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Fluid, Electrolyte and Acid-Base Balance

Fluid, Electrolyte, and Acid-Base Balance

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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%

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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

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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 subdivisionsPlasma – the fluid portion of the bloodInterstitial fluid (IF) – fluid in spaces

between cells Other ECF – lymph, cerebrospinal fluid, eye

humors, synovial fluid, serous fluid, and gastrointestinal secretions

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Fluid Compartments

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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

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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

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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 cationChloride is the major anion

Intracellular fluids have low sodium and chloridePotassium is the chief cationPhosphate is the chief anion

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Extracellular and Intracellular Fluids 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

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Extracellular and Intracellular Fluids Proteins, phospholipids, cholesterol, and

neutral fats account for:90% of the mass of solutes in plasma60% of the mass of solutes in interstitial fluid97% of the mass of solutes in the

intracellular compartment

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Electrolyte Composition of Body Fluids

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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

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Extracellular and Intracellular Fluids

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

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Continuous Mixing of Body Fluids

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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%)

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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)

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Water Intake and Output

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Regulation of Water Intake

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

other stimuli

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Regulation of Water Intake

Thirst is quenched as soon as we begin to drink water

Feedback signals that inhibit the thirst centers include:Moistening of the mucosa of the mouth and

throatActivation of stomach and intestinal stretch

receptors

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Regulation of Water Intake: Thirst Mechanism

Figure 26.5

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Regulation of Water Output

Obligatory water losses include:Insensible water losses from lungs and skinWater that accompanies undigested food

residues in feces Sensible water loss of 500ml in urine

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

Urine solutes must be flushed out of the body in water

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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

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Mechanisms and

Consequences of ADH Release

Figure 26.6

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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: cottonmouth, thirst, dry flushed skin, and oliguria

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

Other consequences include hypovolemic shock and loss of electrolytes

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Disorders of Water Balance: Dehydration

Figure 26.7a

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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

This leads to nausea, vomiting, muscular cramping, cerebral edema, disorientation, convulsions, coma and death

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Disorders of Water Balance: Hypotonic Hydration

Figure 26.7b

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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 capillary hydrostatic pressure

Increased blood pressure, capillary permeability, incompetent venous valves, localized blood vessel blockage, congestive heart failure, hypertension, high blood volume

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Disorders of Water Balance: Edema

Increased capillary permeabilityDue to inflammation

Decreased blood colloid osmotic pressureHypoproteinemiaForces fluids out of capillary beds at the

arterial endsFluids fail to return at the venous endsResults from protein malnutrition, liver

disease, or glomerulonephritis

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Edema

Increased interstitial colloid osmotic pressureBlocked (or surgically removed) lymph

vessels cause leaked proteins to accumulate in interstitial fluid

Interstitial fluid accumulation results in low blood pressure and severely impaired circulation

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

electrolyte balance usually refers only to salt balance

Salts are important for:Neuromuscular excitabilitySecretory activityMembrane permeabilityControlling fluid movements

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

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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 ECFContribute 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

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Sodium in Fluid and Electrolyte Balance 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 pressureSodium ions leaking into cells and being

pumped out against their electrochemical gradient

Sodium concentration in the ECF normally remains stable

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Sodium in Fluid and Electrolyte Balance Changes in plasma sodium levels affect:

Plasma volume, blood pressureICF and interstitial fluid volumes

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

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Regulation of Sodium Balance: Aldosterone Sodium reabsorption

65% of sodium in filtrate is reabsorbed in the proximal tubules

25% is reclaimed in the DCT When aldosterone levels are high, all

remaining Na+ is actively reabsorbed Water follows sodium if tubule permeability has

been increased with ADH

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Regulation of Sodium Balance: Aldosterone

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 stimulationDecreased filtrate osmolalityDecreased stretch (due to decreased blood

pressure) Renin catalyzes the production of angiotensin

II, which prompts aldosterone release

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Regulation of Sodium Balance: Aldosterone

Low aldosterone cause Na excretion and water will follow it

High aldosterone levels will cause Na absorption. For the water to be absorbed ADH must also be present

Adrenal cortical cells are also 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

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Regulation of Sodium Balance:

Aldosterone

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Cardiovascular System Baroreceptors Baroreceptors alert the brain of increases in

blood volume (hence increased blood pressure) Sympathetic nervous system impulses to

the kidneys declineAfferent arterioles dilateGlomerular filtration rate risesSodium and water output increase

