The urinary system

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Human Anatomy & Physiology SEVENTH EDITION

Elaine N. Marieb

Katja Hoehn

PowerPoint® Lecture Slides

prepared by Vince Austin,

Bluegrass Technical

and Community College

C H

A P

T E

R

25 The Urinary System

P A R T A


Kidney Functions

Filter 200 liters of blood daily, allowing toxins,

metabolic wastes, and excess ions to leave the

body in urine

Regulate volume and chemical makeup of the

blood

Maintain the proper balance between water and

salts, and acids and bases


Other Renal Functions

Gluconeogenesis during prolonged fasting

Production of rennin to help regulate blood

pressure and erythropoietin to stimulate RBC

production

Activation of vitamin D


Other Urinary System Organs

Urinary bladder – provides a temporary storage

reservoir for urine

Paired ureters – transport urine from the kidneys to

the bladder

Urethra – transports urine from the bladder out of

the body


Urinary System Organs

Figure 25.1a


Kidney Location and External Anatomy

The kidneys lie in a retroperitoneal position in the superior lumbar region

The right kidney is lower than the left because it is crowded by the liver

The lateral surface is convex; the medial surface is concave

The renal hilus leads to the renal sinus

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


Layers of Tissue Supporting the Kidney

Renal capsule – fibrous capsule that prevents

kidney infection

Adipose capsule – fatty mass that cushions the

kidney and helps attach it to the body wall

Renal fascia – outer layer of dense fibrous

connective tissue that anchors the kidney


Internal Anatomy (Frontal Section)

Cortex – the light colored, granular superficial

region

Medulla – exhibits cone-shaped medullary (renal)

pyramids separated by columns

The medullary pyramid and its surrounding capsule

constitute a lobe

Renal pelvis – flat funnel shaped tube lateral to the

hilus within the renal sinus


PLAY InterActive Physiology ®: Anatomy Review, page 6

Internal Anatomy

Major calyces – large branches of the renal pelvis

Collect urine draining from papillae

Empty urine into the pelvis

Urine flows through the pelvis and ureters to the

bladder

25PPTLect-anim/IP_Urinary_FILES/9-System Suite/ipweb/systems/urinrevw_pg06.html


Internal Anatomy

Figure 25.3b


Blood and Nerve Supply

Approximately one-fourth (1200 ml) of systemic

cardiac output flows through the kidneys each

minute

Arterial flow into and venous flow out of the

kidneys follow similar paths

The nerve supply is via the renal plexus




Renal Vascular Pathway

Figure 25.3c


The Nephron

Nephrons are the structural and functional units

that form urine, consisting of:

Glomerulus – a number of capillaries associated

with a renal tubule

Glomerular (Bowman’s) capsule – blind, cup-

shaped end of a renal tubule that completely

surrounds the glomerulus


The Nephron

Renal corpuscle – the glomerulus and its

Bowman’s capsule

Glomerular endothelium – fenestrated epithelium

that allows solute-rich, virtually protein-free filtrate

to pass from the blood into the glomerular capsule

PLAY InterActive Physiology ®: Urinary: Anatomy Review, pages 7-9



The Nephron

Figure 25.4a, b


Renal Tubule

Proximal convoluted tubule (PCT) – composed of

cuboidal cells with numerous microvilli and

mitochondria

Reabsorbs water and solutes from filtrate and

secretes substances into it


Renal Tubule

Loop of Henle – a hairpin-shaped loop of the renal tubule

Proximal part is similar to the proximal convoluted tubule

Proximal part is followed by the thin segment (simple squamous cells) and the thick segment (cuboidal to columnar cells)

Distal convoluted tubule (DCT) – cuboidal cells without microvilli that function more in secretion than reabsorption


Renal Tubule

Figure 25.4b


Connecting Tubules

The distal portion of the distal convoluted tubule

nearer to the collecting ducts


Connecting Tubules

Two important cell types are found here

Intercalated cells

Cuboidal cells with microvilli

Function in maintaining the acid-base balance of

the body

Principal cells

Cuboidal cells without microvilli

Help maintain the body’s water and salt balance

PLAY InterActive Physiology ®: Anatomy Review, pages 12–15, 17–19



Nephrons

Cortical nephrons – 85% of nephrons; located in the cortex

Juxtamedullary nephrons:

Are located at the cortex-medulla junction

Have loops of Henle that deeply invade the medulla

Have extensive thin segments

Are involved in the production of concentrated urine


Nephron Anatomy

Figure 25.5a


Capillary Beds of the Nephron

Every nephron has two capillary beds

Glomerulus

Peritubular capillaries

Each glomerulus is:

Fed by an afferent arteriole

Drained by an efferent arteriole


Capillary Beds of the Nephron

Blood pressure in the glomerulus is high because:

Arterioles are high-resistance vessels

Afferent arterioles have larger diameters than

efferent arterioles

Fluids and solutes are forced out of the blood

throughout the entire length of the glomerulus


Capillary Beds

Peritubular beds are low-pressure, porous

capillaries adapted for absorption that:

Arise from efferent arterioles

Cling to adjacent renal tubules

Empty into the renal venous system

Vasa recta – long, straight efferent arterioles of

juxtamedullary nephrons


Capillary Beds

Figure 25.5a


Vascular Resistance in Microcirculation

Afferent and efferent arterioles offer high

resistance to blood flow

Blood pressure declines from 95mm Hg in renal

arteries to 8 mm Hg in renal veins


Vascular Resistance in Microcirculation

Resistance in afferent arterioles:

