Urinary System Chapter 25

Urinary System: Anatomy Kidneys Ureters Urinary Bladder Urethra Urethral opening Figure 25.1a Urinary System: Anatomy

Renal Anatomy Paired retroperitoneal bean-shaped organs Located in the dorsal upper lumbar region Encased in the renal fat pad

Renal Anatomy: Internal Figure 25.3b Superficial: renal cortex Renal medulla: deep to the cortex Contains medullary pyramids separated by renal columns Medullary pyramids end in the papilla Renal pelvis: merges with the ureter

Renal Anatomy: Functional Nephron: the functional unit of the kidney Figure 25.4b

Nephron: Anatomy Bowman’s capsule is continuous with the Proximal convoluted tubule (PCT); cells cuboidal with microvilli Loop of Henle Descending limb; simple squamous Ascending limb; simple cuboidal to columnar Distal convoluted tubule; cuboidal Collecting duct; cuboidal Figure 25.4b

Nephron Cortical nephrons: located in the renal cortex (about 80%) Juxtamedullary nephrons: at the cortical-medullary junction with the loop of Henle deep into the medulla Figure 25.5a

Nephron: Anatomy Afferent arteriole Efferent arteriole Glomerulus: fenestrated capillaries Efferent arteriole Peritubular capillaries (PCT and DCT) involved in reabsorption Vasa recta (medullary loop of Henle) involved in forming concentrated urine Figure 25.5a

Nephron: Anatomy Afferent arteriole bifurcates to form the - Figure 25.7a Afferent arteriole bifurcates to form the - Glomerulus (a capillary bed encased in the glomerular capsule) which is drained by the - Efferent arteriole {The only arteriole g capillary g arteriole sequence in the body}

Nephron: Anatomy Figure 25.7a Glomerular (Bowman’s) capsule surrounds the glomerulus Podocytes adhere to the glomerulus (visceral membrane) Spaces between the foot processes of the podocytes form filtration slits Capsular space surrounded by simple squamous epithelium (parietal membrane)

Nephron: Anatomy Figure 25.7a Figure 25.7c Filtration membrane; lies between the capillary blood and the capsular space Fenestrated endothelium of the capillaries Visceral membrane of glomerulus (podocytes) Fused basement membranes

Nephron: Anatomy Juxtaglomerular (JG) apparatus Figure 25.6 Juxtaglomerular (JG) apparatus DCT in close proximity to the afferent arteriole JG cells around the afferent arteriole sense blood pressure and produce renin Macula densa cells in DCT sense flow rate and chemical or osmotic changes in the filtrate

Mechanisms of Urine formation Kidneys filter ~ 180 L of fluid/day Urine production ~ 1.8 L/day

Mechanisms of Urine Formation Urine formation involves three phases Glomerular filtration Tubular reabsorption Tubular secretion Figure 25.8

Glomerular Filtration Figure 25.9 A passive process due to hydrostatic pressure across the filtration membrane Filtration membrane: extremely permeable to water and solutes (molecules < 3nm pass freely) Glomerular blood pressure is higher than other capillary beds (55mm Hg rather than 18mm Hg) Filtrate formed is a protein free filtrate of plasma

Glomerular Filtration Figure 25.9 Composed of 3 forces: Glomerular hydrostatic pressure (HPg) = glomerular blood pressure [Blood g capsule] Colloid osmotic pressure (OPg) = osmotic flow toward blood; [Capsule g blood] Capsular hydrostatic pressure (HPc) = pressure exerted by capsular fluid Net Filtration Pressure (NFP)

Glomerular Filtration Net Filtration Pressure (NFP) NFP = HPg – (OPg + HPc) = 55 – (30 + 15) = 10mm Hg Figure 25.9

Glomerular Filtration Rate (GFR) GFR = volume of filtrate formed each minute 3 factors Total surface area available for filtration Filtration membrane permeability NFP: pressure changes have dramatic impact on filtrate volume. Normal GFR = 120-125 ml/min

Glomerular Filtration Rate (GFR) Regulation of GFR: Intrinsic Extrinsic GFR needs to be held within a narrow range for appropriate reabsorption to occur

Regulation of GFR: Intrinsic Renal autoregulation: Myogenic mechanism: Afferent arteriole smooth muscle responds to stretch h systemic BP g Afferent constriction i systemic BP g Afferent dilation Both help to maintain GFR

