Aspek Biokimia

Sistem Urinarius

Yurika Sandra

Bagian Biokimia FK-YARSI

Peran dan Fungsi Ginjal
Sistema Urinarius
Dua ginjal
Tempat penyaringan darah dan
pembuatan urin
Dua Ureter
Saluran yang dilalui urin dari ginjal
ke VU
Satu VU
Tempat penampungan urin
sebelum dibuang
Satu urethra
Membawa urin ke luar tubuh
 Nephron
Merupakan unit-unit pembangun
ginjal
Nephron berperan menjaga
keseimbangan cairan
Ginjal dibangun oleh 1,2 juta
nephron/ginjal.
Nephron
Struktur Nephron
 Struktur Nephron
Satu unit nephron terdiri atas:
Pembuluh darah
Arteriol afferen
Glomerulus
Arteriol efferen
Tubulus Renalis:
Proximal convoluted tubule
loop of Henle
distal convoluted tubule
Collecting tubule
 Struktur Nephron
Proximal
Glomerula Convolute
r capsule d Tubule
Glomerulus
(PCT)
Distal
Convolute
d Tubule
(DCT)

Collecting
Duct
Nephron
Loop
The Nephron glomerulus
proximal
convolute
efferent arteriole
d tubule
blood

distal
convolute
d tubule
blood

afferent arteriole

Loop of Henle
Struktur Nephron
Fungsi Ginjal

1. Menyaring plasma darah,

memisahkan zat-zat buangan,
mereabsorbsi zat-zat yang
dibutuhkan ke dalam darah, dan
membuang zat-zat buangan
2. Mengatur volume darah dan
osmolaritas darah.
3. Menghasilkan hormon: renin,
eritropoietin, kalsitriol
4. Mengatur keseimbangan asam basa
5. Detoksifikasi radikal superoksida dan
obat
Fungsi Ginjal

Proses metabolisme menghasilkan

berbagai zat buangan/sisa terutama
CO2 & senyawa nitrogen (Nitrogenous
wastes)
Sistem respirasi berperan membuang
CO2
Sistem urinarius berperan membuang
keduanya
Nitrogenous wastes

A. Produk metabolisme protein

Protein dipecah menjasi asam amino (AA)
AA di resintesis menjadi protein
Kelebihan AA akan dimetabolisme
Gugus amin dipecah menghasilkan
ammonia (NH3) yang bersifat toksik
2NH3 + CO2 H2NCONH2 (Urea)
Ammonia lebih toksik dibanding urea
Urea merupakan 50% dari semua
komponen buangan nitrogen
Nitrogenous wastes

B. Produk metabolisme asam nukleat

Asam nukleat dipecah menjadi
nukleotida dengan melepaskan basa
nitrogen
Basa nitrogen akan dikonversi menjadi
asam urat.
Efek toksik asam urat lebih ringan
Jumlahnya lebih sedikit dibanding urea
Nitrogenous wastes

C. Produk metabolisme kreatinin

fosfat
Kreatinin fosfat dipecah menjadi
kreatinin
Kreatinin kurang toksik dibanding
ammonia
Jumlahnya lebih banyak dibanding
urea
Urine Formation
The kidney produces urine through 4
steps.
14-7
Glomerular
Filtrate

Tubular fluid

Urine
Glomerular
Filtration
The Filtration
Membrane
From the plasma to the capsular
space, fluid passes through three
barriers.
The Filtration
Membrane
Almost any molecule smaller than 3
nm can pass freely through the
filtration membrane into the capsular
space.

These include:
Water, electrolytes, glucose, amino acids, lipids,
vitamins, and nitrogenous wastes

Kidney infections and trauma commonly damage the

filtration membrane and allow plasma proteins or blood
cells to pass through.
Filtration Pressure
Glomerular filtration follows the same principles that
govern filtration in other capillaries.
Glomerular Filtration Rate
(GFR)
is the amount of filtrate formed per minute
by the two kidneys combined.
For the average adult male, GFR is about
125 ml/min.
This amounts to a rate of 180 L/day.
An average of 99% of the filtrate is
reabsorbed, so that only 1-2 L of urine per
day is excreted.
GFR must be precisely
controlled.
If GFR is too high
increase in urine output
threat of dehydration and electrolyte
depletion.

