Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

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

Table 27-3 A Review of Important Terms Relating to Acid–Base Balance


Acid-Base Balance

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

Alkalosis or alkalemia – arterial blood pH rises above 7.45

Acidosis or acidemia – arterial pH drops below 7.35

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFigure 24.5 2

The narrow range of normal pH of the ECF, and the conditions that result from pH shifts outside the normal range

The pH of the ECF(extracellular fluid)normally ranges from7.35 to 7.45.

pH

When the pH of plasma falls below7.5, acidemia exists. Thephysiological state that results iscalled acidosis.

When the pH of plasma risesabove 7.45, alkalemia exists.The physiological state thatresults is called alkalosis.

Severe acidosis (pH below 7.0) can be deadlybecause (1) central nervous system functiondeteriorates, and the individual may becomecomatose; (2) cardiac contractions grow weak andirregular, and signs and symptoms of heart failuremay develop; and (3) peripheral vasodilationproduces a dramatic drop in blood pressure,potentially producing circulatory collapse.

Severe alkalosis is alsodangerous, but serious casesare relatively rare.

Extremelyacidic

Extremelybasic


pH and enzyme function

Hydrogen ion concentration has a widespread effect on the function of the body's enzyme systems.

The hydrogen ion is highly reactive and will combine with bases or negatively charged ions at very low concentrations.

Proteins contain many negatively charged and basic groups within their structure.

Thus, a change in pH will alter the degree ionization of a protein, which may in turn affect its functioning.

At more extreme hydrogen ion concentrations a protein's structure may be completely disrupted (the protein is then said to be denatured).


Sources of Hydrogen Ions Most hydrogen ions originate from cellular

metabolism Breakdown of phosphorus-containing proteins

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

acid Fat metabolism yields organic acids and ketone

bodies Transporting carbon dioxide as bicarbonate

releases hydrogen ions


Volatile acid comes from carbohydrate and fat metabolism Can leave solution and enter the atmosphere (e.g. carbonic

acid – H2CO3) Breaks in the lungs to carbon dioxide and water In the tissues CO2 reacts with water to form carbonic acid,

which dissociate to give hydrogen ions and bicarbonate ions This reaction occurs spontaneously, but happens faster with

the presence of carbonic anhydrase (CA) PCO2 and pH are inversely related

Types of acids in the body

CO2 + H20 H2CO3 HCO3- + H+


Types of acids in the body Fixed acids

Acids that do not leave solution (e.g. sulfuric and phosphoric acids – produced during catabolism of amino acids)

Eliminated by the kidneys Organic acids

by-products of anerobic metabolism such as lactic acid, ketone bodies


Acid-Base Balance Hydrogen ion and pH balance in the body

Figure 20-18

Fatty acidsAmino acids

CO2 (+ H2O)Lactic acidKetoacids

CO2 (+ H2O)

H+ input

H+ output

Plasma pH7.38–7.42

Buffers:• HCO3

– in extracellular fluid• Proteins, hemoglobin, phosphates in cells• Phosphates, ammonia in urine

H+


Buffers Buffers - compound

that limits the change in hydrogen ion concentration (and so pH) when hydrogen ions are added or removed from the solution.

http://www.nda.ox.ac.uk/wfsa/html/u13/u1312f03.htm


Buffer systems Two types of buffer in the body Chemical buffers

Bicarbonate, phosphate and protein systems Substance that binds H+ and remove it from the solution if its

concentration rises or release it if concentration decreases Fast reaction within seconds

Physiological respiratory (fast reaction – few minutes) or urinary (slow

reaction – hours to days) Regulates pH by controlling the body’s output of bases,

acids or CO2

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFigure 24 Section 2 1

The major factors involved in the maintenanceof acid-base balance

Active tissuescontinuously generatecarbon dioxide, which insolution forms carbonicacid. Additional acids,such as lactic acid, areproduced in the course ofnormal metabolicoperations.

Tissue cells

Buffer Systems

Normalplasma pH(7.35–7.45)

Buffer systems cantemporarily store H

and thereby provideshort-term pHstability.

The respiratory systemplays a key role byeliminatingcarbon dioxide.

The kidneys play a majorrole by secretinghydrogen ions into the urine and generatingbuffers that enter thebloodstream. The rate ofexcretion rises and fallsas needed to maintainnormal plasma pH. As a result, the normal pH ofurine varies widely butaverages 6.0—slightlyacidic.


