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Urinary SystemI. Kidneys

A. Anatomy1. External Anatomy (Review Anatomy)

a. Kidneys are retroperitonealb. Right kidney is lower due to liverc. Terms:

(1) renal capsule, renal adipose capsule, hilum (small amount)2. Internal Anatomy

a. Gross structures:(1) Cortex(2) Medulla(3) Renal pyramids

(a) Medullary rays - extend from pyramids into cortex(b) Renal column - extension of cortex between pyramids(c) Renal papillae - tip of pyramid

(4) Minor and Major calyces(5) Renal pelvis(6) Ureter

b. Microscopic structures of kidney(1) Nephron - basic funct ional unit of the

kidney(a) Consists of renal corpuscle, proximal

convoluted tubule, loop of Henle(nephron loop), distal convolutedtubule.

(b) 1,300,000 nephrons / kidney(c) 1/3 must be functional for survival

(2) renal corpuscle - enlarged end ofnephron(a) glomerulus - network of capillaries.

i) fenestrae (windows) - ii) Afferent arteriole - supplies blood to glomerulusiii) Efferent arteriole - drains glomerulus

(b) Bowman’s capsule - surrounds theglomerulusi) parietal layer - outer layer simple

squamous epitheliumii) visceral layer - inner layer made of

podocytesiii) fenestrae - openings in capillary walls.iv) filtration slits - between the podocytes

surrounding capillaries(c) Filtration membrane

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i) composed of capillary endothelium (withfenestrae), basement membrane,podocytes (with filtration slits)

ii) urine passes from capillary to lumenof Bowman’s capsule

(3) juxtaglomerular apparatus(a) juxtaglomerular cells - smooth muscle

cells form a cuff around the afferentand efferent arteriole

(b) macula densa - specialized cells inportion of distal convoluted tubule incontact with the afferent arteriole /juxtaglomerular cells.

(4) Proximal convoluted tubule(a) simple cuboidal epi.(b) contain microvilli on luminal

surface(5) Loope of Henle (nephric loop)

(a) desending limbi) similar in structure to

proximal tubuleii) thin near endiii) change form simple cuboidal

to simple squam.(b) ascending limb

i) transit ion form simplesquamous to simple cuboidal

(6) Distal Convoluted tubule(a) simple cuboidal with no microvilli

(7) Collecting ducts(a) simple cuboidal (b) extend through the medulla to papillae.

3. Arteries and Veinsa. Renal artery - b. segmental a.c. interlobar - within renal columnsd. Arcuate a. - across base of pyramide. Interlobular a. - project into cortex.f. Afferent a. g. Glomerulush. Efferent a.i. Peritubular capillaries - around proximal and distal convoluted tubules

(1) vasa recta - enter medulla along with loopsj. Interlobular v.k. Arcuate veinsl. Interlobar veins

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m. Renal vein

4. Ureters and urinary bladdera. Ureters - extend inferiorly from kidney from renal pelvisb. Urinary bladder

(1) muscular container. (2) size depends on presence of urine(3) Trigone - triangular area between two ureters and urethra(4) Urethra

(a) internal urinary sphincter - smooth muscle(b) external urinary sphincter - skeletal muscle

II. Urine ProductionNephron is the functional unit of the kidney - produces urine3 steps to Urine production - filtration, reabsorption, secretion

(Fig. 26.8)a. Filtration - movement of materialacross the filtration membrane intoBoman’s capsule as a result ofpressure.b. reabsorption of solutes acrossnephron wall back into the blood byactive transport and co-transportmechanisms.c. reabsorption of water back intothe blood by osmosisd. secretion of solutes across thewall of the nephron into filtrate.

Urine produced consists of thesubstances filltered and secreted intothe nephron minus the substancesreabsorbed.