GFR: Intrinsic Tubuloglomerular feedback (macula densa) Figure 25.6 Tubuloglomerular feedback (macula densa) Macula densa cells of Juxtaglomerular (JG) Apparatus sense filtrate flow rate & osmotic signals [NaCl] i Flow or i OSM promotes afferent arteriole dilation h Flow or h OSM promotes afferent arteriole constriction

Regulation of GFR: Extrinsic Extrinsic control: Neural & Hormonal Neural = SNS Stress shunts blood to vital organs: Norepinephrine causes vasoconstriction of afferent arterioles & inhibits filtrate formation Triggers renin / angiotensin system (hormonal)

Regulation of GFR: Extrinsic Renin / angiotensin system Other factors: Prostaglandins Nitric Oxide Adenosine Endothelin Atrial Natriuretic Peptide

Extrinsic GFR regulation Figure 25.6 Renin release: Reduced stretch (i.e. i BP) stimulates JG cells to release renin Stimulation of macula densa that cause vasodilation (decreased flow or decreased OSM) also causes JG cells to release renin Direct stimulation of JG cells by b-adrenergic receptors (SNS)

Renin/Angiotensin System Renin acts on Angiotensin to form Angiotensin I Angiotensin I is converted to Angiotensin II By Angiotensin Converting Enzyme (ACE) in lung capillary endothelium.

Renin/Angiotensin System Angiotensin II: actions Vasoconstrictor: h systemic BP Enhances Na+ reabsorption in PCT (Proximal Convoluted Tube) Stimulates the adrenal cortex to release aldosterone causing renal tubule reabsorption of Na+

Renin/Angiotensin System Angiotensin II: actions Vasoconstriction of efferent arteriole is greater than afferent resulting in h HPg which helps to maintain GFR near normal Causes mesangial cells to reduce surface area of glomerular capillaries which i GFR Stimulates thirst centers

Regulation of GFR: Extrinsic Other factors: Prostaglandins (PGE2, PGI2) vasodilators in response to SNS & angiotensin II: oppose effects of norepinephrine and angiotensin II Nitric Oxide: vasodilator from vascular endothelium Adenosine: systemic vasodilator but acts to constrict renal vasculature Endothelin: vasoconstrictor from vascular endothelium Atrial Natriuretic Peptide (ANP) Responds to h BP to inhibit Renin/Angiotensin system

Figure 25.10

Tubular Reabsorption Every 45 min the entire blood plasma volume is filtered by the kidneys. Most tubular contents are reclaimed (reabsorbed).

Routes of Water and Solute Reabsorption Three membrane barriers Luminal membrane Basolateral membrane Endothelial membrane Figure 25.11

Routes of Water and Solute Reabsorption Na+ Reabsorption: Diffuses into tubular cell (co-transport) Luminal membrane Actively transported to interstitial fluid Basolateral membrane Diffusion through endothelium Endothelial membrane Na+ reabsorption provides energy & mechanisms for reabsorbing most other solutes Figure 25.12

Reabsorption of water / ions / nutrients Passive tubular reabsorption: Na+ ions establish an electro-chemical gradient favoring anions (Cl- & HCO3-) Na+ establishes an osmotic gradient allowing water (via aquaporins) to leave water permeable region (PCT & Loop) As water leaves the tubules the remaining solutes become more concentrated & follow their diffusion gradient out of the filtrate (cations, fatty acids, urea)

Reabsorption of water / ions / nutrients Secondary active transport: Na+ moves down its diffusion gradient in co-transport with specific substances (glucose, amino acids, lactate, vitamins, most cations) Transport maximum for various solutes is dependent upon the number of carriers for Na+ co-transport Plasma proteins: endocytosed & hydrolyzed to amino acids

Non-Reabsorbed Substances Non-reabsorption due to: Lack of carriers Lipid insolubility Molecules too large to pass through membrane pores Non-reabsorbed substances are usually nitrogenous wastes Urea (50-60% reclaimed) Creatinine: not reabsorbed

Proximal Convoluted Tubule (PCT); Reabsorption PCT is the most active in reabsorption: All glucose, lactate, & amino acids Most Na+, H2O, HCO3- , CL- and K+ 65% Na+ and H2O 90% HCO3- 50% CL- 55% K+ Figure 25.4b Table 25.1 Summary of Tubular Reabsorption

Loop of Henle; Reabsorption Descending limb: H2O reabsorbed by osmosis Ascending limb: Na+, Cl-, K+ active transport Ca2+, Mg2+ passive transport Figure 25.4b

Distal Convoluted Tubule; Reabsorption Na+ : Aldosterone mediated Ca2+ : PTH mediated Cl- : diffusion H2O : osmosis Figure 25.4b