If GFR is too low

insufficient excretion of wastes.

The only way to adjust GFR from moment to

moment is to change glomerular blood
pressure.
Renal Autoregulation
the ability of the kidneys to
maintain a relatively stable GFR
in spite of the changes (75 -
175 mmHg) in arterial blood
pressure.
Regulation of Filtration
Pressure

14-11
The nephron has two ways to
prevent drastic changes in GFR
when blood pressure rises:

1) Constriction of the afferent arteriole

to reduce blood flow into the
glomerulus

2) Dilation of the efferent arteriole to

allow the blood to flow out more easily.

Change in an opposite direction if blood pressure falls

 Tubular
Reabsorption
Only about 1% of the glomerular
fitrate actually leaves the body
because the rest (the other
99%) is reabsorbed into the
blood while it passes through
the renal tubules and ducts.
This is called tubular
reabsorption and occurs via
three mechanisms. They are:
Osmosis
Diffusion, and
Active Transport.
Reabsorption in Proximal
Convoluted Tubules
- The proximal convoluted
tubule (PCT) is formed by one
layer of epithelial cells with
long apical microvilli.

- PCT reabsorbs about 65% of

the glomerular filtrate and
return it to the blood.
Routes of
Proximal Tubular
Reabsorption

1) transcellular
route

2) paracellular
route
PCT

peritubular capillary
Mechanisms of Proximal Tubular
Reabsorption

1. Solvent drag
2. Active transport of sodium.
3. Secondary active transport of glucose, amino acids, and
other nutrients.
4. Secondary water reabsorption via osmosis
5. Secondary ion reabsorption via electrostatic attraction
6. Endocytosis of large solutes
 1) Solvent drag
Proteins stay
driven by high colloid
osmotic pressure (COP)
in the peritubular H2O
capillaries
Water is reabsorbed by
osmosis and carries all
other solutes along.

Proteins
Both routes are
involved.
2) Active transport of sodium
Sodium pumps (Na-K ATPase) in basolateral membranes
transport sodium out of the cells against its concentration
gradient using ATP.

Na+ Na+

K+

capillary PCT cell Tubular

lumen
 There are also pumps for other
ions

Ca++ Ca++

capillary PCT cell Tubular

lumen
3) Secondary active transport of glucose, amino acids,
and other nutrients

- Various cotransporters can carry both Na+ and other

solutes. For example, the sodium-dependent glucose
transporter (SDGT) can carry both Na+ and glucose.

Na+

Na+
K+

Glucose
capillary PCT cell
3) Secondary active transport of glucose, amino acids,
and other nutrients

Amino acids and many other nutrients are

reabsorbed by their specific cotransporters with
sodium.

Na+

Na+
K+

amino acids

capillary PCT cell

4) Secondary water reabsorption via osmosis
Sodium reabsorption makes both intracellular and
extracellular fluid hypertonic to the tubular fluid.
Water follows sodium into the peritubular capillaries.

Na+ Na+

H2O

capillary PCT cell Tubular

lumen
5) Secondary ion reabsorption
via electrostatic attraction
Negative ions tend to follow the positive sodium ions by
electrostatic attraction.

Na Na+

Cl-

capillary PCT cell Tubular

lumen
 6) Endocytosis of large solutes
The glomerulus filters a small amount of protein from the blood.
The PCT reclaims it by endocytosis, hydrolzes it to amino acids,
and releases these to the ECF by facilitated diffusion.

amino acids protein

capillary PCT cell Tubular

lumen
The Transport Maximum

There is a limit to the amount of solute that the renal tubule can
reabsorb because there are limited numbers of transport proteins
in the plasma membranes.

If all the transporters are occupied as solute molecules pass

through, some solute will remain in the tubular fluid and appear in
the urine.

