URINARY SYSTEM

Part I
Mrbv, md
 HOMEOSTASIS
• Altering blood composition, pH, volume, pressure
• Maintaining blood osmolarity
• Excreting waste and foreign substances
• Producing hormones
 Functions of the Kidney
1. Regulation of blood ionic composition
2. Regulation of blood pH
3. Regulation of blood volume
4. Regulation of blood pressure
5. Maintenance of Blood pressure
6. Maintenance of blood osmolarity
7. Production of hormones
8. Regulation of blood glucose level
9. Excretion of wastes and foreign substances
 Regulation of blood ionic composition
• The kidneys help regulate several ions :
– Sodium (Na+), Potassium ( K+), Calcium ( Ca2+), Chloride (Cl-), phosphate ions
(HPO42+ )

Regulation of blood pH
• Kidneys excrete variable amounts of hydrogen ions (H +), and conserve bicarbonate
(HCO3)
• Important for the buffer of H+ in the blood
 Regulation of blood volume
• By conserving or eliminating water in the urine
• Increase in blood volume, increases blood pressure
• Decrease in blood volume, decreases blood pressure

Regulating blood pressure

• Regulate blood pressure by secreting the enzyme Renin
• Activates the Renin-Angiotensin-System
• Increased Renin, increase in blood pressure
 Regulation of blood glucose
• Separately regulating loss of water and loss of solutes in urine
• The kidneys maintain a constant blood osmolarity close to 300 mOsm/liter

Production of hormones
• Calcitriol : active form of vitamin D. This helps maintain calcium homeostasis
• Erythropoietin: stimulates the production of red blood cells

Maintenance of blood osmolarity

• Like in the liver, the kidneys can use gluconeogenesis (synthesis of new glucose molecules)
• They can release glucose into the blood to help maintain a normal blood glucose level
 Excretion of waste and foreign substances
• Excrete in urine substances that have no useful function in the body
• These include
– AMMONIA and UREA from deamination of amino acids
– BILIRUBIN from catabolism of hemoglobin
– CREATININE from the breakdown of creatine phosphate in muscle fibers
– URIC ACID from catabolism of nucleic aciddds
– Others: drugs and environmental toxins
 ANATOMY and HISTOLOGY
• Paired kidneys: red, kidney-bean shaped, above the waist between the peritoneum
and the posterior wall of the abdomen (retropritoneal)

• Location: last thoracic vertebra and third lumber vertebra (T12-L3)

• Right kidney is slightly lower than the left kidney

 External Anatomy of the Kidney
• Adult kidney: 10-12cm (4-5in) long, 5-7cm (2-3in) wide, 3cm (1in) thick. About the
size of a bath soap
• Mass: 135-150g (4.5-50z).
• Medial border: CONCAVE; faces the vertebral column
• Renal hilum: where the ureter emerges, along with blood vessels, lymphatic vessels,
nerves
• 3 layers of tissue around each kidney
– Renal capsule: deep layer
– Adipose capsule : middle layer
– Renal fascia: anchors the kidney to the surrounding structures and abdominal wall
 Internal Anatomy of the Kidneys
• Renal parenchyma: Renal Cortex and Renal Medulla which is the functional portion
of the kidney
• Renal cortex:
– Superficial, light red area
– Smooth capsule, extending from renal capsule to base of the renal pyramids
– Divided into CORTICAL ZONE (outer) and JUXTAMEDULLARY ZONE (inner)
• Renal Medulla:
– Deep, darker reddish-brown
– Consists of the Renal pyramids(base) and the Renal papilla (apex)
 Renal Parenchyma
• Nephrons: Functional unit of the kidney
• Urine forms by the nephrons drain into the large papillary ducts
• Papillary ducts drain into the minor and major calyces (cup-like structures)
• Each kidneys has
– 8-18 minor calyces
– 2-3 major calyces

Renal Sinus
• Cavity where the hilum expands into
• Contains part of the renal pelvis, the calyces and branches of renal blood vessel and
nerves
• Adipose tissues help stabilize the position in the renal sinus
 Blood and Nerve Supply of the Kidneys
• Abundant
• 20-25% of resting cardiac output via Right and Left Renal Arteries
• In adults, Blood flow is 1200mL/minute
• Arterial Supply:
Abdominal aorta Renal artery segmental arteries
interlobar arteries arcuate arteries Interlobular arteries
afferent arterioles each nephron glomerulus
 Venous Supply
• Glomerulus efferent arteriole peritubuluar capillaries vasa recta
peritubular venules interlobularar veins arcuate veins interlobar veins
inferior vena cava
 Nephron
• Functional unit of kidney
• 2 parts:
– Renal Corpuscle : where plasma is filtered
– Glomerulus
– Bowman’s Capsule
– Renal Tubule : where the filtered fluid passes
– Proximal convoluted tubule
– Loop of Henle
– Distal convoluted tubule
 Glomerular Capsule
• “Bowman’s Capsule”
• Visceral layer: simple squamous epithelial cells (PODOCYTES)
• Parietal Layer: simple squamous epithelium

