Introducton Renal Physiolgy

Physiology Department
Medical School, University of Methodist Indonesia
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
 Renal functions
• 1- Regulation of plasma ionic composition
• 2- Regulation of plasma volume
• 3- Regulation of plasma osmolarity
• 4- Regulation of plasma hydrogen ion
concentration (pH)
• 5- Removal of metabolic wastes and
foreign substances
• 6- Secondary endocrine organ
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
Figure 18.1
Kidney anatomy
Nephron
The juxta-glomerular apparatus

Figure 18.5
Blood supply to the kidney

Figure 18.6
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
Renal exchange processes
• 1- Glomerular filtration – in renal capsule
• 2- Reabsorption – in renal tubules
• 3- Secretion – in renal tubules
 Glomerular filtration

• Plasma is filtered through

fenestrated epithelium

• About 180 liters of plasma

are filtered per day  filtrate

• Filtrate = plasma - proteins

• About 2 liters of urine

produced per day
Overall fluid movement in the kidneys
Forces acting on filtration

• Glomerular capillary hydrostatic

pressure  due to blood hydrostatic
pressure against capillary wall (BHP)

• Glomerular osmotic pressure due to

the presence of solutes (proteins) in
the blood (BOP)

• Bowman’s capsule hydrostatic

pressure  pressure of filtrate against
Bowman’s capsule wall (CHP)

• Bowman’s capsule osmotic pressure

 due to the pressure of solutes in the
filtrate (COP)

• Net filtration rate  fluid moves from

the glomerulus into the capsule
Glomerular filtration

• The glomerular filtration

rate (GFR) = volume of
plasma filtered per unit of
time = 125 ml/min  180
liters per day

• Filtration fraction =
GFR/renal plasma flow =
20%
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
 Reabsorption:
Proximal convoluted
tubule (PCT)
• Glucose, amino-acid, sodium
will be pumped out of the
tubules, by active transport
(ATP needed)
• Chloride will follow sodium into
the peritubular space
(accumulation of positive
charges draws chloride out)
• Water will move into the
peritubular space because of
osmosis
• Some compounds present in
high concentration in the
filtrate but low in the blood can
move through diffusion
 Glucose reabsorption

• The transporter for glucose on the basolateral membrane has a limited

capacity to carry glucose back into the blood. If blood glucose rises
above 180 mg/dl, some of the glucose fails to be reabsorbed and
remains in the urine  glucosuria
 Reabsorption:
Proximal convoluted
tubule (PCT)
• 70% of sodium and water
are reabsorbed in PCT

• Reabsorption is not
regulated

• Amino-acids, glucose
should be 100%
reabsorbed at the end of
the PCT

• The filtrate, at the end of

the PCT should be iso-
osmolar to the filtrate at
the beginning
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
Reabsorption: Loop of Henle

• Characteristics of Loop of Henle:

-- Descending tubule: permeable to
water has no sodium pumps

-- Ascending loop: thick epithelium is

impermeable to water but has
many sodium pumps

-- Na+, Cl- and K+ are pumped out

into the interstitial fluid  Cl-
follows (electrochemical gradient)
 water follows by osmosis =
counter-current multiplier

-- formation of an osmotic gradient in

the renal medulla which is
important for water reabsorption in
the CT
Figure 19.7 (1 of 6)
Figure 18.4
 Reabsorption: Loop of Henle
• Additional filtrate is reabsorbed

• The filtrate is concentrated as it travels

through the loop but returns to a
concentration similar to the other end.

• Reabsorption in this segment is also (like

PCT) not regulated
 So, why is the loop of Henle
useful?
• The longer the loop, the
more concentrated the
filtrate and the medullary
IF become

• Importance: the collecting

tubule runs through the
hyperosmotic medulla  Desert animals have long nephron
more ability to reabsorb Loop  More H2O is reabsorbed
H2O
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
Reabsorption: DCT and CT
• DCT and CT tubular walls are
different from the PCT and
Loop of Henle wall:

-- DCT and CT walls have tight

junctions and the membrane is
impermeable to water

-- the cell membrane has

receptors able to bind and
respond to various hormones:
ADH, ANP and aldosterone

-- The binding of hormones will

modify the membrane
permeability to water and ions
Reabsorption: DCT and CT

ADH is low  no binding to receptors ADH is released by post. Pituitary

 H2O is not reabsorbed back into Binds to receptors in CT
the blood channels open  H2O moves
H2O remains in the renal tubule into the IF and blood  low urine
 high urine volume volume
 Regulation of ADH secretion

• The neurosecretory neurons

for ADH (in the hypothalamus)
are located near the center
monitoring blood osmotic
pressure
 if BOP ↑ ADH secretion and
release ↑  water reabsorption ↑
 blood is diluted  BOP↓
(typical homeostatic regulation)

 If BOP ↓  ADH secretion and

release ↓  H2O reabsorption ↓
 BOP ↑  urine volume ↑

 Lack of ADH? Symptoms?

 Sodium regulation
• Hypernatremia causes water
retention and high blood
pressure
• Hyponatremia  hypotension

• Because sodium is tightly

linked to BP, BP is regulating
sodium movement in the
tubules

• Recall that BP directly affects

GFR  GFR is sensed by the
macula densa of the Juxta-
glomerular Apparatus (JGA)

• If too low, the juxta-glomerular

cells of the JGA secrete renin
into the blood
 Sodium regulation
• As a result, aldosterone
will be secreted by the
adrenal cortex 
promotes sodium
reabsorption in the DCT
and CT.

