Body Water ContentBody Water Content

Infants have low body fat, low bone mass, and Infants have low body fat, low bone mass, and are 73% or more waterare 73% or more water

Total water content declines throughout lifeTotal water content declines throughout life Healthy males are about 60% water; healthy Healthy males are about 60% water; healthy

females are around 50%females are around 50%

Body Water ContentBody Water Content

This difference reflects females’:This difference reflects females’: Higher body fat Higher body fat Smaller amount of skeletal muscleSmaller amount of skeletal muscle

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

Fluid CompartmentsFluid Compartments Water occupies two main fluid compartmentsWater occupies two main fluid compartments Intracellular fluid (ICF) – about two thirds by Intracellular fluid (ICF) – about two thirds by

volume, contained in cellsvolume, contained in cells Extracellular fluid (ECF) – consists of two Extracellular fluid (ECF) – consists of two

major subdivisionsmajor subdivisions Plasma – the fluid portion of the bloodPlasma – the fluid portion of the blood Interstitial fluid (IF) – fluid in spaces between cellsInterstitial fluid (IF) – fluid in spaces between cells

Other ECF – lymph, cerebrospinal fluid, eye Other ECF – lymph, cerebrospinal fluid, eye humors, synovial fluid, serous fluid, and humors, synovial fluid, serous fluid, and gastrointestinal secretionsgastrointestinal secretions

Composition of Body FluidsComposition of Body Fluids

Water is the universal solvent Water is the universal solvent Solutes are broadly classified into:Solutes are broadly classified into:

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

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

Electrolytes have greater osmotic power than Electrolytes have greater osmotic power than nonelectrolytesnonelectrolytes

Water moves according to osmotic gradientsWater moves according to osmotic gradients

Electrolyte ConcentrationElectrolyte Concentration

Expressed in milliequivalents per liter Expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical (mEq/L), a measure of the number of electrical charges in one liter of solutioncharges in one liter of solution

mEq/L = (concentration of ion in [mg/L]/the mEq/L = (concentration of ion in [mg/L]/the atomic weight of ion) atomic weight of ion) number of electrical number of electrical charges on one ioncharges on one ion

For single charged ions, 1 mEq = 1 mOsm For single charged ions, 1 mEq = 1 mOsm For bivalent ions, 1 mEq = 1/2 mOsmFor bivalent ions, 1 mEq = 1/2 mOsm

Extracellular and Intracellular Extracellular and Intracellular FluidsFluids

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

Extracellular fluids are similar (except for the Extracellular fluids are similar (except for the high protein content of plasma)high protein content of plasma) Sodium is the chief cationSodium is the chief cation Chloride is the major anionChloride is the major anion

Intracellular fluids have low sodium and Intracellular fluids have low sodium and chloridechloride Potassium is the chief cationPotassium is the chief cation Phosphate is the chief anionPhosphate is the chief anion

Extracellular and Intracellular Extracellular and Intracellular FluidsFluids

Sodium and potassium concentrations in extra- Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites and intracellular fluids are nearly opposites

This reflects the activity of cellular ATP-This reflects the activity of cellular ATP-dependent sodium-potassium pumpsdependent sodium-potassium pumps

Electrolytes determine the chemical and Electrolytes determine the chemical and physical reactions of fluidsphysical reactions of fluids

Extracellular and Intracellular Extracellular and Intracellular FluidsFluids

Proteins, phospholipids, cholesterol, and Proteins, phospholipids, cholesterol, and neutral fats account for:neutral fats account for: 90% of the mass of solutes in plasma90% of the mass of solutes in plasma 60% of the mass of solutes in interstitial fluid60% of the mass of solutes in interstitial fluid 97% of the mass of solutes in the intracellular 97% of the mass of solutes in the intracellular

compartmentcompartment

Electrolyte Composition of Body Electrolyte Composition of Body FluidsFluids

Fluid Movement Among Fluid Movement Among CompartmentsCompartments

Compartmental exchange is regulated by Compartmental exchange is regulated by osmotic and hydrostatic pressuresosmotic and hydrostatic pressures

Leakage of fluid from the blood is picked up by Leakage of fluid from the blood is picked up by lymphatic vessels and returned to the lymphatic vessels and returned to the bloodstreambloodstream

Exchanges between interstitial and intracellular Exchanges between interstitial and intracellular fluids are complex due to the selective fluids are complex due to the selective permeability of the cellular membranespermeability of the cellular membranes

Two-way water flow is substantialTwo-way water flow is substantial

Extracellular and Intracellular Extracellular and Intracellular FluidsFluids

Ion fluxes are restricted and move selectively Ion fluxes are restricted and move selectively by active transportby active transport

