THE URINARY SYSTEM

URINE FORMATION
dr. Sri Lestari Sulistyo Rini, M.Sc
Major Functions of the Kidneys
and
the Urinary System
1. Regulation of blood ionic composition :
sodium, potassium, bicarbonate, etc
2. Maintenance of blood osmolarity
3. Regulation of blood volume
4. Regulation of blood pressure
5. Regulation of blood pH
- Blood pH must be approx. 7.4
6. Release of hormones :
calcitriol – active form of Vitamin D,
helps control calcium homeostasis.
erythropoietin – stimulates RBC
production
renin- RAAS
7. Regulation of blood glucose levels via
gluconeogenesis
8. Nutrient balance : amino acids,
proteins, glucose, vitamins,
electrolytes
9. Excretion of wastes, foreign substances
: urea, creatinine, ammonium, uric
acid
10. Detoxification of Drug and Toxins
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)

Blood flow within the kidney is not

distributed uniformly.
Distribution
cortex ------ 90% of RBF
medulla ----- 8-10% of RBF

It is much higher in the renal cortex

than in the medulla.
Steps in urine formation
Filtration - water and small molecules
removed from blood

Reabsorption - water and essential

molecules returned to
blood

Secretion - wastes and excess salt

added from body fluid to
filtrate (urine)
Glomerular Filtration
Filtrasi Glomerulus

Pgc pgc Pt
Filtrasi Glomerulus
 Glomerular Filtration

• Glomerular capillaries and Bowman's

capsule form a filter for blood
– Fenestrated capillaries contain large
pores between its endothelial cells
• Big enough to allow any plasma
molecule to pass
• 100-400 times more permeable
than other capillaries
Filtration Membrane
• Fenestrated endothelium
– 70-90nm pores exclude blood cells
• Basement membrane
– proteoglycan gel, negative charge
excludes molecules > 8nm
– blood plasma 7% protein,
glomerular filtrate 0.03%
• Filtration slits
– podocyte arms have pedicels with
negatively charged filtration slits,
allow particles < 3nm to pass
 Glomerular Filtration
• Plasma proteins – mostly excluded from
the filtrate because of large size and
negative charge
– Slit diaphragms lined with negative
charges repel negatively-charged
proteins
– Some protein 0,03% (especially
albumin) normally enters the filtrate but
most is reabsorbed, or transported
across the PCT
– Filtered albumin reabsorptionis
performed by receptor-mediated
endocytosis
• 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)
 Functions of 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
Reabsorption by PCT Cells

Figure 25.12
Chapter 25: Urinary System 19
 REABSORPTION OF OLIGOPEPTIDES AND PROTEINS
(after A.Despopoulos & S.Silbernagl, Color Atlas of Physiology, 2003)
 Nonreabsorbed Substances
• Substances are not reabsorbed if
they:
– Lack carriers
– Are not lipid soluble
– Are too large to pass through
membrane pores
• Urea, creatinine, and uric acid are the
most important nonreabsorbed
substances
 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
Secondary Active Transport
The value of plasma glucose concentration
glucose in urine
Normal range 80 ~ 120 mg/100ml (-)
Increase 160 ~ 180 mg/100ml (+)
(180 ~ 200 mg/100ml)

This value is called the renal glucose threshold

Further increase urine glucose
>300 mg/100ml
glucose reabsorption attains a maximal constant
rate
Tubular reabsorption of glucose (Tm or TmG)
normal value: male : 375 mg/(min•1.73m2)
female: 300 mg/(min •1.73m2)
 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)

 Secretion
Excessive amounts of potassium,
sodium and some drugs are secreted
from the bloodstream into the
filtrate as it passes through the
nephron.
• In addition, pH is regulated as
either hydrogen ions or ammonium
ions are secreted from the blood
into the filtrate.
Secretion in the Proximal Tubule
• Bile salts, oxalate, urate and catecholamines
are secreted into the proximal tubule.
Many of the substances secreted are
metabolic end-products.
• Many drugs are secreted, including
penicillin.
• Para-aminohippuric acid (PAH) is rapidly
secreted through the same transporter used
to secrete penicillin. PAH is a derivative of
para-aminobenzoic acid (PABA) – used by
bacteria to make folic acid.
 Processes of the DCT

1. Active secretion of ions, acids, drugs,

and toxins
2. Selective reabsorption of sodium
and calcium ions from tubular fluid
3. Selective reabsorption of water:
– concentrates tubular fluid
 Tubular secretion

Process Structure Substance Active/passiv

e
Tubular secretion PCT H+ Active
NH4+ (ammonium)
&
DCT
Creatinine
Toxins
Drugs
Neurotransmitters
 Countercurrent multiplication
– Process by which a progressively increasing
osmotic gradient is formed as a result of
countercurrent flow
– Symporters in thick ascending limb of loop of
Henle cause buildup of Na+ and Cl- in renal
medulla, cells impermeable to water
– Countercurrent flow establishes gradient as
reabsorbed Na+ and Cl- become increasingly
concentrated
– Cells in collecting duct reabsorb more water and
urea
– Urea recycling causes a buildup of urea in the
renal medulla
 Countercurrent Multiplier
 Recaptures NaCl and returns it to renal medulla
 Descending limb
◦ reabsorbs water but not salt
◦ concentrates tubular fluid
 Ascending limb
◦ reabsorbs Na+, K+, and Cl-
◦ maintains high osmolarity of renal medulla
◦ impermeable to water
◦ tubular fluid becomes hypotonic
 Recycling of urea: collecting duct-medulla
◦ urea accounts for 40% of high osmolarity of
medulla
 Countercurrent exchange

