Renal Physiology 1

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Renal Physiology 1

• Dr Derek Scott
• d.scott_at_abdn.ac.uk
• See also your renal lectures from BI25B2. These
  are still on the School of Medical Sciences
  Website.

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Aims Content of this lecture

• To provide you with a reminder of what you
  covered in the dim and distant past at level 2!
• Brief review of renal anatomy
• Explanation of kidney function
• The 3 basic renal processes
• Processes of filtration at glomerular capillaries
• Processes of reabsorption at peritubular
  capillaries
• Renal handling of Na, K, glucose and amino
  acids
• The countercurrent multiplier

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Renal system important points

• Kidneys have excellent blood supply 0.5 total
  body weight but 20 of CO.
• Kidneys process plasma portion of blood by
  removing substances from it, and in a few cases,
  by adding substances to it.
• Works with cardiovascular system (and others!) in
  integrated manner

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The functional unit of the kidney the nephron

• Total of about 2.5 million in the 2 kidneys.
• Each nephron consists of 2 functional components
• The tubular component (contains what will
  eventually become urine)
• The vascular component (blood supply)
• The mechanisms by which kidneys perform their
  functions depends upon the relationship between
  these two components.

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Glomerulus and Bowmans capsule

• Glomerular filtrate drains into Bowmans space,
  and then into proximal convoluted tubule.
• Endothelium has pores to allow small molecules
  through.
• Podocytes have negative charge. This and the
  basement membrane stops proteins getting through
  into tubular fluid.
• Macula densa senses GFR by Na
• Juxtaglomerular (JG) apparatus includes JG cells
  that secrete renin.
• JGA helps regulate renal blood flow, GFR and also
  indirectly, modulates Na balance and systemic BP

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Functions of the kidneys

• Regulation of H2O and inorganic ion balance
  most important function!
• Removal of metabolic waste products from blood
  and excretion in urine.
• In kidney disease, build-up of waste serious, but
  not a bad as ECF volume and composition
  disturbances.
• Removal of foreign chemicals in the blood (e.g.
  drugs) and excretion in urine.
• Gluconeogenesis
• Endocrine functions (e.g. renin, erythropoetin,
  1,25-dihydroxyvitamin D)

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The three basic renal processes

• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
• GFR is very high 180l/day. Lots of opportunity
  to precisely regulate ECF composition and get rid
  of unwanted substances.
• N.B. it is the ECF that is being regulated, NOT
  the urine.

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Glomerular filtration

• GFR controlled by diameters of afferent and
  efferent arterioles
• Sympathetic vasoconstrictor nerves
• ADH and RAAS also have an effect on GFR.
• Autoregulation maintains blood supply and so
  maintains GFR. Also prevents high pressure surges
  damaging kidneys.
• Unique system of upstream and downstream
  arterioles.

• Remember high hydrostatic pressure (PGC) at
  glomerular capillaries is due to short, wide
  afferent arteriole (low R to flow) and the long,
  narrow efferent arteriole (high R).

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GFR depends on diameters of afferent and efferent
arterioles
Glomerulus
Afferent arteriole
Efferent arteriole
?GFR
?GFR
Glomerular filtrate
Eff. Art. dilatation
Eff. Art. constriction
Aff. Art. constriction
Aff. Art. dilatation
Ang II (high dose), Noradrenaline (Symp nerves),
Endothelin, ADH, Prost. Blockade)
Prostaglandins, Kinins, Dopamine (low dose), ANP,
NO
Angiotensin II (low dose)
Angiotensin II blockade
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Peritubular reabsorption

• Peritubular capillaries provide nutrients for
  tubules and retrieve the fluid the tubules
  reabsorb.
• Oncotic P is greater than hydrostatic P in these
  capillaries, so therefore get reabsorption NOT
  filtration.
• Must occur since we filter 180l/day, but only
  excrete 1-2l/day of urine.
• Reabsorb 99 H2O, 100 glucose, 99.5 Na and 50
  urea. Most of this occurs at proximal convoluted
  tubule.

