Renal Physiology

1
Renal Physiology

• Jim Pierce
• Bi 145b
• Lecture 5, 2008-9

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Renal Function

• We talked about
• Body Water
• Body Sodium
• Kidney Anatomy
• But how do we process body fluids?

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Renal Function

• There is a Cardiac Output
• There is a Renal Blood Flow
• There is a Renal Plasma Flow
• A portion of the RPF goes to the glomerulus
• There is a Glomerular Filtration Rate
• Filtration Produces the initial urine load
• Reabsorption and Secretion will alter it

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Renal Function
Conservation Of Mass!
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Renal Function
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Renal Function

• What goes into kidney?
• 25 of Cardiac Output
• 1.5 Liters per Minute
• This is true regardless of blood pressure.

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Renal Blood Flow
Dog Experiment
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Renal Blood Flow

• We expect
• Flow to be a function of Pressure Gradient
• We findFlow to be constant
• ThereforeVascular Resistance changes in
  responseto a change in Blood Pressure

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Renal Blood Flow

• As Pressure goes Up
• Resistance goes Up
• As Pressure goes Down
• Resistance goes Down
• When maximally dilated, flow falls

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Renal Blood Flow
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Renal Blood Flow

• Almost all arterial blood goes to glomerulus
• Enters via Afferent Arteriole
• Exits via Efferent Arteriole

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Renal Blood Flow

• Afterwards, all blood continuesthrough theVasa
  Recta
• (Misnomer)

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Renal Blood Flow

• This shouldnt besurprising
• This allows thekidney to movethings
  betweenurine and blood

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Renal Blood Flow

• Ultimately, Bloodis filtered in the Glomerulus
• Blood is Processed in the Medulla
• Blood returns via the veins

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Renal Blood Flow

• We need to understand
• Renal Blood Flow
• Glomerular Filtration
• Urine Processing
• Renal Response and Homeostasis

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Renal Function
Principle 1 What you get out of itis what you
put into it
Artery in Vein Out Urine Out
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Renal Function
What Goes In?
Red Cells go in via arteryRed Cells go out via
vein
So were reallyinterested in Renal Plasma Flow
Artery in Plasma Red Cells
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Renal Function
Renal Plasma Flow (RPF)
Artery in Plasma Red Cells
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Renal Function
Renal Plasma Flow (RPF)arrives at the glomerulus
Some of it is filtered into the urine Some of it
continues in the blood vessels
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Renal Function
The GFR (Glomerular Filtration Rate) is the flow
across the glomerular membrane Into the urinary
space
This will eventually be processedby the Nephron
into real urine
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Renal Function
Renal Plasma Flow (RPF)
So how do we figureout these differentflows for
the kidney?
Conservation of Mass
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Renal Function
Amount (grams) Concentration Volume
Amount in
Amount Out Urine
Amount Out Blood
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Renal Function
So if were smart and pick something X that is
not processed by the kidney
Amount in
Amount Out Urine
Amount Out By Blood
Then
The amount excreted the amount of plasma
filtered
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Renal Function
Inulin is one such molecule
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Renal Function
But we also recognize that for every
molecule Some of it is excreted Some of it is
not
The clearance of X is the glomerular filtration
rateand also the secretion or absorption of X.
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Renal Function
In the case of Inulin, since thetubules do
nothing, Clearance GFR
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Renal Function
Para-amino hippuric acid (PAH) is both
filteredand excreted by the tubules So if done
right 100 of PAH Exits Via the Urine So
Clearance RPF
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Renal Function
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Renal Function
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Renal Function
So we can take advantage of conservation of
mass to calculate Renal Blood Flow Renal Plasma
Flow Glomerular Filtration
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Renal Function
So we can take advantage of conservation of
mass to calculate Renal Blood Flow Renal Plasma
Flow Glomerular Filtration
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Renal Function

• Cardiac Output 5 L / min
• Renal Blood Flow 25 of CO 1200 cc / min
  total 600 cc / min per kidney
• Renal Plasma Flow RBF / (1 Hct) 650 cc /
  min total 325 cc / min per kidney

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Renal Function

• Renal Plasma Flow 650 cc / min total
• Renal Cortex 500 cc / min
• Outer Medulla 125 cc / min
• Inner Medulla 25 cc / min

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Renal Function
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Renal Function

• Urine Formation
• Renal Blood Flow
• Glomerular Filtration
• Reabsorption
• Water
• Solute
• Secretion

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Renal Function
The Glomerulus produces filtrate
The Nephron processes it to urine
But How?
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Glomerulus

