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    ACID BASE BALANCE &

    BODY FLUID

    Ani Retno Prijanti

    Renal and Body Fluids ModuleJuni 2008

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    Continuous Mixing of Body Fluids

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    Water Balance and ECFOsmolality

    To remain properly hydrated, water intake

    must equal water output

    Water intake sourcesIngested fluid (60%) and solid food

    (30%)

    Metabolic water or water of oxidation(10%)

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    Water Balance and ECFOsmolality

    Water output

    Urine (60%) and feces (4%)

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

    Increases in plasma osmolality triggerthirst 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 12%

    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 centersinclude:

    Moistening of the mucosa of the mouth and

    throatActivation of stomach and intestinal stretch

    receptors

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    Regulation of Water Intake: ThirstMechanism

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    Regulation of Water Output

    Obligatory water losses include:

    Insensible water losses from lungs and skin

    Water that accompanies undigested food residues infeces

    Sensible water loss of 500ml in urine

    Kidneys excrete 900-1200 mOsm of solutes to maintainblood 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 toADH 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 includeprolonged fever; excessive sweating,vomiting, ordiarrhea; severe blood loss; and traumatic burns

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    Electrolyte BalanceElectrolytes are salts, acids, and bases, but

    electrolyte balance usually refers only to saltbalance

    Salts are important for:Neuromuscular excitabilitySecretory activityMembrane permeability

    Controlling fluid movements

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

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    Sodium in Fluid and ElectrolyteBalance

    Changes in plasma sodium levels affect:

    Plasma volume, blood pressure

    ICF and interstitial fluid volumes

    Renal acid-base control mechanisms arecoupled to sodium ion transport

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    Regulation of Sodium Balance:Aldosterone

    Sodium reabsorption65% of sodium in filtrate is reabsorbed in the

    proximal tubules

    25% is reclaimed in the DCT

    When aldosterone levels are high, all remainingNa+ is actively reabsorbed

    Water follows sodium if tubule permeability hasbeen 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, whichreleases renin in response to:

    Sympathetic nervous system stimulationDecreased filtrate osmolality

    Decreased stretch (due to decreased blood

    pressure)

    Renin catalyzes the production of angiotensin II, whichprompts aldosterone release

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    Regulation of Sodium Balance:Aldosterone

    Low aldosterone cause Na excretion and water willfollow 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 (diminishedurine output and increased blood volume) slowly

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    What is the acid base balance

    Acid-base balance is defined by theconcentration of hydrogen ions.

    In order to achieve homeostasis, theremust be a balance between the intake or

    production of hydrogen ions and the netremoval of hydrogen ions from the body.

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    An Acid

    Molecules containing hydrogen atoms thatcan release hydrogen ions in solutions arereferred to as an acid.

    An example of an acid is hydrochloric acid(HCL)

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    A Base

    A base is an ion that can accept ahydrogen ion.

    An example of a base is is the bicarbonateion.( HCO3-)

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    How is Acid-Base balancemeasured

    Hydrogen ion concentration is expressedon a logarithm scale using pH units(part/percentage hydrogen).

    7.0 being neutral

    Body systems carefully control pH of thebody within the range of 7.35-7.45

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    pH

    A low pH corresponds to a high hydrogenion concentration

    The term Acidosis refers to the additionof excess hydrogen ions and the body hasa pH that falls below 7.35

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    pH

    A high pH corresponds to a low hydrogenconcentration

    The term Alkalosis refers to excessremoval of hydrogen ions from the bodyand has a pH that rises above 7.45

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    How the Body defends againstfluctuations in pH

    Three Systems in the body:

    1.Buffers in the blood

    2.Respiration through the lungs

    3.Excretion by the kidneys

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    Buffers in the Blood

    Buffers are substances that neutralizeacids or bases

    Bicarbonate which is a base and carbonicacid in the body fluids protect the bodyagainst changes in acidity

    These buffer systems serve as a first lineof defense against changes in the acid-base balance

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    Respiration through the lungs

    Carbon Dioxide which is formed duringcellular metabolism forms carbonic acid inthe blood decreasing the pH

