Renal Physiology

• Renal system


  Regulatory organ that maintains water balance, electrolyte balance, and acid-base balance in the extracellular fluid through the formation of urine

  
• Kidney


  • Previously regarded as an important excretory organ, excreting water and waste products in urine
  • Actually a powerful regulatory organ which maintains water balance, electrolyte balance, and acid-base balance in the extracellular fluid
• Urine formation


  Adjusting the volume and composition of urine in response to changes in dietary intake or metabolism to regulate the body balance of water, various electrolytes, acids, and bases
• Nephron


  Functional unit of the kidney, consisting of a glomerulus and a single long tubule
• Bowman's capsule


  • Consists of an inner visceral layer that closely surrounds the glomerular capillaries and an outer parietal layer that is continuous with the first segment of the tubule
• Renal microcirculation


  1. Glomerular capillaries are between two arteriolar vessels (afferent and efferent arterioles)

  2. Efferent arterioles lead into capillary networks that surround tubules in the cortex (peritubular capillaries)

  3. Efferent arterioles from glomeruli deep in the cortex next to the medulla contribute blood to vessels that extend into the medulla (vasa rectae)
• Juxtaglomerular apparatus


  Consists of the juxtaglomerular (JG) cells, the macula densa, and extraglomerular mesangial cells<|>JG cells contain the enzyme renin, a component of the renin-angiotensin-aldosterone system involved in the regulation of blood volume and blood pressure<|>Macula densa is a specific region of the wall of the distal tubule where the cellular nuclei appear to be bunched closely together
• Glomerular filtration


  Movement of water and solutes from the plasma in the glomerulus, across the glomerular-capsule membrane, and into the capsular space of the Bowman's capsule

  
• Glomerular filtration barrier


  • Consists of the capillary endothelium, the inner layer of Bowman's capsule, and a basement membrane between the two cell layers
  • Acts like a sieve, allowing substances up to a molecular weight of about 65,000 to pass through, while blood cells and most plasma proteins are too large to pass

  
• Proteinuria


  Presence of abnormal amounts of protein in voided urine, often associated with kidney diseases that primarily affect the glomeruli
• Effective filtration pressure


  The pressure tending to force fluid out of the capillary, usually considered to be the difference between the blood (hydrostatic) pressure in the capillary and the osmotic pressure generated by the plasma proteins
• Glomerular filtration rate (GFR) and renal blood flow (RBF) remain relatively stable in normally hydrated animals despite minor short-term fluctuations in arterial blood pressure, due to renal autoregulation
• Prerenal renal failure


  Renal failure caused by low blood pressure and renal vasoconstriction, which can reduce glomerular filtration to the point of renal failure
• The GFR of mammals is normally about 100 times that of urine flow rate, allowing for continuous filtration of the plasma and rapid removal of unwanted or toxic substances from the body
• If substances can readily pass through the glomerular filtration barrier and are not reabsorbed from the renal tubules, they are rapidly eliminated via the urine
• Prerenal renal failure


  • Low blood pressure and renal vasoconstriction can reduce glomerular filtration to the point of renal failure
• Glomerular filtration rate (GFR)


  Normally about 100 times that of urine flow rate (typical values for GFR are 3–5 mL/kg body weight per minute). 120-125 ml/min
• High GFR relative to urine flow

  Allows for a continuous filtration of the plasma and the rapid removal of unwanted or toxic substances from the body
• Substances that can readily pass through the glomerular filtration barrier and are not reabsorbed from the renal tubules

  Rapidly eliminated via the urine
• Reabsorption


  Movement of molecules out of the tubule and into the peritubular blood
• Secretion


  Movement of the molecules out of the peritubular blood into the tubule for excretion
• Active transport (requires energy)

  • Sodium, glucose, amino acids, calcium, potassium, phosphate, urate ions
  • Hydrogen ions are actively secreted in some parts of the tubule
  • Each actively transported substances has a transport maximum (Tm) rate
• Transport Maximum (Tm)


