renal system spring 2016-student - iowa state university...learning objectives renal system •...

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Learning Objectives Renal System

• Blood filtration through the glomerulus

• How Glomerular filtration rate is regulated

– Intrinsic and extrinsic mechanisms

• Formation of urine

• Control of urine concentration

© 2013 Pearson Education, Inc.

Figure 26.4 Major sources of water intake and output.

Metabolism 10%

Foods 30%

Beverages 60%

Feces 4%

Sweat 8%

Insensible lossvia skin andlungs 28%

Urine 60%

Average outputper day

Average intakeper day

250 ml

750 ml

1500 ml

2500 ml

100 ml

200 ml

700 ml

1500 ml

Urinary System Organs

• Kidneys are major excretory organs

• Urinary bladder is the temporary storage reservoir for urine

• Ureters transport urine from the kidneys to the bladder

• Urethra transports urine out of the body

Figure 25.1

Esophagus (cut)Inferior vena cava

Adrenal gland

Hepatic veins (cut)

Renal arteryRenal hilumRenal vein

Iliac crest

Kidney

Ureter

UrinarybladderUrethra

Aorta

Rectum (cut)

Uterus (part of female reproductive system)

Kidney Functions

• Removal of toxins, metabolic wastes, and excess ions from the blood

• Regulation of blood volume, chemical composition, and pH

Kidney Functions

• Gluconeogenesis during prolonged fasting

• Endocrine (hormone) functions

– Renin: regulation of blood pressure and kidney function

• Activation of vitamin D (metabolism)

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Kidney Anatomy

• Retroperitoneal, in the superior lumbar region

• Right kidney is lower than the left

• Convex lateral surface, concave medial surface

• Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilum

• Size of bar of soap

Kidney Anatomy

• Layers of supportive tissue1. Renal fascia

• The anchoring outer layer of dense fibrous connective tissue

2. Perirenal fat capsule • A fatty cushion

3. Fibrous capsule• Prevents spread of infection to kidney

Figure 25.3

Renal cortex

Renal medulla

Major calyx

Papilla ofpyramidRenal pelvis

Ureter

Minor calyx

Renal column

Renal pyramid in renal medulla

Fibrous capsule

Renalhilum

(a) Photograph of right kidney, frontal section (b) Diagrammatic view

Figure 25.4a

Cortical radiate vein

Cortical radiate artery

Arcuate vein

Arcuate artery

Interlobar vein

Interlobar artery

Segmental arteries

Renal artery

Renal vein

Renal pelvis

Ureter

Renal medulla

Renal cortex

(a) Frontal section illustrating major blood vessels

Figure 25.4b

Aorta

Renal artery

Segmental artery

Interlobar artery

Arcuate artery

Cortical radiate artery

Afferent arteriole

Glomerulus (capillaries)

Nephron-associated blood vessels(see Figure 25.7)

Inferior vena cava

Renal vein

Interlobar vein

Arcuate vein

Cortical radiatevein

Peritubularcapillariesand vasa recta

Efferent arteriole

(b) Path of blood flow through renal blood vessels

Nephrons

• Structural and functional units that form urine

• ~1 million per kidney

• Two main parts

1. Glomerulus: a tuft of capillaries

2. Renal tubule: begins as cup‐shaped glomerular (Bowman’s) capsule surrounding the glomerulus

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Figure 25.5

Nephrons

• Renal corpuscle

– Glomerulus + capsule

• Fenestrated _______________ glomerular endothelium

– Allows filtrate to pass from plasma into the glomerular capsule

Renal Tubule

• Glomerular capsule

• Parietal layer: simple squamous epithelium– Support

– _______‐in filtrate formation

• Visceral layer: branching epithelial podocytes– Extensions terminate in foot processes that cling to basement membrane

– Filtration slits allow filtrate to pass into the capsular space

Glomerular capsule: parietal layer

Figure 25.5

Fenestratedendotheliumof the glomerulus

Podocyte

Basementmembrane

Glomerular capsule: visceral layer

Renal Tubule• Proximal convoluted tubule (PCT)

