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Renal Physiology
Renal Physiology
Lecture Outline
• General Functions of the Urinary System
• Quick overview of the functional anatomy
of the urinary system
• How the nephron works & is controlled
• Micturition
General Functions
• Produce & expel urine
• Regulate the volume and composition of the
extracellular fluid
– Control pH
– Control blood volume & blood pressure
– Controls osmolarity
– Controls ion balance
• Production of hormones
– Renin
– EPO
Overview of Function Anatomy
The System
• Urinary system consists of:
Kidneys
Ureters
Urinary Bladder
Urethra
– The functional unit of the system
Conducting & Storage
components
Overview of Functional Anatomy
The Kidney
• Divided into an outer
cortex
• And an inner medulla
• The functional unit of
this kidney is the
nephron
– Which is located in
both the cortex and
medullary areas
renal
pelvis
Overview of Functional Anatomy
The Kidney
• The nephron consists of:
– Vascular components
• Afferent & efferent
arterioles
• Glomerulus
• Peritubular capillaries
• Vasa recta
– Tubular components
• Proximal convoluted
tubule
• Distal convoluted tubule
• Nephron loop (loop of
Henle)
• Collecting duct
– Tubovascular component
• Juxtaglomerular appartus
The Nephron
• Simplified view of its functions
• Glomerular
Filtration
• Tubular
Reabsorption
• Tubular
Secretion
• Excretion
The Nephron
• Locations for filtration, reabsorption,
secretion & excretion
Nephron
Filtration
• First step in urine formation
– No other urinary function would occur without
this aspect!
• Occurs in the glomerulus due to
– Filtration membrane &
• Capillary hydrostatic pressure
• Colloid osmotic pressure
• Capsular hydrostatic pressure
Nephron
Filtration Membrane
• Capillaries are fenestrated
• Overlying podocytes with pedicels form
filtration slits
• Basement membrane between the two
Nephron
Glomerular Filtration
• Barriers
– Mesanglial cells can alter blood flow through
capillaries
– Basal lamina alters filtration as well by
• Containing negatively charged glycoproteins
– Act to repel negatively charged plasma proteins
– Podocytes form the final barrier to filtration
by forming “filtration slits”
Nephron
Glomerular Filtration
• Forces
– Blood hydrostatic pressure (PH)
• Outward filtration pressure
of 55 mm Hg
– Constant across capillaries
due to restricted outflow
(efferent arteriole is smaller
in diameter than the afferent
arteriole)
– Colloid osmotic pressure (π)
• Opposes hydrostatic pressure
at 30 mm Hg
• Due to presence of proteins in
plasma, but not in glomerular
capsule (Bowman’s capsule)
– Capsular hydrostatic pressure
(Pfluid)
• Opposes hydrostatic pressure
at 15 mm Hg
Nephron
Glomerular Filtration
• 10 mm Hg of filtration pressure
– Not high, but has a large surface area and nature of
filtration membrane
– creates a glomerular filtration rate (GFR) of 125
ml/min which equates to a fluid volume of 180L/day
entering the glomerular capsule.
• Plasma volume is filtered 60 times/day or 2 ½ times per hour
• Requires that most of the filtrate must be reabsorbed, or we
would be out of plasma in 24 minutes!
– Still…. GFR must be under regulation to meet the
demands of the body.
Nephron
Glomerular Filtration
• 10 mm Hg of filtration pressure
– Not high, but has a large surface area and nature of filtration
membrane
– creates a glomerular filtration rate (GFR) of 125 ml/min which
equates to a fluid volume of 180L/day entering the glomerular
capsule.
• Plasma volume is filtered 60 times/day or 2 ½ times per hour
• Requires that most of the filtrate must be reabsorbed, or we would
be out of plasma in 24 minutes!
– GFR maintains itself at the
relatively stable rate of 180L/day
by
• Regulation of blood flow
through the arterioles
– Changing afferent and
efferent arterioles has
different effects on GFR
Nephron
Regulation of GFR
• How does GFR remain relatively constant
despite changing mean arterial pressure?