  The maximum rate at which a substance can be reabsorbed, e.g. glucose in an adult man has a Tm of about 375 mg/min
• Plasma Threshold


  The blood level at which the amount of a substance presented to the tubules by glomerular filtration exceeds the transport maximum, e.g. glucose in an adult man has a plasma threshold of 3 mg/ml
• Passive transport (does not require energy)


  Diffusion, osmosis<|>Passive potassium (K) secretion in distal tubule and collecting duct
• Proximal tubule transport


  • Glucose and amino acids (normally 100%) are reabsorbed from the filtrate by cells of the proximal tubule using secondary active transport with a sodium-linked co-transporter
  • Substances that require membrane transporters for reabsorption have limits to the amount that can be reabsorbed (transport maximum)
• Renal threshold


  The blood level at which the amount of a substance presented to the tubules by glomerular filtration exceeds the transport maximum
• Bicarbonate reabsorption in proximal tubule

  • Proximal tubule reabsorbs almost 85–90% of the bicarbonate ions in the initial filtrate
  • Bicarbonate ions are converted to carbon dioxide and water under the influence of the enzyme carbonic anhydrase
  • Sodium accompanies the bicarbonate ions to maintain electrical neutrality
• Sodium and chloride reabsorption in proximal tubule


  • Cells of the proximal tubule reabsorb 70–75% of the sodium and chloride in the initial filtrate
  • Percentage reabsorbed can be increased by angiotensin II and sympathetic nerves
• Secretion in proximal tubule


  • Organic compounds (e.g toxins, metabolic waste products-drugs, H+ and K+ ions, ammonium ions, creatinine, urea and some hormones) are actively transported from blood into the renal tubule
• Secretion in collecting duct

  • Principle cells reabsorb Na+ and secrete K+
  • K+ secretion is increased by increased Na+ delivery and increased filtrate flow
  • K+ secretion can be increased by aldosterone
• Proximal tubule


  • 80% of all reabsorption and secretion occurs here
  • Most filtered sodium, chloride, water and bicarbonate are reabsorbed here
  • Wall is permeable to water
  • Tubular and interstitial fluid are isotonic
  • Reabsorption based on the Tm concept

  
• Descending loop of Henle


  • No active transport
  • Water diffuses out of tubules, sodium secreted into the tubules
  • Tubular and interstitial fluid become hypertonic
• Ascending loop of Henle


  • Wall not permeable to water
  • Sodium and chloride actively reabsorbed
  • Tubular fluid leaving this segment becomes hypotonic (100 mosmole/L)
  • Sodium reabsorption aided by aldosterone
• Counter-current mechanism


  Mechanism that depends on streams of flow moving in opposite directions, usually close to each other<|>The ascending and descending limbs of the loop of Henle amplify the osmolyte (sodium chloride) transport properties
• Distal tubule


  • In the presence of ADH, water is reabsorbed and tubular fluid becomes isotonic
  • In the absence of ADH, tubular fluid remains hypotonic - diuresis
  • Sodium actively reabsorbed (aided by aldosterone), some with chloride ions, some with exchanged with H ions
• Collecting duct


  • Accounts for 4–5% of the kidney's reabsorption of sodium and 5% of the kidney's reabsorption of water
  • In the absence of ADH, water in the renal filtrate enters the urine, promoting diuresis
  • When ADH is present, aquaporins allow for the reabsorption of water, inhibiting diuresis
  • Participates in the regulation of chloride, potassium, hydrogen ions, and bicarbonate
• Chloride ions


  Some with exchanged with H ions
• Collecting duct


  Final component of the kidney to influence the body's electrolyte and fluid balance<|>Accounts for 4–5% of the kidney's reabsorption of sodium and 5% of the kidney's reabsorption of water<|>At times of extreme dehydration, over 24% of the filtered water may be reabsorbed in the collecting duct system<|>The wide variation in water reabsorption levels for the collecting duct system reflects its dependence on hormonal activation
• In the absence of ADH


  Water in the renal filtrate is left alone to enter the urine, promoting diuresis