urinary and reproduction system

• Excretion


  The removal of organic waste products from body fluids
• Waste products removed by excretion

  • Urea (from amino acid catabolism)
  • Creatinine (from muscle tissue)
  • Uric acid (from purine catabolism)
• Elimination


  The discharge of waste products into the environment
• Functions of the urinary system


  • Regulate blood volume and pressure
  • Regulate plasma [ion]
  • Stabilize blood pH (Acid-Base balance)
  • Conserve nutrients
  • Regulate erythropoiesis
  • Detoxification of blood
  • Activate Vitamin D3
  • Gluconeogenesis

  
• Urinary system


  • Consists of 2 kidneys (right kidney slightly lower than left due to position of liver)
  • Urinary tract: ureters (2), urinary bladder and urethra

  
• Renal Corpuscle


  Includes the renal capsule (Bowman's capsule) and the glomerulus

  
• Juxtaglomerular Apparatus


  • Macula densa (epithelial cells of distal tubule near renal corpuscle)
  • Juxtaglomerular cells (unusual smooth muscle cells in wall of afferent and efferent arteriole)
  • Collectively known as the juxtaglomerular complex
  • Secrete erythropoietin and renin
• Glomerular Filtration


  • Filtration of blood within renal corpuscle
  • Filtrate that is formed, proceeds through the renal tubules

  
• Tubular Reabsorption


  Movement of H2O and solutes from renal tubules (now "tubular fluid"), to blood in peritubular capillaries

  
• Tubular Secretion


  Transport of substances from blood in the peritubular capillaries back into renal tubules (back into the tubular fluid)

  
• Filtration membrane


  • Filter between the blood and capsular space
  • Fenestrated glomerular capillary endothelium
  • Basal lamina: collagen fibers within the extracellular matrix prevent filtration of plasma proteins (very small proteins may pass; most do not)
  • Filtration slits formed by visceral later of glomerular capsule (Podocytes)
• Filtrate Composition


  • Water, electrolytes, small proteins, glucose, amino acids and other dissolved solutes
  • Waste includes: urea, ammonium ions, uric acid and creatinine
• Glomerular Filtration Rate (GFR)


  • Volume of filtrate formed by both kidneys per minute
  • 125 mL/min (180 L/day)
  • Filtration of plasma volume roughly 65x/day
  • Only 1-2 liters per day of urine output!

  
• Net Filtration Pressure (NFP)

  • NFP = (GHP – CsHP) – (BCOP – CCOP)
  • Glomerular Hydrostatic Pressure (GHP): favors filtration
  • Capsular Hydrostatic Pressure (CsHP): opposes filtration
  • Blood Colloid Osmotic Pressure (BCOP): opposes filtration
  • Capsular Colloid Osmotic Pressure (CCOP): favors filtration
• Regulation of Glomerular Filtration Rate

  • Autoregulation (Myogenic Mechanism and Tubuloglomerular Feedback)
  • Hormonal (Renin-Angiotensin-Aldosterone System and Atrial Natriuretic Peptide)
  • Neural Control (Sympathetic Nervous System)
• Osmolarity


  • Reflects the number of solute particles (i.e. ions, glucose, fatty acids, etc…) in a solution
  • Units: Osmoles/Liter (Osm/L) or milliosmoles/Liter (mOsm/L)
  • Osmolarity of body fluids is approximately 300 mOsm/L
• Transport Maximum (Tm)


  • Reflects saturation point of carriers for a specific molecule
  • Renal threshold: the plasma concentration at which a substance begins to appear in the urine
  • Renal thresholds vary by substance (Glucose: 180 mg/dL, Amino acids: 65mg/dL)

  
• Paracellular transport


  Between cell passage; passive movement (water or solute moving with their concentration gradients)
• Transcellular transport


  Through the cell (apical to basolateral surface); may be passive or active
• Carrier-mediated Transport


  May be facilitated diffusion, primary or secondary active transport; subject to transport maximum
• Proximal Tubule (PT)


  • Reabsorbs 60-70% of the filtrate produced
  • Reabsorption of 99% of organic nutrients (i.e. glucose, amino acids, etc…)
  • Active and passive reabsorption of Na+ and other ions
  • Reabsorption of H2O
  • Epithelium: simple cuboidal with microvilli
• Glucose Reabsorption in Proximal Tubule

  • Movement from PCT to tubular cells and peritubular capillaries via Na+-Dependent Glucose Transporter
  • Cl- reabsorption is passive as H2O reabsorption increases [ion] in PCT favoring movement down [ ] gradient into peritubular capillaries
  • K+, Mg2+, HCO3- reabsorption is active using ion pumps to move ions from PCT to tubular cells and into peritubular capillaries
  • Obligatory water reabsorption as reabsorption of solute creates an osmotic gradient that drives the reabsorption of H2O via aquaporins
• Proximal Tubule Secretion


  Secretion of H+ that diffuse from peritubular capillaries and are formed during metabolism
• Proximal Tubule: Reabsorption


