Renal System ANSC

• The Renal System is the focus of this lecture
• The major function of the renal/urinary system is to filter animal blood plasma, balancing appropriate levels of animal water and blood molecules and removing metabolic waste
• Molecules filtered through the renal system and found in urine reflect animal physiology, particularly, endocrine and metabolic activities
• Other important functions of the renal system


  • Maintaining normal physiological levels of ions/solutes as well as pH
  • Maintaining appropriate animal blood volume and pressure through regulation of animal water retention
  • Secretion of erythropoietin (EPO) to increase red blood cell numbers
  • Activation of vitamin D for calcium absorption in the digestive tract
  • Release of pheromones
• Kidneys


  Organs important for blood plasma filtration, water/molecule reabsorption, waste removal and finally, urine formation

  
• Ureters


  Tubes (1 per kidney) that transport urine to the bladder
• Bladder


  Organ in mammals that holds urine
• Urethra


  Tube that transports urine from bladder to external environment for excretion
• Renal Cortex


  • Outer most region of kidney –location of plasma filtration

  
• Renal Medulla


  • Inner region of kidney –osmotic potential

  
• Renal Pelvis


  • Area in which urine is collected before entering ureter
• Renal Hilus


  • Area where vessels, neurons and ureters enter and/or leave the kidney

  
• Nephron


  Small, microscopic tubule system responsible for blood plasma filtration, secretion, reabsorption and osmo-concentration and ultimately, urine formation. Millions within each kidney

  
• Filtration at glomerulus


  1. Plasma contents except large proteins are filtered into tubule

  2. Some capillaries outside the bowman's capsule secrete molecules into tubule system
• Reabsorption along nephron tubule


  1. Important molecules needed by the animal are reabsorbed back out of tubule before reaching the renal pelvis and ureters

  2. Waste/toxic substances continue to the renal pelvis, ureters and bladder for excretion
• Bowman's capsule


  • Collects the glomerular filtrate
• Proximal tubule


  • Uncontrolled reabsorption and secretion of selected substances occur here
• Loop of Henle


  • Establishes an osmotic gradient in the renal medulla that is important in the kidney's ability to produce urine of varying concentration
• Distal tubule and collecting duct

  • Variable, controlled reabsorption of Na+ and H2O and secretion of K+ and H+ occur here; fluid leaving the collecting duct is urine, which enters the renal pelvis
• Afferent arteriole


  • Carries blood to the glomerulus
• Glomerulus


  • A tuft of capillaries that filters plasma into the tubular component (bowman's capsule)
• Efferent arteriole


  • Carries blood from the glomerulus
• Peritubular capillaries


  • Supply the renal tissue with oxygen and makes exchanges with the fluid in the tubular lumen
• Reabsorption of substances from tubule lumen


  Substances are reabsorbed out of tubule lumen into the interstitial space and then peritubular capillaries to re-enter blood circulation
• Na-K ATPase Pump


  Major driver of reabsorption by primary and secondary active transport
• Reabsorption of sodium


  1. Na+/K+ ATPase pump in tubule cell basolateral membrane drives transport of sodium by channels and carriers from tubule lumen through apical cell membrane into cell

  2. Water and chloride follow sodium through channels

  3. Activity of glucose and amino acid carriers (secondary active transport)
• Reabsorption of water


  1. In the proximal tubule, water is passively reabsorbed by osmosis through aquaporin channels (AQP-1) that are always present

  2. Distal tubule and collecting duct: Water reabsorption can be increased by the hormone vasopressin –increases activity of tubule cell aquaporin channels (AQP-2)
• Reabsorption of glucose and amino acids

  1. 100% of glucose typically reabsorbed along proximal tubule

  2. If concentrations of blood glucose increase and more is filtered, the reabsorption capacity can be exceeded
• Transport of sodium by channels and carriers

  1. From tubule lumen through apical cell membrane into cell

  2. Water and chloride follow sodium through channels

  3. Activity of glucose and amino acid carriers (secondary active transport)
• Distal tubule and collecting duct specific


  The steroid hormone aldosterone increases number of tubule cell sodium pumps and channels for sodium reabsorption –hormone regulated
• Reabsorption of Water


  1. In the proximal tubule, water is passively reabsorbed by osmosis through aquaporin channels (AQP-1) that are always present

  2. Distal tubule and collecting duct specific: Water reabsorption can be increased by the hormone vasopressin –increases activity of tubule cell aquaporin channels (AQP-2)
• Reabsorption of Glucose and Amino Acids


  1. 100% of glucose typically reabsorbed along proximal tubule

  2. If concentrations of blood glucose increase and more is filtered, glucose will be reabsorbed from the tubule until reaching a threshold (channels or carriers are maxed), after which, glucose begins to be excreted in the urine
• Glomerular Filtration


  • It is important for the animal to regulate the rate of plasma filtration in the kidney. Too much filtration results in loss of important substances and water
  • Mechanisms that regulate filtration involve modifications to the glomerulus
• Glomerular Filtration Rate (GFR)


  • The volume of plasma filtered from the renal glomerular capillaries per unit of time
  • GFR in an adult human is ~110 mL/min or ~150 liters of plasma/day
  • GFR depends mostly on net filtration pressure in glomeruli
  • GRF reflects kidney function
• Blood Urea Nitrogen (BUN)

  Creat (Creatinine)

  eGFR (estimated GFR)


  eGFR estimated using creatinine levels, age, sex, height and weight
• Glomerular Filtration Rate (GFR)


  • The structure of the glomerulus promotes filtration
  • Efferent arteriole radius is smaller than afferent arteriole. This increases capillary blood pressure inside glomerulus
  • Helps to overcome opposing pressures resulting in a net filtration pressure into bowman's capsule
• Afferent Arteriole Control of GFR


  1. Reducing the radius (vasoconstriction) reduces blood flow into glomerulus and reduces filtration

  2. Achieved by special smooth muscle cells (juxtaglomerular cells; JG cells) around afferent arterial

  3. This is important to correct for fluctuations in animal MAP that would affect filtration and animal water or solute balance

  4. An increase in animal MAP would greatly increase GFR and animal solute and water loss
• Intrinsic Control of GFR


  Autoregulation prevents unintentional shifts in GFR (and solute and water loss) due to fluctuations in MAP. Achieved by two mechanisms:

  Myogenic activity: The more the JG cells stretch due to increased blood pressure, the more they constrict reducing blood flow into glomerulus

  Tubuloglomerular feedback (TGF): The distal tubule can sense changes in sodium concentrations and filtrate volume. Special distal tubule cells (collectively called the macula densa) sense sodium and filtrate volume and release paracrine factors (ADP, adenosine and nitric oxide) that effect JG cell contraction and afferent arterial vasoconstriction
• Juxtaglomerular apparatus (JGA)


  Location where ascending distal tubule, after loop of Henle, contacts glomerulus

  Allows paracrine communication between Macula densa (distal tubule epithelial cells) and Juxtaglomerular cells (smooth muscle cells around afferent arteriole)
• Extrinsic Control of GFR


  Sympathetic nervous system contracts JG cells causing afferent arterial vasoconstriction, decreasing GFR and reduced solute and water loss. Helps to avoid excessive filtration and maintain appropriate blood volume and pressure

  Arterial and low-pressure baroreceptors sense low blood pressure, activate medulla oblongata and the sympathetic nervous system. Contributes to long-term adjustment of blood volume and pressure by avoiding plasma filtration and solute and water loss