chapter 18

Functions of the Urinary System

  • The urinary system, primarily through the kidneys, performs several critical functions:
    • Regulation of ionic composition of plasma:
      • Kidneys control excretion of specific ions in urine, influencing their plasma concentration.
      • Examples of ions regulated: Sodium (Na^+$), Potassium (K^+$), Calcium (Ca^{2+}$), Chloride (Cl^-$), and Hydrogen Phosphate (HPO42−HPO_4^{2-}).
    • Regulation of plasma volume and blood pressure:
      • Kidneys regulate water excretion rate, directly affecting plasma volume and blood pressure.
    • Regulation of plasma osmolarity:
      • Kidneys control water excretion relative to solutes, directly affecting plasma osmolarity.
    • Regulation of plasma pH:
      • Kidneys regulate excretion of bicarbonate (HCO_3^-$) and hydrogen (H^+$) ions.
      • Affects hydrogen ion concentration in plasma, thus influencing blood pH.
      • Works in conjunction with the lungs for acid-base balance.
    • Removal of waste products:
      • Kidneys eliminate metabolic byproducts (urea, uric acid) and foreign substances.
      • Foreign substances include pesticides, toxins, drugs, and food additives.

Impact on Body Fluids

  • Kidneys significantly influence the volume and composition of all body fluids.
    • Water and small solutes freely exchange between extracellular fluid (ECF) components.
    • Systemic capillary beds allow free exchange between plasma and interstitial fluid via bulk flow.
    • Interstitial fluid composition affects intracellular fluid composition.

Other Functions of the Urinary System

  • Secretion of Erythropoietin:
    • Kidneys secrete erythropoietin, a hormone regulating erythrocyte (red blood cell) production.
  • Secretion of Renin:
    • Kidneys secrete renin, an enzyme required for angiotensin II production.
    • Angiotensin II plays a crucial role in blood pressure control as discussed in previous lectures.
  • Activation of Vitamin D3:
    • Kidneys activate vitamin D3 (calcitriol), regulating calcium and phosphate levels in the blood.
    • Calcitriol regulates calcium and phosphate absorption in the digestive tract.

Renal Anatomy

  • Two Major Regions:
    • Renal Cortex: Outer portion of the kidneys.
    • Renal Medulla: Inner portion, containing renal pyramids.
  • Renal Pyramids:
    • Conical structures within the medulla.
    • Tips of pyramids are called papillae.
    • Collecting ducts drain into minor calyces, which merge into major calyces, converging at the renal pelvis (initial part of the ureter).
  • Nephrons:
    • Functional units of the kidney located in pyramids and overlying cortex.
    • Millions of nephrons per kidney filter blood, modify filtered plasma, and form urine.
  • Nephron Components:
    • Renal Corpuscle: Site of plasma filtration.
    • Renal Tubules: Adjust filtrate composition to form urine.

Blood Supply to the Kidneys

  • Blood enters through renal arteries, branching into:
    • Segmental arteries.
    • Interlobar arteries (between pyramids).
    • Arcuate arteries (between medulla and cortex).
    • Interlobular arteries (branching up into the cortex).
    • Microcirculation and arterioles supplying blood to nephrons.

Detailed Nephron Structure

  • Renal Corpuscle:
    • Glomerulus: Capillary bed where plasma is filtered.
    • Glomerular Capsule (Bowman's Capsule): Surrounds the glomerulus and collects filtrate.
  • Renal Tubules:
    • Proximal Convoluted Tubule (PCT).
    • Nephron Loop (Loop of Henle): Straight portion with a hairpin turn.
    • Distal Convoluted Tubule (DCT): Last part of the nephron.
    • Collecting Duct: Receives filtrate from multiple nephrons (not specific to one nephron).
  • Afferent and Efferent Arterioles:
    • Blood enters the renal corpuscle via the afferent arteriole.
    • Blood exits via the efferent arteriole.
    • Afferent arteriole generally has a slightly larger diameter than the efferent arteriole.
    • Two arterioles allow greater regulation of glomerular filtration by adjusting blood flow.

Types of Nephrons

  • Cortical Nephrons:
    • 85% of nephrons.
    • Renal tubules primarily in the cortex.
    • Primarily involved in urine formation.
  • Juxtamedullary Nephrons:
    • 15% of nephrons.
    • Nephron loop extends deep into the renal medulla.
    • Maintain osmotic gradient in the renal medulla, crucial for water reabsorption, water conservation and urine concentration.