– Process by which solutes and water are

passively exchanged between blood of the
vasa recta and interstitial fluid of the renal
medulla as a result of countercurrent flow

– Vasa recta is a countercurrent exchanger

– Osmolarity of blood leaving vasa recta is
only slightly higher than blood entering
– Provides oxygen and nutrients to medulla
without washing out or diminishing gradient
 Countercurrent Exchange System
• Formed by vasa recta
– provide blood supply to medulla
– do not remove NaCl from medulla
• Descending capillaries
– water diffuses out of blood
– NaCl diffuses into blood
• Ascending capillaries
– water diffuses into blood
– NaCl diffuses out of blood
 Urea
The high osmolarity of the medullary
interstitium increase H2O absorption
when H2O permeability is high (ADH).
This creates a concentrated urine.
•When there is a H2O deficit
and ADH is high, urea
becomes concentrated in the
distal tubule and cortical
collecting tubule when H2O is
reabsorbed.
•This high [urea] reaches the
medullary collecting duct.
There, ADH increases
permeability to urea and
activates urea transporters.
•Thus, urea diffuses out into
the interstitial fluid and
increases the osmolarity.
Urea Recirculation
 Distal tubule
The proximal half of the distal tubule is avidly
permeable to solute but it is impermeable to
water which also causes a further dilution of the
filtrate
The permeability of the late distal and the
cortical collecting duct is under the influence of
ADH hormone

The distal half with the subsequent cortical

collecting tubule are made up of characteristic
cells;
Principal cells and
the Intercalated cells.
The P-cells reabsorbs sodium and water
from the lumen with secretion of
potassium

The I-cells secretes hydrogen and

reabsorbs potassium and bicarbonate.
The I-cells secrete hydrogen ion by an
active
The distal tubule and the cortical
collecting tubule is impermeable to urea.
 Medullary collecting duct
Water is absorbed under the influence
of ADH
Unlike the cortical collecting duct, it is
permeable to urea.
It also secrete a large quantity of
hydrogen and hence plays a role in acid
base concentration.
 Formation of Dilute Urine

• Collecting ducts remain impermeable to

water; no further water reabsorption
occurs
• Sodium and selected ions can be
removed by active and passive
mechanisms
• Urine osmolality can be as low as 50
mOsm (one-sixth that of plasma)
 Formation of Dilute Urine
• Filtrate is diluted in the ascending
loop of Henle
• Dilute urine is created by allowing
this filtrate to continue into the renal
pelvis
• This will happen as long as
antidiuretic hormone (ADH) is not
being secreted
 Formation of Concentrated
Urine

• Antidiuretic hormone (ADH) inhibits

diuresis
• This equalizes the osmolality of the
filtrate and the interstitial fluid
• In the presence of ADH, 99% of the
water in filtrate is reabsorbed
 Formation of Water Pores:
Mechanism of Vasopressin Action
Formation of Dilute and Concentrated Urine
Review:

Concentrated vs. Dilute Urine

In presence of ADH: No ADH:
Insertion of H2O pores DCT & CD
into tubular luminal impermeable to
CM H2 O
At maximal H2O Osmolarity can
permeability: Net H2O
plunge to ~ 50
movement stops at
equilibrium mOsm

Maximum osmolarity of
urine up to 1200 mOsm
Summary of Tubule Characteristics

Tubule Active NaCl Permeability

Segment Transport H2 O NaCl Urea

Proximal ++ +++ + +
Thin Desc. 0 +++ + +
Thin Ascen. 0 0 + +
Thick Ascen. +++ 0 0 0
Distal + +ADH 0 0
Cortical Coll. + +ADH 0 0
Inner Medullary + +ADH 0 +ADH
Coll.
Integration Renal – Cardiovascular –
Respiratory System
RENAL SYSTEM

Effective
circulating
volume control, Acid-base
ECF osmolality, balance
blood pressure All of these are
constantly changing,
trying to maintain
HOMEOSTASIS!

CARDIOVASCULAR RESPIRATORY
SYSTEM SYSTEM

Gas exchange, ACE

 REFERENCES
• Ganong W.F, Review of Medical Physiology, 22nd
edition, The McGraw-Hill Companies, 2005
• Guyton A.C, Hall E.J, Textbook of Medical Physiology,
11th edition, Elsevier Saunders, Philadelphia, 2006
• Rhoades R, Tanner G, Medical Physiology, 2nd edition,
Lippincott Williams & Wilkins, 2003
• Vander et al, Human Physiology: The Mechanism of
Body function, 8th edition, The McGraw Hill Companies,
2001
Terima Kasih