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2/29/2016

Figure 26.4 Major sources of water intake and output. Learning Objectives Renal System

100 ml Feces 4% • Blood filtration through the Metabolism 10% 250 ml Sweat 8% 200 ml Insensible loss • How Glomerular filtration rate is regulated Foods 30% 750 ml 700 ml via skin and – Intrinsic and extrinsic mechanisms lungs 28% • Formation of urine 2500 ml

• Control of urine concentration Urine 60% Beverages 60% 1500 ml 1500 ml

Average intake Average output © 2013 Pearson Education, Inc.per day per day

Urinary System Organs Hepatic veins (cut) Esophagus (cut) Inferior vena cava • Kidneys are major excretory organs Adrenal gland • is the temporary storage Aorta reservoir for urine Iliac crest • transport urine from the kidneys to the bladder

• transports urine out of the body Rectum (cut) Uterus (part of female reproductive ) bladder Urethra

Figure 25.1

Kidney Functions Kidney Functions

• Removal of toxins, metabolic wastes, and • Gluconeogenesis during prolonged fasting excess ions from the blood • Endocrine (hormone) functions • Regulation of blood volume, chemical – Renin: regulation of blood pressure and kidney composition, and pH function • Activation of vitamin D (metabolism)

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Kidney Anatomy Kidney Anatomy

• Retroperitoneal, in the superior lumbar region • Layers of supportive tissue • Right kidney is lower than the left 1. • The anchoring outer layer of dense fibrous connective • Convex lateral surface, concave medial surface tissue • Ureters, renal blood vessels, lymphatics, and 2. Perirenal fat capsule nerves enter and exit at the hilum • A fatty cushion 3. Fibrous capsule • Size of bar of soap • Prevents spread of infection to kidney

Cortical radiate vein Cortical radiate artery Renal hilum Arcuate artery Interlobar vein

Renal medulla Interlobar artery Segmental arteries Renal vein Major calyx Renal artery Papilla of pyramid Renal pelvis Ureter Minor calyx Ureter

Renal pyramid in renal medulla Renal column Renal cortex Fibrous capsule

(a) Photograph of right kidney, frontal section (b) Diagrammatic view (a) Frontal section illustrating major blood vessels

Figure 25.3 Figure 25.4a

Aorta Inferior vena cava Renal artery Renal vein Segmental artery Interlobar vein • Structural and functional units that form Interlobar artery Arcuate vein urine

Cortical radiate Arcuate artery • ~1 million per kidney vein • Two main parts Peritubular Cortical radiate artery capillaries 1. Glomerulus: a tuft of capillaries and Afferent arteriole 2. Renal tubule: begins as cup‐shaped glomerular

Glomerulus (capillaries) (Bowman’s) capsule surrounding the glomerulus

Nephron-associated blood vessels (see Figure 25.7) (b) Path of blood flow through renal blood vessels

Figure 25.4b

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Nephrons

• – Glomerulus + capsule • Fenestrated ______glomerular endothelium – Allows filtrate to pass from plasma into the glomerular capsule

Figure 25.5

Glomerular capsule: Renal Tubule parietal layer

• Glomerular capsule Basement • Parietal layer: simple squamous epithelium membrane – Support – ______‐in filtrate formation Fenestrated • Visceral layer: branching epithelial endothelium of the glomerulus – Extensions terminate in foot processes that cling to basement membrane Glomerular capsule: visceral layer – Filtration slits allow filtrate to pass into the capsular space

Figure 25.5

Renal Tubule Renal Tubule • Proximal convoluted tubule (PCT) – Cuboidal cells with dense microvilli and large • with descending and ascending mitochondria limbs – Functions in reabsorption and secretion – Thin segment usually in descending limb – Confined to the cortex – Simple squamous epithelium – Freely permeable to water Microvilli Mitochondria – Thick segment of ascending limb • Cuboidal to columnar cells

Highly infolded plasma membrane

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Renal Tubule Collecting Ducts • (DCT) • Receive filtrate from many nephrons – Cuboidal cells with very few microvilli • – Function more in secretion than reabsorption Fuse together to deliver urine through papillae into minor calyces – Confined to the cortex