Capillary Beds in the Kidneys

  • Peritubular Capillaries:
    • Efferent arteriole of cortical nephrons branches into these.
    • Surround renal tubules of cortical nephrons in the renal cortex.
  • Vasa Recta:
    • Efferent arteriole of juxtamedullary nephrons forms these capillary beds.
    • Extend into the renal medulla, surrounding nephron loops of juxtamedullary nephrons.

Renal Exchange Processes

  • Filtration:
    • Bulk flow of materials from plasma in glomerulus into Bowman's capsule.
    • Water and solutes filter into Bowman's capsule, then enter the renal tubules.
    • A non-specific process, excluding proteins.
  • Reabsorption:
    • Selective transport of molecules from filtrate back into the bloodstream.
    • Molecules are transported out of renal tubules into interstitial fluid, then diffuse into capillary beds.
    • Prevents elimination of important substances in urine.
  • Secretion:
    • Selective transport of molecules from blood into the filtrate.
    • Substances that did not get filtered are transported from peritubular capillaries into renal tubules for elimination in urine.

Glomerular Filtration

  • Movement of protein-free plasma from glomerulus into Bowman's capsule.
    • Water and small solutes enter the capsular space; proteins are restricted.
    • Passive process driven by Starling forces.
  • Kidneys receive ~20% of cardiac output, resulting in significant filtration:
    • 125 ml/min or 180 liters/day.
    • Small solutes, water, and metabolic waste products are filtered.
    • Plasma proteins are kept inside capillaries to maintain osmotic pressure.
  • Proteinuria:
    • Proteins in urine, observed in conditions like diabetes and high blood pressure.
    • Can affect osmotic pressure of the blood.

Filtration Barrier

  • Glomerular capsule (Bowman's capsule) has two layers:
    • Visceral Layer: Inner layer directly surrounding glomerulus.
    • Parietal Layer: Outer layer of the capsule.
  • Filtrate crosses three barriers to enter Bowman's capsule:
    • Fenestrated Capillary Endothelium: Pores enhance movement of materials out of capillaries.
    • Basement Membrane: Primary barrier for restricting proteins.
    • Visceral Epithelium of Bowman's Capsule: Contains podocytes and filtration slits which add another layer of filtration.
    • These three layers form the glomerular membrane or filtration barrier.

Starling Forces and Glomerular Filtration Pressure

  • Two Starling forces favor filtration:

    • Glomerular Capillary Hydrostatic Pressure: Blood pressure in glomerular capillaries.
      • Normally high (~60 mmHg) due to afferent arteriole diameter being larger than efferent arteriole.
      • High-pressure makes glomerular capillaries vulnerable to damage from increases in blood pressure.
    • Bowman's Capsule Osmotic Pressure: Osmotic pressure due to non-permeating solutes (proteins).
      • Normally zero (~0 mmHg) as proteins should not enter the filtrate.
      • Net filtration pressure is these two forces combined

  • Two forces oppose filtration:

    • Bowman's Capsule Hydrostatic Pressure: Pressure exerted by the filtrate on capillary walls.
      • Normally high (~15 mmHg) due to filtrate restriction within the capsule.
    • Glomerular Osmotic Pressure: Pressure exerted by proteins restricted in the plasma.
      • Draws filtrate back into the glomerulus (~29 mmHg).

  • Net Glomerular Filtration Pressure:

    • Calculated using the same equation as systemic capillaries:

    • GlomerularFiltrationPressure=(GlomerularCapillaryHydrostaticPressure+Bowman′sCapsuleOsmoticPressure)−(Bowman′sCapsuleHydrostaticPressure+GlomerularOsmoticPressure)Glomerular Filtration Pressure = (Glomerular Capillary Hydrostatic Pressure + Bowman's Capsule Osmotic Pressure) - (Bowman's Capsule Hydrostatic Pressure + Glomerular Osmotic Pressure)

    • GlomerularFiltrationPressure=(60+0)−(15+29)Glomerular Filtration Pressure = (60 + 0) - (15 + 29)

    • GlomerularFiltrationPressure=16<br/>ormalfontmmHgGlomerular Filtration Pressure = 16 <br /> ormalfont mmHg

    • Positive pressure indicates net movement of fluids out of glomerulus into Bowman's capsule.

