Lecture Outline

• General Functions of the Urinary System

• Quick overview of the functional anatomy
Renal Physiology of the urinary system
• How the nephron works & is controlled
• Micturition

General Functions Overview of Function Anatomy

The System

• Produce & expel urine • Urinary system consists of:

• Regulate the volume and composition of the Kidneys – The functional unit of the system
extracellular fluid
Ureters
– Control pH
– Control blood volume & blood pressure
– Controls osmolarity Conducting & Storage
Urinary Bladder
– Controls ion balance components

• Production of hormones Urethra

– Renin
– EPO

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Overview of Functional Anatomy Overview of Functional Anatomy
The Kidney The Kidney

• Divided into an outer

cortex • The nephron consists of:
– Vascular components
• And an inner medulla • Afferent & efferent
arterioles
• Glomerulus
• Peritubular capillaries

• The functional unit of • Vasa recta

– Tubular components
renal
pelvis this kidney is the • Proximal convoluted
tubule
nephron • Distal convoluted tubule
• Nephron loop (loop of
– Which is located in Henle)
• Collecting duct
both the cortex and – Tubovascular component
medullary areas • Juxtaglomerular appartus

The Nephron The Nephron

• Locations for filtration, reabsorption,
• Simplified view of its functions
secretion & excretion
• Glomerular
Filtration
• Tubular
Reabsorption
• Tubular
Secretion
• Excretion

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Nephron Nephron
Filtration Filtration Membrane
• Capillaries are fenestrated
• First step in urine formation
• Overlying podocytes with pedicels form
– No other urinary function would occur without filtration slits
this aspect! • Basement membrane between the two
• Occurs in the glomerulus due to
– Filtration membrane &
• Capillary hydrostatic pressure
• Colloid osmotic pressure
• Capsular hydrostatic pressure

Nephron Nephron
Glomerular Filtration Glomerular Filtration

• Barriers • Forces
– Blood hydrostatic pressure (PH)
– Mesanglial cells can alter blood flow through • Outward filtration pressure
of 55 mm Hg
capillaries – Constant across capillaries
due to restricted outflow
(efferent arteriole is smaller
– Basal lamina alters filtration as well by in diameter than the afferent
arteriole)
– Colloid osmotic pressure (π)
• Containing negatively charged glycoproteins • Opposes hydrostatic pressure
– Act to repel negatively charged plasma proteins at 30 mm Hg
• Due to presence of proteins in
– Podocytes form the final barrier to filtration plasma, but not in glomerular
capsule (Bowman’s capsule)
by forming “filtration slits” – Capsular hydrostatic pressure
(Pfluid)
• Opposes hydrostatic pressure
at 15 mm Hg

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Nephron Nephron
Glomerular Filtration Glomerular Filtration

• 10 mm Hg of filtration pressure • 10 mm Hg of filtration pressure

– Not high, but has a large surface area and nature of filtration
– Not high, but has a large surface area and nature of membrane
filtration membrane – creates a glomerular filtration rate (GFR) of 125 ml/min which
– creates a glomerular filtration rate (GFR) of 125 equates to a fluid volume of 180L/day entering the glomerular
capsule.
ml/min which equates to a fluid volume of 180L/day • Plasma volume is filtered 60 times/day or 2 ½ times per hour
entering the glomerular capsule. • Requires that most of the filtrate must be reabsorbed, or we would
• Plasma volume is filtered 60 times/day or 2 ½ times per hour be out of plasma in 24 minutes!
• Requires that most of the filtrate must be reabsorbed, or we – GFR maintains itself at the
relatively stable rate of 180L/day
would be out of plasma in 24 minutes!
by
– Still…. GFR must be under regulation to meet the • Regulation of blood flow
demands of the body. through the arterioles
– Changing afferent and
efferent arterioles has
different effects on GFR

Nephron Nephron
Regulation of GFR Autoregulation of GFR

• How does GFR remain relatively constant 2. Tubulooglomerular feedback at the JGA
despite changing mean arterial pressure?
1. Myogenic response – Fluid flow is monitored in the tubule where it
• Typical response to stretch of arteriolar smooth muscle due comes back between the afferent and efferent
to increased blood pressure:
– increase stretch results in smooth muscle contraction and arterioles
decreased arteriole diameter
– Causes a reduction in GFR • Forms the juxtaglomerular apparatus
• If arteriole blood pressure decreases slightly, GFR only – Specialized tubular cells in the JGA form the macula
increases slightly as arterioles dilate densa
– Due to the fact that the arterioles are normally close to maximal
dilation – Specialized contractile cells in the afferent arteriole in the
– Further drop in bp (below 80mmHg) reduced GFR and JGA are called granular cells or juxtaglomerular cells
conserves plasma volume
2. Tubulooglomerular feedback at the JGA
3. Hormones & ANS

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Juxtaglomerular Apparatus Nephron
Regulation of GFR