• Filtered fluid is then transported to the “BOWMAN’S SPACE”

• The many footlike projections of these cells (pedicels) wrap
• around the single layer of endothelial cells of the glomerular
• capillaries and form the inner wall of the capsule
Renal Tubule & Collecting Duct
 Nephron
• Number of nephrons constant at birth
• Any increase in kidney size: d/t growth of individual nephron
• Macula densa : crowded cells in columnar tubule
• Juxtaglomerular Apparatus: JG cells and the Macula densa
– Helps regulate blood pressure within the kidneys
– Principal Cells : ADH receptors and Aldosterone receptors
– Intercalated cells: blood pH homeostasis
• Signs of kidney dysfunction until less than 25% remain of the normal functioning
nephrons
 Renal Physiology
Basic functions
nephrons & collecting ducts
1. Glomerular Filtration
– 1st step of urine production
– Water and MOST solutes from plasma move into glomerular capsule then into
renal tubule
2. Tubular Reabsorption
– Cells reabsorb 99% filtered water and many useful solutes
– Reabsorption: return of substances to the bloodstream
– Absorption: entry of new substances into the body (GI tract)
3. Tubular Secretion
– Removes a substance from the blood
 Solutes in the fluid that drains into the renal pelvis remain in the
urine and are excreted. The rate of urinary excretion of any solute is
equal to its rate of glomerular filtration, plus its rate of secretion, minus
its rate of reabsorption

By filtering, reabsorbing, and secreting, nephrons help maintain

homeostasis of the blood’s volume and composition. The situation is
somewhat analogous to a recycling center: Garbage trucks dump refuse
into an input hopper, where the smaller refuse passes onto a conveyor
belt (glomerular filtration of plasma). As the conveyor belt carries the
garbage along, workers remove useful items, such as aluminum cans,
plastics, and glass containers (reabsorption). Other workers place
additional garbage left at the center and larger items onto the conveyor
belt (secretion). At the end of the belt, all remaining garbage falls into a
truck for transport to the landfill (excretion of wastes in urine).
 Glomerular Filtration
• Glomerular filtrate: fluid that enters capsular space
• Daily glomerular filtration rate in adults: 150 liters in females, 180 liters in males
• 99% of GFR returns to bloodstream via tubular reabsorption
• Only 1-2 liters are excreted as urine
 Filtration Membrane
• A barrier that permits filtration of water and small solutes,
but prevents filtration of plasma proteins, blood cells, and platelets
3 barriers are:
1. Glomerular endothelial cell
– Has mesangial cells: regulate glomerular filtration
2. Basal Lamina
– Acellular; prevents filtration of larger plasma proteins
3. Filtration slit by podocytes
– it permits the passage of molecules having a diameter smaller than 0.006–0.007
um
1. Glomerular endothelial cells are quite leaky because they have large
fenestrations (pores) that measure 0.07–0.1 m in diameter. This size permits all
solutes in blood plasma to exit glomerular capillaries but prevents filtration of
blood cells and platelets

2. The basal lamina, a layer of acellular material between the endothelium and
the podocytes, consists of minute collagen fibers and proteoglycans in a
glycoprotein matrix; it prevents filtration of larger plasma proteins.

3. Extending from each podocyte are thousands of footlike processes termed

pedicels that wrap around glomerular capillaries. The spaces between pedicels
are the filtration slits. A thin membrane, the slit membrane; it permits the
passage of molecules having a diameter smaller than 0.006–0.007 um, including
water, glucose, vitamins, amino acids, very small plasma proteins, ammonia,
urea, and ions. Less than 1% of albumin, the most plentiful plasma protein,
passes the slit membrane because, with a diameter of 0.007m, it is slightly too
big to get through.
 Net Filtration Pressure
• Glomerular filtration depends on three main pressures.
• One pressure promotes filtration and two pressures oppose filtration

1. Glomerular blood hydrostatic pressure (GBHP)

– Promotes filtration by force; 55 mmHg
2. Capsular hydrostatic pressure (CHP)
– opposes filtration and represents a “back pressure” of about 15 mmHg.
3. Blood colloid osmotic pressure (BCOP)
– opposes filtration. The average BCOP in glomerular capillaries is 30 mmHg
1. Glomerular blood hydrostatic pressure (GBHP)
is the blood pressure in glomerular capillaries. Generally, GBHP is about 55 mmHg.
It promotes filtration by forcing water and solutes in blood plasma through the
filtration membrane.