Collecting Ducts Glomerular capsule: parietal layer Renal cortex Basement Renal medulla membrane Cuboidal cells with microvilli Renal corpuscle Podocyte • Glomerular capsule Renal pelvis Fenestrated Function in maintaining the acid‐ • Glomerulus endothelium Cuboidal cells without Distal of the glomerulus Ureter convoluted Glomerular capsule: visceral layer base balance of the body microvilli tubule Help maintain the body’s Kidney Microvilli Mitochondria Proximal convoluted water and salt balance tubule Highly infolded plasma membrane Cortex Proximal convoluted tubule cells

Medulla

Thick segment Distal convoluted tubule cells Thin segment Principal Loop of Henle • Descending limb • Ascending limb Collecting Loop of Henle (thin-segment) cells duct Principal cell Intercalated cell Intercalated

Collecting duct cells

Figure 25.5

Cortical Juxtamedullary nephron • Has short loop of Henle and glomerulus • Has long loop of Henle and glomerulus Nephrons further from the corticomedullary junction closer to the corticomedullary junction • Efferent arteriole supplies peritubular • Efferent arteriole supplies vasa recta capillaries Efferent arteriole Cortical radiate vein Renal Glomerular capillaries Cortical radiate artery corpuscle (glomerulus) Afferent arteriole • Cortical nephrons—85% of nephrons; almost Glomerular Collecting duct (Bowman’s) capsule Distal convoluted tubule entirely in the cortex Proximal Afferent arteriole convoluted tubule Efferent arteriole • Juxtamedullary nephrons Ascending or thick limb of the loop of Henle Corticomedullary – Long loops of Henle deeply invade the medulla Arcuate vein junction Arcuate artery Vasa recta Cortex Loop of Henle – Extensive thin segments Medulla Renal pelvis Descending – Important in the production of concentrated urine Ureter or thin limb of loop of Henle Kidney

(a)

Figure 25.7a

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Regulation of Urine Concentration and Regulation of Urine Concentration and Volume Volume • Osmolality • Osmolality of body fluids

– Number of solute particles in 1 kg of H2O – – The kidneys maintain osmolality of plasma at – Reflects ability to cause osmosis ~300 mOsm, using countercurrent mechanisms

Countercurrent Mechanism Countercurrent Mechanism

• Occurs when fluid flows in opposite directions • Role of countercurrent mechanisms in two adjacent segments of the same tube – Establish and maintain an osmotic gradient – Filtrate flow in the loop of Henle (countercurrent (300 mOsm to 1200 mOsm) from renal cortex multiplier) through the medulla – Blood flow in the vasa recta (countercurrent – Allow the kidneys to vary urine concentration exchanger) • Loop of Henle and Vasa Recta do NOT flow in opposite directions as name implies

Figure 25.16

Countercurrent Multiplier: Loop of

Cortex Henle Medulla • • Functions because of two factors: 1. Descending limb

– Freely permeable to H2O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluid – Filtrate osmolality increases to ~1200 mOsm

Figure 25.15

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Countercurrent Multiplier: Loop of Osmolality of interstitial fluid Henle (mOsm)

Filtrate entering the H2O NaCI Cortex Active transport loop of Henle is 2. Ascending limb isosmotic to both Passive transport blood plasma and NaCI Water impermeable H2O – Impermeable to H O cortical interstitial 2 fluid. H O NaCI – Selectively permeable to solutes 2 The descending limb: H2O NaCI Outer + – • Permeable to H2O medulla • Na and Cl are passively reabsorbed in the thin • Impermeable to NaCl H2O As filtrate flows, it NaCI segment, actively reabsorbed in the thick segment becomes increasingly H2O concentrated as H2O – Filtrate osmolality decreases to 100 mOsm leaves the tubule by osmosis. The filtrate H2O osmolality increases from Inner • Due to countercurrent flow –able to multiply 300 to 1200 mOsm. medulla Loop of Henle

small changes in solute to form a gradient The ascending limb: (a) Countercurrent multiplier. • Impermeable to H2O The long loops of Henle of the • Permeable to NaCl juxtamedullary nephrons Filtrate becomes increasingly dilute as NaCl leaves, eventually becoming create the medullary hypo-osmotic to blood at 100 mOsm in the cortex. NaCl leaving the osmotic gradient. ascending limb increases the osmolality of the medullary interstitial fluid.

