THE PHYSIOLOGY OF URINE

PRODUCTION

Dr.dr. Sri Lestari Sulistyo Rini, MSc

 Urinary System Functions
Homeostatic Functions of the Urinary System
• Regulates blood volume and blood pressure
» By adjusting volume of water lost in urine
» Releasing erythropoietin and renin (RAA)

• Regulates plasma ion concentrations

» Sodium, potassium, and chloride ions (by controlling quantities
lost in urine)
» Calcium ion levels (through synthesis of calcitriol)
Hormones Produced by the Kidney
• Renin:
– Released from juxtaglomerular apparatus when low blood
flow or low Na+. Renin leads to production of angiotensin
II, which in turn ultimately leads to retention of salt and
water.
• Erythropoietin:
– Stimulates red blood cell development in bone marrow.
Will increase when blood oxygen low and anemia (low
hemoglobin).
• Vitamin D3:
– Enzyme converts Vit D to active form 1,25(OH)2VitD.
Involved in calcium homeostasis.
Homeostatic Functions of Urinary System

• Regulation of blood glucose levels via gluconeogenesis

• Helps stabilize blood pH
» By controlling loss of hydrogen ions and bicarbonate ions in urine
» Blood pH must be approx. 7.4
• Conserves valuable nutrients
» By preventing excretion : amino acids, proteins, glucose, vitamins,
electrolytes
» while excreting organic waste product : urea, creatinine,
ammonium, uric acid
• Assists liver
– In detoxifying poisons
Disposed of in urine and sweat
Ammonia and Urea

• Ammonia is
toxic and highly
water soluble.
• The liver turns
ammonia into
urea, which is
less toxic and
less soluble.
 Major Parts of the Machine
food, water intake oxygen intake

elimination
Digestive System Respiratory System of carbon
dioxide
nutrients, oxygen
water, carbon
salts dioxide

Circulatory System
Urinary System
water
solutes

elimination rapid transport elimination of

of food to and from all excess water
residues living cells salts, wastes
 Mechanisms of renal excretion
Urine is formed in nephrons
About 1 million nephrons per kidney

Each DAY:
Approx 1000-2000 liters of blood flow though kidney.
180 L glomerular filtrate per day
+ 99% - back reabsoption

Renal perfusion at rest + 20% of CO

(this is higher than in heart, brain and liver)
 The Kidneys
Cortical Nephrons
– 85-90% of all nephrons
– Located mostly within superficial cortex of kidney
– Nephron loop (Loop of Henle) is relatively short
– Efferent arteriole delivers blood to a network of
peritubular capillaries

Juxtamedullary Nephrons
– 10-15% of nephrons
– Nephron loops extend deep into medulla
– Peritubular capillaries connect to vasa recta
 Basic Renal
Processes
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion

Urine results from

these three
processes.
– Excretion rate =
filtration rate -
reabsorption rate +
secretion rate
Basic Renal
Processes
 Filtration
– Occurs in renal corpuscle
– Blood pressure
• Forces water and dissolved solutes out of glomerular capillaries
into capsular space
• Produces protein-free solution (filtrate) similar to blood plasma

- Blood Flow Control

Special supporting cells (mesangial cells)
• Between adjacent capillaries
• Control diameter and rate of capillary blood flow
 Capillary Beds of the Nephron
• Blood pressure in the glomerulus is high because:
– Arterioles are high-resistance vessels
– Afferent arterioles have larger diameters than efferent
arterioles
• Fluids and solutes are forced out of the blood throughout the
entire length of the glomerulus

 Afferent and efferent arterioles offer high resistance to blood flow

 Blood pressure declines from 95mm Hg in renal arteries to 8 mm
Hg in renal veins
Creation of high filtration pressure at
the renal glomerulus
 Filtrasi Glomerulus

Pgc pgc Pt
 Glomerular Filtration
• Net Filtration Pressure (NFP)
– Is the average pressure forcing water and dissolved
materials:
• Out of glomerular capillaries
• Into capsular spaces
– At the glomerulus is the difference between:
• Hydrostatic pressure and blood colloid osmotic
pressure across glomerular capillaries
The Renal Corpuscle
Filtrasi Glomerulus
• Previously basement
membrane was
considered as the
primary filter but
recent research found
– Genetic defects in
proteins that
compose the slit
diaphragm results
in massive leakage
of protein in the
filtrate
(proteinuria)
 Glomerular Filtration
• GFR = filtration coefficient (Kf) * net filtration pressure
Kf = permeability * surface area

GFR Is the amount of filtrate kidneys produce each

minute ..average 125 ml/min.. which equates to a fluid
volume of 180L/day entering the glomerular capsule.

