Chapter 26

Urinary System

Urinary System Functions

Removal of metabolic waste products from the blood and their excretion in the urine Removal of foreign chemicals from the blood and their excretion in the urine. Regulation of
Blood volume Concentration of blood solutes: Na+, Cl-, K+, Ca2+, HPO4-2 Acid-base balance Blood cell synthesis

Production of hormones (EPO) and enzymes (Renin) Production of 1,25-dihydroxyvitamin D3

Nephron Functions: Overview

Figure 19-2: Filtration, reabsorption, secretion, and excretion

Fluid filtered from the blood in the glomerular capillaries is altered by reabsorption and secretion along the length of the 1,000,000 nephrons/kidney.

1. Glomerular filtration refers to the movement of fluid and solutes from the glomerular capillaries into Bowmans space.

1. Glomerular filtration refers to the movement of fluid and solutes from the glomerular capillaries into Bowmans space. 2. Tubular secretion refers to the secretion of solutes from the peritubular capillaries into the tubules.

1. Glomerular filtration refers to the movement of fluid and solutes from the glomerular capillaries into Bowmans space. 2. Tubular secretion refers to the secretion of solutes from the peritubular capillaries into the tubules. 3. Tubular reabsorption refers to the movement of materials from the filtrate in the tubules into the peritubular capillaries.

Substance X is filtered and secreted but not reabsorbed. Substance Y is filtered and some of it is reabsorbed. Substance Z is filtered and completely reabsorbed.

Filtration
Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane Filtrate: water, small molecules, ions that can pass through membrane Pressure difference forces filtrate across filtration membrane Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12-30%; averages 21% Renal blood flow rate: 1176 mL/min Renal plasma flow rate: renal blood flow rate X fraction of blood that is plasma: 650 mL/min Filtration fraction: part of plasma that is filtered into lumen of Bowmans capsules; average 19% Glomerular filtration rate (GFR): amount of filtrate produced each minute. About 125 ml/min = 180 L/day (45 gallons/day!!) Average urine production/day: 1-2 L. Most of filtrate must be reabsorbed

Filtration Pressure
(Opposes filtration) (Favors Filtration)

(Opposes filtration)

(Net Filtration Pressure - NFP)

Glomerular Filtration Rate (GFR)

Defined as: The volume of filtrate produced by both kidneys per min
Averages 115 ml/min in women; 125 ml/min in men Totals about 180L/day (45 gallons)
So most filtered water must be reabsorbed or death would ensue from water lost through urination

GFR is directly proportional to the NFP

Increase GFR leads to an increase in NFP Decrease in GFR leads to a decrease in NFP

Changes in GFR normally result from changes in glomerular blood pressure (Gcp)
17-24

Regulation of GFR
Glomerular Filtration Rate
If the GFR is too high:
Fluid flows through tubules too rapidly to be absorbed Urine output rises
Creates threat of dehydration and electrolyte depletion

If the GFR is too low:

Fluid flows sluggishly through tubules Tubules reabsorb wastes that should be eliminated Azotemia develops (high levels of nitrogen-containing substances in the blood)

Only way to adjust GFR moment to moment is to change glomerular blood pressure

As vasodilation and vasoconstriction of the afferent and efferent arterioles alter the blood flow through the glomerular capillaries, there are corresponding alterations in the glomerular filtration rate (GFR).

Renal Autoregulation
Renal autoregulation: the ability of nephrons to adjust their own blood flow and GFR
IF there were no renal autoregulation and MAP rose from 100 mmHg to 125 mmHg, urine output would rise from 1.5 L/day to 45 L/day!!

Two mechanisms used to renal autoregulate:

Myogenic Response
When average BP drops to 70 mm Hg afferent arteriole dilates When average BP increases, afferent arterioles constrict Allows kidney to maintain a constant GFR over wide range of BPs

Tubuloglomerular feedback Increased flow of filtrate sensed by macula densa (MD) Macula densa signals afferent arterioles to constrict

17-27

Extrinsic Control of GFR

When the sympathetic nervous system is at rest: Renal blood vessels are maximally dilated Autoregulation mechanisms prevail Under stress: Norepinephrine is released by the sympathetic nervous system Epinephrine is released by the adrenal medulla Afferent arterioles constrict and filtration is inhibited Note: during fight or flight blood is shunted away from kidneys The sympathetic nervous system also stimulates the reninangiotensin mechanism