    When the pH drops respiration rateincreases this hyperventilation increasesthe amount of CO2 exhaled thereby

    lowering the carbonic acid concentrationand restoring homeostasis

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    Excretion by the Kidneys

    The kidneys play the primary role inmaintaining long term control of Acid-Basebalance

    The kidney does this by selecting whichions to retain and which to excrete

    The kidneys adjust the bodys Acid-Basebalance

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    The Importance of the BodysBuffering Systems

    Can be quickly realized if one considers the lowconcentration of hydrogen ions in the body fluidsand the relatively large amounts of acids

    produced by the body each day Example: 80 milliequvilalants of hydrogen is

    either ingested or produced each day bymetabolism.

    Whereas the hydrogen ion concentration of thebody fluids normally is only about .0004meq/L

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    Acid-Base Balance

    Normal pH

    7.35 7.45

    Alkalosis or alkalemia arterial blood pHrises 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

    metabolism

    Breakdown of phosphorus-containing proteinsreleases phosphoric acid into the ECF

    Anaerobic respiration of glucose produces lacticacid

    Fat metabolism yields organic acids andketone bodies

    Transporting carbon dioxide as bicarbonatereleases hydrogen ions

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    Hydrogen Ion Regulation

    Concentration of hydrogen ions is regulatedsequentially by:

    Chemical buffer systems act within seconds

    The respiratory center in the brain stem actswithin 1-3 minutes

    Renal mechanisms require hours to days toeffect pH changes

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    Chemical Buffer Systems

    Strong acids all their H+ is dissociatedcompletely in water

    Weak acids dissociate partially in water and

    are efficient at preventing pH changes

    Strong bases dissociate easily in water andquickly 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 pHchanges when strong acid or base is added

    Three major chemical buffer systemsBicarbonate buffer systemPhosphate buffer systemProtein buffer system

    Any drifts in pH are resisted by the entirechemical 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)

    Ifstrong 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

    Ifstrong base is added:

    It reacts with the carbonic acid to form

    sodium bicarbonate (a weak base)

    The pH of the solution rises only slightly

    NaOH + H2CO3 = NaHCO3 + H2O

    This system is the only important ECF buffer

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    Phosphate Buffer System

    Nearly identical to the bicarbonate systemIts components are:

    Sodium salts of dihydrogen phosphate(H2PO4), a weak acid

    Monohydrogen phosphate (HPO42), a weak base

    HCl + Na2HPO4 = NaH2PO4 + NaCl

    NaOH + NaH2PO4 = Na2HPO4 + H2O

    This system is an effective buffer in urine andintracellular fluid

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    Protein Buffer System

    Plasma and intracellular proteins are the bodys mostplentiful and powerful buffers

    Some amino acids of proteins have:

    Organic acid groups (weak acids) COOH (carboxyl)

    R-COOHRCOO- + H+Groups that act as weak bases NH2 (amino)

    R-NH2 R-NH3

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

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    Physiological Buffer Systems

    The respiratory system regulation of acid-basebalance 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

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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 dioxideHydrogen ion concentration is reduced

    Alkalosis causes slower, more shallow breathing, causingH+ to increase

    Respiratory system impairment causes acid-baseimbalance (respiratory acidosis or respiratory alkalosis)

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    Renal Mechanisms of Acid-Base Balance

    Chemical buffers can tie up excess acids orbases, but they cannot eliminate them from thebody

    The lungs can eliminate carbonic acid (volatileacid) by eliminating carbon dioxide

    Only the kidneys can rid the body of metabolic

    acids (phosphoric, uric, and lactic acids andketones) and prevent metabolic acidosis

    The ultimate acid-base regulatory organs arethe kidneys

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    Renal Mechanisms of Acid-Base Balance

    The most important renal mechanisms forregulating acid-base balance are:

    Conserving (reabsorbing) or generating new

    bicarbonate ionsExcreting bicarbonate ions

    Losing a bicarbonate ion is the same as

    gaining a hydrogen ion (the blood becomesacidic); reabsorbing a bicarbonate ion is thesame as losing a hydrogen ion (the bloodbecomes alkaline)