Plasma volume is filtered 60 times/day or 2 ½ times per hour

Requires that most of the filtrate must be reabsorbed, or we would
be out of plasma in 24 minutes!

Still…. GFR must be under regulation to meet the demands of the

body.
 The Kidneys
• Three Functions of the Renal Tubule

1. Reabsorb useful organic nutrients that enter filtrate

2. Reabsorb more than 90% of water in filtrate

3. Secrete waste products that failed to enter renal corpuscle

through filtration at glomerulus

The Kidneys
Usually produce concentrated urine 1200–1400 mOsm/L
(four times plasma concentration)
Proximal tubule

• Nutrients (salts,
vitamins, etc.)
are moved out
of the tubule
through active
transport.
• Water follows
the nutrients
by osmosis.
 Transport Mechanisms

Symporter Antiporter
Passive Reabsorption in the late PCT
 Na+ Reabsorption
Tubule area % of Na+ Role of Na+ reabsorption
• An active Na+ - reabsorbed
K+ ATPase pump Proximal tubule 67% Plays role in reabsorbing
in basolateral glucose, amino acids, H2O,
membrane is Cl-, and urea
essential for Na+
reabsorption
Ascending limb 25% Plays critical role in kidneys’
• Of total energy of the loop of ability to produce urine of
spent by Henle varying concentrations
kidneys, 80% is
used for Na+
transport Distal and 8% Variable and subject to
collecting hormonal control; plays role in
tubules regulating ECF volume
REABSORPTION OF OLIGOPEPTIDES AND PROTEINS
• Characteristics of Carrier-Mediated Transport
1. A specific substrate binds to carrier protein that facilitates
movement across membrane
2. A given carrier protein usually works in one direction only
3. Distribution of carrier proteins varies among portions of cell
surface
4. The membrane of a single tubular cell contains many types of
carrier proteins
5. Carrier proteins, like enzymes, can be saturated
 Nonreabsorbed Substances
• A transport maximum (Tm):
– Reflects the number of carriers in the renal tubules
available
– Exists for nearly every substance that is actively
reabsorbed
• When the carriers are saturated, excess of that substance
is excreted
Filtered Load of Glucose
– GFR = 125 mL/min
– Plasma [glucose] =100 mg/dL = 1 mg/ml

– Filtered load of glucose =

(125 mL/min) x (1 mg/mL) = 125 mg/min

Renal Threshold
For a solute which is normally 100% reabsorbed
If solute in filtrate saturates carriers, then some solute
excreted in urine
Solute in plasma that causes solute in filtrate to
saturate carriers and spillover into urine = renal
threshold
 Renal Handling of Glucose
– Plasma [glucose] = 100 mg/dL
– Filtered load glucose = 125 mg/min
– Transport maximum for glucose reabsorption = 375
mg/min

– Theoretical renal threshold = 300 mg/dL

• (GFR x Renal Threshold = Transport Maximum)
– Actual renal threshold = 160–180 mg/dL
• Filtered load = 225 mg/min
 Glucose Reabsorption (continued)

• The amount reabsorbed is proportionate

to the amount filtered
– When the transport maximum of glucose
(TmG) is exceed, the amount of glucose in
the urine rises
– The TmG is about 375 mg/min in men and
300 mg/min in women.
 Selective reabsorption
Process Structure Substance Active/passive

Reabsorption PCT Water (60-70%) Passive (osmosis)

Salts (60-70%) All active

Glucose (100%)
Amino acids
(100%)
Vitamins (100%)
Loop of Henle Water (25%) Passive (osmosis)
Na+/Cl- (25%) Active