Chemical Buffer Systems Three major chemical buffer systems

Bicarbonate buffer system Phosphate buffer system Protein buffer system

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


Bicarbonate Buffer System A mixture of carbonic acid (H2CO3) and its salt, sodium

bicarbonate (NaHCO3) (potassium or magnesium bicarbonates work as well)

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

and form carbonic acid (a weak acid) The pH of the solution decreases only slightly

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

weak base) The pH of the solution rises only slightly

This system is the only important ECF buffer

CO2 + H2O H2CO3 H+ + HCO3¯


The reactions of the carbonic acid–bicarbonate buffer system

CARBONIC ACID–BICARBONATEBUFFER SYSTEM

BICARBONATE RESERVE

Start

CO2 CO2 H2O H2CO3

(carbonic acid)H HCO3

(bicarbonate ion)NaHCO3

(sodium bicarbonate)HCO3

Na

Body fluids contain a large reserve ofHCO3

, primarily in the form of dissolvedmolecules of the weak base sodiumbicarbonate (NaHCO3). This readilyavailable supply of HCO3

is known asthe bicarbonate reserve.

Addition of H

from metabolicactivity

The primary function of the carbonicacid–bicarbonate buffer system is toprotect against the effects of the organicand fixed acids generated throughmetabolic activity. In effect, it takes the H released by these acids and generatescarbonic acid that dissociates into waterand carbon dioxide, which can easily be eliminated at the lungs.

Lungs


Figure 27-9 The Basic Relationship between PCO2 and Plasma pH

PCO2

40–45mm Hg HOMEOSTASIS

If PCO2 rises

When carbon dioxide levels rise, more carbonic acidforms, additional hydrogen ions and bicarbonate ionsare released, and the pH goes down.

PCO2

pH

H2O CO2 H2CO3 HCO3H


Figure 27-9 The Basic Relationship between PCO2 and Plasma pH

pH

PCO2

When the PCO2 falls, the reaction runs in reverse, andcarbonic acid dissociates into carbon dioxide and water.This removes H ions from solution and increases thepH.

pH7.35–7.45

HOMEOSTASIS

If PCO2 falls

H HCO3 H2CO3 H2O CO2


Phosphate Buffer System Nearly identical to the bicarbonate system Its components are:

Sodium salts of dihydrogen phosphate (H2PO4¯),

a weak acid Monohydrogen phosphate (HPO4

2¯), a weak base

This system is an effective buffer in urine and intracellular fluid


Protein Buffer System

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

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

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


Figure 27-11 The Role of Amino Acids in Protein Buffer Systems

Neutral pH

If pH fallsIf pH rises

Amino acidIn alkaline medium, aminoacid acts as an acid

and releases H

In acidic medium, aminoacid acts as a base

and absorbs H


Buffer Systems in Body Fluids

Figure 27.7


Figure 27-10 Buffer Systems in Body Fluids

Buffer Systems

Intracellular fluid (ICF)

Phosphate BufferSystem

Protein Buffer Systems

The phosphatebuffer systemhas an importantrole in bufferingthe pH of the ICFand of urine.

Protein buffer systems contribute to the regulationof pH in the ECF and ICF. These buffer systems interactextensively with the other two buffer systems.

Hemoglobin buffersystem (RBCs only)

Amino acid buffers(All proteins)

Plasma proteinbuffers

The carbonic acid–bicarbonate buffersystem is mostimportant in the ECF.

Carbonic Acid–Bicarbonate BufferSystem

Extracellular fluid (ECF)

occur in


Physiological Buffer Systems – respiratory system The respiratory system regulation of acid-base balance

is a physiological buffering system The respiratory buffering system takes care of

volatile acids – by-products of glucose and fat metabolism

CO2 + H2O H2CO3 H+ + HCO3¯


Physiological Buffer Systems – respiratory system 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


Physiological Buffer Systems – kidneys

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

The lungs can eliminate carbonic acid by eliminating carbon dioxide

Only the kidneys can excrete 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


Physiological Buffer Systems – kidneys The kidney takes care of the non-volatile acid products

By-products of protein metabolism and anaerobic respiration

The kidneys must prevent the loss of bicarbonate ions (re-absorb) that is being constantly filtered from the blood.

Both tasks are accomplished by secretion of hydrogen ions Only about 10% of the hydrogen ions secreted will be

excreted As a result of the H+ excretion the urine is usually acidic


Reabsorption of Bicarbonate

In a person with normal acid-base balance all the HCO3- in

the tubular fluid is consumed by neutralizing H+ - no HCO3

- in the urine

HCO3- molecules are filtered by the glomerulus and than

reabsorbed and appear in the peritubular capillary (most in the PCT).