Figure 25.16a

Osmolality Blood from Passive transport of interstitial efferent fluid arteriole To vein Countercurrent Exchanger: Vasa Recta (mOsm)

NaCI NaCI Cortex • The vasa recta H2O H2O

– NaCI NaCI

H2O H2O

– Deliver blood to the medullary tissues Outer medulla – Protect the medullary osmotic gradient by NaCI NaCI preventing rapid removal of salt, and by removing H2O H2O reabsorbed H O NaCI NaCI 2 H2O H2O Inner medulla Vasa recta

The vasa recta: (b) Countercurrent exchanger. • Highly permeable to H O and solute The vasa recta preserve the 2 • Nearly isosmotic to interstitial fluid due to sluggish blood flow medullary gradient while Blood becomes more concentrated as it descends deeper into removing reabsorbed water the medulla and less concentrated as it approaches the cortex. and solutes.

Figure 25.16b

Role of osmotic gradient?? Formation of Dilute Urine

• Concentration of urine • • Without gradient – unable to raise • Filtrate is diluted in the ascending loop of concentration of urine above 300mOsm Henle • Would not be able to excrete excess solutes • In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine • Na+ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm

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Active transport Passive transport Formation of Concentrated Urine Collecting duct

Descending limb • Depends on the medullary osmotic gradient of loop of Henle DCT and ADH Cortex

NaCI • ADH triggers reabsorption of H2O in the collecting ducts

H2O NaCI Outer • Facultative water reabsorption occurs in the medulla NaCI presence of ADH so that 99% of H2O in filtrate is reabsorbed H2O Urea Inner medulla

Large volume (a) Absence of ADH of dilute urine

Figure 25.17a

Active transport Passive transport Nephron Capillary Beds Collecting duct H2O Descending limb of loop of Henle 1. Glomerulus DCT H2O

Cortex – Afferent arteriole  glomerulus  efferent

H O NaCI 2 arteriole

H2O – Specialized for filtration

H O 2 NaCI – Blood pressure is high because Outer medulla H2O • are smaller in diameter than NaCI Urea efferent arterioles

H2O

H2O Urea • Arterioles are high‐resistance vessels Inner H2O medulla

Small volume of (b) Maximal ADH concentrated urine

Figure 25.17b

Nephron Capillary Beds Nephron Capillary Beds

2. Peritubular capillaries 3. Vasa recta – Low‐pressure, porous capillaries adapted for – Long vessels parallel to long loops of Henle absorption – Arise from efferent arterioles of juxtamedullary – Arise from efferent arterioles nephrons – Cling to adjacent renal tubules in cortex – Function in formation of concentrated urine – Empty into venules

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Mechanisms of Urine Formation Afferent arteriole Glomerular capillaries Efferent arteriole 1. Glomerular filtration Cortical radiate 2. Tubular reabsorption artery Glomerular capsule

– Returns all glucose and amino acids, 99% of Rest of renal tubule water, salt, and other components to the blood containing filtrate 3. Tubular secretion Peritubular – Reverse of reabsoprtion: selective addition to capillary Three major urine renal processes: Glomerular filtration To cortical radiate vein Tubular reabsorption Tubular secretion Urine

Figure 25.10

Filtration membrane • Fenestrated capillary endothelium Filtration Membrane Capillary • Basement membrane • Foot processes of podocyte of glomerular capsule • Porous membrane between the blood and the capsular space • Consists of 1. Fenestrated endothelium of the glomerular capillaries Filtration slit 2. Gel‐like basement membrane (fused basal laminae of the two other layers) Slit diaphragm Plasma Filtrate in 3. Visceral membrane of the glomerular capsule (podocytes capsular with foot processes and filtration slits) space Fenestration Foot processes of podocyte (pore) BLOOD (c) Three parts of the filtration membrane

Figure 25.9c

Filtration Membrane Filtration Membrane

• Allows passage of water and solutes smaller • Glomerular mesangial cells than most plasma proteins – Engulf and degrade macromolecules – Fenestrations prevent filtration of blood cells – Can contract to change the total surface area – Negatively charged basement membrane repels available for filtration large anions such as plasma proteins – Slit diaphragms also help to repel macromolecules BLOOD