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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”

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Maintenance of Blood Pressure Homeostasis

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Atrial Natriuretic Peptide (ANP) 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

Suppressing ADH, renin, aldosterone release

Relaxes vascular smooth muscle Reduces blood pressure and volume

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Mechanisms and

Consequences of ANP

Release

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Influence of Other Hormones on Sodium Balance

Estrogens:Are chemically similar to aldosterone

Enhance NaCl reabsorption by renal tubules

May cause water retention during menstrual cycles

Are responsible for edema during pregnancy

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Influence of Other Hormones on Sodium Balance

Progesterone:Decreases sodium reabsorptionActs as a diuretic, promoting sodium and

water loss Glucocorticoids

Have aldosterone-like effects Increase tubular reabsorption of

sodium and promote edema

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Regulation of Potassium Balance Relative ICF-ECF potassium ion concentration

affects a cell’s resting membrane potentialHyperkalemia decreases the resting

membrane potentialBecause more K+ moves into the ICF

Hypokalemia causes hyperpolarization and nonresponsivenessBecause more K+ moves into the ECF

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Potassium ion excretion increases as K concentration in the ECF risesAldosterone is secreted

Hyperkalemia directly stimulates aldosterone secretion

pH rises

Potassium balance

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Potassium balance

Potassium retention occurs when pH fallsBecause hydrogen ions instead of K are

secreted in exchange for sodium. Hypokalemia causes muscle weakness, and even

paralysis Hyperkalemia and hypokalemia can:

Disrupt electrical conduction in the heartLead to sudden death

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Regulation of Potassium Balance K is also part of the body’s buffer system

Shift of the hydrogen ions in and out of cells leads to corresponding shifts in potassium in the opposite direction

Interferes with activity of excitable cells

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Tubular Secretion and Solute Reabsorption at the DCT

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Tubular Secretion and Solute Reabsorption at the DCT

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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

Collecting duct cells can reabsorb some K+ left in the filtrate

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Influence of Plasma Potassium Concentration High K+ content of ECF favors entry of it into

principal cells and them prompts them to secrete K+

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

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Influence of Aldosterone Aldosterone stimulates potassium ion secretion

by principal cells In cortical collecting ducts, Na+ is reabsorbed,

and 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

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Regulation of Calcium

Ionic calcium in ECF is important for:Blood clottingCell membrane permeabilitySecretory behavior

Hypocalcemia: Increase membranes permeability to Na

Increases excitability Causes muscle tetany

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Regulation of Calcium

Hypercalcemia: Decreases the membrane’s permeability to Na

Membranes become less responsive Inhibits neurons and muscle cellsCardiac arrhythmias

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

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Regulation of Calcium and Phosphate

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

down bone matrixSmall intestine – PTH enhances intestinal

absorption of calciumKidneys – PTH enhances calcium

reabsorption and decreases phosphate reabsorption

Calcium reabsorption and phosphate excretion go hand in hand

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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 secretionRelease of calcium from bone is inhibitedLarger amounts of calcium are lost in feces

and urineMore phosphate is retained

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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

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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

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Acid-Base Balance

Normal pH 7.35 – 7.45

Alkalosis or alkalemia – arterial blood pH rises above 7.45

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

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Sources of Hydrogen Ions Most hydrogen ions originate from cellular

metabolismBreakdown 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

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Hydrogen Ion Regulation

Concentration of hydrogen ions is regulated sequentially by:Chemical buffer systems – act within

secondsThe respiratory center in the brain stem –

acts within 1-3 minutesRenal mechanisms – require hours to days

to effect pH changes

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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)

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Strong and Weak Acids

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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 systemPhosphate buffer systemProtein buffer system

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

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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

HCl + NaHCO3 = H2CO3 + NaCl

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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 slightlyNaOH + H2CO3 = NaHCO3 + H2O

This system is the only important ECF buffer

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Phosphate Buffer System

Nearly identical to the bicarbonate system Its components are:

Sodium salts of dihydrogen phosphate (H2PO4

¯), a weak acidMonohydrogen phosphate (HPO4

2¯), a weak base

HCl + Na2HPO4 = NaH2PO4 + NaClNaOH + NaH2PO4 = Na2HPO4 + H2O

This system is an effective buffer in urine and intracellular fluid

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Protein Buffer System Plasma and intracellular proteins are the body’s

most plentiful and powerful buffers Some amino acids of proteins have:

Organic acid groups (weak acids) –COOH (carboxyl)R-COOH ---RCOO- + H+

Groups that act as weak bases –NH2 (amino)R-NH2---R-NH3

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

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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 waterCarbonic acid and the hydrogen and

bicarbonate ionsCO2 + H2O H2CO3 H+ + HCO3¯

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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)

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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 (volatile 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

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Renal Mechanisms of Acid-Base Balance The most important renal mechanisms for

regulating acid-base balance are:Conserving (reabsorbing) or generating new

bicarbonate ionsExcreting bicarbonate ions

Renal Mechanisms of Acid-Base Balance Acidic blood

Lost bicarbonate ionsGained hydrogen ions

Alkaline bloodReabsorbed bicarbonate ions Lost hydrogen ions

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Renal Mechanisms of Acid-Base Balance Hydrogen ion secretion occurs in the PCT and

in the collecting ducts Hydrogen ions come from the dissociation of

carbonic acid

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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

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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

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Generating New Bicarbonate Ions Two mechanisms carried out collecting ducts

cells generate new bicarbonate ions Both involve renal excretion of acid via

secretion and excretion of hydrogen ions or ammonium ions (NH4

+)

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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) Collecting duct 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

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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

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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

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Ammonium Ion Excretion

Bicarbonate Ion Secretion When the body is in alkalosis some cells of

collecting ducts : Secrete bicarbonate ion Reclaim hydrogen ions and acidify the

blood The mechanism is the opposite of the

bicarbonate ion reabsorption process Even during alkalosis, the nephrons and

collecting ducts excrete fewer bicarbonate ions than they conserve

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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 normal levels fluctuates between 35 and

45 mm Hg

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Respiratory Acidosis

pH below 7.35 PCO2 levels above 45 mm Hg It is the most common cause of acid-base

imbalanceOccurs when a person breathes shallowly,

pneumonia, cystic fibrosis, or emphysema

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Respiratory Alkalosis

pH above 7.45 PCO2 below 35 mm Hg Respiratory alkalosis is a common result of

hyperventilation

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Metabolic Acidosis pH below 7.35 Bicarbonate ion levels below 22 mEq/L Is the second most common cause of acid-

base imbalance Ingestion of too much alcohol, excessive loss

of bicarbonate ions, accumulation of lactic acid, shock, ketosis in diabetic crisis, diarrhea, starvation, and kidney failure

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Metabolic Alkalosis

Blood pH above 7.45 Bicarbonate levels above 26 mEq/L Typical causes are:

Vomiting of the acid contents of the stomachIntake of excess base (e.g., from antacids)Constipation, in which excessive

bicarbonate is reabsorbed

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Respiratory and Renal Compensations Acid-base imbalance due to inadequacy of a

physiological buffer system is compensated for by the other systemThe respiratory system will attempt to

correct metabolic acid-base imbalancesThe kidneys will work to correct imbalances

caused by respiratory disease

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Respiratory Compensation

Metabolic acidosis has low pH:Bicarbonate level is low Pco2 is falling below normal to correct the

imbalanceThe rate and depth of breathing are

elevated

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Respiratory Compensation

Metabolic alkalosis has high pH:High levels of bicarbonate

Correction is revealed by:Rising PCO2 Compensation exhibits slow, shallow

breathing, allowing carbon dioxide to accumulate in the blood

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Renal Compensation To correct respiratory acid-base imbalance,

renal mechanisms are stepped up Respiratory Acidosis has low pH

Has high PCO2 (the cause of acidosis) In respiratory acidosis, the respiratory rate

is often depressed and is the immediate cause of the acidosis

High bicarbonate levels indicate the kidneys are retaining bicarbonate to offset the acidosis

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Renal Compensation

Respiratory Alkalosis has high pHLow PCO2 (the cause of the alkalosis)Low bicarbonate levels

The kidneys eliminate bicarbonate from the body by failing to reclaim it or by actively secreting it

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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

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Problems with Fluid, Electrolyte, and Acid-Base Balance

Occur in the young, reflecting:Low residual lung volumeHigh rate of fluid intake and outputHigh metabolic rate yielding more metabolic

wastesHigh rate of insensible water lossInefficiency of kidneys in infants