Nutrients, respiratory gases, and wastes move Nutrients, respiratory gases, and wastes move unidirectionallyunidirectionally

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

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

Water Balance and ECF Water Balance and ECF OsmolalityOsmolality

To remain properly hydrated, water intake To remain properly hydrated, water intake must equal water output must equal water output

Water intake sourcesWater intake sources Ingested fluid (60%) and solid food (30%)Ingested fluid (60%) and solid food (30%) Metabolic water or water of oxidation (10%)Metabolic water or water of oxidation (10%)

Water Balance and ECF Water Balance and ECF OsmolalityOsmolality

Water outputWater output Urine (60%) and feces (4%)Urine (60%) and feces (4%) Insensible losses (28%), sweat (8%)Insensible losses (28%), sweat (8%)

Increases in plasma osmolality trigger thirst Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH)and release of antidiuretic hormone (ADH)

Regulation of Water IntakeRegulation of Water Intake

The hypothalamic thirst center is stimulated:The hypothalamic thirst center is stimulated: By a decline in plasma volume of 10%–15%By a decline in plasma volume of 10%–15% By increases in plasma osmolality of 1–2%By increases in plasma osmolality of 1–2% Via baroreceptor input, angiotensin II, and other Via baroreceptor input, angiotensin II, and other

stimulistimuli

Regulation of Water IntakeRegulation of Water Intake

Thirst is quenched as soon as we begin to Thirst is quenched as soon as we begin to drink waterdrink water

Feedback signals that inhibit the thirst centers Feedback signals that inhibit the thirst centers include:include: Moistening of the mucosa of the mouth and throatMoistening of the mucosa of the mouth and throat Activation of stomach and intestinal stretch Activation of stomach and intestinal stretch

receptorsreceptors

Regulation of Water OutputRegulation of Water Output

Obligatory water losses include:Obligatory water losses include: Insensible water losses from lungs and skinInsensible water losses from lungs and skin Water that accompanies undigested food residues Water that accompanies undigested food residues

in fecesin feces Obligatory water loss reflects the fact that:Obligatory water loss reflects the fact that:

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

Urine solutes must be flushed out of the body in Urine solutes must be flushed out of the body in waterwater

Influence and Regulation of ADHInfluence and Regulation of ADH Water reabsorption in collecting ducts is proportional Water reabsorption in collecting ducts is proportional

to ADH releaseto ADH release Low ADH levels produce dilute urine and reduced Low ADH levels produce dilute urine and reduced

volume of body fluidsvolume of body fluids High ADH levels produce concentrated urineHigh ADH levels produce concentrated urine Hypothalamic osmoreceptors trigger or inhibit ADH Hypothalamic osmoreceptors trigger or inhibit ADH

releaserelease Factors that specifically trigger ADH release include Factors that specifically trigger ADH release include

prolonged fever; excessive sweating, vomiting, or prolonged fever; excessive sweating, vomiting, or diarrhea; severe blood loss; and traumatic burnsdiarrhea; severe blood loss; and traumatic burns

Disorders of Water Balance: Disorders of Water Balance: DehydrationDehydration

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

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

Signs and symptoms: cottonmouth, thirst, dry Signs and symptoms: cottonmouth, thirst, dry flushed skin, and oliguriaflushed skin, and oliguria

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

Other consequences include hypovolemic Other consequences include hypovolemic shock and loss of electrolytesshock and loss of electrolytes

Disorders of Water Balance: Disorders of Water Balance: Hypotonic HydrationHypotonic Hydration

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

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

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

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

Disorders of Water Balance: Disorders of Water Balance: EdemaEdema

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

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

Factors that accelerate fluid loss include: Factors that accelerate fluid loss include: Increased blood pressure, capillary permeability Increased blood pressure, capillary permeability Incompetent venous valves, localized blood vessel Incompetent venous valves, localized blood vessel

blockage blockage Congestive heart failure, hypertension, high blood Congestive heart failure, hypertension, high blood

volumevolume

EdemaEdema

Hindered fluid return usually reflects an Hindered fluid return usually reflects an imbalance in colloid osmotic pressures imbalance in colloid osmotic pressures

Hypoproteinemia – low levels of plasma Hypoproteinemia – low levels of plasma proteinsproteins Forces fluids out of capillary beds at the arterial Forces fluids out of capillary beds at the arterial

endsends Fluids fail to return at the venous endsFluids fail to return at the venous ends Results from protein malnutrition, liver disease, or Results from protein malnutrition, liver disease, or

glomerulonephritisglomerulonephritis

EdemaEdema

Blocked (or surgically removed) lymph Blocked (or surgically removed) lymph vessels:vessels: Cause leaked proteins to accumulate in interstitial Cause leaked proteins to accumulate in interstitial

fluidfluid Exert increasing colloid osmotic pressure, which Exert increasing colloid osmotic pressure, which

draws fluid from the blooddraws fluid from the blood Interstitial fluid accumulation results in low Interstitial fluid accumulation results in low

blood pressure and severely impaired blood pressure and severely impaired circulationcirculation

