Renal Function 313

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Renal Function 3/13

• What is nitrogenous waste and why must we remove
  it?
• What are the Structures of the glomerulus?
• What are the types of transport in nephron?
• What are the segmental differences along nephron?
• What is GFR and how does GFR change in disease?
• Why does a diabetic have an enormous urine volume
  and dehydration when the blood glucose it too
  high?

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Why do some people develop HAPE? POSITIVE
FEEDBACK LOOP! Remember PO2 at sea level is 159
mmHg and 10,000 feet it is about 100 mmHg. The
blood vessels of some lungs see the low PO2 and
think (inappropriately) that the alveoli are not
being properly ventilated (they are ventilated,
Apparently the air does not contain enough O2
to prevent constriction of the blood vessels,
this causes additional CO2 to accumulate which
locally worsens the conditions and causes
pulmonary blood pressure to increase leading to
edema and even worse ventilations (lower pO2 and
higher local PCO2).
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Overview of Renal Function

• 1) You have two kidneys that clean your blood at
  very high metabolic cost in terms of cardiac
  output and O2 demand.
• 2) Blood wastes, especially toxic nitrogenous
  ones, are removed into glomerular filtrate by the
  kidneys.
• 3) Most of the valuable parts of the 180 L/day of
  filtrate created by the kidneys are reabsorbed by
  the nephron back into blood in the kidneys.
• 4) Hormones, such as ADH and aldosterone, fine
  tune this reabsorption process, in the collecting
  duct or distal nephron.
• 5) About 1 if the filtrate becomes urine that
  exits each kidney in a ureter and travels to the
  bladder for temporary storage and removal.
• 6) Voiding the bladder so urine leaves the body
  by the urethra occurs when a combination of
  voluntary and involuntary nervous sytems work
  together.
• Bonus After the collecting duct, urine quality
  cannot be modified.
• Bonus The kidney is critical for
  erythropoietin/Vit D production.
• Bonus The kidney also helps control blood pH and
  electrolyte levels.

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What are nitrogenous wastes? Why does the kidney
remove nitrogenous wastes from the body? Why is
removal difficult?

• Relative safety of metabolites
• Carbos vs. Fats vs. Protein
• Amino acids release ammonia and toxic nitrogenous
  wastes when they are oxidized.
• Nitrogenous wastes
• Ammonia-
• Urea (50)-
• Uric acid-
• Creatinine-
• Relative water solubility of waste
• Azotemia and exercise
• Uremia and renal failure
• How do we remove waste from the blood, but keep
  the vitamins, minerals, glucose, etc that we need
  in the blood?

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What are the circulatory structures of the
kidney? Why is the kidney so sensitive to
ischemia and infarct?

• Cleaning the blood is VERY expensive in terms of
  ATP used for reabsorption, excretion, and
  secretion.
• Oxygen consumption as of total about 7 AT
  REST
• Cardiac output as of total (at rest) about 20
• What blood vessels bring blood to/from the
  kidney?
• Renal Arteries (Veins)- (Lt/Rt)
• Interlobar Arteries (Veins)-
• Arcutate and Interlobular Arteries (Veins)-
• Afferent Arteriole?(GlomerularCapillaries)?Efferen
  t Arteriole
• The efferent arteriole has three choices it can
  perfuse.
• E.A.?Peritubular Capillaries-
• E.A.?Vasa Recta-
• E.A.?Back interlobular veins?Renal Veins?Vena Cava

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Each kidney has a ONE renal artery in and ONE
renal vein moving blood out. What happens if a
thrombosis blocks an artery?
ONE WAY IN (R.A.) ONE WAY OUT(R.V.)
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THE NEPHRON IS THE FUNCTIONAL UNIT OF THE KIDNEY!
WHAT DOES A NEPHRON DO?

• Major parts and players in the NEPHRON
• Nephrons Filter then Reabsorb!
• Glomerular capillaries site of blood filtration
  (about 180 Liters/day)
• Bowmans Capsule around capillaries
• PCT (65 of reabsorptionmost at start!)
• Loop of Henle (15-20 of reabsorption) Cortical
  LH or Medullary LH
• DCT (5-10 of filtrate of reabsorption)
• Collecting Ducts (0-10 of reabsorption)
• Fine tuning occurs when hormones act on CD!
  Technically CD is not part of nephron
• Filtrate Becomes Urine 180 L filtrate/day?
• _at_90 reabsorpt.?18 L urine/day
• _at_99 reabsorpt.?1.80 L urine/day
• _at_99.5 reabsportion?900ml Urine/day

Loop of H. Medulla
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Glomerulus, PCT, Short Loops, and DCT
Each collecting duct receives filtrate (now
called urine) from many distal convoluted tubules
Long Loops of Henle For Maximal
Water Reabsorption!
Urine passes into the ureters for delivery to
trigone of the bladder
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GLOMEROLAR (or BOWMANS) CAPSULE AND THE
GLOMERULUS IS WHERE FILTRATION OCCURS.

