Urinary System

Topics & Objectives Kidney Glomerular filtration Anatomy Function Glomerular filtration Tubular reabsorption & secretion Urine excretion & plasma clearance

Ultimately regulate ECF volume (receive ~ 20% of cardiac output!) Kidney Functions: Ultimately regulate ECF volume (receive ~ 20% of cardiac output!) Maintain H2O balance in the body Maintain osmolarity Regulation of ECF ions Na+, Cl-, K+, H+, etc. Maintain plasma volume & acid-base balance Excretion of end products and foreign compounds Producing EPO & renin

Figure 14.1 Page 513 Renal cortex Renal medulla Renal pyramid Renal pelvis Renal artery Ureter Renal vein Kidney Aorta Inferior vena cava Ureter Urinary bladder Figure 14.1 Page 513 Urethra

Nephrons ~ 1 million within kidney Functional unit for urine formation Arrangement comprises renal cortex & renal medulla Each nephron composed of: Vascular component Tubular component Medulla Cortex

Figure 14.3 Page 514 Distal Proximal tubule tubule Collecting duct Juxtaglomerular apparatus Efferent arteriole Afferent arteriole Bowman’s capsule Glomerulus Cortex Medulla Peritubular capillaries Loop of Henle Figure 14.3 Page 514 To renal pelvis

Vascular Component: Glomerulus Arterioles Peritubular capillaries Location for H2O and solute filtration from blood Arterioles Afferent: to glomerular capillaries Efferent: drains capillaries No O2 extraction! Peritubular capillaries Supply renal tissue Efferent arteriole Afferent arteriole Glomerulus Peritubular capillaries

Tubular Component: Bowman’s capsule Fluid travels to: Proximal tubule Distal tubule Juxtaglomerular apparatus Bowman’s capsule Collects fluid from glomerulus Fluid travels to: Proximal tubule Loop of Henle Passes through juxtaglomerular apparatus Vascular/tubular component Distal tubule Bowman’s capsule Loop of Henle

Juxtamedullary nephron Cortical nephron Juxtamedullary nephron

Urine Formation Glomerular filtration (protein-free) ~ 20% of the plasma (1st step of urine formation) ~ 50 gallons each day (PV ~ 65x/day) Tubular reabsorption Of the 50 gallons filtered, about 98% reabsorbed Tubular secretion ~ 80% of the plasma into the peritubular capillaries

Figure 14.6 Page 516 80% of the plasma that enters the glomerulus is Afferent arteriole GF Efferent arteriole Glomerulus 80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole. Bowman’s capsule 20% of the plasma that enters the glomerulus is filtered. TR Peritubular capillary TS Kidney tubule (entire length, uncoiled) To venous system (conserved for the body) Urine excretion (eliminated from the body) Figure 14.6 Page 516

Figure 14.7 Page 517 Blood pathway Glomerular capillaries Efferent arteriole Peritubular capillaries Venous blood Glomerular filtration Tubular reabsorption Tubular secretion Filtrate pathway Bowman’s capsule Tubule (from proximal tubule to collecting duct) Urine

Glomerular Filtration

Figure 14.8 (1) Page 518 Glomerular capillary Basement membrane Afferent arteriole Efferent arteriole Glomerulus Glomerular capillary Bowman’s capsule Basement membrane Figure 14.8 (1) Page 518 Proximal convoluted tubule

Glomerular Filtration Endothelial cell Lumen of glomerular capillary pores Basement membrane podocytes Figure 14.8 (3) Page 518 Lumen of Bowman’s capsule

Glomerular Filtration (cont.): Occurs through pressure gradients… Capillary blood pressure (~55mmHg) Favors filtration Plasma osmotic pressure (~30mmHg) Caused by distribution of plasma proteins across glomerular membrane Cannot cross into Bowman’s capsule Bowman’s capsule hydrostatic pressure (~15mmHG) Pressure by the fluid All three pressures determine filtration rate!