Glomerular Filtration Rate (GFR)

  • Volume of plasma filtered in both kidneys per unit time.
    • Typical GFR: ~125 ml/min or 180 liters/day.
    • Total plasma volume (~3 liters) is filtered ~60 times a day.
  • Most filtrate is reabsorbed:
    • 99% of filtrate volume is reabsorbed back into the bloodstream.
  • GFR is maintained constant by intrinsic control mechanisms within a specific mean arterial pressure:
    • GFR is kept constant within a range of 80 to 180 mmHg mean arterial pressure.
    • Maintains proper concentration of water and solutes in plasma. Filtration Fraction
    • GFR divided by the renal plasma flow rate.
  • Filtered Load
    • Quantity of a particular solute that's filtered per unit time.
  • Filteredload=GFR<br/>ormalfont∗PlasmaConcentrationFiltered load = GFR <br /> ormalfont * Plasma Concentration
  • Glomerular filtration rate must remain tightly regulated in the kidneys otherwise it could significantly impact filtration, thus the rate of reabsorption.

Intrinsic Control Mechanisms of GFR

  • Renal autoregulation maintains constant GFR despite systemic arterial pressure changes (80-180 mmHg).
    • Strategies include changing afferent arteriolar resistance and filtration barrier permeability.
    • Mechanisms include:
      • Myogenic regulation of afferent arteriole.
      • Tubuloglomerular feedback.
      • Contraction of mesangial cells.
  • Maintenance of constant GFR is important for regulating urine composition and therefore, plasma composition and volume. Constricting the afferent

Effects of Afferent Arteriole Changes on GFR

  • Constricting the Afferent Arteriole:
    • Causes decreased GFR
  • Dilating the Afferent Arteriole:
    • Causes increased GFR

Myogenic Regulation

  • Smooth muscle cells of afferent arteriole are sensitive to stretch.
    • Rise in mean arterial pressure causes afferent arteriole stretch, leading to constriction.
      • Increases resistance, decreasing glomerular capillary pressure and GFR.
    • Decrease in mean arterial pressure causes afferent arteriole relaxation.
      • Decreases resistance, increasing glomerular capillary pressure and GFR.

Tubuloglomerular Feedback

  • Smooth muscle cells of afferent arteriole sensitive to chemical agents from macula densa cells.
    • Changes in GFR alter tubular fluid flow, affecting paracrine secretion by macula densa cells in the distal convoluted tubule
    • Secrete chemical messengers to relax or constrict the smooth muscle cells in the afferent arteriole.
    • This influences GFR to create a negative feedback loop.

Mesangial Cell Contraction

  • Mesangial cells are modified smooth muscle cells surrounding glomerular capillaries, functioning similarly to precapillary sphincters.
    • Contraction decreases blood flow and surface area for filtration.
    • Increased blood pressure stretches cells, causing contraction decreasing the glomerular filtration rate.

Extrinsic Control Mechanisms of GFR

  • Required when mean arterial pressure falls outside the range of 80 to 180 mmHg.
    • Neural and Hormonal Input.

Sympathetic Division Effects on GFR

  • Sympathetic activity increases during fight or flight, exercise, or major fluid loss.
    • Baroreceptor reflex stimulates vasoconstriction of afferent and efferent arterioles.
      • Increases total peripheral resistance, raising mean arterial pressure.
      • Decreases glomerular filtration rate thus decreases urine output, promotes water conservation.
      • May divert blood flow towards the heart and the brain.
  • Example:
    • In the case of fluid loss through hemorrhage or excessive sweating, the kidney will reduce the ammount of fluid lost through urine production by decreasing GFR via the sympathetic nervous system.

Hormonal Effects on GFR

  • Renin-Angiotensin-Aldosterone System:
    • Activated by decreased blood pressure or blood flow to kidneys.
    • Angiotensin II constricts afferent and efferent arterioles, reducing GFR.
    • Limits urine output to raise blood pressure and blood volume.
  • Atrial Natriuretic Peptide (ANP):
    • Secreted by atria in response to increased blood volume and stretching of the heart.
    • Promotes vasodilation of afferent arteriole and vasoconstriction of efferent arteriole.
    • Increases the GFR promotes and increase in urine output, helping to decrease blood volume.

Reabsorption

  • Movement of substances from renal tubules back into the plasma to retain in blood.
    • Extensive process: ~99% of filtrate is reabsorbed, many substances have 100% reabsorption.
    • Primarily occurs in the proximal convoluted tubule (PCT) and the ascending limb of the loop of Henle (85%).
    • Can be active (requiring energy) or passive. Reabsorbed substances must cross the:
      • Renal Tubule
      • Renal Tubule Epithelium
      • Capillary Endothelium
      • Epithelial cells of renal tubules act as primary barrier to solute reabsorption
        • Tight junctions restrict movement of solutes across the barrier

Mechanisms of Solute Transport

  • Active Reabsorption of Solutes:
    • Molecule moves against its electrochemical gradient.
      • Primary Active Transport: Directly uses ATP.
      • Secondary Active Transport: Uses ion's electrochemical gradient created by primary active transport.
        • Can occur by Co-transport or Counter-transport.
  • Water Reabsorption
    • Passively diffuses down its concentration gradient from the tubular fluid into the plasma
    • Gradient is created by the reabsorbed solutes
  • Passive Reabsorption of Solutes by Diffusion:
    • Occurs after water reabsorption, increasing the concentration of solutes in the tubular fluid, allowing diffusion into the plasma.