DCT Water (5%) Passive (osmosis)

Na+/Cl- (5%) Active

Collecting duct Water (5%) Passive (osmosis)

• Ways of Expressing Osmotic Concentration
– Osmolarity
• Total number of solute particles per liter
• Expressed in osmoles per liter (Osm/L) or milliosmoles
per liter (mOsm/L)
– Body fluids have osmotic concentration of about
300 mOsm/L
Loop of Henle
• Tissue around
the Loop of
Henle is salty,
from active
transport and
diffusion of
sodium chloride.
• The salty
conditions allow
water to diffuse
out of the loop.
• Countercurrent
– Refers to exchange between tubular fluids moving
in opposite directions
• Fluid in descending limb flows toward renal pelvis
• Fluid in ascending limb flows toward cortex

• Multiplication
– Refers to effect of exchange
• Increases as movement of fluid continues
A
V
 Thin descending
limb (permeable to
water; impermeable
to solutes)

Thick ascending
limb (impermeable
to water; active
solute transport)

Renal medulla

Transport of NaCl along the

ascending thick limb results in
the movement of water from
the descending limb.
 Figure 26-13c Countercurrent Multiplication and Concentration of Urine

Renal DCT and collecting

cortex ducts (impermeable
to urea; variable
permeability to
water)

Thin descending
limb (permeable
to water;
impermeable
to urea)

Papillary duct
(permeable to
urea)

Na
Cl
Renal medulla Urea

The permeability characteristics of both the loop and

the collecting duct tend to concentrate urea in the
tubular fluid and in the medulla.
Countercurrent Multiplier System
in the Loop of Henle
 The Function of the Vasa Recta
– To return solutes and water reabsorbed in medulla to
general circulation without disrupting the concentration
gradient
– Some solutes absorbed in descending portion do not
diffuse out in ascending portion
– More water moves into ascending portion than is moved
out of descending portion
– Carries water and solutes out of medulla
– Balances solute reabsorption and osmosis in medulla
Urea Recirculation
Distal tubule
• Active transport
is used to move
more nutrients
out of the
concentrated
urine.
• Some ions,
drugs, and toxins
are actively
pumped into the
tubule.
 Figure 26-8a The Renal Corpuscle

Glomerular capsule

Capsular Glomerular Capsular Visceral

space capillary epithelium epithelium
(podocyte)

Proximal
Efferent convoluted
arteriole tubule
Distal
convoluted
tubule

Macula densa
Juxtaglomerular
cells

Juxtaglomerular
complex

Afferent
arteriole

Important structural features of a renal corpuscle

• Three Processes at the DCT
1. Active secretion of hydrogen or bicarbonate ions,
drugs, and toxins
2. Selective reabsorption of sodium and calcium
ions, urea from tubular fluid
3. Selective reabsorption of water
• Concentrates tubular fluid
• Hydrogen Ion Secretion
– Is generated by dissociation of carbonic acid by enzyme carbonic
anhydrase
– Secretion is associated with reabsorption of sodium

• Secreted by sodium-linked countertransport

• In exchange for Na+ in tubular fluid
– Bicarbonate ions diffuse into bloodstream

• Buffer changes in plasma pH

 Tubular Secretion and Solute Reabsorption at the DCT
Sodium and chloride reabsorption Sodium–potassium exchange in aldosterone
in entire DCT sensitive portion of DCT and collecting duct
Distal
convoluted
Tubular fluid
tubule

Glomerulus

Glomerular Cells of
capsule distal
Collecting convoluted
Proximal tubule
duct
convoluted
tubule
Sodium ions are
reabsorbed in
exchange for
potassium ions;
Nephron loop
these ion pumps
are stimulated by
aldeosterone (A).

