The Urinary System

References
• Primary :
Tortora, G.J and Derrickson, B., 2009. Principles of
Anatomy and Physiology 12th edition.
• Secondary :
Guyton, A.C., 1990. Fisiologi Manusia dan Mekanisme
Penyakit, Penerbit EGC
Ganong, 2005, Review of Medical Physiology, McGraw-
Hill Medical
Martini, Principals of Human Anatomy and Physiology
 Main Topics
• Anatomy dan Physiology
• Filtration Glomerulus
• Reabsorption, Secretion Tubular
• Evaluation of Kidney Function
• Urine transport, storage, elimination
 SISTEM URINARIA
• Sistem urinary adalah
sistem organ yang
memproduksi,
menyimpan, dan
mengalirkan urin. Pada
manusia, sistem ini terdiri
dari dua ginjal, dua ureter
, kandung kemih, dua otot
sphincter, dan uretra.
http://www.wisc-online.
com/objects/AP2504/A
P2504.swf
 Overview of Urinary Function
• Regulate : plasma ion concentration ICF &ECF,
blood pH (acid-base balance), blood pressure,
blood volume
• Remove : metabolic waste (amonia, urea, uric acid, and
creatinine), foreign & wastes substances (toxins, drugs)
• Produce : hormones aldosterone, 1,25-dihydroxy
vitamin D3 (vitamin D activation), renin,
eritropoietin
 Intracellular electrolytes
K (potassium): 3,5-5,5 meq/L
Major cation electrolyte in ICF
Regulates cell exitability
Permeates cell membranes
ICF osmolality
Mg (magnesium): 1,5 – 2,5 meq/L
Contributes to many enzymatic metabolism
Nerve impuls transmission
Muscle response
P (phosphorus):2,5 – 4,5 meq/L
Energy storage
Metabolism:carbohydrate, protein, fat
Hydrogen buffer
 Extracellular electrolytes

Sodium (major cation in ECF): 135 – 145meq/L

serum osmolality
nerve and muscle cells interact
Chloride (major anion in ECF): 96 – 106 meq/L
osmotic pressure
Calcium: ionized 4,5 – 5,1 mg/dL; total 8,9 – 10,1 mg/dL
bone, teeth structure
stabillize the cell membrane and reduce its to
Na permeability
transmit nerve impulses
contract of muscles
coagulate of blood (blood coagulation)
Bicarbonic: acid base regulation
•KIDNEY
 Kidney
• Location
– Lie against the dorsal
body wall
– Beneath the parietal
peritoneum
– In the superior lumbar
region
• Protected by the lower
part of the rib cage
 External Structure of the Kidney
– Renal capsule
• Connective tissue
– Renal artery
• Blood (oxygenated) to the
kidney
– Renal vein
• Receives blood from kidney
– Ureter
• Drains urine

Human Anatomy, 3rd edition

Prentice Hall, © 2001
– Renal hilum : indent where ureter
emerges along with blood vessels,
lymphatic vessels and nerves
– 3 layers of tissue
• Renal capsule – deep layer –
continuous with outer coat of
ureter, barrier against trauma,
maintains kidney shape
• Adipose capsule –fatty tissue
that protects kidney from
trauma and holds it in place
• Renal fascia – superficial layer –
anchors kidney to surrounding
structures and abdominal wall
B. Internal Anatomy of
Kidney
Renal cortex – superficial
• Outer cortical zone
• Inner juxtamedullary zone
• Renal columns – portions of cortex
that extend between renal
pyramids
Renal medulla – inner region
• Several cone shaped renal
pyramids – base faces cortex and
renal papilla points toward hilium
Renal lobe – renal pyramid,
overlying cortex area, and ½ of
each adjacent renal column
 Blood and nerve supply of the kidneys
• Blood supply
– Although kidneys constitute less than 0.5% of total body mass,
they receive 20-25% of resting cardiac output
– Left and right renal artery enters kidney
– Branches into segmental, interlobar, arcuate, interlobular arteries
– Each nephron receives one afferent arteriole
– Divides into glomerulus – capillary ball
– Reunite to form efferent arteriole (unique)
– Divide to form peritubular capillaries or some have vasa recta
– Peritubular venule, interlobar vein and renal vein exits kidney

• Renal nerves are part of the sympathetic autonomic nervous system

– Most are vasomotor nerves regulating blood flow
Blood supply of the kidneys

Copyright 2009, John Wiley & Sons, Inc.