A. Filtration -movement of fluid across the filtration membrane (Table 26.2)1. Renal fraction - part of the total cardiac output that passes through the urine

a. 21% of cardiac output flows through the kidney(1) 5600 ml / min X 21% = 1176 ml / min

2. renal blood flow rate = 1176 ml / min3. Renal plasma flow rate = renal blood flow rate X portion of the blood that is plasma (55%)

a. 1176 ml / min X 0.55 = 646 ml / min.4. Filtration fraction - part of plasma filtered into Boman’s capsule

a. 19% of plasmab. 650 ml / min X 0.19% = 123.5 ml plasma / minc. ~125 ml of filtrate is produced each minuted. Glomerular filtration rate - amount of filtrate produced each minute

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(1) approximately 180 L per daye. 99% is reabsobed - less than 1 % becomes urine

5. Filtration Barriera. Filtration membrane:

(1) Consists of: the capillary endothelium, basement membrane, podocytes(2) stops blood cells and proteins from entering Boman’s capsule

(a) moleucules larger than 7 nm (40,000 daltons)i) albumin - ~7nm enters in small amounts

(3) lets other blood components enter(a) water and solutes of small diameter(b) Small proteins that pass are reabsorbed by endocytosis in proximal tubule.

6. Filtration Pressurea. Result of the sum of the forces that move fluid out of the glomerular capillary into the lumen

of bowman’s capsule and those that move the fluid out of the capsule and into the capillary.b. Forces fluid from capillary into the capsule.

(1) Glomerular capillary pressure = 45 mmHg (much higher than in most capillaries)(2) Capsule pressure = 10 mmHg(3) Colloid osmotic pressure - result of unfiltered plasma proteins remaining in capillary

(a) = 28 mmHg.(4) Total filtration pressure is ~ 10 mmHg.

(a) 45 - 10 -28 = 7 mmHgc. Pressure is determined by the diameter size of afferent and efferent capillaries

(1) afferents and glomerular capillaries have a large diameter and low resistance.(2) efferents have a small diameter and high resistance.

(a) As vessel diameter decreases, resistance to flow increases resulting in a higher pressurein the glomerular capillary.

(3) Diameters are adjustable by the smooth muscle in walls of afferent and efferent arterioles.

B. Tubular reabsorption - movement of substances from the filtrate back into the blood1. Filtrate leaves capsule and travels through the ducts

a. Substances in filtrate must be reabsorbed.b. Solutes to be reabsorbed:

(1) amino acids, glucose, fructose, Na+ , K+, Ca++, HCO3-, Cl-(a) transported across the epithelial cells of nephron by cotransport

(2) Water follows solutes (a) Water is reabsorbed as solutes move back into low pressure peritubular capillaries

c. Urine is composed of high concentrations of:(1) Urea, uric acid, creat inine, K+(2) can be toxic in high concentrations

d. Regulation of the concentration of the urine is regulated by the permeability

and reabsorption characteristics of the different portions of the nephron.(1) 99% of the volume of the filtrate is reabsorbed

2. Transport in the proximal tubule -(remind of structure)

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a. Active transport of Na+ (Basal membrane)(1) from cytoplasm through the basal cell membrane to interstitial fluid (outside duct)(2) creates a low concentration of Na+ in the cell(3) result: net movement of Na+ from high concentration in duct into the cells of the duct.(4) This concentration gradient is the source of energy for other transport mechanisms.

b. Cotransport -(1) Carrier molecules on the Apical membrane:

(a) move amino acids, glucose, phosphate, lactate, chloride ions.(b) are specific

(2) concentration gradient for Na+ ions provides the energy.(3) Cotransported molecules move through the basal membrane by fascilitated diffusion

c. Countertransport is used for H+ ions(1) As Na+ ions move into the cell, H+ ions are move out of the cell.

d. Diffusion between cells.(1) K+, Ca++, Mg++ move from lumen, between cells into interstitial space by diffusion.

e. Water follows Solutes(1) Amino acids, Na++, K+, HCO3-, and Cl- are moved against their concentration gradient(2) Water follows the movement of ions by osmosis

f. 65% of filtrate is reabsorbed in proximal tubule.(1) Concentrat ion of filtrate remains about the same as the interstitial fluid

3. Transport in the Loop of Henlea. Descending limb

(1) concentration of solutes is high in medulla(2) permiability is high to water and moderate to urea, Na+ and other ions(3) water moves out or nephron, some solutes move in(4) filtrate volume is reduced by another 15%(5) filtrate is concentrated (1200 mOsm / L) compared to 300 mOsm / L in blood

b. Ascending limb(1) impermeable to water(2) Na+, K+ and Cl- ions are trasported out of nephron into the interstitial fluid.(3) result:

(a) the concentration of the solutes is reduced to 100mOsm when it reaches the distaltubule

(b) filtrate is much more dilute(lower concentration of solutes) than when it enters theloop of Henle.