• Another hormone, Atrial

Natriuretic Peptide or ANP
promotes sodium dumping
by the DCT and CT.
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
 Secretion and excretion
• Secretion: Selective transport of molecules
from the peritubular fluid to the lumen of
the renal tubules

• Excretion: Molecules are dumped outside

the tubules

• Example of excreted waste products: urea,

excess K+, H+, Ca++
 Clinical applications

• Carbonic anhydrase
inhibitors:

• Osmotic diuretics:

• Thiazide diuretics

• Loop diuretics:

• K+ sparring diuretics:
 Site of Action Mechanisms of Action Predictable Side Effects

Diuretics Diuretic

Osmotic Proximal tubule - impedes water reabsorption - volume contraction often

diuretic Thin descending and indirectly impedes Na+ with increased serum
(e.g., mannitol) limb reabsorption by blocking the osmolality
Distal tubule convective movement of Na+
Collecting ducts

•
Carbonic Proximal tubule - impedes HCO3-, H+, Na+ - HCO3- loss, .: acidosis
anhydrase reabsorption
inhibitors

Loop diuretics TAL - blocks Cl-, Na+ and K+ - increased K+ losses,

(eg. reabsorption (via Na+/K+/2Cl- because of increased Na+
furosemide) pump) delivery with increased
aldosterone

Thiazides Early distal tubule - blocks Cl- reabsorption, - increased K+ losses,

creating intraluminal negative because of increased Na+
charge which impedes Na+ delivery with increased
reabsorption aldosterone

Aldosterone Late distal tubule - blocks Na+/K+ antiports, - increased plasma [K+]
bockers Early collecting impeding Na+ reabsorption and
ducts K+ secretion (K+ sparing effect)
Clinical application: the Glomerular Filtration Rate

• GFR: important value for estimating

the kidney function.

• Calculated by using molecules which

are filtered but not secreted nor
reabsorbed.

• P X GFR = U X V
• P = plasma concentration of A, in
mg/mL
• GFR = glomerular filtration rate of
plasma, in mL/min
• U = urine concentration of A, in mg/mL
• V = rate of urine production in, in
mL/min
• Solving the equation for GFR will give:
• GFR = (U X V)/P

• GFR = (U X V)/P
Clinical application: the Glomerular Filtration Rate

• Best molecule to use: inulin but not occurring naturally in

the body

• Second best: creatinine

• Urea: cannot be used since it is both secreted and

reabsorbed (why is it so?)
 Outline
• Functions
• Anatomy
• Urine formation:
- Filtration
- Reabsorption
- Proximal Convoluted Tubule (PCT)
- Loop of Henle
- Distal Convoluted Tubule (DCT)
- Secretion
• Regulation of GFR
• Micturition
 Regulation of glomerular filtration rate

• GFR needs to be constant (p. 519, Fig.

18.10)

• Changes in BHP will affect GFR

strongly BHP is a function of SBP

• GFR regulation:
- to increase GFR:
**vasoconstrict efferent vessel
** vasodilate afferent vessel
 Regulation of glomerular filtration rate
• Vasoconstriction of the efferent
vessel is under the control of:
--Epinephrine/Norepinephrine
from the ANS
-- Angiotensin II from the renin-
angiotensin system

• Vasodilation of the afferent vessel

is under the control of:
– - paracrines secreted by the
macula densa  stimulate
vasodilation of neighboring vessel
– - myogenic reflex (automatic
constriction of smooth muscles
lining the wall when the artery is
stretched by increased pressure
 Outline
• Functions
• Anatomy
• Renal exchange processes
• Regional specialization of renal tubules
• Excretion
• Regulation of GFR
• Micturition
 Micturition

• Controlled by the sacral

parasympathetic NS

• Stretch sensors in the bladder wall

send impulses to the sacral spine

•  reflex opening of the urethral

smooth muscle

• Impulses also sent to the cortex to

notify the brain of the need to urinate

•  if the moment is OK, the person will

go to the bathroom (hopefully!), and
will open the skeletal (voluntary)
muscle of the urethral sphincter  the
person will be able to urinate
 Micturition: Clinical cases
• What will happen to a
person who has suffered
a spinal cord injury to
T10? Which kind of
problem(s) will (s)he
have?

• Why can’t baby control

urination? What type of
“problem” do they have?

• What about older people

who dribble urine? What
causes that?

Figure 18.21
Applications: Sea-water raft

• Billy is stuck on a raft in

the middle of the ocean,
without food or water.

• In order to get a few extra

hours of life and a chance
to be found ( a boat),
should Billy drink some
sea-water or his own
urine?

• Justify your answer.

 Clinical applications:
• Water intake:
- drink
• Water output
- food - urine
- catabolism - feces
- anabolism
- respiration
• Overall, intake should equal
output

• Urine output should be less

than water intake (drinks)

• Urine is constantly formed at a

minimum rate of about 20-30
ml/h
 Clinical cases
• 1- Martha is a patient in a
nursing home. She is 84 year-
old, senile and weak. She is
bed bound and does not feed
herself anymore. She has a
urinary catheter and you
noticed, at the beginning of
your shift that the bag had a
small amount of dark yellow
urine.
• I&O (intake and output): intake
650 cc and output 250 cc.
• 2- Henrietta is Martha's
roommate, also in not very
good shape. She has been on
IV fluid receiving 100ml/h.
• I&O 900ml. Her urine output is
250 ml (she has a catheter).
• What do you think?
- are the numbers balanced?
- if not, what could be wrong?

• What do you think?

- are the numbers balanced?
- if not, what could be wrong?