Sympathetic Effects
Sympathetic activity constricts afferent arteriole
Helps maintain BP & shunts blood to heart & muscles

17-26

Tubular Reabsorption
(In Reference to Previous Slide)
Filtered loads are enormous E.g. only 40 L of water in body, but 180 L filtered per day Reabsorption of waste products is relatively incomplete Thus, large fractions of their filtered load are excreted in the urine Reabsorption of most useful plasma components is relatively complete Thus, amounts excreted in urine represent very small fraction of filtered load

Tubular Reabsorption: Overview

Tubular reabsorption: occurs as filtrate flows through the lumens of proximal tubule, loop of Henle, distal tubule, and collecting ducts Processes used in reabsorption include:
Diffusion Facilitated diffusion Active transport Cotransport Osmosis

Reabsorbed substances are transported to interstitial fluid and reabsorbed into peritubular capillaries.

Tubular Reabsorption and Secretion

Mechanisms of Reabsorption in the Proximal Convoluted Tubule

Peritubular Capillaries
Blood has unusually high COP here, and BHP is only 8 mm Hg
This favors reabsorption

Water absorbed by osmosis and carries other solutes with it (solvent drag)

Reabsorption of Salt & H20

The PCT returns most molecules & H20 from filtrate back to peritubular capillaries
About 180 L/day of ultrafiltrate produced; only 12 L of urine excreted/24 hours
Urine volume varies according to needs of body Minimum of 400 ml/day urine necessary to excrete metabolic wastes (obligatory water loss)

17-31

PCT
Filtrate in PCT is isosmotic to blood (300 mOsm/L) Thus reabsorption of H20 by osmosis cannot occur without active transport (AT)
Is achieved by AT of Na+ out of filtrate
Loss of + charges causes Cl- to passively follow Na+ Water follows salt by osmosis

17-33

Insert fig. 17.14

Fig 17.15

Glucose & Amino Acid Reabsorption

Filtered glucose & amino acids are normally 100% reabsorbed from filtrate
Occurs in PCT by carrier-mediated cotransport with Na+
Transporter displays saturation if ligand concentration in filtrate is too high
Level needed to saturate carriers & achieve maximum transport rate is transport maximum (Tm)

Glucose & amino acid transporters don't saturate under normal conditions

17-58

Tubular Maximum

Tubular Maximum (TM: Defined as Maximum rate at which a substance can be actively absorbed Each substance has its own tubular maximum Normally, glucose concentration in the plasma (and thus filtrate) is lower than the tubular maximum and all of it is reabsorbed. In diabetes mellitus, tubular load exceeds tubular maximum and glucose appears in urine. Urine volume increases because glucose in filtrate increases osmolality of filtrate reducing the effectiveness of water reabsorption

Significance of PCT Reabsorption

65% Na+, Cl-, & H20 is reabsorbed in PCT & returned to bloodstream An additional 20% is reabsorbed in descending limb of the loop of Henle Thus 85% of filtered H20 & salt are reabsorbed early in tubule
This is constant & independent of hydration levels Energy cost is 6% of calories consumed at rest The remaining 15% is reabsorbed variably, depending on level of hydration
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Medullary Concentration Gradient

In order to concentrate urine (and prevent a large volume of water from being lost), the kidney must maintain a high concentration of solutes in the medulla Interstitial fluid concentration (mOsm/kg) is 300 in the cortical region and gradually increases to 1400 at the tip of the pyramids in the medulla Maintenance of this gradient depends upon
Functions of loops of Henle Vasa recta flowing countercurrent to filtrate in loops of Henle Distribution and recycling of urea

Descending Limb
Is permeable to H20 Is impermeable to salt Because deep regions of medulla are 1400 mOsm, H20 diffuses out of filtrate until it equilibrates with interstitial fluid
This H20 is reabsorbed by capillaries

17-37

Ascending Limb LH
Has a thin segment in depths of medulla & thick part toward cortex Impermeable to H20 Permeable to salt Thick part ATs salt out of filtrate
AT of salt causes filtrate to become dilute (100 mOsm) by end of LH

17-38

AT in Ascending Limb
NaCl is actively extruded from thick ascending limb into interstitial fluid Na+ diffuses into tubular cell with secondary active transport of K+ and Cl-