– Cuboidal cells with dense microvilli and large mitochondria

– Functions in reabsorption and secretion

– Confined to the cortex

Microvilli Mitochondria

Highly infolded plasma membrane

Renal Tubule

• Loop of Henle with descending and ascending limbs

– Thin segment usually in descending limb– Simple squamous epithelium

– Freely permeable to water

– Thick segment of ascending limb

• Cuboidal to columnar cells

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Renal Tubule

• Distal convoluted tubule (DCT)

– Cuboidal cells with very few microvilli

– Function more in secretion than reabsorption

– Confined to the cortex

Collecting Ducts

• Receive filtrate from many nephrons

• Fuse together to deliver urine through papillae into minor calyces

Collecting DuctsCuboidal cells with microvilli

Function in maintaining the acid‐base balance of the body

Principal

Intercalated

Cuboidal cells without microvilliHelp maintain the body’s water and salt balance

Figure 25.5

Fenestratedendotheliumof the glomerulus

Microvilli

Cortex

Medulla

Podocyte

Basementmembrane

Mitochondria

Highly infolded plasmamembrane

Proximalconvolutedtubule

Distalconvolutedtubule

• Descending limb

Loop of Henle

• Ascending limb

• Glomerular capsule

Renal corpuscle

• Glomerulus

Thick segment

Collectingduct

Intercalated cellPrincipal cell

Thin segment

Proximal convoluted tubule cells

Glomerular capsule: parietal layer

Glomerular capsule: visceral layer

Distal convoluted tubule cells

Loop of Henle (thin-segment) cells

Collecting duct cells

Renal cortex

Renal medulla

Renal pelvis

Ureter

Kidney

Nephrons

• Cortical nephrons—85% of nephrons; almost entirely in the cortex

• Juxtamedullary nephrons

– Long loops of Henle deeply invade the medulla

– Extensive thin segments

– Important in the production of concentrated urine

Figure 25.7a

Cortical nephron• Has short loop of Henle and glomerulusfurther from the corticomedullary junction

• Efferent arteriole supplies peritubular capillaries

Juxtamedullary nephron• Has long loop of Henle and glomeruluscloser to the corticomedullary junction

• Efferent arteriole supplies vasa recta

Corticomedullaryjunction

UreterRenal pelvis

Kidney

CortexMedulla

(a)

Cortical radiate veinCortical radiate arteryAfferent arteriole

Afferent arteriole

Collecting ductDistal convoluted tubule

Efferent arteriole

Vasa rectaLoop of HenleArcuate arteryArcuate vein

Peritubular capillaries

Glomerular capillaries (glomerulus)Glomerular(Bowman’s) capsule

Renalcorpuscle

Ascending or thick limb of the loop of Henle

Descendingor thin limb of loop of Henle

Efferent arteriole

Proximalconvoluted tubule

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Regulation of Urine Concentration and Volume

• Osmolality

– Number of solute particles in 1 kg of H2O

– Reflects ability to cause osmosis

Regulation of Urine Concentration and Volume

• Osmolality of body fluids

–

– The kidneys maintain osmolality of plasma at ~300 mOsm, using countercurrent mechanisms

Countercurrent Mechanism

• Occurs when fluid flows in opposite directions in two adjacent segments of the same tube

– Filtrate flow in the loop of Henle (countercurrent multiplier)

– Blood flow in the vasa recta (countercurrent exchanger)

Figure 25.16

Countercurrent Mechanism

• Role of countercurrent mechanisms

– Establish and maintain an osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through the medulla

– Allow the kidneys to vary urine concentration

• Loop of Henle and Vasa Recta do NOT flow in opposite directions as name implies

Figure 25.15

Cortex

Medulla

Countercurrent Multiplier: Loop of Henle

•

• Functions because of two factors:

1. Descending limb

– Freely permeable to H2O, which passes out of the filtrate into the hyperosmotic medullaryinterstitial fluid

– Filtrate osmolality increases to ~1200 mOsm

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Countercurrent Multiplier: Loop of Henle

2. Ascending limb

– Impermeable to H2O

– Selectively permeable to solutes

• Na+ and Cl– are passively reabsorbed in the thin segment, actively reabsorbed in the thick segment

– Filtrate osmolality decreases to 100 mOsm

• Due to countercurrent flow – able to multiply small changes in solute to form a gradient

Figure 25.16a

Loop of Henle

Osmolalityof interstitialfluid(mOsm)

Innermedulla

Outermedulla

CortexActive transport

Passive transport

Water impermeable

(a) Countercurrent multiplier. The long loops of Henle of the juxtamedullary nephronscreate the medullaryosmotic gradient.