2. Capsular hydrostatic pressure (CHP)

is the hydrostatic pressure exerted against the filtration membrane by fluid already
in the capsular space and renal tubule. CHP opposes filtration and represents a “back
pressure” of about 15 mmHg.

3. Blood colloid osmotic pressure (BCOP),

which is due to the presence of proteins such as albumin, globulins, and fibrinogen
in blood plasma, also opposes filtration. The average BCOP in glomerular capillaries is
30 mmHg.
 Net Filtration Pressure
• Net Filtration Pressure (NFP)= GBHP – CHP - BCOP

• NFP = 55 mmHg -15 mmHg - 30 mmHg

=10 mmHg

• Thus, a pressure of only 10 mmHg causes a normal amount of blood plasma (minus
plasma proteins) to filter from the glomerulus into the capsular space.
 Glomerular Filtration Rate
• GFR = 125mL/min in males and 105mL/min in females
• Homeostasis of body requires constant GFR
• GFR is directly related to the pressures that determine net filtration pressure
• GFR is nearly constant when the mean arterial blood pressure is anywhere between
80 and 180 mmHg
3 mechanisms that control GFR
1. renal autoregulation
2. neural regulation
3. hormonal regulation.
 GFR is directly related to the pressures that determine
net filtration pressure; any change in net filtration pressure
will affect GFR. Severe blood loss, for example, reduces
mean arterial blood pressure and decreases the glomerular
blood hydrostatic pressure.

Filtration ceases if glomerular blood hydrostatic pressure

drops to 45 mmHg because the opposing pressures add up
to 45 mmHg. Amazingly, when systemic blood pressure rises
above normal, net filtration pressure and GFR increase very
little
 Renal Autoregulation of GFR
1. Myogenic mechanism
– stretching triggers contraction of smooth muscle cells in the walls of afferent
arterioles
– The myogenic mechanism normalizes renal blood flow and GFR within seconds
after a change in blood pressure
2. Tibuloglomerular feedback
– the macula densa—provides feedback to the glomerulus
– Macula densa cells are thought to detect the increased delivery of Na, Cl, and
water and to inhibit release of nitric oxide (NO) from cells in the juxtaglomerular
apparatus (JGA)
– Tubuloglomerular feedback operates more slowly than the myogenic mechanism
 The kidneys themselves help maintain a constant
renal blood flow and GFR despite normal, everyday
changes in blood pressure, like those that occur
during exercise
Myogenic mechanism= As blood pressure rises, GFR
also rises because renal blood flow increases.
However, the elevated blood pressure stretches the
walls of the afferent arterioles.
In response, smooth muscle fibers in the wall of the
afferent arteriole contract, which narrows the
arteriole’s lumen. As a result, renal blood flow
decreases, thus reducing GFR to its previous
level…Conversely, when arterial blood pressure drops,
the smooth muscle cells are stretched less and thus
relax. The afferent arterioles dilate, renal blood flow
increases, and GFR increases.
 Tibuloglomerular feedback
When GFR is above normal due to elevated systemic blood pressure,
filtered fluid flows more rapidly along the renal tubules. As a result, the
proximal convoluted tubule and loop of Henle have less time to reabsorb Na,
Cl, and water. Macula densa cells are thought to detect the increased delivery
of Na, Cl, and water and to inhibit release of nitric oxide (NO). Because NO
causes vasodilation, afferent arterioles constrict when the level of NO declines.
As a result, less blood flows into the glomerular capillaries, and GFR decreases.
When blood pressure falls, causing GFR to be lower than normal, the opposite
sequence of events occurs, although to a lesser degree
 Neural Regulation of GFR
• Sympathetic ANS fibers release norepinephrine. Norepinephrine causes
vasoconstriction through the activation of Alpha 1 receptors
• At rest:
– sympathetic stimulation is moderately low, the afferent and efferent arterioles are
dilated, and renal autoregulation of GFR prevails
• Moderate Stimulation:
– both afferent and efferent arterioles constrict to the same degree, which decreases GFR
only slightly
• Greater Stimulation:
– During exercise or hemorrhage, vasoconstriction of the afferent arterioles predominates.
As a result, blood flow into glomerular capillaries is greatly decreased, and GFR drops
 Hormonal Regulation of GFR
1. Angiotensin II
– reduces GFR
– very potent vasoconstrictor that narrows both afferent and efferent arterioles
2. Atrial natriuretic peptide (ANP)
– increases GFR
– Released from the cells in the atria of the heart
ANP Stretching of the atria, as occurs when blood volume increases, stimulates
secretion of ANP. By causing relaxation of the glomerular mesangial cells, ANP
increases the capillary surface area available for filtration. Glomerular filtration rate
rises as the surface area increases.