Urine storage
and elimination
Peritubular
fluid

Peritubular
capillary
KEY
Leak channel
Cotransport
Countertransport
Diffusion
Exchange pump
Reabsorption
Aldosterone-
regulated pump Secretion
The basic pattern of the Aldosterone-regulated reabsorption
reabsorption of sodium and of sodium ions, linked to the passive
chloride ions and the secretion of loss of potassium ions
potassium ions
 Tubular Secretion and Solute Reabsorption at the DCT

H+ secretion and HCO3- reabsorption along entire DCT and collecting duct

Distal Tubular fluid

convoluted
tubule Hydrochloric Ammonium
acid chloride

Glomerulus

Glomerular
capsule
Collecting
Proximal
duct
convoluted
tubule

Amino acid
deamination

Nephron loop

Urine storage
and elimination

KEY
Leak channel
Cotransport
Countertransport Sodium bicarbonate
Diffusion
Exchange pump
Reabsorption
Aldosterone-
regulated pump Secretion Hydrogen ion secretion and the acidification of urine occur by two
routes.
• Regulating Water and Solute Loss in the Collecting
System
– By aldosterone
• Controls sodium ion pumps
• Actions are opposed by natriuretic peptides
– By ADH
• Controls permeability to water
• Is suppressed by natriuretic peptides
• Obligatory Water Reabsorption
– Is water movement that cannot be prevented
– Usually recovers 85% of filtrate produced

• Facultative Water Reabsorption

– Controls volume of water reabsorbed along
DCT and collecting system
• 15% of filtrate volume (27 liters/day)
• Segments are relatively impermeable to
water
• Except in presence of ADH
• ADH
– Hormone that causes special water channels (aquaporins 2) to
appear in apical cell membranes
– Increases rate of osmotic water movement
– Higher levels of ADH increase:
• Number of water channels
• Water permeability of DCT and collecting system

• Without ADH
– Water is not reabsorbed
– All fluid reaching DCT is lost in urine
• Producing large amounts of dilute urine
 Formation of Water Pores:
Mechanism of Vasopressin Action
 Formation of Dilute Urine

Tubule Osmolarity

↑ in descending
limb
↓ in ascending
limb
↓ in collecting
duct
Water transport & vasopressin actions
Formation of Dilute and Concentrated Urine
 Regulation of Water Intake

Ion transport
Homeostasis maintained by: Water movement
Kidney function
 Negative Feedback Control of ADH

CONTROLLED CONDITION
Blood osmotic pressure (decreased water
concentration) is increased in response to
some stressor
RETURN TO HOMEOSTASIS
In response, there is increased water
reabsorption, and blood osmotic pressure
decreases
RECEPTOR
Hypothalamic osmoreceptors respond to
increased blood osmotic pressure and
send nerve impulses to appropriate
neurons in hypothalamus EFFECTORS
In response to ADH, aquaporins in distal
tubules and collecting ducts become more
permeable to water
CONTROL CENTER
Hypothalamic neurons, via the posterior
pituitary gland, secrete ADH in the blood
• The Hypothalamus
– Continuously secretes low levels of ADH
• DCT and collecting system are always permeable to
water
– At normal ADH levels
• Collecting system reabsorbs 16.8 liters/day (9.3% of
filtrate)
• Diuresis
– Is the elimination of urine
– Typically indicates production of large volumes
of urine
• Diuretics
– Are drugs that promote water loss in urine
– Diuretic therapy reduces:
• Blood volume
• Blood pressure
• Extracellular fluid volume
 Glomerular Filtration Rate (GFR)
• Homeostatic
• too high,
reabsorbtion
incomplete , lost
in the urine
• too low, wastes
can be
reabsorbed
• Renal autoregulation
• Neural regulation
• Hormonal regulation
Creation of high filtration pressure at
the renal glomerulus
 Juxtaglomerular Apparatus

-phagocityc
-contractile
properties

-secrete Renin
-mechanoreceptors

- monitor salinity
-Chemoreceptors,
- osmoreceptors
Renal Autoregulation of GFR

•  BP  constrict afferent
arteriole, dilate efferent
•  BP  dilate afferent
arteriole, constrict efferent
• Stable for BP range of 80 to
180 mmHg (systolic)
• Cannot compensate for
extreme BP
How Changes in Arteriolar Resistance
Alter RBF and GFR
Decreased GFR
Increased GFR

RBF
RPF RBF
RPF

A B

RBF
RPF RBF
RPF

C D
Tubuloglomerular Feedback
 Sympathetic Effects

• Sympathetic
activity constricts
afferent arteriole
– Helps maintain
BP & shunts
blood to heart
& muscles
 Extrinsic Controls: Renin-Angiotensin
Mechanism