• Fine Capillary Network

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Glomerular Filtration
Starlings Forces are alive and well in the
capillary!
(Theyre a little different, though)
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RBF and GFR
By controlling theafferent and
efferentarterioles, we control Glomerular
Filtration Rate
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RBF and GFR
By controlling theafferent and
efferentarterioles, we also control Renal Blood
Flow
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RBF and GFR
Thus the arterialnature of the
glomerulusallows us to apply steadyhydrostatic
pressureacross the glomerulus,making a filtrate.
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Glomerular Membrane

• Made from
• Endothelium
• BasementMembrane
• Podocytes

The Urine Filter
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Glomerulus

• The endothelialmesh is coatedby cells
  calledPodocytes

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Podocytes
Part of GlomerularMembrane
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TEM Podocytes
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Glomerular Filter

• This filter has several effects because it is a
  gel
• Its composition makes a Pore Size
• Its composition makes a Charge Barrier
• (Just like gel electrophoresis)

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Glomerular Filtration
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Glomerular Filtration
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Renal Function

• To understand urine, we must ask
• What do we start with?
• What is the final product?

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Renal Function

• Plasma / Blood
• Na 135-140 mM
• K 3.5-5 mM
• Cl 105-115 mM
• HCO2 24 mM
• Glucose 60-110 mg / dL

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Urine Formation
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Glomerular Filtration
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Glomerular Filtration

• Liters and Liters are filtered
• 99.9 is reabsorbed
• How and Why?

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Renal Tubular Function

• Passive
• Diffusion / Osmosis
• Solvent Drag
• Facilitated
• Channel, Uniport, Symport, Antiport
• Active
• Primary AT (ATPase)
• Secondary AT (Gradient)

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Renal Tubular Function
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Mechanisms of Absorption
There aredifferences Concentration Gradient Os
molarGradient ChargeGradient
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Absorption and Secretion

• Why go to all this trouble?
• It is more efficient to build a small gradient on
  many small volumes than to build a large gradient
• Waste products are concentrated with no wasted
  energy

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Absorption and Secretion

• The Kidneys Plan
• Process large volumes for efficiency
• Reabsorb Volume
• Fix Osmolarity
• Adjust Acid-Base Balance
• Adjust Electrolytes

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Absorption

• The majority of VOLUME(NaCl and Water)is
  absorbed in the Proximal Tubuleand the Loop of
  Henle

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NaCl Absorption
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Water Metabolism
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Volume Absorption

• How does it do it?
• Move Sodium, let water follow
• Move Sodium, let water follow
• Move Sodium, let water follow

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Proximal Tubule
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Proximal Tubule
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Proximal Tubule
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Proximal Tubule

• Move Sodium
• Let Water Follow
• There is
• Transtubuluar Sodium Gradientusing Na / K ATPase

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Proximal Tubule

• Its also worth noting that anything important is
  retrieved
• GlucoseAmino AcidsHormonesetc

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Proximal Tubule
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Proximal Tubule
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Proximal Tubule

• We retrieve NaCl and H2O (VOLUME)
• We rescue things we want (expensive)
• We also secrete things that cant get filtered
• Organic Anions
• Organic Cations
• Protons

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Organic Cations
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Organic Cations
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Organic Anions
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Organic Anions
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Proximal Tubule
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Absorption
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Loop of Henle

• Why have a medulla?
• Countercurrent exchange allows us to form
  gradients

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Loop of Henle
Solute Otherthan NaCl H20
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Loop of Henle

• Once we have a Osmolarity Gradient,we can
  separate Water and Salt!

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Water Metabolism
As you descendinto higher concentration Water
Moves Out!
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NaCl Absorption

As you ascend into lower concentration You need
to moveSolute Out!
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LoopofHenle
That meanswater impermeability
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NaCl Absorption
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Water Absorption
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Salt versus Water Absorption
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Water Metabolism
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Water Metabolism
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Distal Tubule

• How do we determine whether or not to reabsorb
  water?
• Selective control of water channels

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Distal Tubule
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Distal Tubule and Kidney Plan

• The Proximal Tubule and Loopabsorb VOLUME
• The Loop and Distal Tubuleprepare the Gradient
• The Distal Tubulecontrols OSMOLARITY

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GlomerularBloodFlow
Feedback, too.
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Juxtaglomerular Apparatus
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Distal Tubule and Kidney Plan

• The Distal Tubule is also finishing school
• Acid Base Metabolism
• Potassium and other Electrolyte Control

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Distal Tubule, Collecting Duct
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Distal Tubule, Collecting Duct
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Potassium Secretion
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Potassium Secretion
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Potassium Secretion
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Potassium Secretion
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Potassium Secretion
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Potassium Metabolism
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Potassium Metabolism
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Absorption and Secretion

• The Kidneys Plan
• Process large volumes for efficiency
• Reabsorb Volume
• Fix Osmolarity
• Adjust Acid-Base Balance
• Adjust Electrolytes

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Questions?