Protects glomeruli from fluctuations in systemic

blood pressure

Resistance in efferent arterioles:

Reinforces high glomerular pressure

Reduces hydrostatic pressure in peritubular

capillaries


Juxtaglomerular Apparatus (JGA)

Where the distal tubule lies against the afferent

(sometimes efferent) arteriole

Arteriole walls have juxtaglomerular (JG) cells

Enlarged, smooth muscle cells

Have secretory granules containing renin

Act as mechanoreceptors



Macula densa

Tall, closely packed distal tubule cells

Lie adjacent to JG cells

Function as chemoreceptors or osmoreceptors

Mesanglial cells:

Have phagocytic and contractile properties

Influence capillary filtration



Figure 25.6


Filtration Membrane

Filter that lies between the blood and the interior of the glomerular capsule

It is composed of three layers

Fenestrated endothelium of the glomerular capillaries

Visceral membrane of the glomerular capsule (podocytes)

Basement membrane composed of fused basal laminae of the other layers


Filtration Membrane

Figure 25.7a


Filtration Membrane


Figure 25.7c



Mechanisms of Urine Formation

The kidneys filter the body’s entire plasma volume

60 times each day

The filtrate:

Contains all plasma components except protein

Loses water, nutrients, and essential ions to

become urine

The urine contains metabolic wastes and unneeded

substances


Mechanisms of Urine Formation

Urine formation and adjustment of blood composition involves three major processes

Glomerular filtration

Tubular reabsorption

Secretion

Figure 25.8


Glomerular Filtration

Principles of fluid dynamics that account for tissue fluid in all capillary beds apply to the glomerulus as well

The glomerulus is more efficient than other capillary beds because:

Its filtration membrane is more permeable

Glomerular blood pressure is higher

It has a higher net filtration pressure

Plasma proteins are not filtered and are used to maintain oncotic pressure of the blood


Net Filtration Pressure (NFP)

The pressure responsible for filtrate formation

NFP equals the glomerular hydrostatic pressure

(HPg) minus the oncotic pressure of glomerular

blood (OPg) combined with the capsular

hydrostatic pressure (HPc)

NFP = HPg – (OPg + HPc)


Glomerular Filtration Rate (GFR)

The total amount of filtrate formed per minute by

the kidneys

Factors governing filtration rate at the capillary

bed are:

Total surface area available for filtration

Filtration membrane permeability

Net filtration pressure



GFR is directly proportional to the NFP

Changes in GFR normally result from changes in

glomerular blood pressure



Figure 25.9


Regulation of Glomerular Filtration

If the GFR is too high:

Needed substances cannot be reabsorbed quickly

enough and are lost in the urine

If the GFR is too low:

Everything is reabsorbed, including wastes that are

normally disposed of


Regulation of Glomerular Filtration

Three mechanisms control the GFR

Renal autoregulation (intrinsic system)

Neural controls

Hormonal mechanism (the renin-angiotensin

system)


Intrinsic Controls

Under normal conditions, renal autoregulation

maintains a nearly constant glomerular filtration

rate

Autoregulation entails two types of control

Myogenic – responds to changes in pressure in the

renal blood vessels

Flow-dependent tubuloglomerular feedback –

senses changes in the juxtaglomerular apparatus


Extrinsic Controls

When the sympathetic nervous system is at rest:

Renal blood vessels are maximally dilated

Autoregulation mechanisms prevail (takes over)


Extrinsic Controls

Under stress:

Norepinephrine is released by the sympathetic

nervous system

Epinephrine is released by the adrenal medulla

Afferent arterioles constrict and filtration is

inhibited

The sympathetic nervous system also stimulates

the renin-angiotensin mechanism


Renin-Angiotensin Mechanism

Is triggered when the JG cells release renin

Renin acts on angiotensinogen to release angiotensin I

Angiotensin I is converted to angiotensin II

Angiotensin II:

Causes mean arterial pressure to rise

Stimulates the adrenal cortex to release aldosterone

As a result, both systemic and glomerular hydrostatic pressure rise


Renin Release

Renin release is triggered by:

Reduced stretch of the granular JG cells

Stimulation of the JG cells by activated macula

densa cells

Direct stimulation of the JG cells via 1-adrenergic

receptors by renal nerves

Angiotensin II


Renin Release

Figure 25.10


Other Factors Affecting Glomerular Filtration

Prostaglandins (PGE2 and PGI2)

Vasodilators produced in response to sympathetic stimulation and angiotensin II

Are thought to prevent renal damage when peripheral resistance is increased

Nitric oxide – vasodilator produced by the vascular endothelium

Adenosine – vasoconstrictor of renal vasculature

Endothelin – a powerful vasoconstrictor secreted by tubule cells



Elaine N. Marieb

Katja Hoehn



Bluegrass Technical


C H

A P

T E

R

25 The Urinary System

P A R T B


Tubular Reabsorption

A transepithelial process whereby most tubule

contents are returned to the blood

Transported substances move through three

membranes

Luminal and basolateral membranes of tubule cells

Endothelium of peritubular capillaries

Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed

via paracellular pathways


Tubular Reabsorption

All organic nutrients are reabsorbed

Water and ion reabsorption is hormonally

controlled

Reabsorption may be an active (requiring ATP) or

passive process


Sodium Reabsorption:

Primary Active Transport

Sodium reabsorption is almost always by active

transport

Na+ enters the tubule cells at the luminal

membrane

Is actively transported out of the tubules by a

Na+-K+ ATPase pump


Sodium Reabsorption:

Primary Active Transport

From there it moves to peritubular capillaries due

to:

Low hydrostatic pressure

High osmotic pressure of the blood

Na+ reabsorption provides the energy and the

means for reabsorbing most other solutes


Routes of Water and Solute Reabsorption

Figure 25.11


Reabsorption by PCT Cells

Active pumping of Na+ drives reabsorption of:

Water by osmosis, aided by water-filled pores

called aquaporins

Cations and fat-soluble substances by diffusion

Organic nutrients and selected cations by

secondary active transport


Reabsorption by PCT Cells

PLAY InterActive Physiology ®: Early Filtrate Processing, pages 3–15

Figure 25.12

25PPTLect-anim/IP_Urinary_FILES/9-System Suite/ipweb/systems/earlyfil_pg03.html


Nonreabsorbed Substances

A transport maximum (Tm):

Reflects the number of carriers in the renal tubules

available

Exists for nearly every substance that is actively

reabsorbed

When the carriers are saturated, excess of that

substance is excreted


Nonreabsorbed Substances

Substances are not reabsorbed if they:

Lack carriers

Are not lipid soluble

Are too large to pass through membrane pores

Urea, creatinine, and uric acid are the most

important nonreabsorbed substances


Absorptive Capabilities of Renal Tubules and

Collecting Ducts

Substances reabsorbed in PCT include:

Sodium, all nutrients, cations, anions, and water

Urea and lipid-soluble solutes

Small proteins

Loop of Henle reabsorbs:

H2O, Na+, Cl, K+ in the descending limb

Ca2+, Mg2+, and Na+ in the ascending limb


Absorptive Capabilities of Renal Tubules and

Collecting Ducts

DCT absorbs:

Ca2+, Na+, H+, K+, and water

HCO3 and Cl

Collecting duct absorbs:

Water and urea


Na+ Entry into Tubule Cells

Passive entry: Na+-K+ ATPase pump

In the PCT: facilitated diffusion using symport and

antiport carriers

In the ascending loop of Henle: facilitated

diffusion via Na+-K+-2Cl symport system

In the DCT: Na+-Cl– symporter

In collecting tubules: diffusion through membrane

pores


Atrial Natriuretic Peptide Activity

ANP reduces blood Na+ which:

Decreases blood volume

Lowers blood pressure

ANP lowers blood Na+ by:

Acting directly on medullary ducts to inhibit Na+ reabsorption

Counteracting the effects of angiotensin II

Indirectly stimulating an increase in GFR reducing water reabsorption


Tubular Secretion

Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate

Tubular secretion is important for:

Disposing of substances not already in the filtrate

Eliminating undesirable substances such as urea and uric acid

Ridding the body of excess potassium ions

Controlling blood pH


Regulation of Urine Concentration and

Volume

Osmolality

The number of solute particles dissolved in 1L of water

Reflects the solution’s ability to cause osmosis

Body fluids are measured in milliosmols (mOsm)

The kidneys keep the solute load of body fluids constant at about 300 mOsm

This is accomplished by the countercurrent mechanism


Countercurrent Mechanism

Interaction between the flow of filtrate through the

loop of Henle (countercurrent multiplier) and the

flow of blood through the vasa recta blood vessels

(countercurrent exchanger)

The solute concentration in the loop of Henle

ranges from 300 mOsm to 1200 mOsm

Dissipation of the medullary osmotic gradient is

prevented because the blood in the vasa recta

equilibrates with the interstitial fluid


Osmotic Gradient in the Renal Medulla

Figure 25.13


Loop of Henle: Countercurrent Multiplier

The descending loop of Henle:

Is relatively impermeable to solutes

Is permeable to water

The ascending loop of Henle:

Is permeable to solutes

Is impermeable to water

Collecting ducts in the deep medullary regions are permeable to urea


Loop of Henle: Countercurrent Exchanger

The vasa recta is a countercurrent exchanger that:

Maintains the osmotic gradient

Delivers blood to the cells in the area

PLAY InterActive Physiology ®: Early Filtrate Processing, pages 16–21

25PPTLect-anim/IP_Urinary_FILES/9-System Suite/ipweb/systems/earlyfil_pg16.html


Loop of Henle: Countercurrent Mechanism

Figure 25.14


Formation of Dilute Urine

Filtrate is diluted in the ascending loop of Henle

Dilute urine is created by allowing this filtrate to

continue into the renal pelvis

This will happen as long as antidiuretic hormone

(ADH) is not being secreted


Formation of Dilute Urine

Collecting ducts remain impermeable to water; no further water reabsorption occurs

Sodium and selected ions can be removed by active and passive mechanisms

Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)


Formation of Concentrated Urine

Antidiuretic hormone (ADH) inhibits diuresis

This equalizes the osmolality of the filtrate and the

interstitial fluid

In the presence of ADH, 99% of the water in

filtrate is reabsorbed


PLAY InterActive Physiology ®: Late Filtrate Processing, pages 3–12

Formation of Concentrated Urine

ADH-dependent water reabsorption is called

facultative water reabsorption

ADH is the signal to produce concentrated urine

The kidneys’ ability to respond depends upon the

high medullary osmotic gradient

25PPTLect-anim/IP_Urinary_FILES/9-System Suite/ipweb/systems/latefilt_pg03.html


Formation of Dilute and Concentrated Urine

Figure 25.15a, b


Diuretics

Chemicals that enhance the urinary output include:

Any substance not reabsorbed

Substances that exceed the ability of the renal

tubules to reabsorb it

Substances that inhibit Na+ reabsorption


Diuretics

Osmotic diuretics include:

High glucose levels – carries water out with the glucose

Alcohol – inhibits the release of ADH

Caffeine and most diuretic drugs – inhibit sodium ion reabsorption

Lasix and Diuril – inhibit Na+-associated symporters


Summary of Nephron Function

Figure 25.16


Renal Clearance

The volume of plasma that is cleared of a

particular substance in a given time

Renal clearance tests are used to:

Determine the GFR

Detect glomerular damage

Follow the progress of diagnosed renal disease


Renal Clearance

RC = UV/P

RC = renal clearance rate

U = concentration (mg/ml) of the substance in urine

V = flow rate of urine formation (ml/min)

P = concentration of the same substance in plasma


Physical Characteristics of Urine

Color and transparency

Clear, pale to deep yellow (due to urochrome)

Concentrated urine has a deeper yellow color

Drugs, vitamin supplements, and diet can change

the color of urine

Cloudy urine may indicate infection of the urinary

tract



Odor

Fresh urine is slightly aromatic

Standing urine develops an ammonia odor

Some drugs and vegetables (asparagus) alter the

usual odor



pH

Slightly acidic (pH 6) with a range of 4.5 to 8.0

Diet can alter pH

Specific gravity

Is dependent on solute concentration


Chemical Composition of Urine

Urine is 95% water and 5% solutes

Nitrogenous wastes: urea, uric acid, and creatinine

Other normal solutes include:

Sodium, potassium, phosphate, and sulfate ions

Calcium, magnesium, and bicarbonate ions

Abnormally high concentrations of any urinary

constituents may indicate pathology


Ureters

Slender tubes that convey urine from the kidneys

to the bladder

Ureters enter the base of the bladder through the

posterior wall

This closes their distal ends as bladder pressure

increases and prevents backflow of urine into the

ureters


Ureters

Ureters have a trilayered wall

Transitional epithelial mucosa

Smooth muscle muscularis

Fibrous connective tissue adventitia

Ureters actively propel urine to the bladder via

response to smooth muscle stretch


Urinary Bladder

Smooth, collapsible, muscular sac that stores urine

It lies retroperitoneally on the pelvic floor posterior to the pubic symphysis

Males – prostate gland surrounds the neck inferiorly

Females – anterior to the vagina and uterus

Trigone – triangular area outlined by the openings for the ureters and the urethra

Clinically important because infections tend to persist in this region


Urinary Bladder

The bladder wall has three layers

Transitional epithelial mucosa

A thick muscular layer

A fibrous adventitia

The bladder is distensible and collapses when

empty

As urine accumulates, the bladder expands without

significant rise in internal pressure


Urinary Bladder

Figure 25.18a, b


Urethra

Muscular tube that:

Drains urine from the bladder

Conveys it out of the body


Urethra

Sphincters keep the urethra closed when urine is not being passed

Internal urethral sphincter – involuntary sphincter at the bladder-urethra junction

External urethral sphincter – voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm

Levator ani muscle – voluntary urethral sphincter


Urethra

The female urethra is tightly bound to the anterior vaginal wall

Its external opening lies anterior to the vaginal opening and posterior to the clitoris

The male urethra has three named regions

Prostatic urethra – runs within the prostate gland

Membranous urethra – runs through the urogenital diaphragm

Spongy (penile) urethra – passes through the penis and opens via the external urethral orifice


Urethra

Figure 25.18a, b


Micturition (Voiding or Urination)

The act of emptying the bladder

Distension of bladder walls initiates spinal reflexes that:

Stimulate contraction of the external urethral sphincter

Inhibit the detrusor muscle and internal sphincter (temporarily)

Voiding reflexes:

Stimulate the detrusor muscle to contract

Inhibit the internal and external sphincters


Neural Circuits Controlling Micturition

Figure 25.20a, b



Elaine N. Marieb

Katja Hoehn



Bluegrass Technical


C H

A P

T E

R

26 Fluid,

Electrolyte,

and Acid-Base

Balance


Body Water Content

Infants have low body fat, low bone mass, and are

73% or more water

Total water content declines throughout life

Healthy males are about 60% water; healthy

females are around 50%


Body Water Content

This difference reflects females’:

Higher body fat

Smaller amount of skeletal muscle

In old age, only about 45% of body weight is water


Fluid Compartments

Water occupies two main fluid compartments

Intracellular fluid (ICF) – about two thirds by

volume, contained in cells

Extracellular fluid (ECF) – consists of two major

subdivisions

Plasma – the fluid portion of the blood

Interstitial fluid (IF) – fluid in spaces between cells

Other ECF – lymph, cerebrospinal fluid, eye

humors, synovial fluid, serous fluid, and

gastrointestinal secretions


Fluid Compartments

PLAY InterActive Physiology ®: Introduction to Body Fluids, page 10

Figure 26.1

26PPTLect-anim/IP_FLUIDS_FILES/9-System Suite/ipweb/systems/bodfluid_pg10.html


Composition of Body Fluids

Water is the universal solvent

Solutes are broadly classified into:

Electrolytes – inorganic salts, all acids and bases, and some proteins

Nonelectrolytes – examples include glucose, lipids, creatinine, and urea

Electrolytes have greater osmotic power than nonelectrolytes

Water moves according to osmotic gradients




Electrolyte Concentration

Expressed in milliequivalents per liter (mEq/L), a

measure of the number of electrical charges in one

liter of solution

mEq/L = (concentration of ion in [mg/L]/the

atomic weight of ion) number of electrical

charges on one ion

For single charged ions, 1 mEq = 1 mOsm

For bivalent ions, 1 mEq = 1/2 mOsm


Extracellular and Intracellular Fluids

Each fluid compartment of the body has a distinctive pattern of electrolytes

Extracellular fluids are similar (except for the high protein content of plasma)

Sodium is the chief cation

Chloride is the major anion

Intracellular fluids have low sodium and chloride

Potassium is the chief cation

Phosphate is the chief anion



Sodium and potassium concentrations in extra- and

intracellular fluids are nearly opposites

This reflects the activity of cellular ATP-

dependent sodium-potassium pumps

Electrolytes determine the chemical and physical

reactions of fluids





Proteins, phospholipids, cholesterol, and neutral

fats account for:

90% of the mass of solutes in plasma

60% of the mass of solutes in interstitial fluid

97% of the mass of solutes in the intracellular

compartment


Fluid Movement Among Compartments

Compartmental exchange is regulated by osmotic

and hydrostatic pressures

Net leakage of fluid from the blood is picked up by

lymphatic vessels and returned to the bloodstream

Exchanges between interstitial and intracellular

fluids are complex due to the selective

permeability of the cellular membranes

Two-way water flow is substantial



Ion fluxes are restricted and move selectively by active transport

Nutrients, respiratory gases, and wastes move unidirectionally

Plasma is the only fluid that circulates throughout the body and links external and internal environments

Osmolalities of all body fluids are equal; changes in solute concentrations are quickly followed by osmotic changes

PLAY InterActive Physiology ®: Introduction to Body Fluids, pages 19–22



Water Balance and ECF Osmolality

To remain properly hydrated, water intake must

equal water output

Water intake sources

Ingested fluid (60%) and solid food (30%)

Metabolic water or water of oxidation (10%)


Water Balance and ECF Osmolality

Water output

Urine (60%) and feces (4%)

Insensible losses (28%), sweat (8%)

Increases in plasma osmolality trigger thirst and

release of antidiuretic hormone (ADH)


Regulation of Water Output

Obligatory water losses include:

Insensible water losses from lungs and skin

Water that accompanies undigested food residues in feces

Obligatory water loss reflects the fact that:

Kidneys excrete 900-1200 mOsm of solutes to maintain blood homeostasis

Urine solutes must be flushed out of the body in water

PLAY InterActive Physiology ®: Water Homeostasis, pages 3–10

26PPTLect-anim/IP_FLUIDS_FILES/9-System Suite/ipweb/systems/wathomeo_pg03.html


Influence and Regulation of ADH

Water reabsorption in collecting ducts is proportional to

ADH release

Low ADH levels produce dilute urine and reduced volume

of body fluids

High ADH levels produce concentrated urine

Hypothalamic osmoreceptors trigger or inhibit ADH

release

Factors that specifically trigger ADH release include

prolonged fever; excessive sweating, vomiting, or diarrhea;

severe blood loss; and traumatic burns




Mechanisms and Consequences of ADH

Release

Figure 26.6


Disorders of Water Balance: Dehydration

Water loss exceeds water intake and the body is in negative fluid balance

Causes include: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse

Signs and symptoms: thirst, dry flushed skin, and oliguria (low output of urine, output below 300-500ml/day)

Prolonged dehydration may lead to weight loss, fever, and mental confusion

Other consequences include hypovolemic shock and loss of electrolytes


Disorders of Water Balance:

Hypotonic Hydration

Renal insufficiency or an extraordinary amount of water ingested quickly can lead to cellular overhydration, or water intoxication

ECF is diluted – sodium content is normal but excess water is present

The resulting hyponatremia promotes net osmosis into tissue cells, causing swelling

These events must be quickly reversed to prevent severe metabolic disturbances, particularly in neurons


Disorders of Water Balance: Edema

Atypical accumulation of fluid in the interstitial space, leading to tissue swelling

Caused by anything that increases flow of fluids out of the bloodstream or hinders their return

Factors that accelerate fluid loss include:

Increased blood pressure, capillary permeability

Incompetent venous valves, localized blood vessel blockage

Congestive heart failure, hypertension, high blood volume


Edema

Hindered fluid return usually reflects an imbalance in

colloid osmotic pressures (a form of osmotic pressure

exerted by proteins in blood plasma that usually tends to

pull water into the circulatory system)

Hypoproteinemia – low levels of plasma proteins

Forces fluids out of capillary beds at the arterial ends

Fluids fail to return at the venous ends

Results from protein malnutrition, liver disease, or

glomerulonephritis


Edema

Blocked (or surgically removed) lymph vessels:

Cause leaked proteins to accumulate in interstitial

fluid

Exert increasing colloid osmotic pressure, which

draws fluid from the blood

Interstitial fluid accumulation results in low blood

pressure and severely impaired circulation


Electrolyte Balance

Electrolytes are salts, acids, and bases, but electrolyte balance usually refers only to salt balance

Salts are important for:

Neuromuscular excitability

Secretory activity

Membrane permeability

Controlling fluid movements

Salts enter the body by ingestion and are lost via perspiration, feces, and urine