• Triggers for renin release by granular cells

– Reduced stretch of granular cells (MAP below
80 mm Hg)
– Stimulation of the granular cells by activated macula
densa cells
– Direct stimulation of granular cells via 1-adrenergic
receptors by renal nerves
 Micturition
Once urine enters the renal pelvis, it flows through the ureters and
enters the bladder, where urine is stored.
Micturition is the process of emptying the urinary bladder.
Two processes are involved:
(1) The bladder fills progressively until the tension in its wall rises
above a threshold level, and then
(2) A nervous reflex called the micturition reflex occurs that
empties the bladder.
The micturition reflex is an automatic spinal cord reflex; however,
it can be inhibited or facilitated by centers in the brainstem and
cerebral cortex.
Urine Micturition

stretch
receptors
Micturition (Voiding or Urination)
 Plasma, Filtrate and Urine
Compositions
Amount
Total
Amount in 180 L returned to Amount in
Amount in
of filtrate (/day) blood/d Urine (/day)
Plasma
(Reabsorbed)

Water (passive) 3L 180 L 178-179 L 1-2 L

Protein (active) 200 g 2g 1.9 g 0.1 g

Glucose (active) 3g 162 g 162 g 0g

1g 54 g 24 g 30 g
Urea (passive) (about 1/2) (about 1/2)

0.03 g 1.6 g 0g 1.6 g

Creatinine (all filtered) (none reabsorbed)
Composition and Properties of Urine

Urine Volume
• Normal volume for average adult—1 to 2 L/day
• Polyuria—output in excess of 2 L/day
• Oliguria—output of less than 500 mL/day
• Anuria—0 to 100 mL/day
– Low output from kidney disease, dehydration, circulatory
shock, prostate enlargement
– Low urine output of less than 400 mL/day, the body
cannot maintain a safe, low concentration of waste in the
plasma
• The Composition of Normal Urine
– A urine sample depends on osmotic movement of
water across walls of tubules and collecting ducts
– Is a clear, sterile solution
– Yellow color (pigment urobilin)
• Generated in kidneys from urobilinogens
– Urinalysis, the analysis of a urine sample, is an
important diagnostic tool
Table 26-3 Tubular Reabsorption and Secretion
Table 26-5 General Characteristics of Normal Urine
 Clearance
• Clearance is a general concept that describes the rate at
which substances are removed (cleared) from the plasma.

Renal clearance of a substance is the volume of plasma

completely cleared of a substance per min.
Cs x Ps = Us x V

Cs = Us x V
Ps

Where: Cs = clearance of substance S

Ps = plasma conc. of substance S
Us = urine conc. of substance S
V = urine flow rate
Circadian Rhythm of Cortisol
Secretion
 References

• Hall J.E & Hall J.M, Textbook of Medical Physiology, 14th ed,
Elsevier Saunders, Philadelphia, 2020
• Tortora, D.J. and Derrickson B., 2012, Principles Anatomy &
Physiology, 13th edition, John Wiley & Sons, Inc
• Rhoades R.A & Bell GR., Medical Physiology, 5th ed.,
Wolters Kluwer, Philadelphia, 2018
• Boron, W.F & Boulpaep, E.L., Medical Physiology, 3rd ed,
Elsevier Saunders, Philadelphia, 2017
• Costanzo, L.S, 2010, Physiology, Elsevier Saunders,
Philadelphia
 Link video materi
Sistem urinaria 1 dan 2 (terkait urine formation) :
• https://youtu.be/TVdgsbVDK2c
• https://youtu.be/rNPoZAGJrwE

Regulasi 1 dan 2 ( terkait regulasi GFR)

• https://youtu.be/H9b4qgZqDHs
• https://youtu.be/RVnMbRDDYA0
 Link pertanyaan

• https://
docs.google.com/forms/d/e/1FAIpQLSeD4eNg
4Dt35St_XVlYdGE_C37nh3nHZ0w7FCoLkA93Q
c5XuQ/viewform?usp=sf_link
Terima Kasih