The ascending limb:• Impermeable to H2O• Permeable to NaClFiltrate becomes increasingly dilute as NaCl leaves, eventually becoming hypo-osmotic to blood at 100 mOsm in the cortex. NaCl leaving the ascending limb increases the osmolality of the medullary interstitial fluid.

Filtrate entering the loop of Henle is isosmotic to both blood plasma and cortical interstitial fluid.

The descending limb:• Permeable to H2O• Impermeable to NaClAs filtrate flows, it becomes increasingly concentrated as H2Oleaves the tubule by osmosis. The filtrate osmolality increases from 300 to 1200 mOsm.

H2O

H2O

H2O

H2O

H2O

H2O

H2O

NaCI

NaCI

NaCI

NaCI

NaCI

Countercurrent Exchanger: Vasa Recta

• The vasa recta

–

– Deliver blood to the medullary tissues

– Protect the medullary osmotic gradient by preventing rapid removal of salt, and by removing reabsorbed H2O

Figure 25.16b

NaCIH2O

NaCIH2O

NaCIH2O

NaCIH2O

NaCIH2O

NaCIH2O

NaCIH2O

NaCIH2O

Vasa recta

To vein

Osmolalityof interstitialfluid(mOsm)

Blood fromefferent arteriole

Innermedulla

Outermedulla

Cortex

Passive transport

(b) Countercurrent exchanger. The vasa recta preserve the medullary gradient while removing reabsorbed water and solutes.

The vasa recta:• Highly permeable to H2O and solute• Nearly isosmotic to interstitial fluid due to sluggish blood flowBlood becomes more concentrated as it descends deeper into the medulla and less concentrated as it approaches the cortex.

Role of osmotic gradient??

• Concentration of urine

• Without gradient – unable to raise concentration of urine above 300mOsm

• Would not be able to excrete excess solutes

Formation of Dilute Urine

•

• Filtrate is diluted in the ascending loop of Henle

• 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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Figure 25.17a

Active transport

Passive transport

(a) Absence of ADH Large volumeof dilute urine

Collecting duct

Cortex

NaCI

NaCI

NaCI

Urea

Outermedulla

Innermedulla

DCT

H2O

H2O

Descending limbof loop of Henle

Formation of Concentrated Urine

• Depends on the medullary osmotic gradient and ADH

• ADH triggers reabsorption of H2O in the collecting ducts

• Facultative water reabsorption occurs in the presence of ADH so that 99% of H2O in filtrate is reabsorbed

Figure 25.17b

Active transport

Passive transport

Small volume ofconcentrated urine

Cortex

NaCI

NaCI

NaCI Urea

Urea

H2O

H2O

H2O

H2O

H2O

H2O

H2O

Outermedulla

Innermedulla

(b) Maximal ADH

DCT

Descending limbof loop of Henle

Collecting duct

H2O

H2O

Nephron Capillary Beds

1. Glomerulus

– Afferent arteriole glomerulus efferent arteriole

– Specialized for filtration

– Blood pressure is high because

• Afferent arterioles are smaller in diameter than efferent arterioles

• Arterioles are high‐resistance vessels


2. Peritubular capillaries

– Low‐pressure, porous capillaries adapted for absorption

– Arise from efferent arterioles

– Cling to adjacent renal tubules in cortex

– Empty into venules


3. Vasa recta

– Long vessels parallel to long loops of Henle

– Arise from efferent arterioles of juxtamedullarynephrons

– Function in formation of concentrated urine

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Mechanisms of Urine Formation

1. Glomerular filtration

2. Tubular reabsorption

– Returns all glucose and amino acids, 99% of water, salt, and other components to the blood

3. Tubular secretion

– Reverse of reabsoprtion: selective addition to urine

Figure 25.10

Corticalradiateartery

Afferent arteriole

Glomerular capillaries

Efferent arteriole

Glomerular capsule

Rest of renal tubulecontaining filtrate

Peritubularcapillary

To cortical radiate vein

Urine

Glomerular filtration

Tubular reabsorption

Tubular secretion

Three majorrenal processes:

Figure 25.9c

(c) Three parts of the filtration membrane

Fenestration(pore)

Filtrate incapsularspace

Foot processesof podocyte

Filtration slit

Slit diaphragm

Capillary

Filtration membrane• Fenestrated capillary endothelium• Basement membrane• Foot processes of podocyteof glomerular capsule

Plasma

Filtration Membrane

• Porous membrane between the blood and the capsular space

• Consists of

1. Fenestrated endothelium of the glomerular capillaries

2. Gel‐like basement membrane (fused basal laminae of the two other layers)

3. Visceral membrane of the glomerular capsule (podocyteswith foot processes and filtration slits)

BLOOD

Filtration Membrane

• Allows passage of water and solutes smaller than most plasma proteins

– Fenestrations prevent filtration of blood cells

– Negatively charged basement membrane repels large anions such as plasma proteins

– Slit diaphragms also help to repel macromolecules

BLOOD

Filtration Membrane

• Glomerular mesangial cells

– Engulf and degrade macromolecules

– Can contract to change the total surface area available for filtration

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)

• Volume of filtrate formed per minute by the kidneys (120–125 ml/min)

• Governed by (and directly proportional to)

– Total surface area available for filtration

– Filtration membrane permeability

– Net Filtration Pressure

•

Regulation of Glomerular Filtration

• GFR is tightly controlled by two types of mechanisms

• Intrinsic controls (renal autoregulation)

– Act locally within the kidney

• Extrinsic controls

– Nervous and endocrine mechanisms that maintain blood pressure, but affect kidney function

Intrinsic Controls

• Maintains a nearly constant GFR when MAP is in the range of 80–180 mm Hg

• Two types of renal autoregulation

– Myogenic mechanism

– Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus

MAP = mean arterial pressure

Intrinsic Controls: Myogenic Mechanism

• BP constriction of afferent arterioles

– Helps maintain normal GFR

– Protects glomeruli from damaging high BP

• BP dilation of afferent arterioles

– Helps maintain normal GFR

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Intrinsic Controls: Tubuloglomerular Feedback Mechanism

• Flow‐dependent mechanism directed by the macula densa cells

• If GFR increases, filtrate flow rate increases in the tubule

• Filtrate NaCl concentration will be high because of insufficient time for reabsorption

Intrinsic Controls: TubuloglomerularFeedback Mechanism

• Macula densa cells of the JGA respond to NaCl by releasing a vasoconstricting chemical that acts on the afferent arteriole GFR

• The opposite occurs if GFR decreases.

Figure 25‐08

Extrinsic Controls: Sympathetic Nervous System

• Under normal conditions at rest

– Renal blood vessels are dilated

– Renal autoregulation mechanisms prevail

Extrinsic Controls: Sympathetic Nervous System

• Under extreme stress

– Norepinephrine is released by the sympathetic nervous system

– Epinephrine is released by the adrenal medulla

– Both cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin

Extrinsic Controls: Renin‐Angiotensin Mechanism

• Triggered when the granular cells of the JGA release renin

angiotensinogen (a plasma globulin)

angiotensin I

angiotensin converting enzyme (ACE)

angiotensin II

RENIN

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Effects of Angiotensin II

1. Constricts arteriolar smooth muscle, causing MAP (mean arterial pressure) to rise

2. Stimulates the reabsorption of Na+

– Acts directly on the renal tubules

– Triggers adrenal cortex to release

3. Stimulates the hypothalamus to release ADH and activates the thirst center

Effects of Angiotensin II

4. Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption

5. Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration

Extrinsic Controls: Renin‐Angiotensin Mechanism

• Triggers for renin release by granular cells

– Reduced stretch of granular cells (MAP below 80 mm Hg)

– Stimulation of the granular cells by activated macula densa cells

– Direct stimulation of granular cells via 1‐adrenergic receptors by renal nerves

STEP 2; Tubular Reabsorption

• A selective transepithelial process– All organic nutrients (glucose, amino acids) are reabsorbed

– Water and ion re‐absorption are hormonally regulated

• Includes active and passive process

• Two routes– Transcellular

– Paracellular

Ca2+, Mg2+, K+,

Na+

Tubular Reabsorption

• Transcellular route

– Luminal membranes of tubule cells

– Cytosol of tubule cells

– Basolateral membranes of tubule cells

– Endothelium of peritubular capillaries

Tubular Reabsorption

• Paracellular route

– Between cells

– Limited to water movement and reabsorption of Ca2+, Mg2+, K+, and some Na+ in the PCT where tight junctions are leaky