Electrolyte BalanceElectrolyte Balance Electrolytes are salts, acids, and bases, but Electrolytes are salts, acids, and bases, but

electrolyte balance usually refers only to salt electrolyte balance usually refers only to salt balancebalance

Salts are important for:Salts are important for: Neuromuscular excitabilityNeuromuscular excitability Secretory activitySecretory activity Membrane permeabilityMembrane permeability Controlling fluid movementsControlling fluid movements

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

Sodium in Fluid and Electrolyte Sodium in Fluid and Electrolyte BalanceBalance

Sodium holds a central position in fluid and Sodium holds a central position in fluid and electrolyte balanceelectrolyte balance

Sodium salts:Sodium salts: Account for 90-95% of all solutes in the ECFAccount for 90-95% of all solutes in the ECF Contribute 280 mOsm of the total 300 mOsm ECF Contribute 280 mOsm of the total 300 mOsm ECF

solute concentrationsolute concentration Sodium is the single most abundant cation in Sodium is the single most abundant cation in

the ECFthe ECF Sodium is the only cation exerting significant Sodium is the only cation exerting significant

osmotic pressureosmotic pressure

Sodium in Fluid and Electrolyte Sodium in Fluid and Electrolyte BalanceBalance

The role of sodium in controlling ECF volume The role of sodium in controlling ECF volume and water distribution in the body is a result and water distribution in the body is a result of:of: Sodium being the only cation (positively charged Sodium being the only cation (positively charged

ion) to exert significant osmotic pressureion) to exert significant osmotic pressure Sodium ions leaking into cells and being pumped Sodium ions leaking into cells and being pumped

out against their electrochemical gradientout against their electrochemical gradient Sodium concentration in the ECF normally Sodium concentration in the ECF normally

remains stableremains stable

Sodium in Fluid and Electrolyte Sodium in Fluid and Electrolyte BalanceBalance

Changes in plasma sodium levels affect:Changes in plasma sodium levels affect: Plasma volume, blood pressurePlasma volume, blood pressure ICF and interstitial fluid volumesICF and interstitial fluid volumes

Renal acid-base control mechanisms are Renal acid-base control mechanisms are coupled to sodium ion transportcoupled to sodium ion transport

Regulation of Sodium Balance: Regulation of Sodium Balance: AldosteroneAldosterone

Sodium reabsorptionSodium reabsorption 65% of sodium in filtrate is reabsorbed in the 65% of sodium in filtrate is reabsorbed in the

proximal tubules proximal tubules 25% is reclaimed in the loops of Henle25% is reclaimed in the loops of Henle

When aldosterone levels are high, all When aldosterone levels are high, all remaining Naremaining Na++ is actively reabsorbed is actively reabsorbed

Water follows sodium if tubule permeability Water follows sodium if tubule permeability has been increased with ADHhas been increased with ADH

Regulation of Sodium Balance: Regulation of Sodium Balance: AldosteroneAldosterone

The renin-angiotensin mechanism triggers the The renin-angiotensin mechanism triggers the release of aldosteronerelease of aldosterone

This is mediated by the juxtaglomerular This is mediated by the juxtaglomerular apparatus, which releases renin in response to:apparatus, which releases renin in response to: Sympathetic nervous system stimulationSympathetic nervous system stimulation Decreased filtrate osmolalityDecreased filtrate osmolality Decreased stretch (due to decreased blood Decreased stretch (due to decreased blood

pressure)pressure) Renin catalyzes the production of angiotensin Renin catalyzes the production of angiotensin

II, which prompts aldosterone releaseII, which prompts aldosterone release

Regulation of Sodium Balance: Regulation of Sodium Balance: AldosteroneAldosterone

Adrenal cortical cells are directly stimulated to Adrenal cortical cells are directly stimulated to release aldosterone by elevated Krelease aldosterone by elevated K++ levels in the levels in the ECFECF

Aldosterone brings about its effects Aldosterone brings about its effects (diminished urine output and increased blood (diminished urine output and increased blood volume) slowlyvolume) slowly

Cardiovascular System Cardiovascular System BaroreceptorsBaroreceptors

Baroreceptors alert the brain of increases in Baroreceptors alert the brain of increases in blood volume (hence increased blood blood volume (hence increased blood pressure) pressure) Sympathetic nervous system impulses to the Sympathetic nervous system impulses to the

kidneys declinekidneys decline Afferent arterioles dilateAfferent arterioles dilate Glomerular filtration rate risesGlomerular filtration rate rises Sodium and water output increaseSodium and water output increase

