the bladder
s mooth mus cle via the s ame pelvic nerves
occurs .

• It is “ s elf-regenerative” , s ubs ides , then re-
generates again until the external
s phincter is relaxed and urination can

Innervation
Parasympathetic
Pre-glanglionic  S2, S3, S4 unite to form Pelvic nerves
Post-ganglionic  onto detrusor muscle & internal sphincter

Sympathetic
Pre-ganglionic  L1, L2, L3
Post-ganglionic  onto trigone, neck, & internal sphincter
Little to do with bladder contraction
o--------- o------------------------------------------
Ach NE

Innervation con’t…
Afferents (sensory nerves)
Pelvic nerve: impulses due to bladder fullness; micturition reflex;
pain impulses
Hypogastric nerve: pain impulses
Pudendal nerve: sensory impulses from urethra

Somatic Efferent (Pudendal nerve)
Impulses originate in S1 and S2; innervate external sphincter
Mediate voluntary control of micturition

• Internal s phincter
-det usormuscl in t bl dderneck w t nor lykeeps t
r e he a hose one mal he
bl dderneck a post ior
a nd er
ur hr empt ofur a t efor pr ent
et a y ine nd her e ev s
empt oft bl dderunt t pr e in t ma patoft
ying he a il he essur he in r he
bl dderexceeds acr ica l el
a it l ev

• E xternal s phincter
-l yerofv unt r skel a muscl w surounds t ur hr a it
a ol ay et l e hich r he et a s
pa t ough t ur a dia a
sses hr he ogenit l phr gm
-underv unt r cont ola ca conciousl pr entur t ev w
ol ay r nd n y ev inaion en hen
inv unt r cont ol ae at ing t empt t bl dder
ol ay r s r tempt o y he a

Bladder Filling and Micturition
Bladder Filling:
1. Empty bladder: 0 pressure
2. 30 - 50 mls of urine  5 - 10 cm H2O
3. 50 - 300 ml little pressure change
4. With filling, increased
activity of external sphincter
(maintains continence, or control of
excretory functions)
5. > 300 - 400 ml  discomfort;
leads to urgency

Start of Micturition:
1. As bladder fills, micturition (bladder)
contractions begin to appear
a. Last from a few seconds to more
than a minute
b. Pressure peaks (micturition
waves) may rise a few cm H2O to
more than 100 cm H2O
c. Caused by micturition reflex

Micturition Con’t…
2. Micturition reflex (does not need the
brain)
a. Filling stimulates sensory stretch
receptors
b. Afferent impulses in Pelvic nerve
c. Signal reflexively sent back to
bladder via efferent parasympathetic
fibers in the Pelvic nerve
d. Detrusor muscle contracts, then
relaxes
2. Micturition reflex - continued
e. As bladder fills, micturition reflex occurs
more frequently, with greater
contraction of bladder wall (positive
feedback loop)
• Micturition powerful enough then
another signal is sent through Pudendal
nerve to inhibit external sphincter
(internal relaxes passively when
pressure is 20 - 40 cm H2O)
• Voluntary relaxation of external
sphincter allows for urination
• Flow thru urethra stimulates
parasympathic system, sustaining
bladder contraction

Renal physiology

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