BLOOD

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STEP 1; Glomerular Filtration

• Passive mechanical process driven by hydrostatic pressure • The glomerulus is a very efficient filter because – Its filtration membrane is very permeable and it has a large surface area – Glomerular blood pressure is higher (55 mm Hg) than other capillaries • Molecules >5 nm are not filtered (e.g., plasma proteins) and function to maintain colloid osmotic pressure of the blood •

Glomerular Filtration Rate (GFR) Regulation of Glomerular Filtration

• Volume of filtrate formed per minute by the • GFR is tightly controlled by two types of kidneys (120–125 ml/min) mechanisms • Governed by (and directly proportional to) • Intrinsic controls (renal autoregulation) – Total surface area available for filtration – Act locally within the kidney – Filtration membrane permeability • Extrinsic controls – Net Filtration Pressure – Nervous and endocrine mechanisms that maintain • blood pressure, but affect kidney function

Intrinsic Controls: Myogenic Intrinsic Controls Mechanism • Maintains a nearly constant GFR when MAP is •  BP  constriction of afferent arterioles in the range of 80–180 mm Hg – Helps maintain normal GFR • Two types of renal autoregulation – Protects glomeruli from damaging high BP – Myogenic mechanism •  BP  dilation of afferent arterioles – Tubuloglomerular feedback mechanism, which – Helps maintain normal GFR senses changes in the juxtaglomerular apparatus

MAP = mean arterial pressure

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Intrinsic Controls: Tubuloglomerular Intrinsic Controls: Tubuloglomerular Feedback Mechanism Feedback Mechanism • Flow‐dependent mechanism directed by the • cells of the JGA respond to macula densa cells NaCl by releasing a vasoconstricting chemical • If GFR increases, filtrate flow rate increases in that acts on the afferent arteriole GFR the tubule • The opposite occurs if GFR decreases. • Filtrate NaCl concentration will be high because of insufficient time for reabsorption

Extrinsic Controls: Sympathetic Nervous System • Under normal conditions at rest – Renal blood vessels are dilated – Renal autoregulation mechanisms prevail

Figure 25‐08

Extrinsic Controls: Sympathetic Extrinsic Controls: Renin‐Angiotensin Nervous System Mechanism • Under extreme stress • Triggered when the granular cells of the JGA – Norepinephrine is released by the sympathetic release renin nervous system angiotensinogen (a plasma globulin) – Epinephrine is released by the adrenal medulla RENIN – Both cause constriction of afferent arterioles, angiotensin I inhibiting filtration and triggering the release of angiotensin converting renin enzyme (ACE)  angiotensin II

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Effects of Angiotensin II Effects of Angiotensin II

1. Constricts arteriolar smooth muscle, causing 4. Constricts efferent arterioles, decreasing MAP (mean arterial pressure) to rise peritubular capillary hydrostatic pressure 2. Stimulates the reabsorption of Na+ and increasing fluid reabsorption – Acts directly on the renal tubules 5. Causes glomerular mesangial cells to – Triggers adrenal cortex to release contract, decreasing the surface area 3. Stimulates the hypothalamus to release ADH available for filtration and activates the thirst center

Extrinsic Controls: Renin‐Angiotensin STEP 2; Tubular Reabsorption Mechanism • Triggers for renin release by granular cells • A selective transepithelial process – Reduced stretch of granular cells (MAP below – All organic nutrients (glucose, amino acids) are 80 mm Hg) reabsorbed – – Stimulation of the granular cells by activated Water and ion re‐absorption are hormonally regulated macula densa cells Ca2+, • Includes active and passive process Mg2+, K+, – Direct stimulation of granular cells via 1‐ Na+ adrenergic receptors by renal nerves • Two routes – Transcellular – Paracellular

Tubular Reabsorption Tubular Reabsorption

• Transcellular route • Paracellular route – Luminal membranes of tubule cells – Between cells – Cytosol of tubule cells – Limited to water movement and reabsorption of – Basolateral membranes of tubule cells Ca2+, Mg2+, K+, and some Na+ in the PCT where – Endothelium of peritubular capillaries tight junctions are leaky