Cardiovascular System Cardiovascular System BaroreceptorsBaroreceptors

This phenomenon, called pressure diuresis, This phenomenon, called pressure diuresis, decreases blood pressuredecreases blood pressure

Drops in systemic blood pressure lead to Drops in systemic blood pressure lead to opposite actions and systemic blood pressure opposite actions and systemic blood pressure increasesincreases

Since sodium ion concentration determines Since sodium ion concentration determines fluid volume, baroreceptors can be viewed as fluid volume, baroreceptors can be viewed as “sodium receptors”“sodium receptors”

Atrial Natriuretic Peptide (ANP)Atrial Natriuretic Peptide (ANP) Reduces blood pressure and blood volume by Reduces blood pressure and blood volume by

inhibiting:inhibiting: Events that promote vasoconstrictionEvents that promote vasoconstriction NaNa++ and water retention and water retention

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

Has potent diuretic and natriuretic effectsHas potent diuretic and natriuretic effects Promotes excretion of sodium and waterPromotes excretion of sodium and water Inhibits angiotensin II productionInhibits angiotensin II production

Influence of Other Hormones on Influence of Other Hormones on Sodium BalanceSodium Balance

Estrogens:Estrogens: Enhance NaCl reabsorption by renal tubulesEnhance NaCl reabsorption by renal tubules May cause water retention during menstrual cyclesMay cause water retention during menstrual cycles Are responsible for edema during pregnancyAre responsible for edema during pregnancy

Influence of Other Hormones on Influence of Other Hormones on Sodium BalanceSodium Balance

Progesterone:Progesterone: Decreases sodium reabsorptionDecreases sodium reabsorption Acts as a diuretic, promoting sodium and water Acts as a diuretic, promoting sodium and water

lossloss Glucocorticoids – enhance reabsorption of Glucocorticoids – enhance reabsorption of

sodium and promote edemasodium and promote edema

Regulation of Potassium BalanceRegulation of Potassium Balance

Relative ICF-ECF potassium ion concentration Relative ICF-ECF potassium ion concentration affects a cell’s resting membrane potentialaffects a cell’s resting membrane potential Excessive ECF potassium decreases membrane Excessive ECF potassium decreases membrane

potentialpotential Too little KToo little K++ causes hyperpolarization and causes hyperpolarization and

nonresponsivenessnonresponsiveness

Regulation of Potassium BalanceRegulation of Potassium Balance

Hyperkalemia and hypokalemia can:Hyperkalemia and hypokalemia can: Disrupt electrical conduction in the heartDisrupt electrical conduction in the heart Lead to sudden deathLead to sudden death

Hydrogen ions shift in and out of cellsHydrogen ions shift in and out of cells Leads to corresponding shifts in potassium in the Leads to corresponding shifts in potassium in the

opposite directionopposite direction Interferes with activity of excitable cellsInterferes with activity of excitable cells

Regulatory Site: Cortical Regulatory Site: Cortical Collecting DuctsCollecting Ducts

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

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

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

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

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

Influence of Plasma Potassium Influence of Plasma Potassium ConcentrationConcentration

High KHigh K++ content of ECF favors principal cells content of ECF favors principal cells to secrete Kto secrete K++

Low KLow K++ or accelerated K or accelerated K++ loss depresses its loss depresses its secretion by the collecting ductssecretion by the collecting ducts

Influence of AldosteroneInfluence of Aldosterone Aldosterone stimulates potassium ion secretion Aldosterone stimulates potassium ion secretion

by principal cellsby principal cells In cortical collecting ducts, for each NaIn cortical collecting ducts, for each Na++

reabsorbed, a Kreabsorbed, a K++ is secreted is secreted Increased KIncreased K++ in the ECF around the adrenal in the ECF around the adrenal

cortex causes:cortex causes: Release of aldosteroneRelease of aldosterone Potassium secretionPotassium secretion

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

Regulation of CalciumRegulation of Calcium

Ionic calcium in ECF is important for:Ionic calcium in ECF is important for: Blood clottingBlood clotting Cell membrane permeabilityCell membrane permeability Secretory behaviorSecretory behavior

Hypocalcemia:Hypocalcemia: Increases excitability Increases excitability Causes muscle tetanyCauses muscle tetany

Regulation of CalciumRegulation of Calcium

Hypercalcemia:Hypercalcemia: Inhibits neurons and muscle cellsInhibits neurons and muscle cells May cause heart arrhythmias May cause heart arrhythmias