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Figure 25.13

Activetransport

Passivetransport

Peri-tubular

capillary

2

4

4

3

31

1 2 43

Filtratein tubulelumen

Transcellular

Paracellular

Paracellular

Tight junction Lateral intercellular space

Capillaryendothelialcell

Luminalmembrane

Solutes

H2O

Tubule cell Interstitialfluid

Transcellular

Basolateralmembranes

1 Transport across the luminal membrane.2 Diffusion through the cytosol.

4 Movement through the interstitial fluid and into the capillary.

3 Transport across the basolateralmembrane. (Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces.)

Movement via thetranscellular route involves:

The paracellular routeinvolves:

• Movement through leaky tight junctions, particularly in the PCT.

Sodium Reabsorption

• Na+ (most abundant cation in filtrate)

– Primary active transport out of the tubule cell by Na+‐K+ ATPase in the basolateral membrane

– Na+ passes in through the luminal membrane by secondary active transport or facilitated diffusion mechanisms

Sodium Reabsorption

• Low hydrostatic pressure and high osmotic pressure in the peritubular capillaries

• Promotes bulk flow of water and solutes (including Na+)

• Na+ reabsorption provides the energy and the means for reabsorbing most other substances

Reabsorption of Nutrients, Water, and Ions

• Organic nutrients are reabsorbed by secondary active transport

– Transport maximum (Tm) reflects the number of carriers in the renal tubules available

– When the carriers are saturated, excess of that substance is excreted

– Example

Reabsorption of Nutrients, Water, and Ions

• Water is reabsorbed by osmosis, aided by water‐filled pores called aquaporins

• Cations and fat‐soluble substances follow by diffusion

Figure 25.14

1 At the basolateral membrane, Na+ is pumped into the interstitial space by the Na+-K+

ATPase. Active Na+ transport creates concentration gradients that drive:

2 “Downhill” Na+ entry at theluminal membrane.

4 Reabsorption of water byosmosis. Water reabsorptionincreases the concentration of the solutes that are left behind. These solutes can then be reabsorbed asthey move down their concentration gradients:

3 Reabsorption of organic nutrients and certain ions by cotransport at the luminal membrane.

5 Lipid-solublesubstances diffuse by the transcellular route.6 Cl– (and other anions), K+, and urea diffuse by the paracellular route.

Filtratein tubulelumen

GlucoseAmino

acidsSome

ionsVitamins

Lipid-solublesubstances

Nucleus

Tubule cell

Paracellularroute

Interstitialfluid

Peri-tubular

capillary

Tight junction

Primary active transport

Passive transport (diffusion)Secondary active transport

Transport protein

Ion channel or aquaporin

Cl–, Ca2+, K+

and otherions, urea

Cl–

3Na+

2K+

3Na+

2K+

K+

H2O

Na+

6

5

4

3

2

1

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Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

• PCT

– Site of reabsorption

• 65% of Na+ and water

• All nutrients

• Ions

• Small proteins

• Any plasma proteins removed by endocytosisand degraded


• Loop of Henle

– Descending limb: H2O

– Ascending limb: Na+, K+, Cl


• DCT and collecting duct

– Reabsorption is hormonally regulated

–• Ca2+ (Para Thyroid Hormone)

• Water (Anti Diuretic Hormone)

• Na+ (Aldosterone and Anti Natriuretic Peptide)


• Mechanism of Aldosterone

– Targets collecting ducts (principal cells) and distal DCT

– Promotes synthesis of luminal Na+ and K+ channels

– Promotes synthesis of basolateral Na+‐K+ ATPases

– Little to no Na+ leaves in urine

STEP 3; Tubular Secretion

• Reabsorption in reverse

– K+, H+, NH4+, creatinine, and organic acids move

from peritubular capillaries or tubule cells into filtrate

• Disposes of substances that are bound to plasma proteins

Two ways to eliminate unwanted substances

Don’t reabsorb them

OR

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

renal system spring 2016-student - iowa state university...learning objectives renal system •...

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