 Nephron

Nephron: The functional

unit of the kidney
Each kidney is made up
of about 1 million
nephrons
Each nephrons has two
major components:
1) Renal corpuscle
2) Renal tubule
 Type nephron
Cortical nephron – 80-85% of nephrons
Renal corpuscle in outer portion of cortex and short
loops of Henle extend only into outer region of medulla
-- blood flow through cortex is rapid
Juxtamedullary nephron – other 25-20%
Renal corpuscle deep in cortex & long loops of Henle
extend deeply into medulla.– blood flow through vasa
recta in medulla is slow
Ascending limb has thick and thin regions
Enable kidney to secrete very dilute or very
concentrated urine
Cortical nephron
Juxtamedullary
nephron
 Nephron – functional units of kidney
– 2 major parts
• Renal corpuscle – filters blood Bowman’s
1 capsule
plasma (1)
– Glomerulus – capillary
network : filtration 2
– Glomerular (Bowman’s) Collec
capsule ting
duct
• Renal tubule – filtered fluid 4
passes into
– Proximal convoluted tubule
(2) 3
– Descending and ascending
3
loop of Henle (nephron loop)
(3)
– Distal convolutedCopyright
tubule (4)
2009, John Wiley & Sons, Inc.
 Structures and functions of a nephron
Renal corpuscle Renal tubule and collecting duct

Afferent Glomerular
arteriole capsule

Fluid in Urine
1 Filtration from blood renal tubule (contains
plasma into nephron excreted
substances)
2 Tubular reabsorption 3 Tubular secretion
Efferent from fluid into blood from blood into fluid
arteriole

Blood
(contains
reabsorbed
Peritubular capillaries substances)

Copyright 2009, John Wiley & Sons, Inc.

• RENAL CORPUSCLE
• GLOMERULUS : FILTRATION
 Glomerulus : FILTRATION
• Blood enters glomerular capillary
by moves from the afferent
arteriole (high pressure filter)
• Filters out of renal corpuscle :
glomerular filtrate (plasma like
fluid)
• Large molecules such as protein,
blood cells and platelets stay
behind
• Dissolved solutes such as H2O,
NaCl & H+ pass into the
Bowman’s capsule
 Glomerular filtration
• Filtration membrane – endothelial cells of glomerular
capillaries and podocytes encircling capillaries
– Permits filtration of water and small solutes
– Prevents filtration of most plasma proteins, blood
cells and platelets
– 3 barriers to cross – glomerular endothelial cells
fenestrations, basal lamina between endothelium
and podocytes and pedicels of podocytes create
filtration slits
– Volume of fluid filtered is large because of large
surface area, thin and porous membrane, and
high glomerular capillary blood pressure

Copyright 2009, John Wiley & Sons, Inc.

Glomerular Filtration

Figure 26.10a,
b
• Glomerular Filtrate Rate (GFR)
 Glomerular Filtration Rate (GFR)
• Volume of plasma filtered / unit time
• Approx. 125 ml/min = 180 L /day
• Urine output is about 1- 2 L /day
• About 99% of filtrate is reabsorbed
– Homeostasis requires kidneys maintain a
relatively constant GFR
• Too high GFR – substances pass too
quickly and are not reabsorbed
• Too low GFR – nearly all reabsorbed and
some waste products not adequately
excreted
Copyright 2009, John Wiley & Sons, Inc.
28
 GFR influenced by:
• Factors that alter filtration pressure
change GFR. These include:
– Increased renal blood flow -- Increased GFR
– Decreased plasma protein -- Increased GFR.
– Hemorrhage -- Decreased capillary BP --
Decreased GFR

29
 Juxtaglomerular apparatus
• Juxtaglomerular cells
lie in the wall of
afferent arteriole
• Macula densa in final
portion of loop of Henle
– monitor Na+ and Cl-
conc. and water
• Control blood flow into
the glomerulus
• Control glomerular
filtration
 Qualities of agents to measure GFR
Inulin: (Polysaccharide from Dahlia plant)
• Freely filterable at glomerulus
• Does not bind to plasma proteins
• Biologically inert
• Non-toxic, neither synthesized nor metabolized
in kidney
• Neither absorbed nor secreted
• Does not alter renal function
• Can be accurately quantified
• Low concentrations are enough (10-20 mg/100
ml plasma)
Qualities of agents to measure GFR