Calcium balance is controlled by parathyroid Calcium balance is controlled by parathyroid hormone (PTH) and calcitoninhormone (PTH) and calcitonin

Regulation of Calcium and Regulation of Calcium and PhosphatePhosphate

PTH promotes increase in calcium levels by PTH promotes increase in calcium levels by targeting:targeting: Bones – PTH activates osteoclasts to break down Bones – PTH activates osteoclasts to break down

bone matrixbone matrix Small intestine – PTH enhances intestinal Small intestine – PTH enhances intestinal

absorption of calciumabsorption of calcium Kidneys – PTH enhances calcium reabsorption and Kidneys – PTH enhances calcium reabsorption and

decreases phosphate reabsorptiondecreases phosphate reabsorption Calcium reabsorption and phosphate excretion Calcium reabsorption and phosphate excretion

go hand in handgo hand in hand

Regulation of Calcium and Regulation of Calcium and PhosphatePhosphate

Filtered phosphate is actively reabsorbed in the Filtered phosphate is actively reabsorbed in the proximal tubulesproximal tubules

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

High or normal ECF calcium levels inhibit PTH High or normal ECF calcium levels inhibit PTH secretionsecretion Release of calcium from bone is inhibitedRelease of calcium from bone is inhibited Larger amounts of calcium are lost in feces and urineLarger amounts of calcium are lost in feces and urine More phosphate is retainedMore phosphate is retained

Influence of CalcitoninInfluence of Calcitonin

Released in response to rising blood calcium Released in response to rising blood calcium levelslevels

Calcitonin is a PTH antagonist, but its Calcitonin is a PTH antagonist, but its contribution to calcium and phosphate contribution to calcium and phosphate homeostasis is minor to negligiblehomeostasis is minor to negligible

Regulation of Anions (negatively Regulation of Anions (negatively charged ion)charged ion)

Chloride is the major anion accompanying Chloride is the major anion accompanying sodium in the ECFsodium in the ECF

99% of chloride is reabsorbed under normal 99% of chloride is reabsorbed under normal pH conditionspH conditions

When acidosis occurs, fewer chloride ions are When acidosis occurs, fewer chloride ions are reabsorbed reabsorbed

Other anions have transport maximums and Other anions have transport maximums and excesses are excreted in urineexcesses are excreted in urine

Acid-Base BalanceAcid-Base Balance

Normal pH of body fluidsNormal pH of body fluids Arterial blood is 7.4Arterial blood is 7.4 Venous blood and interstitial fluid is 7.35Venous blood and interstitial fluid is 7.35 Intracellular fluid is 7.0Intracellular fluid is 7.0

Alkalosis or alkalemia – arterial blood pH Alkalosis or alkalemia – arterial blood pH rises above 7.45rises above 7.45

Acidosis or acidemia – arterial pH drops Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis)below 7.35 (physiological acidosis)

Sources of Hydrogen IonsSources of Hydrogen Ions Most hydrogen ions originate from cellular Most hydrogen ions originate from cellular

metabolismmetabolism Breakdown of phosphorus-containing proteins Breakdown of phosphorus-containing proteins

releases phosphoric acid into the ECFreleases phosphoric acid into the ECF Anaerobic respiration of glucose produces lactic Anaerobic respiration of glucose produces lactic

acidacid Fat metabolism yields organic acids and ketone Fat metabolism yields organic acids and ketone

bodiesbodies Transporting carbon dioxide as bicarbonate Transporting carbon dioxide as bicarbonate

releases hydrogen ionsreleases hydrogen ions

Hydrogen Ion RegulationHydrogen Ion Regulation

Concentration of hydrogen ions is regulated Concentration of hydrogen ions is regulated sequentially by:sequentially by: Chemical buffer systems – act within secondsChemical buffer systems – act within seconds The respiratory center in the brain stem – acts The respiratory center in the brain stem – acts

within 1-3 minuteswithin 1-3 minutes Renal mechanisms – require hours to days to effect Renal mechanisms – require hours to days to effect

pH changespH changes

Chemical Buffer SystemsChemical Buffer Systems

Strong acids – all their HStrong acids – all their H++ is dissociated is dissociated completely in water completely in water

Weak acids – dissociate partially in water and Weak acids – dissociate partially in water and are efficient at preventing pH changesare efficient at preventing pH changes

Strong bases – dissociate easily in water and Strong bases – dissociate easily in water and quickly tie up Hquickly tie up H++

Weak bases – accept HWeak bases – accept H++ more slowly (e.g., more slowly (e.g., HCOHCO33

¯̄ and NH and NH33))

Chemical Buffer SystemsChemical Buffer Systems

One or two molecules that act to resist pH One or two molecules that act to resist pH changes when strong acid or base is addedchanges when strong acid or base is added