Types of Reabsorption

  • Nonregulated Reabsorption:
    • Occurs mostly in the proximal tubule and loop of Henle.
    • Proximal tubule epithelium acts as a mass reabsorber.
      • ~70% of sodium, water, and ions are reabsorbed here.
      • Glucose and other solutes may have 100% reabsorption.
    • Coupling of solute and water reabsorption.
      • anatomical features of the proximal tubule epithelium that allow for this nonregulated reabsorption:
        • Leaky Tight Junctions
        • Brush Border on Apical Surface
        • Mitochondria
  • Regulated Reabsorption:
    • Occurs in the distal convoluted tubule and the collecting ducts.
      • anatomical features of the epithelium this section that allow for regulated reabsorption.
        • Tight Tight Junctions
        • Not a Prominent Brush Border
        • Fewer Mitochondria
        • Receptors for the Hormones that will Influence Reabsorption. Aldosterone, Atrial Natriuretic Peptide, and Antidiuric Hormone
          • Aldosterone - Stimulate Sodium Reabsorption
      • ANP - Inhibits Sodium Reabsorption
      • ADH - Stimulates water reabsorption

Secretion

  • Molecules move from the plasma and interstitial fluid (blood) into the renal tubules to become part of the filtrate (urine).
    • The renal tubule epithelium and capillary endothelium are still the barriers that exist.
    • Increases solute concentration of urine and decreases solute concentration of the plasma.
    • Examples:
      • Ions.
      • Hydrogen
      • Potassium
      • Metabolic Waste Products.
      • Coline
      • Creatinine

Excretion

  • Elimination of solutes and water from the body in the form of urine.
    • Affets the volume and the composition of the plasma in the body.
  • The amount of water that must be excreted to eliminate the excess solutes that are in the body: 400ml - 470ml. (Obligatory Water Loss).
  • Substances that enter to the renal tubules will be in the excretion rate unless it is reabsorbed.
    ExcretionRate=FiltrationRate+SecretionRate−ReabsorptionRateExcretion Rate = Filtration Rate + Secretion Rate - Reabsorption Rate

Renal Clearance

  • The volume of plasma from which a substance is completely removed by the kidneys per unit time.
    • Tells us the rate at which a solute is excreted.
    • RenalClearance=<br/>ormalfontExcretionRate<br/>ormalfont/PlasmaConcentrationRenal Clearance = <br /> ormalfont {Excretion Rate <br /> ormalfont / Plasma Concentration}
    • Tells how the kidneys handle one solute vs. another
    • Tells how the excretion rate will affect the solute plasma concentration relative to others
    • Estimates GFR and renal blood flow rate
      • Renal clearance calculation uses the same formula used for finding GFR
    • The amount of that clearance would equal the glomerular filtration rate if a substance gets filtered but is not reabsorbed or secreted.
      • The amount of clearance is less than the glomerular filtration rate if a substance if filtered and reabsorbed that is.
      • The amount of clearance is more than the glomerular filtration rate is a substance if filtered and secreted.
    • Clinically, inulin is used to estimate glomerular filtration rate.
      • Is an estimate because it gets filtered but not reabsorbed or secreted. Has been noted as the Gold Standard in helping to measure this value. It is more invasive.
        • Creatinine clearance is what is used in order to avoid and get accurate reading without the use on inulin being pushed in the body because it is something found already in the body.

Micturition (Urination)

  • Ureters connect kidneys to the bladder, using peristalsis to propel urine.
    • Bladder is made up of smooth muscle fibers that are collectivley know as the Detrusor Muscle.
  • Bladder Anatomy:
    • Stores Smooth muscle known as Detrusor Muscle.
    • The Smooth Muscle fiber in the neck of the bladder converged and overlapped to form this area of the the wall which serves are the Internal Uretheral Sphicter.
    • Is under the control of the sympathetic and parasympathetic divisions of the autonomic
    • External Uretheral Sphicter which is a skelettal muscle that serves the same function of control of the urination of the bladder by voluntary means. Located in the pelvic floor.
    • Imporper funcioning of any of these two shincter = Urinary Incontinence.