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Movement via the 3 Transport across the basolateral The paracellular route transcellular route involves: involves: membrane. (Often involves the lateral intercellular spaces because • Movement through Sodium Reabsorption 1 Transport across the membrane transporters transport ions leaky tight junctions, luminal membrane. into these spaces.) particularly in the PCT. 2 Diffusion through the 4 Movement through the interstitial cytosol. fluid and into the capillary. • + Tight junction Lateral intercellular space Na (most abundant cation in filtrate) Filtrate Tubule cell Interstitial – Primary active transport out of the tubule cell by in tubule fluid Peri- lumen Capillary tubular + + endothelial capillary Na ‐K ATPase in the basolateral membrane cell – + Paracellular Na passes in through the luminal membrane by H2O 1 243 secondary active transport or facilitated diffusion Luminal Transcellular mechanisms membrane 1 Transcellular 3 4 2 Solutes 3 4 Active transport Paracellular Basolateral membranes Passive transport

Figure 25.13

Reabsorption of Nutrients, Water, and Sodium Reabsorption Ions • Low hydrostatic pressure and high osmotic • Organic nutrients are reabsorbed by pressure in the peritubular capillaries secondary active transport • Promotes bulk flow of water and solutes – Transport maximum (Tm) reflects the number of (including Na+) carriers in the renal tubules available • Na+ reabsorption provides the energy and the – When the carriers are saturated, excess of that substance is excreted means for reabsorbing most other substances – Example

Reabsorption of Nutrients, Water, and

Ions 1 At the basolateral membrane, Na+ is pumped into the interstitial space by the Na+-K+ • Water is reabsorbed by osmosis, aided by ATPase. Active Na+ transport Nucleus creates concentration gradients Filtrate Interstitial Peri- that drive: water‐filled pores called aquaporins in tubule Tubule cell fluid tubular 2 “Downhill” Na+ entry at the lumen capillary luminal membrane. 3 Reabsorption of organic + • Cations and fat‐soluble substances follow by Na 2 nutrients and certain ions by + + 3Na 3Na cotransport at the luminal Glucose 1 membrane. 2K+ 2K+ diffusion Amino 3 4 Reabsorption of water by acids K+ osmosis. Water reabsorption Some increases the concentration of ions the solutes that are left 4 Vitamins behind. These solutes can H2O then be reabsorbed as they move down their Lipid-soluble 5 concentration gradients: substances 5 Lipid-soluble – 2+ + 6 Cl , Ca , K Cl– substances diffuse by the and other transcellular route. Tight junction Paracellular ions, urea route 6 Cl– (and other anions), + Primary active transport Transport protein K , and urea diffuse by the Secondary active transport Ion channel or aquaporin paracellular route. Passive transport (diffusion)

Figure 25.14

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Reabsorptive Capabilities of Renal Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Tubules and Collecting Ducts • PCT • Loop of Henle

– Site of reabsorption – Descending limb: H2O • 65% of Na+ and water – Ascending limb: Na+, K+, Cl • All nutrients • Ions • Small proteins • Any plasma proteins removed by endocytosis and degraded

Reabsorptive Capabilities of Renal Reabsorptive Capabilities of Renal Tubules and Collecting Ducts Tubules and Collecting Ducts • DCT and collecting duct • Mechanism of Aldosterone – Reabsorption is hormonally regulated – Targets collecting ducts (principal cells) and distal – DCT • Ca2+ (Para Thyroid Hormone) – Promotes synthesis of luminal Na+ and K+ channels • Water (Anti Diuretic Hormone) – Promotes synthesis of basolateral Na+‐K+ ATPases • Na+ (Aldosterone and Anti Natriuretic Peptide) – Little to no Na+ leaves in urine

Two ways to eliminate unwanted STEP 3; Tubular Secretion substances • Reabsorption in reverse + + + Don’t reabsorb them – K , H , NH4 , creatinine, and organic acids move from peritubular capillaries or tubule cells into filtrate OR • Disposes of substances that are bound to plasma proteins Secrete them into the filtrate

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Tubular Secretion

• Eliminates undesirable substances that have been passively reabsorbed (e.g., urea and uric acid) • Rids the body of excess K+ • Controls blood pH by altering amounts of H+ – or HCO3 in urine

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