• The cells of the

macula densa
monitor NaCl
concentration in the
fluid moving into the
dital convoluted
tubule.
– If GFR increases,
then NaCl
movement also
increases as a
result
– Macula densa cells
send a paracrine
message (unknown
for certain) causing
the afferent
arteriole to
contract,
decreasing GFR
and NaCl movment

Nephron Nephron
Regulation of GFR Regulation of GFR
3. Hormones & ANS
– Autoregulation does a pretty good job, however
• Renin-Angiotensin-Aldosterone System
extrinsic control systems can affect a change by
overriding local autoregulation factors by
• Changing arteriole resistance
– Sympathetic innervation to both afferent and efferent
arterioles
» Acts on alpha receptors causing vasoconstriction
» Used when bp drops drastically to reduce GFR and
conserve fluid volume
• Changing the filtration coefficient
– Release of renin from the granular cells (JG cells) of the JGA (or low NaCl
initiates the renin-angiotensin-aldosterone system (RAAS) flow in JGA)
» Angiotensin II is a strong vasoconstrictor
– Prostaglandins
» Vasodilators
– These hormones may also change the configuration of the
mesanglial cells and the podocytes, altering the filtration
coefficient

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Nephron Nephron
Tubular Reabsorption Tubular Reabsorption

• GFR = 180 L/day, >99% is reabsorbed • Na+ reabsorption

– Why so high on both ends? – An active process
• Allows material to be cleared from plasma quickly • Occurs on the basolateral membrane (Na+/K+ ATPase)
and effectively if needed – Na+ is pumped into the interstitial fluid
• Allows for easy tuning of ion and water balance – K+ is pumped into the tubular cell
– Reabsorption • Creates a Na+ gradient that can be utilized for 2º active
• Passive and Active Transport Processes transport
• Most of the reabsorption takes place in the PCT
Movement may be
via epithelial
transport (through
the cells) or by
paracellular
pathways (between
the epithelial cells)

Nephron Nephron
Tubular Reabsorption Tubular Reabsorption

• Secondary Active Transport utilizing Na+ • The transport membrane proteins

– Will reach a saturation point
gradient (Sodium Symport) • They have a maximum transport rate = transport maximum
– Used for transporting (Tm)
– The maximum number
• Glucose, amino acids, ions, metabolites of molecules that can be
transported per unit of
time
– Related to the plasma
concentration called the
renal threshold…
» The point at which
saturation occurs and
Tm is exceeded

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 Nephron Nephron
Tubular Reabsorption Tubular Reabsorption

• Glucose Reabsorption • Where does filtered material go?

– Glucose is filtered and reabsorbed hopefully 100%
• Glucose excreted = glucose filtered – glucose reabsorbed – Into peritubular capillaries because in the
capillaries there exists
• Low hydrostatic pressure
• Higher colloid osmotic pressure
Implication of
no glucose
transports past
the PCT?

Nephron Nephron
Tubular Secretion Excretion & Clearance

• Tubular secretion is the movement of material Filtration – reabsorption + secretion = Excretion

from the peritubular capillaries and interstitial
space into the nephron tubules • The excretion rate then of a substance (x) depends on
– Depends mainly on transport systems – the filtration rate of x
– Enables further removal of unwanted substances – if x is reabsorbed, secreted or both
– Occurs mostly by secondary active transport • This just tells us excretion, but not much about how the
nephron is working in someone
– If something is filtered, not reabsorbed, and – This is done by testing a known substance that should be
secreted… the clearance rate from plasma is greater filtered, but neither reabsorbed or secreted
than GFR! • 100% of the filtered substance is excreted and by monitoring
• Ex. penicillin – filtered and secreted, not reabsorbed plasma levels of the substance, a clearance rate can be determined
– 80% of penicillin is gone within 4 hours after administration

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Nephron Nephron
Excretion & Clearance Excretion & Clearance

• Inulin • The relationship between clearance and

– A plant excretion using a few examples
product that is
filtered but not
reabsorbed or
secreted
– Used to
determine
clearance rate
and therefore
nephron
function

Nephron Nephron
Excretion & Clearance Urine Concentration & Dilution

• Urine normally exits the nephron in a dilute

state, however under hormonal controls, water
reabsorption occurs and can create an
extremely concentrated urine.
– Aldosterone & ADH are the two main hormones that
drive this water reabsorption
• Aldosterone creates an obligatory response
– Aldosterone increases Na+/K+ ATPase activity and therefore
reabsorption of Na+… where Na+ goes, water is obliged to
follow
• ADH creates a facultative response
– Opens up water channels in the collecting duct, allowing for the
reabsorption of water via osmosis

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Micturition Micturition
• Once excreted, urine travels via the paired • Reflex Pathway
ureters to the urinary bladder where it is
held (about ½ L)
• Sphincters control movement out of the
bladder
– Internal sphincter – smooth muscle (invol.)
– External sphincter – skeletal muscle (vol.)