1. Myogenic response
• Typical response to stretch of arteriolar smooth muscle due
to increased blood pressure:
– increase stretch results in smooth muscle contraction and
decreased arteriole diameter
– Causes a reduction in GFR
• If arteriole blood pressure decreases slightly, GFR only
increases slightly as arterioles dilate
– Due to the fact that the arterioles are normally close to maximal
dilation
– Further drop in bp (below 80mmHg) reduced GFR and
conserves plasma volume
2. Tubulooglomerular feedback at the JGA
3. Hormones & ANS
Nephron
Autoregulation of GFR
2. Tubulooglomerular feedback at the JGA
– Fluid flow is monitored in the tubule where it
comes back between the afferent and efferent
arterioles
• Forms the juxtaglomerular apparatus
– Specialized tubular cells in the JGA form the macula
densa
– Specialized contractile cells in the afferent arteriole in the
JGA are called granular cells or juxtaglomerular cells
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
Regulation of GFR
3. Hormones & ANS
– Autoregulation does a pretty good job, however
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
initiates the renin-angiotensin-aldosterone system (RAAS)
» 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
Nephron
Regulation of GFR
• Renin-Angiotensin-Aldosterone System
(or low NaCl
flow in JGA)
• GFR = 180 L/day, >99% is reabsorbed
– Why so high on both ends?
• Allows material to be cleared from plasma quickly
and effectively if needed
• Allows for easy tuning of ion and water balance
– Reabsorption
• Passive and Active Transport Processes
• Most of the reabsorption takes place in the PCT
Nephron
Tubular Reabsorption
Movement may be
via epithelial
transport (through
the cells) or by
paracellular
pathways (between
the epithelial cells)
Nephron
Tubular Reabsorption
• Na+ reabsorption
– An active process
• Occurs on the basolateral membrane (Na+/K+ ATPase)
– Na+ is pumped into the interstitial fluid
– K+ is pumped into the tubular cell
• Creates a Na+ gradient that can be utilized for 2º active
transport
Nephron
Tubular Reabsorption
• Secondary Active Transport utilizing Na+
gradient (Sodium Symport)
– Used for transporting
• Glucose, amino acids, ions, metabolites
Nephron
Tubular Reabsorption
• The transport membrane proteins
– Will reach a saturation point
• They have a maximum transport rate = transport maximum
(Tm)
– The maximum number
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
Nephron
Tubular Reabsorption
• Glucose Reabsorption
– Glucose is filtered and reabsorbed hopefully 100%
• Glucose excreted = glucose filtered – glucose reabsorbed
Implication of
no glucose
transports past
the PCT?
Nephron
Tubular Reabsorption
• Where does filtered material go?
– Into peritubular capillaries because in the
capillaries there exists
• Low hydrostatic pressure
• Higher colloid osmotic pressure
Nephron
Tubular Secretion
• Tubular secretion is the movement of material
from the peritubular capillaries and interstitial
space into the nephron tubules
– Depends mainly on transport systems
– Enables further removal of unwanted substances
– Occurs mostly by secondary active transport
– If something is filtered, not reabsorbed, and
secreted… the clearance rate from plasma is greater
than GFR!
• Ex. penicillin – filtered and secreted, not reabsorbed
– 80% of penicillin is gone within 4 hours after administration
Nephron
Excretion & Clearance
Filtration – reabsorption + secretion = Excretion
• The excretion rate then of a substance (x) depends on
– the filtration rate of x
– if x is reabsorbed, secreted or both
• This just tells us excretion, but not much about how the
nephron is working in someone
– This is done by testing a known substance that should be
filtered, but neither reabsorbed or secreted
• 100% of the filtered substance is excreted and by monitoring
plasma levels of the substance, a clearance rate can be determined
Nephron
Excretion & Clearance
• Inulin
– A plant
product that is
filtered but not
reabsorbed or
secreted
– Used to
determine
clearance rate
and therefore
nephron
function
Nephron
Excretion & Clearance
• The relationship between clearance and
excretion using a few examples
Nephron
Excretion & Clearance
Nephron
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
Micturition
• Once excreted, urine travels via the paired
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.)