• Arterial Supply of Renal Corpuscles
  (capillaries)
• Afferent Arteriole (IN) and Efferent Arteriole
  (OUT)
• Glomerular capillaries (corpuscles) in between
• Efferent Arterioles deliver some blood into a
  second set of capillaries (peritubular or vasa
  recta)yes this is a portal system! ?
• Glomerular Capillaries are under high pressure
• These capillaries are rich in fenestrations (80nm
  wide) that allow selected materials in blood to
  pass through to capsular space (exit blood).
• Basement Membrane Fenestra (8 nm)-
• Podocytes and slits (Fenestra 30nm)
• Large proteins (negative charge) are excluded
  based on size and charge, everything else can
  pass fenestrations, please dont forget that
  protein charge is very important!
• What happens to urine protein content if pores
  get too big?

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The key to the glomerulus is having fenestra that
are large enough to allow large amounts of fluid
to be filtered, yet small enough so that cells
and proteins are unable to be filtered! Plasma
proteins are negatively charged and the sides of
slits are negatively charged (this creates charge
repulsion). It is also important to have
supporting structures on the back side of the
basement membrane to hold things in place
(podocytes).
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Lets consider the forces that create filtrate at
he start of a glomerular capillary!

• Hydrostatic pressure in capillary 60 mmHg out
  of capillary
• Hydrostatic pressure in capsule -18 mmHg out of
  capillary
• Osmotic pressure in plasma -28 mmHg into
  capillary
• Osmotic pressure in filtrate 0 mmHg essentially
  zero!
• Hopefully NO protein was filtered!
• Net Filtration Pressure
• (60out)(18out) (-28in) (0) 42 - 28
  14 mmHg OUT!
• Therefore fluid is filtered from the start of the
  glomerular capillary, through the fenestrations,
  and into the glomerular capsule (this is called
  glomerular filtration!!)
• Volume filtrate/Time glomerular filtration
  rate (GFR)
• Blood is very viscous (thick) after leaving
  glomerular capillaries!

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GLOMERULAR FILTRATION RATE (GFR) IS VOLUME OF
FILTRATE PRODUCED/MINUTE (ml fluid entering
capsule/minute)

• Facts Kidney size(fist), location(retroperitoneal
  ), number (2)
• Why do we clinically measure renal function
  (filtration rate)?
• Filtration is a function of hydrostatic
  pressures blood pressure in capillary vs.
  hydrostatic pressure in capsule. It is also a
  function of oncotic pressure created by
  hydrogen-bonds of water to protein in the blood
  (protein should not be in filtrate).
• Typical GFR125 ml/minute this is V.I.P.
• This is typically split by the two kidneys, if
  you lose one all 125 ml/minutes goes to the one
  remaining kidney.
• How much is this per day? 125 ml/min(60min/hr)(24h
  r/day) 180,000ml/day
• What happens to GFR if bacteria infect the kidney
  and erode the slits (fenestrations)?
• What happens to GFR if the blood pressure is too
  high or low?
• What happens to GFR if the bladder cant drain?

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PROXIMAL CONVULUTED TUBULE IS THE FIRST PART OF
THE NEPHRON TO RECLAIM VALUABLE SALTS AND WATER
FROM THE FILTRATE THAT WAS JUST FORMED.

• 65 of water reabsorption occurs along the PCT!
• How Much Is This? (180L)(0.65) 120 L (60 L
  left in filtrate)
• Tubular Epithelium Luminal, Basolateral,
  Interstitial
• Tight Junctions-
• Na/K-ATPase pushes ions into interstitium
• Secondary Active Tx Na-Glucose Co-transport
• Solvent Drag pulls water into peritubular
  capillary
• Filtrate not to different from what it was at
  start except that volume is reduced 65 (120 L is
  now only 60L).
• Fluids and reabsorbed materials are then
  transferred to peritubular capillaries and
  whisked away to the renal vein.

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The key to reabsorption in all parts of the
nephron (and PCT) is that if you pump ions out of
the filtrate, water will follow via solvent drag.
Many pumps help make this possible.