  • Reabsorption of 60-70% of the filtrate produced
  • Reabsorption of 99% of organic nutrients (i.e. glucose, amino acids, etc.)
  • Active and passive reabsorption of Na+ and other ions
  • Reabsorption of H2O
• Epithelium


  Simple cuboidal with microvilli
• Glucose Reabsorption


  1. Movement from PCT to tubular cells and peritubular capillaries

  2. Na+-Dependent Glucose Transporter
• Cl- Reabsorption


  1. Passive Reabsorption

  2. H2O reabsorption increases [ion] in PCT favoring movement down [ ] gradient into peritubular capillaries
• K+, Mg2+, HCO3- Reabsorption


  1. Active Reabsorption

  2. Ion pumps utilized to move ions from PCT to tubular cells and into peritubular capillaries
• Obligatory water reabsorption


  • Reabsorption of solute creates an osmotic gradient that drives the reabsorption of H2O via aquaporins
  • Increased osmolarity of peritubular fluid drives the reabsorption of H2O from the PCT into the peritubular capillaries
• Proximal Tubule: Secretion


  1. Secretion of H+

  2. Diffuse from peritubular capillaries and are formed during diffusion of CO2 from proximal tubule into tubular cell

  3. Counter-transport into proximal tubule for Na+

  4. Site of toxin/drug excretion

  5. Site of uric acid secretion, creatinine, urea and ammonium ions
• Nephron Loop: Characteristics


  • Thin segment (squamous epithelium): most of the descending limb, permeable to H2O, impermeable to solute
  • Thick segment (cuboidal epithelium): most of the ascending limb, impermeable to H2O and solute, Active transport of Na+ and Cl- into peritubular fluid (reabsorption), Na+-K+/2 Cl- co-transporter
• Cortical Nephrons


  • Additional water is reabsorbed in the descending limb, driven by active reabsorption of Na+ and Cl- in the ascending limb
• Distal Convoluted Tubule and Medullary Collecting System

  • Tubular fluid volume now about 15% of initial volume
  • Urea and other wastes now constitute a higher proportion of the solutes
  • Distal Tubule (DT) and Collecting Ducts (CD) perform final adjustment of urine content, largely under hormonal control
  • Na+ and Cl- are actively reabsorbed in exchange for K+ or H+ in both the DT and CD
  • Aldosterone increases Na+ reabsorption by increasing the synthesis and insertion of Na+ channels and Na+/K+ pumps into tubular cells
  • DT is also primary site for Ca2+ reabsorption, under the direction of parathyroid hormone and calcitrol
  • Antidiuretic hormone increases permeability of principle cells to water by increasing insertion of aquaporins into principle cell membranes
  • Atrial natriuretic peptide induces natriuresis, which is excretion of Na+ ions, inhibits release of aldosterone and ADH
  • Medullary collecting system is impermeable to water without ADH, permeable to urea and reabsorbs some Na+, Cl-, and HCO3-

  
• Nephron Loop: Vasa Recta and the Countercurrent Exchanger

  1. Countercurrent multiplication: need to maintain the osmotic gradient within the medulla in order to drive water reabsorption and concentrate urine; this requires the countercurrent exchanger and urea recycling associated with juxtamedullary nephrons

  2. Urea recycling involves diffusion from collecting and papillary ducts into the renal medulla, where a small amount re-enters the descending limb of nephron loop

  
• Urine Volume and Concentration: The Role of Countercurrent Multiplication


  1. The countercurrent multiplier in the ascending limb of the nephron loop established the medullary interstitial gradient by pumping NaCl into the interstitial fluid

  2. Reabsorption of ions and urea in the medullary collecting duct adds to the gradient

  3. Countercurrent exchanger of the vasa recta allows perfusion of inner medulla while maintaining interstitial gradient

  4. 80-85% of water reabsorbed along proximal tubule and nephron loop (obligatory water reabsorption)

  5. Large volume of filtrate at the distal tubule ≈ large volume of urine if no additional water is reabsorbed!

  6. Urine volume and osmolarity precisely controlled by circulating [ADH] (facultative water reabsorption)

  
• As [ADH] increases


  More water is reabsorbed, urine volume decreases and osmolarity increases
• As [ADH] decreases


  Less water is reabsorbed, urine volume increases and osmolarity decreases
• Euhydration


  Normal body water content, normal blood volume and plasma osmolarity, plasma [ADH] maintains permeability of distal tubule and collecting duct to water, generate approximately 2L urine per day with an osmolarity of 500-800 mOsm/L

  
• Dehydration


  State of body water loss, decreases blood volume and increases plasma osmolarity, activation of osmoreceptors increases ADH release, water conservation increases, which decreases urine volume and increases urine osmolarity (1200-1400 mOsm/L)
• Hyperhydration


  State of excess body water, increases blood volume and decreases plasma osmolarity, inhibition of osmoreceptors decreases ADH release, less water is conserved which increases urine volume and decreases urine osmolarity (50-100 mOsm/L)