Three major chemical buffer systems Three major chemical buffer systems Bicarbonate buffer systemBicarbonate buffer system Phosphate buffer systemPhosphate buffer system Protein buffer systemProtein buffer system

Any drifts in pH are resisted by the entire Any drifts in pH are resisted by the entire chemical buffering systemchemical buffering system

Bicarbonate Buffer SystemBicarbonate Buffer System

A mixture of carbonic acid (HA mixture of carbonic acid (H22COCO33) and its ) and its

salt, sodium bicarbonate (NaHCOsalt, sodium bicarbonate (NaHCO33) (potassium ) (potassium

or magnesium bicarbonates work as well)or magnesium bicarbonates work as well) If strong acid is added:If strong acid is added:

Hydrogen ions released combine with the Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak bicarbonate ions and form carbonic acid (a weak acid) acid)

The pH of the solution decreases only slightlyThe pH of the solution decreases only slightly

Bicarbonate Buffer SystemBicarbonate Buffer System

If strong base is added:If strong base is added: It reacts with the carbonic acid to form sodium It reacts with the carbonic acid to form sodium

bicarbonate (a weak base)bicarbonate (a weak base) The pH of the solution rises only slightlyThe pH of the solution rises only slightly

This system is the only important ECF bufferThis system is the only important ECF buffer

Phosphate Buffer SystemPhosphate Buffer System

Nearly identical to the bicarbonate system Nearly identical to the bicarbonate system Its components are:Its components are:

Sodium salts of dihydrogen phosphate (HSodium salts of dihydrogen phosphate (H22POPO44¯̄), a ), a

weak acidweak acid Monohydrogen phosphate (HPOMonohydrogen phosphate (HPO44

2¯2¯), a weak base), a weak base

This system is an effective buffer in urine and This system is an effective buffer in urine and intracellular fluidintracellular fluid

Protein Buffer SystemProtein Buffer System

Plasma and intracellular proteins are the Plasma and intracellular proteins are the body’s most plentiful and powerful buffersbody’s most plentiful and powerful buffers

Some amino acids of proteins have:Some amino acids of proteins have: Free organic acid groups (weak acids) Free organic acid groups (weak acids) Groups that act as weak bases (e.g., amino groups)Groups that act as weak bases (e.g., amino groups)

Amphoteric molecules are protein molecules Amphoteric molecules are protein molecules that can function as both a weak acid and a that can function as both a weak acid and a weak baseweak base

Physiological Buffer SystemsPhysiological Buffer Systems

The respiratory system regulation of acid-base The respiratory system regulation of acid-base balance is a physiological buffering systembalance is a physiological buffering system

There is a reversible equilibrium between:There is a reversible equilibrium between: Dissolved carbon dioxide and waterDissolved carbon dioxide and water Carbonic acid and the hydrogen and bicarbonate Carbonic acid and the hydrogen and bicarbonate

ionsions COCO22 + H + H22O O H H22COCO33 H H++ + HCO + HCO33¯̄

Physiological Buffer SystemsPhysiological Buffer Systems During carbon dioxide unloading, hydrogen ions are During carbon dioxide unloading, hydrogen ions are

incorporated into waterincorporated into water When hypercapnia or rising plasma HWhen hypercapnia or rising plasma H++ occurs: occurs:

Deeper and more rapid breathing expels more carbon Deeper and more rapid breathing expels more carbon dioxidedioxide

Hydrogen ion concentration is reducedHydrogen ion concentration is reduced Alkalosis causes slower, more shallow breathing, Alkalosis causes slower, more shallow breathing,

causing Hcausing H++ to increase to increase Respiratory system impairment causes acid-base Respiratory system impairment causes acid-base

imbalance (respiratory acidosis or respiratory alkalosis)imbalance (respiratory acidosis or respiratory alkalosis)

Renal Mechanisms of Acid-Base Renal Mechanisms of Acid-Base BalanceBalance

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

The lungs can eliminate carbonic acid by The lungs can eliminate carbonic acid by eliminating carbon dioxideeliminating carbon dioxide

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

The ultimate acid-base regulatory organs are the The ultimate acid-base regulatory organs are the kidneyskidneys

Renal Mechanisms of Acid-Base Renal Mechanisms of Acid-Base BalanceBalance

The most important renal mechanisms for The most important renal mechanisms for regulating acid-base balance are:regulating acid-base balance are: Conserving (reabsorbing) or generating new Conserving (reabsorbing) or generating new

bicarbonate ionsbicarbonate ions Excreting bicarbonate ionsExcreting bicarbonate ions

Losing a bicarbonate ion is the same as Losing a bicarbonate ion is the same as gaining a hydrogen ion; reabsorbing a gaining a hydrogen ion; reabsorbing a bicarbonate ion is the same as losing a bicarbonate ion is the same as losing a hydrogen ionhydrogen ion