4. Transport in the Distal Tubule and Collecting Ducta. Na+ and Cl- ions are active transported across the wallb. Osmolarity changes from cortex (300 mOsm) to medulla (1200 mOSm)c. Permeability is dependent on the pressence of ADH

(1) ADH increases permeability of cell to water(a) water moves by osmosis out of tubule and duct

(2) No ADH: Cells are impermiable to water (a) water remains in the nephron

(3) Fitrate movemement summary:

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(a) 65% of filtrate removed in proximal tubule(b) 15% in loop of Henle(c) 19% in distal tubule and collecting duct when ADH is present

5. Changes in the Concentration of Solutes in the Nephrona. Urea - enters the nephron at the same concentration as the blood

(1) it is only passively reabsorbed(a) 40-60% taken back up while 99% of water is reabsorbed(b) Result:

i) concentration of urea increases as water is removed.ii) Urea is excreted from the body

b. Urate ions, creatinine sulfates, phosphates and nitrates are removed in a similar way.(1) removal of toxic substances maintains homeostasis

C. Tubular Secretion - active transport of substances into the nephron.1. Can be act ive or passive2. Ammonia is synthesized in the epithelial cells of ducts and passively diffuses into the nephron3. H+, K+ ions are actively transported into the nephron (Proximal and distal tubules)4. Penicillin - not normally found in the body is actively transported out.

D. Urine concentration mechanism1. Kidney can produce urine of varying concentrations

a. From 65 to 1200 mOsm / Lb. When large volumes of water are consumed the kidney produces large amounts of dilute urinec. When water is limited the urine is concentrated.d. Homeostatis is maintained at 300 mOsm / L

2. Medullary concentration gradienta. Osmolarity in tips of renal pyramids reaches 1200 mOsm/kg tissueb. Depends on vasa recta, loop of Henle and distribution of urea.

(1) Vasa recta(a) reabsorb water and solutes that enter the interstitial fluid(b) must reabsorb water etc while maintaining a high concentration of solutes in the

medullary interstitial fluid.(c) forms a countercurrent system (note blood flow is reversed to tubule flow)

i) Blood flows from cortex to the medulla and back in parallel tubules to the loop ofHenle but in a reversed direction of flow (ie. Counter current).

ii) As if blood flows to the medullaa) water diffuses from the blood into the interstitial spaceb) solutes flow from concentrated interstitial fluid into blood

iii) At apex a) blood is the same concentration as the interstitial fluid

iv) Medulla to cortexa) solutes diffuse out of vasa recta into interstitial fluidb) water diffuses into the blood.

v) blood leaving is only slightly more concentrated than blood entering(2) Loop of Henle

(a) Countercurrent multiplier systemi) increases the concentration of Na+ ions within the medulla while making the

filtrate dilute.

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ii) the countercurrent system is assisted by active transport mechanismsa) moves solutes from the lumen of ascending limb to interstitial fluidb) ascending limb is not permiable to water. c) water is carried away

iii) makes the concentrating function of the kidney more efficient iv) Active transport of solutes helps maintian a high concentration of solutes in the

interstitial fluid of the medullav) filtrate in ascending limb decreases from 1200mOsm to 100 mOsm/kg.

(3) Urea(a) Urea diffuses into descending limb of loop(b) Ascending limb of the loop of Henle and distal tubules are not permeable to urea(c) collecting duct are permiable(d) urea diffuses out of collecting duct and into the descending limb(e) Result: A high concentration of Urea is maintained in the medulla

3. Summary of Changes in Filtrate Volume and Concentrationa. 180 L of filtrate enters the nephron each dayb. 65% reabsorbed in the proximal tubule

(1) solutes are transported from the lumen into the interstitial fluid(2) water follows - proximal tubule is permeable to water

c. 15% of filtrate is reabsorbed in the descending loop of Henle(1) Loop passes through the concentrated fluid of the medulla(2) Descending limb is permeable to water(3) Water diffuses out of the tubule into the concentrated interstitial fluid.(4) Concentration inside = concentration outside by apex of medulla.

d. Ascending Limb is not permeable to water(1) Na+, K+ and Cl- are actively transported out of the filtrate and into the interstitial fluid(2) Result: No change in volume but concentration drops to 100mOsm/L (less concentrated

than cortex)e. Distal tubule and collecting duct are permeable to water if ADH is present.