Sodium in Fluid and Electrolyte Balance

Sodium holds a central position in fluid and electrolyte balance

Sodium salts:

Account for 90-95% of all solutes in the ECF

Contribute 280 mOsm of the total 300 mOsm ECF solute concentration

Sodium is the single most abundant cation in the ECF

Sodium is the only cation exerting significant osmotic pressure



The role of sodium in controlling ECF volume and

water distribution in the body is a result of:

Sodium being the only cation to exert significant

osmotic pressure

Sodium ions leaking into cells and being pumped

out against their electrochemical gradient

Sodium concentration in the ECF normally

remains stable



Changes in plasma sodium levels affect:

Plasma volume, blood pressure

ICF and interstitial fluid volumes

Renal acid-base control mechanisms are coupled to

sodium ion transport

PLAY InterActive Physiology ®: Electrolyte Homeostasis, pages 4–6, 18–22

26PPTLect-anim/IP_FLUIDS_FILES/9-System Suite/ipweb/systems/elehomeo_pg04.html


Regulation of Sodium Balance: Aldosterone

Sodium reabsorption

65% of sodium in filtrate is reabsorbed in the

proximal tubules

25% is reclaimed in the loops of Henle

When aldosterone levels are high, all remaining

Na+ is actively reabsorbed

Water follows sodium if tubule permeability has

been increased with ADH



The renin-angiotensin mechanism triggers the release of aldosterone

This is mediated by the juxtaglomerular apparatus, which releases renin in response to:

Sympathetic nervous system stimulation

Decreased filtrate osmolality

Decreased stretch (due to decreased blood pressure)

Renin catalyzes the production of angiotensin II, which prompts aldosterone release



Adrenal cortical cells are directly stimulated to

release aldosterone by elevated K+ levels in the

ECF

Aldosterone brings about its effects (diminished

urine output and increased blood volume) slowly





Figure 26.8


Cardiovascular System Baroreceptors

Baroreceptors alert the brain of increases in blood

volume (hence increased blood pressure)

Sympathetic nervous system impulses to the

kidneys decline

Afferent arterioles dilate

Glomerular filtration rate rises

Sodium and water output increase


Cardiovascular System Baroreceptors

This phenomenon, called pressure diuresis,

decreases blood pressure

Drops in systemic blood pressure lead to opposite

actions and systemic blood pressure increases

Since sodium ion concentration determines fluid

volume, baroreceptors can be viewed as “sodium

receptors”


Maintenance of Blood Pressure Homeostasis

Figure 26.9


Atrial Natriuretic Peptide (ANP)

Reduces blood pressure and blood volume by inhibiting:

Events that promote vasoconstriction

Na+ and water retention

Is released in the heart atria as a response to stretch (elevated blood pressure)

Has potent diuretic and natriuretic effects

Promotes excretion of sodium and water

Inhibits angiotensin II production


Mechanisms and Consequences of ANP

Release

Figure 26.10


Influence of Other Hormones on Sodium

Balance

Estrogens:

Enhance NaCl reabsorption by renal tubules

May cause water retention during menstrual cycles

Are responsible for edema during pregnancy


Influence of Other Hormones on Sodium

Balance

Progesterone:

Decreases sodium reabsorption

Acts as a diuretic, promoting sodium and water

loss

Glucocorticoids – enhance reabsorption of sodium

and promote edema


Regulation of Potassium Balance

Relative ICF-ECF potassium ion concentration

affects a cell’s resting membrane potential

Excessive ECF potassium decreases membrane

potential

Too little K+ causes hyperpolarization and

nonresponsiveness


Regulation of Potassium Balance

Hyperkalemia and hypokalemia can:

Disrupt electrical conduction in the heart

Lead to sudden death

Hydrogen ions shift in and out of cells

Leads to corresponding shifts in potassium in the

opposite direction

Interferes with activity of excitable cells


Regulatory Site: Cortical Collecting Ducts

Less than 15% of filtered K+ is lost to urine regardless of need

K+ balance is controlled in the cortical collecting ducts by changing the amount of potassium secreted into filtrate

Excessive K+ is excreted over basal levels by cortical collecting ducts

When K+ levels are low, the amount of secretion and excretion is kept to a minimum

Type A intercalated cells can reabsorb some K+ left in the filtrate


Influence of Plasma Potassium Concentration

High K+ content of ECF favors principal cells to

secrete K+

Low K+ or accelerated K+ loss depresses its

secretion by the collecting ducts

PLAY InterActive Physiology ®: Electrolyte Homeostasis, pages 28–32



Influence of Aldosterone

Aldosterone stimulates potassium ion secretion by principal cells

In cortical collecting ducts, for each Na+ reabsorbed, a K+ is secreted

Increased K+ in the ECF around the adrenal cortex causes:

Release of aldosterone

Potassium secretion

Potassium controls its own ECF concentration via feedback regulation of aldosterone release


Regulation of Calcium

Ionic calcium in ECF is important for:

Blood clotting

Cell membrane permeability

Secretory behavior

Hypocalcemia:

Increases excitability

Causes muscle tetany


Regulation of Calcium

Hypercalcemia:

Inhibits neurons and muscle cells

May cause heart arrhythmias

Calcium balance is controlled by parathyroid

hormone (PTH) and calcitonin


Regulation of Calcium and Phosphate

PTH promotes increase in calcium levels by targeting:

Bones – PTH activates osteoclasts to break down bone matrix

Small intestine – PTH enhances intestinal absorption of calcium

Kidneys – PTH enhances calcium reabsorption and decreases phosphate reabsorption

Calcium reabsorption and phosphate excretion go hand in hand


Regulation of Calcium and Phosphate

Filtered phosphate is actively reabsorbed in the proximal tubules

In the absence of PTH, phosphate reabsorption is regulated by its transport maximum and excesses are excreted in urine

High or normal ECF calcium levels inhibit PTH secretion

Release of calcium from bone is inhibited

Larger amounts of calcium are lost in feces and urine

More phosphate is retained


Influence of Calcitonin

Released in response to rising blood calcium levels

Calcitonin is a PTH antagonist, but its contribution

to calcium and phosphate homeostasis is minor to

negligible

PLAY InterActive Physiology ®: Electrolyte Homeostasis, pages 33–37



Regulation of Anions

Chloride is the major anion accompanying sodium

in the ECF

99% of chloride is reabsorbed under normal pH

conditions

When acidosis occurs, fewer chloride ions are

reabsorbed

Other anions have transport maximums and

excesses are excreted in urine


Acid-Base Balance

Normal pH of body fluids

Arterial blood is 7.4

Venous blood and interstitial fluid is 7.35

Intracellular fluid is 7.0

Alkalosis or alkalemia – arterial blood pH rises

above 7.45

Acidosis or acidemia – arterial pH drops below

7.35 (physiological acidosis)


Sources of Hydrogen Ions

Most hydrogen ions originate from cellular metabolism

Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF

Anaerobic respiration of glucose produces lactic acid

Fat metabolism yields organic acids and ketone bodies

Transporting carbon dioxide as bicarbonate releases hydrogen ions


Hydrogen Ion Regulation

Concentration of hydrogen ions is regulated

sequentially by:

Chemical buffer systems – act within seconds

The respiratory center in the brain stem – acts

within 1-3 minutes

Renal mechanisms – require hours to days to effect

pH changes


Chemical Buffer Systems

Strong acids – all their H+ is dissociated

completely in water

Weak acids – dissociate partially in water and are

efficient at preventing pH changes

Strong bases – dissociate easily in water and

quickly tie up H+

Weak bases – accept H+ more slowly (e.g., HCO3¯

and NH3)

PLAY InterActive Physiology ®: Acid/Base Homeostasis, pages 3–10

26PPTLect-anim/IP_FLUIDS_FILES/9-System Suite/ipweb/systems/acihomeo_pg03.html


Strong and Weak Acids

Figure 26.11


Chemical Buffer Systems

One or two molecules that act to resist pH changes

when strong acid or base is added

Three major chemical buffer systems

Bicarbonate buffer system

Phosphate buffer system

Protein buffer system

Any drifts in pH are resisted by the entire chemical

buffering system


Bicarbonate Buffer System

A mixture of carbonic acid (H2CO3) and its salt,

sodium bicarbonate (NaHCO3) (potassium or

magnesium bicarbonates work as well)

If strong acid is added:

Hydrogen ions released combine with the

bicarbonate ions and form carbonic acid (a weak

acid)

The pH of the solution decreases only slightly


Bicarbonate Buffer System

If strong base is added:

It reacts with the carbonic acid to form sodium

bicarbonate (a weak base)

The pH of the solution rises only slightly

This system is the only important ECF buffer

PLAY InterActive Physiology ®: Acid/Base Homeostasis, pages 16–17



Phosphate Buffer System

Nearly identical to the bicarbonate system

Its components are:

Sodium salts of dihydrogen phosphate (H2PO4¯), a

weak acid

Monohydrogen phosphate (HPO42¯), a weak base

This system is an effective buffer in urine and

intracellular fluid


Protein Buffer System

Plasma and intracellular proteins are the body’s

most plentiful and powerful buffers

Some amino acids of proteins have:

Free organic acid groups (weak acids)

Groups that act as weak bases (e.g., amino groups)

Amphoteric molecules are protein molecules that

can function as both a weak acid and a weak base

PLAY InterActive Physiology ®: Acid/Base Homeostasis, page 19



Physiological Buffer Systems

The respiratory system regulation of acid-base

balance is a physiological buffering system

There is a reversible equilibrium between:

Dissolved carbon dioxide and water

Carbonic acid and the hydrogen and bicarbonate

ions

CO2 + H2O H2CO3 H+ + HCO3¯

PLAY InterActive Physiology ®: Acid/Base Homeostasis, page 20–26



Physiological Buffer Systems

During carbon dioxide unloading, hydrogen ions are

incorporated into water

When hypercapnia or rising plasma H+ occurs:

Deeper and more rapid breathing expels more carbon dioxide

Hydrogen ion concentration is reduced

Alkalosis causes slower, more shallow breathing, causing H+

to increase

Respiratory system impairment causes acid-base imbalance

(respiratory acidosis or respiratory alkalosis)




Renal Mechanisms of Acid-Base Balance

Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body

The lungs can eliminate carbonic acid by eliminating carbon dioxide

Only the kidneys can rid the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis

The ultimate acid-base regulatory organs are the kidneys



The most important renal mechanisms for

regulating acid-base balance are:

Conserving (reabsorbing) or generating new

bicarbonate ions

Excreting bicarbonate ions

Losing a bicarbonate ion is the same as gaining a

hydrogen ion; reabsorbing a bicarbonate ion is the

same as losing a hydrogen ion



Hydrogen ion secretion occurs in the PCT and in

type A intercalated cells

Hydrogen ions come from the dissociation of

carbonic acid




Reabsorption of Bicarbonate

Carbon dioxide combines with water in tubule cells, forming carbonic acid

Carbonic acid splits into hydrogen ions and bicarbonate ions

For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by the PCT cells

Secreted hydrogen ions form carbonic acid; thus, bicarbonate disappears from filtrate at the same rate that it enters the peritubular capillary blood



Reabsorption of Bicarbonate

Carbonic acid formed in filtrate dissociates to release carbon dioxide and water

Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ion secretion

Figure 26.12



Generating New Bicarbonate Ions

Two mechanisms carried out by type A

intercalated cells generate new bicarbonate ions

Both involve renal excretion of acid via secretion

and excretion of hydrogen ions or ammonium ions

(NH4+)




Hydrogen Ion Excretion

Dietary hydrogen ions must be counteracted by generating new bicarbonate

The excreted hydrogen ions must bind to buffers in the urine (phosphate buffer system)

Intercalated cells actively secrete hydrogen ions into urine, which is buffered and excreted

Bicarbonate generated is:

Moved into the interstitial space via a cotransport system

Passively moved into the peritubular capillary blood


Hydrogen Ion Excretion

In response to

acidosis:

Kidneys generate

bicarbonate ions

and add them to the

blood

An equal amount of

hydrogen ions are

added to the urine

Figure 26.13


Ammonium Ion Excretion

This method uses ammonium ions produced by the

metabolism of glutamine in PCT cells

Each glutamine metabolized produces two

ammonium ions and two bicarbonate ions

Bicarbonate moves to the blood and ammonium

ions are excreted in urine


Ammonium Ion Excretion

Figure 26.14


Bicarbonate Ion Secretion

When the body is in alkalosis, type B intercalated cells:

Exhibit bicarbonate ion secretion

Reclaim hydrogen ions and acidify the blood

The mechanism is the opposite of type A intercalated cells and the bicarbonate ion reabsorption process

Even during alkalosis, the nephrons and collecting ducts excrete fewer bicarbonate ions than they conserve




Respiratory Acidosis and Alkalosis

Result from failure of the respiratory system to balance pH

PCO2 is the single most important indicator of respiratory inadequacy

PCO2 levels

Normal PCO2 fluctuates between 35 and 45 mm Hg

Values above 45 mm Hg signal respiratory acidosis

Values below 35 mm Hg indicate respiratory alkalosis


Respiratory Acidosis and Alkalosis

Respiratory acidosis is the most common cause of

acid-base imbalance

Occurs when a person breathes shallowly, or gas

exchange is hampered by diseases such as

pneumonia, cystic fibrosis, or emphysema

Respiratory alkalosis is a common result of

hyperventilation


Metabolic Acidosis

All pH imbalances except those caused by abnormal blood carbon dioxide levels

Metabolic acid-base imbalance – bicarbonate ion levels above or below normal (22-26 mEq/L)

Metabolic acidosis is the second most common cause of acid-base imbalance

Typical causes are ingestion of too much alcohol and excessive loss of bicarbonate ions

Other causes include accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure


Metabolic Alkalosis

Rising blood pH and bicarbonate levels indicate

metabolic alkalosis

Typical causes are:

Vomiting of the acid contents of the stomach

Intake of excess base (e.g., from antacids)

Constipation, in which excessive bicarbonate is

reabsorbed


Respiratory and Renal Compensations

Acid-base imbalance due to inadequacy of a

physiological buffer system is compensated for by

the other system

The respiratory system will attempt to correct

metabolic acid-base imbalances

The kidneys will work to correct imbalances

caused by respiratory disease


Respiratory Compensation

In metabolic acidosis:

The rate and depth of breathing are elevated

Blood pH is below 7.35 and bicarbonate level is low

As carbon dioxide is eliminated by the respiratory system, PCO2 falls below normal

In respiratory acidosis, the respiratory rate is often depressed and is the immediate cause of the acidosis


Respiratory Compensation

In metabolic alkalosis:

Compensation exhibits slow, shallow breathing,

allowing carbon dioxide to accumulate in the blood

Correction is revealed by:

High pH (over 7.45) and elevated bicarbonate ion

levels

Rising PCO2




Renal Compensation

To correct respiratory acid-base imbalance, renal

mechanisms are stepped up

Acidosis has high PCO2 and high bicarbonate levels

The high PCO2 is the cause of acidosis

The high bicarbonate levels indicate the kidneys

are retaining bicarbonate to offset the acidosis


Renal Compensation

Alkalosis has Low PCO2 and high pH

The kidneys eliminate bicarbonate from the body

by failing to reclaim it or by actively secreting it


Developmental Aspects

Water content of the body is greatest at birth (70-80%) and declines until adulthood, when it is about 58%

At puberty, sexual differences in body water content arise as males develop greater muscle mass

Homeostatic mechanisms slow down with age

Elders may be unresponsive to thirst clues and are at risk of dehydration

The very young and the very old are the most frequent victims of fluid, acid-base, and electrolyte imbalances


Problems with Fluid, Electrolyte, and Acid-

Base Balance

Occur in the young, reflecting:

Low residual lung volume

High rate of fluid intake and output

High metabolic rate yielding more metabolic

wastes

High rate of insensible water loss

Inefficiency of kidneys in infants

Science

The urinary system