Collecting Duct; Reabsorption Most reabsorption in collecting duct due to hormonal influences Na+ : Aldosterone vs ANP HCO3-, H+, K+, Cl- : passive transport & co-transport H2O : ADH dependent Urea: facilitated diffusion

Tubular Secretion Important functions: Tubules also secrete substances into the filtrate. H+, K+, NH4+, creatinine & organic acids Important functions: Disposes of substances not in original filtrate (certain drugs) Replaces substances in filtrate that were reabsorbed (urea/uric acid) Disposes of excess K+ Controls pH (Ch. 26) Urine consists of filtered & secreted substances

Tubular Secretion Important functions: Figure 25.4b Important functions: Disposes of substances not in the original filtrate (certain drugs) Replaces elements in filtrate that were reabsorbed (urea/uric acid) Disposes of excess K+ Controls pH (Ch. 26) Urine consists of filtered & secreted substances

Regulation of Urine Concentration and Volume Body fluids kept @ ~ 300 mOsm (milliosmoles) Counter current multiplier: Interaction between the filtrate in the juxtamedullary Loop of Henle & blood flow in vasa recta.

Regulation of Urine Concentration Osmotic Gradient in the Renal Medulla Capillary Beds Loop of Henle: Countercurrent Mechanism Figure 25.5a Figure 25.13 Figure 25.14

Counter Current Multiplier Descending loop: freely permeable to H2O impermeable to solutes H2O leaves filtrate by osmosis Filtrate becomes highly concentrated to 1200 mOsm at deepest portion of loop Figure 25.14

Counter Current Multiplier Ascending Loop impermeable to H2O permeable to NaCl Most NaCl re-absorption occurs in ascending thick segment Filtrate becomes more dilute as it ascends (100 mOsm) Figure 25.14 Interstitial fluid develops a concentration gradient that is maintained by the movement of H2O and NaCl.

Counter Current Multiplier Medullary Collecting Ducts are permeable to urea Urea diffuses into interstitium Urea makes a large contribution to the increased interstitial osmolality Figure 25.14

Vasa Recta: Counter Current Exchanger Slow blood flow Freely permeable to H2O & NaCl As blood descends it loses H2O & gains NaCl As blood ascends into cortex it gains H2O & loses NaCl Protects medullary gradient by preventing rapid removal of salt Figure 25.14

Loop of Henle: Countercurrent Mechanism Figure 25.14

Regulation of Urine Concentration and Volume Dilute urine: reaches the end of Ascending Loop Production of dilute urine requires nothing further Absence of ADH

Regulation of Urine Concentration and Volume Concentrated urine: ADH dependent reabsorption of H2O from collecting ducts ADH induces production of aquaporin complexes in collecting duct

Formation of Dilute and Concentrated Urine Figure 25.15a, b

Regulation of Urine Concentration and Volume Diuretics: Osmotic (retains H2O in filtrate) Inhibition of ADH Inhibition of Na+ reabsorption

Urine Physical Characteristics: Clear/yellow Slight aroma g develops ammonia on standing pH: usually ~ 6.0 (range 4.0-8.0) Specific gravity: 1.001-1.035 Chemical Composition: 95% H2O 5% Solutes: mostly urea, uric acid & creatinine

Ureters Tri-layered: Mucosa Muscularis Adventitia Moves urine by peristalsis Figure 25.18a, b

Urinary Bladder Tri-layered: Mucosa: transitional epithelium Figure 25.18a, b Tri-layered: Mucosa: transitional epithelium Muscularis: Detrusor muscle Adventitia: except superior portion – which has a peritoneal covering Capacity: 800-1000ml

Urinary Bladder Figure 25.18a, b

Urethra Thin walled muscular tube Figure 25.18a, b Thin walled muscular tube Internal urethral sphincter: involuntary External urethral sphincter: voluntary

Urethra Females: short urethra g external urethral orifice Figure 25.18a, b Females: short urethra g external urethral orifice Males: prostatic urethra g membranous urethra g penile urethra g external urethral orifice

Urine Storage Storage reflex: As bladder fills a sympathetic spinal cord reflex causes; Contraction of internal & external urethral sphincters Inhibition of contraction of detrusor muscle Figure 25.20a

Micturition (Voiding or Urination) Activation by visceral afferent fibers Stimulates Pontine Micturation center which then: Stimulates contraction of detrusor muscle Inhibits contraction of internal sphincter Inhibits sympathetic & somatic fibers allowing relaxation of external sphincter Voluntary contraction of external sphincter can postpone voiding Figure 25.20b