Creatinine:
End product of muscle creatine metabolism
Used in clinical setting to measure GFR but
less accurate than inulin method
Small amount secrete from the tubule
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 15,0 99.4
Chloride (meq/day) 19,440 19,260 18,0 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
 Estimate Renal Function
• Goal: to assess the need of dossage adjustment
• COCKROFT-GAULT
CrCl = 1 (pria) or 0.85 (wanita) x(140-umur) x BB
Serum creatinine(mol/L) or mg/dL x 72
BB: gunakan IBW jika BB > IBW
IBW : Pria : 50+2.3 kg/inch over 5 kaki (TB>150 cm)
Wanita: 45.5 + 2.3 kg/inch over 5 kaki (TB>150 cm)
• Pengukuran CrCl melalui urin tampung 24 jam
CrCl= Uvol x [UCr]
[Cr*] x t
* kadar pada midpoint pengumpulan urin
Populasi: Critically ill, trauma, post-op
34
Creatinine Clearance
EXAMPLE:

UCr = 72 mg/dl
SCr = 2.0 mg/dl
V = 2 liters
time = 24 hours

72 mg/dl  2000 ml / day

CrCl   50 ml/min
2.0 mg/dl  24 hrs / day  60 min/hour
 Estimate Renal Function
• Modified Diet in Renal Disease (MDRD)
• GFR (mL/min/1.73 m2) = 186 x [Cr] – 1.154 x
(Age) – 0.203 x (0.742 if female) x (1.210 if
African – American)
• SCr: serum creatinine in mg/dL; age in years

36
• RENAL TUBULE
 Renal tubule and collecting duct
• Proximal convoluted tubule cells have microvilli
with brush border – increases surface area
• Last part of distal convoluted tubule and
collecting duct
–Principal cells – receptors for antidiuretic
hormone (ADH) and aldosterone
–Intercalated cells – role in blood pH
homeostasis

Copyright 2009, John Wiley & Sons, Inc.

40
Tubular reabsorption and tubular secretion
• Reabsorption – (returning needed substances of
filtered water and many solutes into the blood)
– About 99% of filtered water reabsorbed
– Normally glucose is totally reabsorbed
– Proximal convoluted tubule cells make largest
contribution
– Both active and passive processes
• Secretion – (moving wastes from blood to the
filtrate to be excreted in urine), substances move
from peritubular capillaries into tubules – a second
chance to remove substances from blood.
– Helps control blood pH & eliminate substances from the
body ex toxins and foreign
Copyright substances
2009, John Wiley & Sons, Inc.
• TUBULAR REABSORPTION
 Reabsorption
• Structures: convoluted tubules, loop of henle
• Selective reabsorption occurs by both active
and passive transport
• Carrier molecules move Na+ ions across cell
membranes, negative ions (Cl- etc) follow
• Reabsorption occurs until the threshold level
is reached.
• Excess salt remains in the nephron and is
excreted with the urine.
 Reabsorption
• Glucose and amino acids attach to carrier
molecules, which drives them out of the nephron
and into the blood.
• Urea and uric acid diffuse from the nephron back
into the blood but less is reabsorbed than was
originally filtered.
• Solutes actively transported out of the nephron
create an osmotic gradient that draws water from
it.
• As water is reabsorbed from the nephron,
remaining solutes become more concentrated.
 Tubular Reabsorption
• Proximal Tubules: GF: 120-125 mL/min
– Reabsorption of Na (55%), Cl, phosphate, amino acids,
glucose and bicarbonate (85%). Secretion of proton (CA)
• Loop of Henle: (30 mL/min)
– Na/K/2Cl Cotransporter (25% Na reabsorbed)
– Water impermeable: Hypertonic medullary inst
– Ca & Mg paracellular diffusion
• Distal Tubules:
– EDT: Na/Cl cotransporter; Ca/Na counter transport
– LDT: Na Channels, K channels, H pump: Aldosterone reg.
• Collecting Tubules: 5-10 mL/min
– Water channels: Aldosterone regulated
• Ureters: 1-2 mL/min (stored inbladder until voiding)
• REABSORPTION IN PROXIMAL TUBULE
47
Summary of Tubular Resorptive Processes
 Two pathways of the
reabsorption:

Lumen
Transcellular
Cells Pathway

Plasma Paracellular
transport
Reabsorption routes: paracellular reabsorption
and transcellular reabsorption
Reabsorption and secretion in the proximal
convoluted tubule
Mechanism of Transport

1, Primary Active Transport

2, Secondary Active Transport

3, Pinocytosis

4, Passive Transport
 Primary Active Transport
Sodium-potassium pumps in basolateral membrane only
 Secondary active transport
Symporters for glucose, amino acids, lactic acid, water-soluble
vitamins, phosphate and sulfate
Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be
secreted
Tubular Tubular Cell
Tubular Cell Interstitial
Tubular lumen Interstitial
co-transport Fluid counter-transport
lumen (symport) (antiport) Fluid

out in out in

Na+
Na+

H+
glucose
Counter-transporters will move one
Co-transporters will move one moiety, e.g. moiety, e.g. H+, in the opposite direction to
glucose, in the same direction as the Na+. the Na+.
Secondary Active Transport
 Pinocytosis
Some parts of the tubule, especially the
proximal tubule, reabsorb large
molecules such as proteins by
pinocytosis.
Passive Transport
Reabsorption and secretion in the proximal
convoluted tubule
REABSORPTION IN LOOP HENLE
 Reabsorption in the loop of Henle
– Chemical composition of tubular fluid quite different
from filtrate
• Glucose, amino acids and other nutrients reabsorbed
– Responsible for producing a concentrated urine by
forming a concentration gradient within the medulla of
kidney.
– When ADH is present, water is reabsorbed and urine is
concentrated.
– Na+-K+-2Cl- symporters function in Na+ and Cl-
reabsorption – promotes reabsorption of cations
– Little or no water is reabsorbed in ascending limb –
osmolarity decreases
 Na+–K+-2Cl- symporter in the thick
ascending limb of the loop of Henle

Copyright 2009, John Wiley & Sons, Inc.

• REABSORPTION IN THE EARLY & LATE DISTALE
CONVOLUTED TUBULE AND COLLECTING DUCT

What happens here depends on ADH

Aldosterone affects Na+ and K+
ADH – facultative water reabsorption
Parathyroid hormone – increases Ca++ reabsorption
Tubular secretion to rid body of substances: K+, H+,
urea, ammonia, creatinine and certain drugs
Secretion of H+ helps maintain blood pH (can also
reabsorb bicarb and generate new bicarb)
 Reabsorption and secretion in the early & late
distale convoluted tubule and collecting duct
• Reabsorption on the early distal convoluted tubule
– Na+-Cl- symporters reabsorb Na+ and Cl-
– Major site where parathyroid hormone stimulates
reabsorption of Ca+ depending on body’s needs
• Reabsorption and secretion in the late distal convoluted
tubule and collecting duct
– 90-95% of filtered solutes and fluid have been returned
by now
– Principal cells reabsorb Na+ and secrete K+
– Intercalated cells reabsorb K+ and HCO3- and secrete H+
– Amount of water reabsorption and solute reabsorption
and secretion depends on body’s needs
•GFR  125 ml/min (180L/day)
•(about 1% is excreted)
 Summary of Urine Formation
Site Process
1. glomerulus/  The movement of fluids from the blood into the
Bowman’s Bowman's capsule of the nephron
capsule  blood plasma forced through walls of glomerulus
*FILTRATION into Bowman’s capsule by pressure
 water and dissolved solutes (Na+Cl-, glucose,
proteins, amino acids, H+) move out of blood via
fluid pressure into Bowman’s Capsule