1) Changes in BP 2) Osmotic pressure Look at Table 14.1! 3) Hydrostatic pressure

GFR Regulation Autoregulation Extrinsic sympathetic control Prevents spontaneous changes in GFR Vasoconstriction & vasodilation Myogenic mechanism – response to stretch Tubuloglomerular feedback mechanism Extrinsic sympathetic control Long-term regulation of arterial BP Sympathetic nervous system (no parasympathetic activity) Baroreceptor reflex

GFR autoregulation Alterations in arteriolar afferent & efferent blood pressures Afferent arteriole Glomerulus Efferent arteriole Glomerular capillary blood pressure Arterial blood pressure (increases blood flow into the glomerulus) Net filtration pressure Figure 14.10 Page 520 GFR

GFR autoregulation (cont.) Glomerulus Glomerular capillary blood pressure Afferent arteriole Efferent arteriole Net filtration pressure Vasoconstriction (decreases blood flow into the glomerulus) GFR

GFR autoregulation Glomerulus Afferent arteriole Glomerular capillary blood pressure Efferent arteriole Net filtration pressure Vasodilation (increases blood flow into the glomerulus) GFR

GFR Autoregulation – Tubuloglomerular feedback Smooth muscle cells within afferent arteriole Granular cells – secretory capabilities Tubular cells (macula densa) Detect changes in the rate of fluid passing through tubule Bring about vasoconstriction or vasodilation Efferent arteriole Distal tubule Bowman’s capsule Afferent

Efferent arteriole Smooth muscle cell Macula densa Distal tubule Afferent Granular cells Podocyte Glomerular capillaries Lumen of Bowman’s capsule Endothelial

Arterial blood pressure Driving pressure into glomerulus Glomerular capillary pressure GFR Rate of fluid flow through tubules Stimulation of macula densa cells to release vasoactive chemicals Chemicals released that induce afferent arteriolar vasoconstriction Blood flow into glomerulus Glomerular capillary pressure to normal GFR to normal

Extrinsic Control – Baroreceptors Response to decreased BP Sympathetically induced vasoconstriction Afferent arterioles (sympathetically innervated) Response to increased BP Sympathetic stimulation decreases

arteriolar vasoconstriction Short-term adjustment for Long-term adjustment for Arterial blood pressure Arterial blood pressure Detection by aortic arch and carotid sinus baroreceptors Cardiac output Sympathetic activity Total peripheral resistance Generalized arteriolar vasoconstriction Afferent arteriolar vasoconstriction Glomerular capillary blood pressure GFR Urine volume Conservation of fluid and salt Arterial blood pressure

Tubular Reabsorption

Figure 14.6 Page 516 Afferent Efferent arteriole arteriole Glomerulus GF Efferent arteriole Glomerulus Bowman’s capsule TR Peritubular capillary Figure 14.6 Page 516

Tubular reabsorption: Ultimately attempting to maintain body’s internal environment Proper composition & volume Table 14.2 Filtered substance reabsorbed Filtered substance excreted Water 99 1 Sodium 99.5 0.5 Glucose 100 Urea (waste product) 50 Phenol (waste product)

Transepithelial transport Material must pass through the cells (5 steps) Tubular lumen epithelial cell Peritubular capillary Plasma Tight junction 4) Interstitial fluid 1) Luminal membrane 2) Cytosol 3) Basolateral membrane 5) Capillary wall Figure 14.17 Page 526 Transepithelial transport

Passive & Active Reabsorption Passive: all steps follow electrochemical or osmotic gradients Active: any one of the steps requiring energy Sodium (80% of kidney’s total energy requirement) ~ 67% in proximal tubule ~ 25% in loop of Henle ~ 8% in distal and collecting tubules Glucose Phosphate Constant percentage of Na+ reabsorption

Na+ pumped out against concentration gradient Creates higher concentration in interstitial fluid & allows for passive diffusion back into lumen Lumen Tubular cell Interstitial fluid Peritubular capillary Diffusion Na+ channel Active transport Basolateral Na+– K+ ATPase carrier Diffusion Figure 14.18 Page 527

Distal tubule (~ 8% of total reabsorption) is hormonally regulated Related to total Na+ load in body Changes in ECF affect osmotic pressures ex: Increased Na+ in ECF causes increased H2O in ECF Ultimately regulates blood pressure Renin-angiotensin-aldosterone system ↑ Atrial natriuretic peptide ↓

Within juxtaglomerular apparatus… Granular cells release renin In response to fall of NaCl/ ECF volume/ BP Recognized by intrarenal baroreceptors Sympathetic response to secrete more renin Ultimately trying to increase plasma volume

Figure 14.19 Page 529 H2O conserved Adrenal cortex Liver Kidney Lungs NaCl / ECF volume / Arterial blood pressure H2O conserved Adrenal cortex Liver Kidney Lungs Kidney Na+ (and CI–) osmotically hold more H2O in ECF Na+ (and CI–) conserved Angiotensin- converting enzyme Renin Na+ reabsorption by kidney tubules ( CI– reabsorption follows passively) Angiotensinogen Angiotensin I Angiotensin II Aldosterone Vasopressin Thirst Arteriolar vasoconstriction H2O reabsorption by kidney tubules Fluid intake Figure 14.19 Page 529

