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
Glomerular Convoluted
capsule Tubule (PCT)
Glomerulus
Distal
Convoluted
Tubule (DCT)

Collecting Duct

Nephron Loop
The Nephron glomerulus
proximal
convoluted
efferent arteriole
tubule
blood

distal
convoluted
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
 Renal Blood Supply
• Blood flow to the two kidneys is normally about 22 per cent of
the cardiac output, or 1100 ml/min.
• The renal artery enters the kidney through the hilum and then
branches progressively to form the interlobar arteries, arcuate
arteries, interlobular arteries (also called radial arteries), and
afferent arterioles, which lead to the glomerular capillaries,
where large amounts of fluid and solutes (except the plasma
proteins) are filtered to begin urine formation.
• The distal ends of the capillaries of each glomerulus coalesce to
form the efferent arteriole, which leads to a second capillary
network. the peritubular capillaries, that surrounds the renal
tubules.
URINE FORMATION
• The rates at which different substances are excreted in the
urine represent the sum of three renal processes:
1. glomerular filtration,
2. reabsorption of substances from the renal tubules into the
blood, and
3. secretion of substances from the blood into the renal tubules.
• Expressed mathematically:
Urinary excretion rate = Filtration rate - Reabsorption rate +
Secretion rate
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 capillaries H2O
• Water is reabsorbed by
osmosis and carries all other
solutes along.
• Both routes are involved.

Proteins
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.
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
Concentrating Urine by Collecting Duct

1. The collecting duct (CD)

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

2. CD reabsorbs water.

collecting
duct

urine
Concentrating Urine by Collecting Duct

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

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

• 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

• 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.

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)
receptors
or
2) deficiency of insulin receptors (Type
II).
insulin
- Diabetes mellitus features high glucose
in the blood (hyperglycemia) cell

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 hinders

water reabsorption by osmosis, high glucose in
causing polyuria. filtrate

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
1. 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 bladder is
Once voluntary
controlled controlby
predominantly has developed, center
a micturition emptying of the
in the bladder
pons. This center
is controlled
receives signals predominantly by a micturition
from stretch receptors center inthis
and integrates the pons.
information
withThis center
cortical inputreceives signals
concerning the from stretch receptors
appropriateness andat the
of urinating
integrates
moment. this back
It sends information
impulses with cortical input
to stimulate concerning
relaxation of thethe
external
appropriateness of urinating at the moment. It sends back
sphincter.
impulses to stimulate relaxation of the external sphincter.

Voluntary
control
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
Creatinine (g/day) 1.8 0 1.8 0
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