REABSORBTION takes place in the region – Loop of Henle

2. proximal tubule  The transfer of essential solutes and most water
*REABSORBTION back into the blood stream.
 passive: water by osmosis, K+
 active: NaCl (Na+, Cl- follows) , HCO3-, Glucose,
Amino acids
 Na+ ions leave (active) … take –ve ions with them
(attraction)
 As solutes are drawn out of the nephron into the
cells surrounding the nephron they create an
osmotic gradient.
3. descending limb water follows (passively) due to
(permeable to concentration gradient, ions actively
water) pumped from nephron –
*REABSORBTION (as water leaves) salt becomes
concentrated in filtrate at bottom of
descending loop
4. ascending limb thin portion of ascending is
(permeable to salt) permeable to salt – salt leaves with
*REABSORBTION concentration grad. (passively)
Salt continues to leave in thick
segment of loop (actively pumped)
5. distal tube More substances transported out of the nephron
*REABSORBTION into the blood (i.e. bicarbonate – for pH
adjustment )
water follows – more leaves with the concentration
grad.
Drugs, poisons can be removed from blood into
filtrate here too.
The stuff left in the nephron that is not reabsorbed
*SECRETION Formation of urine … purpose
6. collecting duct to release any toxins and drugs that have
not been filtered
What is a kidney Maintain the electrolyte balance of the
stone? body (if positive sodium ions are
= hard mass reabsorbed then positive ions like
developed from potassium must be secreted to keep the
crystals that separate
from the urine within
balance).
the urinary tract. Acid-base balance (usually it is an acid
Do not normally form being secreted, essentially a proton plus
due to inhibitors in whatever it is attached to).
urine.
Note: Acidic juices like cranberry cause our
Common type of
stone contains urine to be quite acidic which helps protect
calcium in against UTIs and prevent kidney stones.
combination with Note: The bicarbonate ion is never secreted
either oxalate or since it is used as a buffer in the
phosphate.
maintenance of our blood pH.
http://msjensen.cehd.umn. Wastes removed from body – sent to
edu/1135/Links/Animations
/Flash/0041-swf_micturition bladder via
_re.swf
• PRODUCE : aldosterone, 1,25-
dihydroxy vitamin D3 (vitamin
D activation), renin,
eritropoietin
 The kidneys
• Produce calcitriol and erythropoietin (EPO) and the
enzyme rennin
• Calcitriol = stimulates calcium and phosphate ion
absorption along the digestive tract
• EPO stimulates red blood cell production by bone
marrow
• Renin converts angiotensinogen to angiotensin I
• Angiotensin I is converted to angiotensin II at the
lungs
• Angiotensin II:
1. Stimulates production of aldosterone by the
adrenal glands
2. Stimulates release of ADH by the pituitary
gland
3. Promotes thirst
4. Elevates blood pressure
Endocrine Functions of the Kidneys
 Renin-Angiotensin System

• Renin – enzyme secreted by

juxtaglomerular cells in the
kidneys in response to low
blood pressure/volume
• Leads to a cascade of
reactions that results in
production of angiotensin
II, a vasoconstrictor
• Angiotensin II stimulates
aldosterone production
from adrenal glands
• Blood pressure increases
 Aldosterone

• Released from the adrenal

glands on top of the kidneys
• Leads to conservation of
sodium (and sometimes
water) and the excretion of
potassium
• Raises blood pressure by
increasing blood volume
 Aldosterone

• Aldosterone - when blood volume and

blood pressure decrease
• Stimulates principal cells in collecting
duct to reabsorb more Na+ and Cl- and
secrete more K+
 Erythropoietin

• It is produced by mesangial cells of the kidney.

Interstitial fibroblasts in the kidney in close
association with peritubular capillary and tubular
epithelial cells
• A second response to low blood pressure is the
release of erythropoietin.
• Erythropoietin travels to the bone marrow and
stimulates the production of new blood cells.
Endocrine Functions of the Kidneys
Summary of filtration, reabsorption, and
secretion in the nephron and collecting duct

Copyright 2009, John Wiley & Sons, Inc.

Regulation of urine composition

 Anti-diuretic hormone(ADH)
 Aldosterone
 Renin-angiotensin system
ADH
ADH
Aldosterone
 Concentration of Urine
• ADH (antidiuretic
hormone - released from
pituitary gland) enhances
the reabsorption of water
in the collecting ducts
No
• Triggered when blood ADH
With
pressure and volume are ADH
low
• Makes urine very
concentrated
• Urine is dilute when ADH
is not present
ADH vs. No ADH

ADH
No ADH present