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ACID BASE BALANCE & BODY FLUIDAni 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 sources

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

Metabolic water or water of oxidation (10%)

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Water Balance and ECFOsmolality

• Water outputUrine (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 todrink water

Feedback signals that inhibit the thirst centersinclude:

Moistening of the mucosa of the mouth andthroatActivation of stomach and intestinal stretchreceptors

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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 skinWater that accompanies undigested food residues in

fecesSensible 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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Electrolyte BalanceElectrolytes are salts, acids, and bases, but

electrolyte balance usually refers only to saltbalance

Salts are important for:Neuromuscular excitabilitySecretory activityMembrane permeabilityControlling 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 pressureICF 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 tubules25% is reclaimed in the DCT

When aldosterone levels are high, all remaining Na+ 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 therelease of aldosteroneThis is mediated by the juxtaglomerular apparatus, which releases renin in response to:

Sympathetic nervous system stimulationDecreased filtrate osmolalityDecreased stretch (due to decreased bloodpressure)

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 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 torelease 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 the concentration of hydrogen ions.

• In order to achieve homeostasis, there must be a balance between the intake or production of hydrogen ions and the net removal of hydrogen ions from the body.

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An Acid

• Molecules containing hydrogen atoms that can release hydrogen ions in solutions are referred 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 a hydrogen ion.

• An example of a base is is the bicarbonate ion.( HCO3-)

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How is Acid-Base balance measured

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

• 7.0 being neutral• Body systems carefully control pH of the

body within the range of 7.35-7.45

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pH

• A low pH corresponds to a high hydrogen ion concentration

• The term “Acidosis” refers to the addition of excess hydrogen ions and the body has a pH that falls below 7.35

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pH

• A high pH corresponds to a low hydrogen concentration

• The term “Alkalosis” refers to excess removal of hydrogen ions from the body and has a pH that rises above 7.45

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How the Body defends against fluctuations in pH

Three Systems in the body:

1.Buffers in the blood2.Respiration through the lungs3.Excretion by the kidneys

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Buffers in the Blood

• Buffers are substances that neutralize acids or bases

• Bicarbonate which is a base and carbonic acid in the body fluids protect the body against changes in acidity

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

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Respiration through the lungs

• Carbon Dioxide which is formed during cellular metabolism forms carbonic acid in the blood decreasing the pH

• When the pH drops respiration rate increases this hyperventilation increases the amount of CO2 exhaled thereby lowering the carbonic acid concentration and restoring homeostasis

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Excretion by the Kidneys

• The kidneys play the primary role in maintaining long term control of Acid-Base balance

• The kidney does this by selecting which ions to retain and which to excrete

• The kidneys adjust the body’s Acid-Base balance

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The Importance of the Body’s Buffering Systems

• Can be quickly realized if one considers the low concentration of hydrogen ions in the body fluids and the relatively large amounts of acids produced by the body each day

• Example: 80 milliequvilalants of hydrogen is either ingested or produced each day by metabolism.

• Whereas the hydrogen ion concentration of the body 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 pH rises above 7.45

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

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Sources of Hydrogen IonsMost hydrogen ions originate from cellular

metabolism

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

Anaerobic respiration of glucose produces lactic acid

Fat metabolism yields organic acids 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 – acts within 1-3 minutes

Renal 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 andare 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 ormagnesium bicarbonates work as well)

If strong acid is added:Hydrogen ions released combine with the

bicarbonate ions and form carbonic acid (aweak acid)

The pH of the solution decreases onlyslightly

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 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 SystemPlasma 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 thatcan 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 andbicarbonate ions

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3¯

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Physiological Buffer SystemsDuring carbon dioxide unloading, hydrogen ions

are incorporated into water

When hypercapnia or rising plasma H+ occurs:Deeper and more rapid breathing expels morecarbon dioxideHydrogen ion concentration is reduced

Alkalosis causes slower, more shallow breathing, causing H+ 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 metabolicacids (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 newbicarbonate ions

Excreting bicarbonate ions

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

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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 ofcarbonic acid

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Reabsorption of BicarbonateCarbon 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 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 in filtrate dissociates torelease carbon dioxide and water

• Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ionsecretion

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Generating New BicarbonateIons

Two mechanisms carried out collecting ductscells generate new bicarbonate ions

Both involve renal excretion of acid viasecretion and excretion of hydrogen ions orammonium ions (NH4+)

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Hydrogen Ion ExcretionDietary 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 systemPassively moved into the peritubular capillary blood

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Hydrogen Ion Excretion

In response to acidosis:

•�Kidneys generatebicarbonate 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 producedby the metabolism of glutamine in PCT cells

Each glutamine metabolized produces twoammonium ions and two bicarbonate ions

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

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Ammonium ion Excretion

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Bicarbonate Ion Secretion

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

Exhibit bicarbonate ion secretionReclaim hydrogen ions and acidify the blood

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

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

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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 acidosisValues below 35 mm Hg indicate respiratory alkalosis

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Respiratory Acidosis and Alkalosis

Respiratory acidosis is the most common cause of acid-base imbalanceOccurs when a person breathes shallowly,or gas exchange is hampered by diseasessuch as pneumonia, cystic fibrosis, oremphysema

Respiratory alkalosis is a common result ofhyperventilation

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Metabolic Acidosis

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

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

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

Typical causes are ingestion of too muchalcohol and excessive loss of bicarbonateionsOther causes include accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure

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Metabolic Alkalosis

Rising blood pH and bicarbonate levels indicate metabolic alkalosis

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 aphysiological buffer system is compensated forby the other system

The respiratory system will attempt tocorrect metabolic acid-base imbalances

The kidneys will work to correct imbalancescaused 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 areelevated

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Respiratory Compensation

Metabolic alkalosis has high pH:High levels of bicarbonate

Correction is revealed by:Rising PCO2Compensation 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 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

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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 fromthe body by failing to reclaim it or byactively 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