    R l M h i f A id

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    Renal Mechanisms of Acid-Base Balance

    Hydrogen ion secretion occurs in the PCTand 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 bicarbonateions

    For each hydrogen ion secreted, a sodium ion and abicarbonate ion are reabsorbed by thePCT cells

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

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    Reabsorption of Bicarbonate

    Carbonic acid formed infiltrate dissociates torelease carbon dioxideand water

    Carbon dioxide then

    diffuses into tubulecells, where it acts totrigger further hydrogenionsecretion

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    Generating New BicarbonateIons

    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 bygenerating new bicarbonate

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

    Collecting duct cells actively secrete hydrogen ions intourine, which is buffered and excreted

    Bicarbonate generated is:

    Moved into the interstitial space via a cotransport systemPassively moved into the peritubular capillary blood

    H drogen Ion E cretion

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    Hydrogen Ion Excretion

    In response to acidosis:

    Kidneys generatebicarbonate ions and

    add them to the blood

    An equal amount ofhydrogen ions are

    added to the urine

    A i I E ti

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    Ammonium Ion Excretion

    This method uses ammonium ions producedby the metabolism of glutamine in PCT cells

    Each glutamine metabolized produces twoammonium ions and two bicarbonate ions

    Bicarbonate moves to the blood and ammoniumions are excreted in urine

    Ammonium ion Excretion

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    Ammonium ion Excretion

    Bi b t I S ti

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    Bicarbonate Ion Secretion

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

    Exhibit bicarbonate ion secretionReclaim hydrogen ions and acidify the blood

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

    Even during alkalosis, the nephrons and collecting ducts

    excrete fewer bicarbonate ions than they conserve

    R i t A id i d Alk l i

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    Respiratory Acidosis and Alkalosis

    Result from failure of the respiratory system tobalance pH

    PCO2 is the single most important indicator of respiratory

    inadequacy

    PCO2 levelsNormal PCO2 fluctuates between 35 and 45mm HgValues above 45 mm Hg signal respiratory acidosis

    Values below 35 mm Hg indicate respiratory alkalosis

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    Respiratory Acidosis and Alkalosis

    Respiratory acidosis is the most common cause ofacid-base imbalance

    Occurs when a person breathes shallowly,

    or gas exchange is hampered by diseasessuch as pneumonia, cystic fibrosis, or

    emphysema

    Respiratory alkalosis is a common result ofhyperventilation

    M t b li A id i

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    Metabolic Acidosis

    All pH imbalances except those caused by abnormal bloodcarbon dioxide levels

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

    Metabolic acidosis is the second most common cause ofacid-base imbalance

    Typical causes are ingestion of too much

    alcohol and excessive loss of bicarbonateionsOther causes include accumulation of lactic acid,shock, ketosis in diabetic crisis, starvation, andkidney failure

    M t b li Alk l i

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    Metabolic Alkalosis

    Rising blood pH and bicarbonate levelsindicate metabolic alkalosis

    Typical causes are:

    Vomiting of the acid contents of thestomach

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

    Constipation, in which excessivebicarbonate is reabsorbed

    R i t d R l C ti

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    Respiratory and Renal Compensations

    Acid-base imbalance due to inadequacy of aphysiological 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

    R i t C ti

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    Respiratory Compensation

    Metabolic acidosis has low pH:

    Bicarbonate level is low

    Pco2 is falling below normal to correctthe imbalance

    The rate and depth of breathing are

    elevated

    R i t C ti

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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 toaccumulate in the blood

    Renal Compensation

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    Renal Compensation

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

    Respiratory Acidosis has low pHHas high PCO2 (the cause of acidosis)

    In respiratory acidosis, the respiratory rateis often depressed and is the immediate

    cause of the acidosisHigh bicarbonate levels indicate the kidneys

    are retaining bicarbonate to offset theacidosis

    Renal Compensation

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    Renal Compensation

    Respiratory Alkalosis has high pH

    Low 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

    Developmental Aspects

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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 contentarise as males develop greater muscle mass

    Homeostatic mechanisms slow down with age

    Elders may be unresponsive to thirst clues and are atrisk of dehydration

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