Inhibits aldosterone & renin secretion Helps correct NaCl / ECF volume / Arterial blood pressure Helps correct Cardiac atria Atrial natriuretic peptide Na+ reabsorption by kidney tubules Salt-conserving renin-angiotensin- aldosterone system Smooth muscle of afferent arterioles Sympathetic nervous system Inhibits aldosterone & renin secretion Afferent arteriolar vasodilation Cardiac output Total peripheral resistance GFR Na+ excretion in urine Arterial blood pressure Figure 14.20 Page 530 Na+ and H2O filtered H2O excretion in urine

Glucose and amino acid reabsorption Na+ dependent secondary active transport Co-transporters that do not require energy Maximal reabsorption rate depends on substance

No energy required Cotransport carrier Glucose carrier Basolateral border Energy Na+–K+ pump Blood vessel Luminal border

Phosphate & Calcium reabsorption Dependent upon total body content Regulated by kidneys Hormonally (parathyroid hormone) Na+ reabsorption responsible for passive reabsorption of Cl-, H2O, and urea

H2O (passive) reabsorption 80% in proximal tubules & loops of Henle Lumen Proximal tubular cell Peritubular capillary Interstitial fluid Osmosis Water channel Figure 14.22 Page 533 Hydrostatic pressure Osmosis

Urea (passive) reabsorption Glomerulus Bowman’s capsule Beginning of proximal tubule End of = Urea molecules Peritubular capillary Urea (passive) reabsorption Waste product of protein Becomes increasingly concentrated 125 ml of filtrate Na+ (active) H2O (osmosis) Na+ (active) H2O (osmosis) 44 ml of filtrate Figure 14.23 Page 534 Passive diffusion of urea down its concentration gradient

Tubular Secretion

Figure 14.6 Page 516 Afferent Efferent arteriole arteriole Glomerulus GF Bowman’s capsule Peritubular capillary TS Kidney tubule (entire length, uncoiled) Figure 14.6 Page 516

Organic anions & cations Tubular secretion: Hydrogen ions (H+) Acid-base regulation throughout the body Potassium (K+) Early reabsorption into tubules not regulated Secretion in distal tubules regulated Na+-K+ pump Aldosterone Organic anions & cations Foreign compounds, chemical messengers

Aldosterone - dual regulation 1) Na+ & K+ Na+/ ECF volume/ arterial pressure Aldosterone - dual regulation 1) Na+ & K+ Renin Angiotensin I Plasma K+ Angiotensin II Figure 14.25 Page 536 Aldosterone Tubular K+ secretion Tubular Na+ reabsorption Urinary K+ excretion Urinary Na+ excretion

Plasma Clearance

Substance: Filtered NOT reabsorbed NOT secreted All filtered plasma is Peritubular capillary Glomerulus All filtered plasma is cleared of substance Tubule In urine Fig. 14.26a Page 539

Substance: Filtered NOT secreted Completely reabsorbed None of filtered plasma is cleared of substance

Substance: Filtered NOT secreted Partially reabsorbed Portion of filtered plasma is cleared of substance

Substance: Filtered Secreted NOT reabsorbed ALL of filtered plasma is cleared of substance

Regulation of plasma H2O Fluids & solutes Normal balance in body fluids called isotonic 300 mosm/liter Hypotonic Too much H2O compared to solute (osmolality < 300) Hypertonic Too little H2O compared to solute (osmolality > 300) Osmotic gradient maintained in interstitial fluid of medulla Dependent upon hydration levels

Fig. 14.28a (2) Page 542 From proximal tubule To distal tubule Medullary interstitial fluid Medullary interstitial fluid Descending limb of loop of Henle of juxtamedullary nephron Ascending limb of loop of Henle of juxtamedullary nephron Fig. 14.28a (2) Page 542 Initial scene

Step 1

From proximal tubule To distal tubule Step 2

Step 3

From proximal tubule To distal tubule Step 4

Step 5

From proximal tubule To distal tubule Step 6 and on

Further regulation Vasopressin Anti-diuretic hormone from hypothalamus Tubular lumen filtrate Distal tubular cell Peritubular capillary plasma Water channel Increases permeability of luminal membrane to H2O by inserting new water channels Figure 14.29 Page 544