Example of diabetes

Na+

Glucose
 high glucose in blood

high glucose in
filtrate

Exceeds Tm for
glucose

Glucose in urine
Reabsorption in the
Nephron Loop
 The primary purpose is to
establish a high
extracellular osmotic
concentration.

The thick ascending limb

reabsorbs solutes but is
impermeable to water.
Thus, the tubular fluid
becomes very diluted
while extracellular fluid
becomes very
concentrated with
solutes.

mOsm/L
The high osmolarity enables the collecting duct to
concentrate the urine later.
Reabsorption in Distal
Convoluted Tubules
 Fluid arriving in the DCT still
contains about 20% of the
water and 10% of the salts
of the glomerular filtrate.

A distinguishing feature of
these parts of the renal
tubule is that they are
subject to hormonal
control.
Aldosterone

a. secreted from adrenal gland in

response to a Na+ or a K+ in
blood
b. to increase Na+ absorption and
K+ secretion in the DCT and
cortical portion of the collecting
duct.

c. helps to maintain blood volume

and pressure.
Atrial Natriuretic Factor
- secreted by the atrial
myocardium in response to high
blood pressure.

- It inhibits sodium and water

reabsorption, increases the
output of both in the urine, and
thus reduces blood volume and
pressure.
Tubular Secretion
- Renal tubule extracts chemicals from the blood and secretes
them into the tubular fluid.

- serves the purposes of waste removal and acid-base balance.

H+
H+

capillary PCT cell Tubular

lumen
entrating Urine by Collecting Duct

1. The collecting duct (CD)

begins in the cortex,
where it receives tubular Cortex
fluid from numerous
nephrons.

2. CD reabsorbs water.

collecting
duct

urine
1. Driving force
The high osmolarity of
extracellular fluid generated by
NaCl and urea, provides the
driving force for water
reabsorption.
2. Regulation Cortex
The medullary portion of
the CD is not permeable to medulla
NaCl but permeable to
water, depending on ADH.

mOsm/L
urine
Control of Urine Concentration depends on the body's
state of hydration.

a. In a state of full hydration,

antidiuretic hormone (ADH) is not
secreted and the CD permeability to
water is low, leaving the water to be
excreted. Cortex

medulla

b. In a state of dehydration, ADH

is secreted; the CD permeability to
water increases. With the increased
reabsorption of water by osmosis,
the urine becomes more
concentrated.

mOsm/L
urine
No more reabsorption after tubular fluid leaving CD

Cortex

medulla

urine
urine
 Urine Properties
Composition and Properties of Urine

Fresh urine is clear, containing no blood cells and

little proteins. If cloudy, it could indicate the
presence of bacteria, semen, blood, or menstrual
fluid.
Substance Blood Plasma Urine
(total amount) (amount per day)

Urea 4.8 g 25 g

Uric acid 0.15 g 0.8 g

Creatinine 0.03 g 1.6 g

Potassium 0.5 g 2.0 g

Chloride 10.7 g 6.3 g

Sodium 9.7 g 4.6 g

Protein 200 g 0.1 g

HCO3- 4.6 g 0g

Glucose 3g 0g
Urine Volume

An average adult produces 1-2 L of urine per day.

a. Excessive urine output is called polyuria.

b. Scanty urine output is oliguria.
c. An output of less than 400 mL/day is
insufficient to excrete toxic wastes.
Diabetes
is chronic polyuria resulting from various metabolic
disorders, including Diabetes mellitus and
Diabetes insipidus
Diabetes mellitus
pancreatic cell
- caused by either insulin
1) deficiency of insulin (Type I)
receptor
or
2) deficiency of insulin
s
receptors (Type II).
insulin
- Diabetes mellitus features high
glucose in the blood cell
(hyperglycemia)

glucose

cell
glycogen

blood
 high glucose

- When glucose in tubular

fluid exceeds the transport
maximum (180 mg/100 ml),
it appears in urine
(glycosuria).

- Glucose in tubular fluid high glucose in

hinders water reabsorption filtrate
by osmosis, causing
polyuria.
Retain H2O
by osmosis

high
urine
volume
Diabetes insipidus

- is caused by inadequeate
ADH secretion.