Renal Mechanisms of Acid-Base Renal Mechanisms of Acid-Base BalanceBalance

Hydrogen ion secretion occurs in the PCT and Hydrogen ion secretion occurs in the PCT and in type A intercalated cellsin type A intercalated cells

Hydrogen ions come from the dissociation of Hydrogen ions come from the dissociation of carbonic acidcarbonic acid

Reabsorption of BicarbonateReabsorption of Bicarbonate

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

Carbonic acid splits into hydrogen ions and Carbonic acid splits into hydrogen ions and bicarbonate ionsbicarbonate ions

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

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

Reabsorption of BicarbonateReabsorption of Bicarbonate

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

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

Figure 26.12

Generating New Bicarbonate Generating New Bicarbonate IonsIons

Two mechanisms carried out by type A Two mechanisms carried out by type A intercalated cells generate new bicarbonate intercalated cells generate new bicarbonate ionsions

Both involve renal excretion of acid via Both involve renal excretion of acid via secretion and excretion of hydrogen ions or secretion and excretion of hydrogen ions or ammonium ions (NHammonium ions (NH44

++))

Hydrogen Ion ExcretionHydrogen Ion Excretion Dietary hydrogen ions must be counteracted by Dietary hydrogen ions must be counteracted by

generating new bicarbonategenerating new bicarbonate The excreted hydrogen ions must bind to The excreted hydrogen ions must bind to

buffers in the urine (phosphate buffer system)buffers in the urine (phosphate buffer system) Intercalated cells actively secrete hydrogen Intercalated cells actively secrete hydrogen

ions into urine, which is buffered and excretedions into urine, which is buffered and excreted Bicarbonate generated is:Bicarbonate generated is:

Moved into the interstitial space via a cotransport Moved into the interstitial space via a cotransport systemsystem

Passively moved into the peritubular capillary Passively moved into the peritubular capillary bloodblood

Hydrogen Ion ExcretionHydrogen Ion Excretion

In response to In response to acidosis:acidosis: Kidneys generate Kidneys generate

bicarbonate ions bicarbonate ions and add them to the and add them to the bloodblood

An equal amount of An equal amount of hydrogen ions are hydrogen ions are added to the urineadded to the urine

Figure 26.13

Ammonium Ion ExcretionAmmonium Ion Excretion

This method uses ammonium ions produced This method uses ammonium ions produced by the metabolism of glutamine in PCT cellsby the metabolism of glutamine in PCT cells

Each glutamine metabolized produces two Each glutamine metabolized produces two ammonium ions and two bicarbonate ions ammonium ions and two bicarbonate ions

Bicarbonate moves to the blood and Bicarbonate moves to the blood and ammonium ions are excreted in urineammonium ions are excreted in urine

Bicarbonate Ion SecretionBicarbonate Ion Secretion When the body is in alkalosis, type B When the body is in alkalosis, type B

intercalated cells:intercalated cells: Exhibit bicarbonate ion secretionExhibit bicarbonate ion secretion Reclaim hydrogen ions and acidify the bloodReclaim hydrogen ions and acidify the blood

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

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

Respiratory Acidosis and Respiratory Acidosis and AlkalosisAlkalosis

Result from failure of the respiratory system to Result from failure of the respiratory system to balance pHbalance pH

PPCO2CO2 is the single most important indicator of is the single most important indicator of respiratory inadequacyrespiratory inadequacy

PPCO2CO2 levels levels Normal PNormal PCO2CO2 fluctuates between 35 and 45 mm Hg fluctuates between 35 and 45 mm Hg Values above 45 mm Hg signal respiratory acidosisValues above 45 mm Hg signal respiratory acidosis Values below 35 mm Hg indicate respiratory Values below 35 mm Hg indicate respiratory

alkalosisalkalosis

Respiratory Acidosis and Respiratory Acidosis and AlkalosisAlkalosis

Respiratory acidosis is the most common Respiratory acidosis is the most common cause of acid-base imbalancecause of acid-base imbalance Occurs when a person breathes shallowly, or gas Occurs when a person breathes shallowly, or gas

exchange is hampered by diseases such as exchange is hampered by diseases such as pneumonia, cystic fibrosis, or emphysemapneumonia, cystic fibrosis, or emphysema

Respiratory alkalosis is a common result of Respiratory alkalosis is a common result of hyperventilationhyperventilation

Metabolic AcidosisMetabolic Acidosis All pH imbalances except those caused by All pH imbalances except those caused by

abnormal blood carbon dioxide levelsabnormal blood carbon dioxide levels Metabolic acid-base imbalance – bicarbonate Metabolic acid-base imbalance – bicarbonate

ion levels above or below normal (22-26 ion levels above or below normal (22-26 mEq/L) mEq/L)