(1) With ADH - water diffuses from the concentrated filtrate into the interstitial fluid.(2) 19% of filtrate is reabsorbed.

f. 1% of filtrate remains as urine.

III. Regulation of Urine Concentration and VolumeA. Urine can be dilute or very concentrated and can be produced in small or large amounts

1. Filtrate reabsorption in the proximal tubule and descending limb is obligatory2. Reabsorption in the distal tubule and collecting duct is regulated

a. Homeostasis is maintained by these segmentsb. Regulation involves hormonal mechanisms, autoregulation and the nervous system.

B. Hormonal Mechanisms1. Antidiuretic Hormone

a. Released from posterior pitutitary - (1) made in supraoptic nucleus which has osmoreceptors.(2) regulated by blood pressure (baroreceptors) in aorta that send signals to supraoptic

b. Blood volume decrease, BP decreases and/or osmolarity increases (1) result:

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(a) greater release of ADH and (b) greater reabsorption of water from distal tubule and collecting duct

c. Volume increases and osmolarity decreases (1) result:

(a) decrease in ADH release(b) decrease in reabsorption of water from distal tubule and collecting duct

d. Diabetes insipidus - large volume, no taste (1) due to insufficient ADH production(2) 10 - 20 L of urine produced / day

e. Diabetes mellitus- large volume w/ glucose

2. Renin-Angiotensin-Aldosteronea. Renin

(1) produced by the juxtaglomerular apparatus(2) Rate of production increases as BP decreases or Na+ (Cl-)concentration decreases(3) monitored by the macula densa

b. Renin causes angiotensinogen to be converted to angiotensin I c. Angiotensin I is converted to angiotensin II in the lungs.d. Angiotensin II

(1) is a potent vasoconstrictor and (2) activates the zona glomerulosa of adrenal to produce aldosterone.

e. Aldosterone(1) increase the expression/ synthesis of transport proteins for Na+ ions across the membrane(2) Result: increased reabsorption (active transport) of Na+ in ascending limb of Loop and

excretion of K+ and H+

3. Atrial Natuiuretic Hormonea. Secreted by cardiac muscleb. BP increase causes increase in productionc. ANH inhibits ADH secretiond. Decrease in ADH causes large amounts of dilute urine to be produced.e. Blood volume and pressure drops.

C. Autoregulation

1. Involves changes in the degree of constriction in the afferent arterioles - thus changing the rate offiltation.

2. Mechanism unclear3. BP increase results in constriction of afferent arterioes

a. Prevents an increase in renal blood flow and filtration pressure / filtrate formation4. BP decreases - dilation of the afferent arteriole

a. Prevents a decrease in renal blood flow and filtration pressure

D. Effect fo Sympathetic Stimulation of Kidney Function1. Sympathetic neurons:

a. innervate blood vessels releasing NE and b. constricting small arteries and afferent arteioles

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2. Decreases renal blood flow and filtrate formation.3. Shock or intense exercise decreases the rate of urine formation.4. Extreme shock can reduce blood flow to the kidney to the degree that normal metabolism is

affected - results in kidney tissue damage .

IV. Urine MovementA. Urine Flow Through the Nephron and the Ureters

1. Flow into the renal pelvis is due to hydrostatic pressure generated at the glomerulus2. Urine flows through ureters due to peristaltic movement in the ureters.

a. Peristaltic movement can generate pressure of 50 mmHg.b. Pressure in the bladder compresses the ureter at the trigone prevent ing backflow of urinec. Bladder pressure increases as bladder is filled d. Capacity 400-500 ml no change in pressuree. Above 500 ml pressure increases causing a micturition reflex

B. Micturition Reflex