- Due to the shortage of

ADH, water reabsorption in
CD is compromised,
leading to polyuria.

urine
Diuresis

refers to excretion of large amount of urine.

Natriuresis
refers to enhanced urinary excretion of sodium
Diuretics

- are chemicals that increase urine

volume. They are used for treating
hypertension and congestive heart
failure because they reduce overall
fluid volume.

- work by either increasing glomerular

filtration or reducing tubular
reabsorption. Caffeine falls into the
former category; alcohol into the
latter (alcohol suppresses the release
of ADH).
Many diuretics produce osmotic
diuresis by inhibiting sodium
reabsorption
Renal Function Tests
Renal Clearance
a. the volume of blood plasma from
which a particular waste is removed
in 1 minute.

b. can be measured indirectly by

measuring the waste concentration in
blood and urine, and the urine
volume.
2. Glomerular Filtration
Rate
a. Measuring GFR requires a substance that is
not secreted or reabsorbed at all. Inulin, a
polymer of fructose, is suitable.

b. Inulin filtered by the glomeruli remains in

the renal tubule and appears in the urine;
none is reabsorbed, and the tubule does
not secrete it. For this solute, GFR is equal
to the renal clearance.
 Hemodialysis

artificially clearing wastes from the blood

1) Dialysis
machine

- efficient

- inconvenient
2) Continuous
ambulatory
peritoneal
dialysis (CAPD)
Dialysis
fluid
- The peritoneal
membrane is a natural
dialysis membrane

- convenient

- less efficient
Urine Storage and
Elimination
The Ureters
The ureters are muscular tubes leading from the renal
pelvis to the lower bladder.
The Urinary Bladder
- is a muscular sac on the floor of the pelvic cavity.

- is highly distensible and expands superiorly.

The openings of the two ureters and the urethra mark a triangular
area called the trigone on the bladder floor.
The Urethra
- conveys urine from the urinary bladder to the outside
of the body.

Females male
3-4 cm ~18 cm

greater risk of
urinary tract
infections
The male urethra has three
regions:

1. prostatic urethra
2. membranous urethra
3. penile urethra.

1.

2.

3.

Difficulty in voiding urine

with enlarged prostate
In both sexes:
- internal urethral sphincter- under involuntary control.
- external urethral sphincter - under voluntary control

internal urethral sphincter

external urethral sphincter

 Voiding Urine in infants

micturition reflex
When the bladder contains about 200 ml of urine, stretch receptors in
the wall send impulses to the spinal cord. Parasympathetic signals return
to stimulate contraction of the bladder and relaxation of the internal
urethral sphincter.

Spinal
cord
 Voiding Urine in adults
2. Once voluntary control has developed, emptying of the
Once is
bladder voluntary control
controlled has developed,
predominantly emptying of
by a micturition center
in the
the bladder
pons. Thisis center
controlled predominantly
receives signals fromby stretch
a
micturition
receptors and center in the
integrates thispons. This center
information with receives
cortical input
signals from
concerning stretch receptors
the appropriateness and integrates
of urinating this
at the moment.
It information
sends back with cortical
impulses input concerning
to stimulate relaxationtheof the
appropriateness
external sphincter. of urinating at the moment. It
sends back impulses to stimulate relaxation of the
external sphincter.

Voluntary
control
Autoregulation of High Filtration Pressure
Filtration, reabsoption, and excretion rates of
substances by the kidneys

Filtered Reabsorbed Excreted Reabsorbed

(meq/24h) (meq/24h) (meq/24h) (%)

Glucose (g/day) 180 180 0

100
Bicarbonate (meq/day) 4,320 4,318 2
> 99.9
Sodium (meq/day) 25,560 25,410 150
99.4
Chloride (meq/day) 19,440 19,260 180
99.1
Water (l/day) 169 167.5 1.5
99.1
Urea (g/day) 48 24 24 50
Acid Base Balance

Proximal tubule also secretes H+ and

absorbs HCO3-
Used to regulate pH
With pH, H+ secretion and
HCO3- reabsorption
www2.kumc.edu/ki/physiology/course/figures.htm
SELESAI