Micturition
• Reflex Pathway

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Renal phsyiology

  • 3. Lecture Outline • General Functions of the Urinary System • Quick overview of the functional anatomy of the urinary system • How the nephron works & is controlled • Micturition
  • 4. General Functions • Produce & expel urine • Regulate the volume and composition of the extracellular fluid – Control pH – Control blood volume & blood pressure – Controls osmolarity – Controls ion balance • Production of hormones – Renin – EPO
  • 5. Overview of Function Anatomy The System • Urinary system consists of: Kidneys Ureters Urinary Bladder Urethra – The functional unit of the system Conducting & Storage components
  • 6. Overview of Functional Anatomy The Kidney • Divided into an outer cortex • And an inner medulla • The functional unit of this kidney is the nephron – Which is located in both the cortex and medullary areas renal pelvis
  • 7. Overview of Functional Anatomy The Kidney • The nephron consists of: – Vascular components • Afferent & efferent arterioles • Glomerulus • Peritubular capillaries • Vasa recta – Tubular components • Proximal convoluted tubule • Distal convoluted tubule • Nephron loop (loop of Henle) • Collecting duct – Tubovascular component • Juxtaglomerular appartus
  • 8. The Nephron • Simplified view of its functions • Glomerular Filtration • Tubular Reabsorption • Tubular Secretion • Excretion
  • 9. The Nephron • Locations for filtration, reabsorption, secretion & excretion
  • 10. Nephron Filtration • First step in urine formation – No other urinary function would occur without this aspect! • Occurs in the glomerulus due to – Filtration membrane & • Capillary hydrostatic pressure • Colloid osmotic pressure • Capsular hydrostatic pressure
  • 11. Nephron Filtration Membrane • Capillaries are fenestrated • Overlying podocytes with pedicels form filtration slits • Basement membrane between the two
  • 12. Nephron Glomerular Filtration • Barriers – Mesanglial cells can alter blood flow through capillaries – Basal lamina alters filtration as well by • Containing negatively charged glycoproteins – Act to repel negatively charged plasma proteins – Podocytes form the final barrier to filtration by forming “filtration slits”
  • 13. Nephron Glomerular Filtration • Forces – Blood hydrostatic pressure (PH) • Outward filtration pressure of 55 mm Hg – Constant across capillaries due to restricted outflow (efferent arteriole is smaller in diameter than the afferent arteriole) – Colloid osmotic pressure (π) • Opposes hydrostatic pressure at 30 mm Hg • Due to presence of proteins in plasma, but not in glomerular capsule (Bowman’s capsule) – Capsular hydrostatic pressure (Pfluid) • Opposes hydrostatic pressure at 15 mm Hg
  • 14. Nephron Glomerular Filtration • 10 mm Hg of filtration pressure – Not high, but has a large surface area and nature of filtration membrane – creates a glomerular filtration rate (GFR) of 125 ml/min which equates to a fluid volume of 180L/day entering the glomerular capsule. • Plasma volume is filtered 60 times/day or 2 ½ times per hour • Requires that most of the filtrate must be reabsorbed, or we would be out of plasma in 24 minutes! – Still…. GFR must be under regulation to meet the demands of the body.