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Renal transport systems

• Lots of transporter proteins for different
  molecules/ions so they can be reabsorbed.
• They all have maximum transport (TM) capacities
  where transport saturates i.e. 10mmol/l for
  glucose.
• Over this value, you excrete the excess in urine,
  so can be useful sign of disease either in
  kidneys or other systems.
• Amino acids also have a high TM value because you
  try and preserve as much of these useful
  nutrients as possible.

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Na absorption

• Na absorbed by active transport mechanisms, NOT
  by TM mechanism. Basolateral ATPases establish a
  gradient across the tubule wall.
• Proximal tubule is very permeable to Na, so ions
  flow down gradient, across membranes.
• Microvilli create large surface area for
  absorption.
• Electrical gradient created also draws Cl-
  across.
• H2O follows Na due to osmotic force.
• Means fluid left in tubule is concentrated.

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Glucose handling

• Glucose absorption also relies upon the Na
  gradient.
• Most reabsorbed in proximal tubule.
• At apical membrane, needs Na/glucose
  cotransporter (SGLT)
• Crosses basolateral membrane via glucose
  transporters (GLUTs), which do not rely upon Na.

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Amino acid handling

• Preserve as much of these essential nutrients as
  possible.
• Can be absorbed by GI tract, products of protein
  catabolism, or de novo synthesis of nonessential
  amino acids.
• TM values lower than that of glucose, so can
  excrete excess in urine.
• Amino acid transporters rely upon Na gradient at
  apical membrane, but a couple of exceptions
  dont.
• Exit across basolateral membrane via diffusion ,
  but again, some exceptions rely on Na.

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K handling

• K is major cation in cells and balance is
  essential for life.
• Small change from 4 to 5.5 mmoles/l
  hyperkalaemia ventric. fibrillation death.
• To 3.5 mmoles/l hyperpolarise arrhythmias and
  paralysis death.
• Reabsorb K at proximal tubule.
• Changes in K excretion due to changes in K
  secretion in distal tubule
• Medullary trapping of K helps to maximise K
  excretion when K intake is high.

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K handling

• K reabsorption along the proximal tubule is
  largely passive and follows the movement of Na
  and fluid (in collecting tubules, may also rely
  active transport).
• K secretion occurs in cortical collecting tubule
  (principal cells), and relies upon active
  transport of K across basolateral membrane and
  passive exit across apical membrane into tubular
  fluid.

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Modulation of K secretion
Luminal factors
Stimulators Inhibitors
? Flow rate ? K
? Na ? Cl-
? Cl- ? Ca2
? HCO3- Ba2
-ve luminal voltage Amiloride
Selected Diuretics
Peritubular Factors
Stimulators Inhibitors
? K intake pH
? K Adrenaline
pH
Aldosterone
ADH
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Countercurrent Multiplier

• Countercurrent is easy, fluid flows down the
  descending limb and up the ascending limb.
• The critical characteristics of the loops which
  make them countercurrent multipliers are
• 1. The ascending limb of the loop of Henle
  actively co-transports Na and Cl- ions out of
  the tubule lumen into the interstitium. The
  ascending limb is impermeable to H2O.
• 2. The descending limb is freely permeable to H2O
  but relatively impermeable to NaCl.
• H2O that moves out of tubule into intersitium is
  removed the blood vessels called vasa recta
  thus gradients maintained and H2O returned to
  circulation.

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formation of hyperosmotic urine
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Osmolality of fluid along nephron

• Red water restriction
• Blue high water intake
• Initial concentration of tubular fluid at loop of
  Henle, then finally at collecting ducts.

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Role of urea in concentrating urine

• Urea very useful in concentrating urine.
• High protein diet more urea more concentrated
  urine.
• Kidneys filter, reabsorb and secrete urea.
• Urea excretion rises with increasing urinary flow.

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Urea recycling

• Urea toxic at high levels, but can be useful in
  small amounts.
• Urea recycling causes buildup of high urea in
  inner medulla.
• This helps create the osmotic gradient at loop of
  Henle so H2O can be reabsorbed.