Insert fig. 17.15

17-39

AT in Ascending Limb continued

Na+ is AT across basolateral membrane by Na+/ K+ pump Cl- passively follows Na+ down electrical gradient K+ passively diffuses back into filtrate

17-40

Countercurrent Multiplier System

Countercurrent flow & proximity allow descending & ascending limbs of LH to interact in way that causes osmolarity to build in medulla Salt pumping in thick ascending part raises osmolarity around descending limb, causing more H20 to diffuse out of filtrate
This raises osmolarity of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolarity around descending limb (positive feedback) Process repeats until equilibrium is reached when osmolarity of medulla is 1400

17-41

Vasa Recta
Is important component of countercurrent multiplier Permeable to salt, H20 (via aquaporins), & urea Recirculates salt, trapping some in medulla interstitial fluid Reabsorbs H20 coming out of descending limb Descending section has urea transporters Ascending section has fenestrated capillaries

17-42

Effects of Urea
Urea contributes to high osmolality in medulla
Deep region of collecting duct is permeable to urea & transports it

17-43

Osmotic Gradient in the Renal Medulla

Figure 25.13

Urine Concentrating Mechanisms

17-44

Collecting Duct (CD)

Plays important role in water conservation Is impermeable to salt in medulla Permeability to H20 depends on levels of ADH

17-45

ADH
Is secreted by posterior pituitary in response to dehydration Stimulates insertion of aquaporins (water channels) into plasma membrane of CD When ADH is high, H20 is drawn out of CD by high osmolality of interstitial fluid
& reabsorbed by vasa recta

17-46

Formation of Concentrated Urine

ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine ADH stimulates formation of aquaporins in membrane of tubule cells. Increases water reabsorption from filtrate The kidneys ability to respond depends upon the high medullary osmotic gradient

Urine Movement
Hydrostatic pressure forces urine through nephron Peristalsis moves urine through ureters from region of renal pelvis to urinary bladder. Occur from once every few seconds to once every 2-3 minutes
Parasympathetic stimulation: increase frequency Sympathetic stimulation: decrease frequency

Ureters enter bladder obliquely through trigone. Pressure in bladder compresses ureter and prevents backflow

Composition and Properties of Urine

Appearance
almost colorless to deep amber; yellow color due to urochrome, from breakdown of hemoglobin (RBCs)

Odor - as it stands bacteria degrade urea to ammonia Specific gravity

density of urine ranges from 1.001 -1.028

Osmolarity - (blood - 300 mOsm/L) ranges from

50 mOsm/L to 1,200 mOsm/L in dehydrated person

pH - range: 4.5 - 8.2, usually 6.0 Chemical composition: 95% water, 5% solutes
urea, NaCl, KCl, creatinine, uric acid

Neural Control of Micturition

Micturition Reflex

Micturition Reflex
Filling of bladder stimulates stretch receptors.
Stimulate parasympathetic fibers which:
inhibits contraction of the external urethral sphincter stimulates contraction of the detrusor muscle of the bladder

Urine Volume
Normal volume - 1 to 2 L/day Polyuria > 2L/day Oliguria < 500 mL/day Anuria - 0 to 100 mL/day

Diuretics
Effects
urine output blood volume

Uses
hypertension and congestive heart failure

Mechanisms of action
GFR tubular reabsorption

Kidney Diseases
In acute renal failure, ability of kidneys to excrete wastes & regulate blood volume, pH, & electrolytes is impaired
Rise in blood creatinine & decrease in renal plasma clearance of creatinine Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs

Glomerulonephritis is inflammation of glomeruli

Autoimmune attack against glomerular capillary basement membranes
Causes leakage of protein into urine resulting in decreased colloid osmotic pressure & resulting edema

17-80

Kidney Diseases continued

In renal insufficiency, nephrons have been destroyed as a result of a disease
Clinical manifestations include salt & H20 retention & uremia (high plasma urea levels)
Uremia is accompanied by high plasma H+ & K+ which can cause uremic coma

Treatment includes hemodialysis

Patient's blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane Urea & other wastes are removed

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Diabetes
Chronic polyuria of metabolic origin With hyperglycemia and glycosuria
diabetes mellitus I and II, insulin
hyposecretion/insensitivity

gestational diabetes, 1 to 3% of pregnancies ADH hyposecretion diabetes insipidus; CD water reabsorption