Metabolic acidosis is the second most common Metabolic acidosis is the second most common cause of acid-base imbalancecause of acid-base imbalance Typical causes are ingestion of too much alcohol Typical causes are ingestion of too much alcohol

and excessive loss of bicarbonate ionsand excessive loss of bicarbonate ions Other causes include accumulation of lactic acid, Other causes include accumulation of lactic acid,

shock, ketosis in diabetic crisis, starvation, and shock, ketosis in diabetic crisis, starvation, and kidney failurekidney failure

Metabolic AlkalosisMetabolic Alkalosis

Rising blood pH and bicarbonate levels Rising blood pH and bicarbonate levels indicate metabolic alkalosisindicate metabolic alkalosis

Typical causes are:Typical causes are: Vomiting of the acid contents of the stomachVomiting of the acid contents of the stomach Intake of excess base (e.g., from antacids)Intake of excess base (e.g., from antacids) Constipation, in which excessive bicarbonate is Constipation, in which excessive bicarbonate is

reabsorbedreabsorbed

Respiratory and Renal Respiratory and Renal CompensationsCompensations

Acid-base imbalance due to inadequacy of a Acid-base imbalance due to inadequacy of a physiological buffer system is compensated physiological buffer system is compensated for by the other systemfor by the other system The respiratory system will attempt to correct The respiratory system will attempt to correct

metabolic acid-base imbalancesmetabolic acid-base imbalances The kidneys will work to correct imbalances The kidneys will work to correct imbalances

caused by respiratory diseasecaused by respiratory disease

Respiratory CompensationRespiratory Compensation

In metabolic acidosis:In metabolic acidosis: The rate and depth of breathing are elevated The rate and depth of breathing are elevated Blood pH is below 7.35 and bicarbonate level is lowBlood pH is below 7.35 and bicarbonate level is low As carbon dioxide is eliminated by the respiratory system, As carbon dioxide is eliminated by the respiratory system,

PPCO2CO2 falls below normal falls below normal

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

Respiratory CompensationRespiratory Compensation

In metabolic alkalosis:In metabolic alkalosis: Compensation exhibits slow, shallow breathing, Compensation exhibits slow, shallow breathing,

allowing carbon dioxide to accumulate in the allowing carbon dioxide to accumulate in the bloodblood

Correction is revealed by:Correction is revealed by: High pH (over 7.45) and elevated bicarbonate ion High pH (over 7.45) and elevated bicarbonate ion

levelslevels Rising PRising PCO2CO2

Renal CompensationRenal Compensation

To correct respiratory acid-base imbalance, To correct respiratory acid-base imbalance, renal mechanisms are stepped uprenal mechanisms are stepped up

Acidosis has high PAcidosis has high PCO2 CO2 and high bicarbonate and high bicarbonate

levelslevels The high PThe high PCO2 CO2 is the cause of acidosis is the cause of acidosis The high bicarbonate levels indicate the kidneys The high bicarbonate levels indicate the kidneys

are retaining bicarbonate to offset the acidosisare retaining bicarbonate to offset the acidosis

Renal CompensationRenal Compensation

Alkalosis has Low PAlkalosis has Low PCO2CO2 and high pH and high pH The kidneys eliminate bicarbonate from the body The kidneys eliminate bicarbonate from the body

by failing to reclaim it or by actively secreting itby failing to reclaim it or by actively secreting it

Developmental AspectsDevelopmental Aspects Water content of the body is greatest at birth Water content of the body is greatest at birth

(70-80%) and declines until adulthood, when it (70-80%) and declines until adulthood, when it is about 58%is about 58%

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

Homeostatic mechanisms slow down with ageHomeostatic mechanisms slow down with age Elders may be unresponsive to thirst clues and Elders may be unresponsive to thirst clues and

are at risk of dehydrationare at risk of dehydration The very young and the very old are the most The very young and the very old are the most

frequent victims of fluid, acid-base, and frequent victims of fluid, acid-base, and electrolyte imbalanceselectrolyte imbalances

Problems with Fluid, Electrolyte, Problems with Fluid, Electrolyte, and Acid-Base Balanceand Acid-Base Balance

Occur in the young, reflecting:Occur in the young, reflecting: Low residual lung volumeLow residual lung volume High rate of fluid intake and outputHigh rate of fluid intake and output High metabolic rate yielding more metabolic High metabolic rate yielding more metabolic

wasteswastes High rate of insensible water lossHigh rate of insensible water loss Inefficiency of kidneys in infants Inefficiency of kidneys in infants