  • 15. Nephron Glomerular Filtration • 10 mm Hg of filtration pressure – Not high, but has a large surface area and nature of filtration membrane – creates a glomerular filtration rate (GFR) of 125 ml/min which equates to a fluid volume of 180L/day entering the glomerular capsule. • Plasma volume is filtered 60 times/day or 2 ½ times per hour • Requires that most of the filtrate must be reabsorbed, or we would be out of plasma in 24 minutes! – GFR maintains itself at the relatively stable rate of 180L/day by • Regulation of blood flow through the arterioles – Changing afferent and efferent arterioles has different effects on GFR
  • 16. Nephron Regulation of GFR • How does GFR remain relatively constant despite changing mean arterial pressure? 1. Myogenic response • Typical response to stretch of arteriolar smooth muscle due to increased blood pressure: – increase stretch results in smooth muscle contraction and decreased arteriole diameter – Causes a reduction in GFR • If arteriole blood pressure decreases slightly, GFR only increases slightly as arterioles dilate – Due to the fact that the arterioles are normally close to maximal dilation – Further drop in bp (below 80mmHg) reduced GFR and conserves plasma volume 2. Tubulooglomerular feedback at the JGA 3. Hormones & ANS
  • 17. Nephron Autoregulation of GFR 2. Tubulooglomerular feedback at the JGA – Fluid flow is monitored in the tubule where it comes back between the afferent and efferent arterioles • Forms the juxtaglomerular apparatus – Specialized tubular cells in the JGA form the macula densa – Specialized contractile cells in the afferent arteriole in the JGA are called granular cells or juxtaglomerular cells
  • 19. 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
  • 20. Nephron Regulation of GFR 3. Hormones & ANS – Autoregulation does a pretty good job, however 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 initiates the renin-angiotensin-aldosterone system (RAAS) » 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
  • 21. Nephron Regulation of GFR • Renin-Angiotensin-Aldosterone System (or low NaCl flow in JGA)
  • 22. • GFR = 180 L/day, >99% is reabsorbed – Why so high on both ends? • Allows material to be cleared from plasma quickly and effectively if needed • Allows for easy tuning of ion and water balance – Reabsorption • Passive and Active Transport Processes • Most of the reabsorption takes place in the PCT Nephron Tubular Reabsorption Movement may be via epithelial transport (through the cells) or by paracellular pathways (between the epithelial cells)
  • 23. Nephron Tubular Reabsorption • Na+ reabsorption – An active process • Occurs on the basolateral membrane (Na+/K+ ATPase) – Na+ is pumped into the interstitial fluid – K+ is pumped into the tubular cell • Creates a Na+ gradient that can be utilized for 2º active transport
  • 24. Nephron Tubular Reabsorption • Secondary Active Transport utilizing Na+ gradient (Sodium Symport) – Used for transporting • Glucose, amino acids, ions, metabolites
  • 25. Nephron Tubular Reabsorption • The transport membrane proteins – Will reach a saturation point • They have a maximum transport rate = transport maximum (Tm) – The maximum number 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
  • 26. Nephron Tubular Reabsorption • Glucose Reabsorption – Glucose is filtered and reabsorbed hopefully 100% • Glucose excreted = glucose filtered – glucose reabsorbed Implication of no glucose transports past the PCT?
  • 27. Nephron Tubular Reabsorption • Where does filtered material go? – Into peritubular capillaries because in the capillaries there exists • Low hydrostatic pressure • Higher colloid osmotic pressure
  • 28. Nephron Tubular Secretion • Tubular secretion is the movement of material from the peritubular capillaries and interstitial space into the nephron tubules – Depends mainly on transport systems – Enables further removal of unwanted substances – Occurs mostly by secondary active transport – If something is filtered, not reabsorbed, and secreted… the clearance rate from plasma is greater than GFR! • Ex. penicillin – filtered and secreted, not reabsorbed – 80% of penicillin is gone within 4 hours after administration
  • 29. Nephron Excretion & Clearance Filtration – reabsorption + secretion = Excretion • The excretion rate then of a substance (x) depends on – the filtration rate of x – if x is reabsorbed, secreted or both • This just tells us excretion, but not much about how the nephron is working in someone – This is done by testing a known substance that should be filtered, but neither reabsorbed or secreted • 100% of the filtered substance is excreted and by monitoring plasma levels of the substance, a clearance rate can be determined
  • 30. Nephron Excretion & Clearance • Inulin – A plant product that is filtered but not reabsorbed or secreted – Used to determine clearance rate and therefore nephron function
  • 31. Nephron Excretion & Clearance • The relationship between clearance and excretion using a few examples
  • 33. Nephron 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
  • 34. Micturition • Once excreted, urine travels via the paired 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.)