The re-absorption is not direct – the luminar surface of the tubular cells can not absorb HCO3

-

The kidney cells can also generate new HCO3- if needed


Reabsorption of Bicarbonate

Figure 26.12


Buffers in Urine

The ability to eliminate large numbers of H+ in a normal volume of urine depends on the presence of buffers in urine

Carbonic acid–bicarbonate buffer system

Phosphate buffer system

Ammonia buffer system


Figure 27-13a Kidney Tubules and pH Regulation

The three major buffering systems in tubular fluid,which are essential to the secretion of hydrogen ions

Cells of PCT,DCT, andcollectingsystem

Peritubularfluid

Peritubularcapillary

Carbonic acid–bicarbonatebuffer system

Phosphate buffer system

Ammonia buffer system

KEY Countertransport

Active transport

Exchange pump

Cotransport

Reabsorption

Secretion

Diffusion


Renal Responses to Acidosis

1. Secretion of H+

2. Activity of buffers in tubular fluid

3. Removal of CO2

4. Reabsorption of NaHCO3–


Renal Responses to Alkalosis

1. Rate of secretion at kidneys declines

2. Tubule cells do not reclaim bicarbonates in

tubular fluid

3. Collecting system transports HCO3– into tubular

fluid while releasing strong acid (HCl) into

peritubular fluid


Figure 27-13c Kidney Tubules and pH Regulation

KEY Countertransport

Active transport

Exchange pump

Cotransport

Reabsorption

Secretion

Diffusion

The response ofthe kidney tubuleto alkalosis

Tubular fluidin lumen

Carbonicanhydrase


Acid–Base Balance Disturbances Respiratory Acid–Base Disorders

Result from imbalance between: CO2 generation in peripheral tissues

CO2 excretion at lungs

Cause abnormal CO2 levels in ECF

Metabolic Acid–Base Disorders Result from:

Generation of organic or fixed acids Conditions affecting HCO3

- concentration in ECF


Respiratory Acidosis and Alkalosis Result from failure of the respiratory system to balance pH PCO2 is the most important indicator of respiratory

inadequacy PCO2 levels

Normal PCO2 fluctuates between 35 and 45 mm Hg

Values above 45 mm Hg signal respiratory acidosis Values below 35 mm Hg indicate respiratory alkalosis


Respiratory Acidosis and Alkalosis Respiratory acidosis is the most common cause of

acid-base imbalance Occurs when a person breathes shallowly, or gas

exchange is slowed down by diseases such as pneumonia, cystic fibrosis, or emphysema

Respiratory alkalosis is a common result of hyperventilation


Figure 27-15a Respiratory Acid–Base Regulation

Responses to Acidosis

Respiratory compensation:Stimulation of arterial and CSF chemo-receptors results in increasedrespiratory rate.

Renal compensation:H ions are secreted and HCO3

ions are generated.

Buffer systems other than the carbonicacid–bicarbonate system accept H ions.

Respiratory Acidosis

Elevated PCO2 results

in a fall in plasma pH

HOMEOSTASISDISTURBED

Hypoventilationcausing increased PCO2

HOMEOSTASISNormal

acid–basebalance

HOMEOSTASISRESTORED

Plasma pHreturns to normal

Decreased PCO2

Decreased H andincreased HCO3

Combined Effects

IncreasedPCO2

Respiratory acidosis


Figure 27-15b Respiratory Acid–Base Regulation

HOMEOSTASISDISTURBED

Hyperventilationcausing decreased PCO2

Respiratory Alkalosis

Lower PCO2 results

in a rise in plasma pH

Responses to Alkalosis

Respiratory compensation:Inhibition of arterial and CSFchemoreceptors results in a decreasedrespiratory rate.

Renal compensation:H ions are generated and HCO3

ionsare secreted.Buffer systems other than the carbonic acid–bicarbonate system release H

ions.Respiratory alkalosis

DecreasedPCO2

Combined Effects

Increased PCO2

Increased H anddecreased HCO3

HOMEOSTASISRESTORED

Plasma pHreturns to normal

Normalacid–base

balance

HOMEOSTASIS


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

imbalance Can be a result of:

Failure of the kidney to excrete metabolic acids Renal acidosis is either the inability of kidney to excrete

H+ or to re- absorb bicarbonate ion Diarrhea – most common reason of metabolic acidosis

Loss of large amounts of sodium bicarbonate in the feces (which is normal component of the feces)

Diabetes mellitus – results in breakdown of fat that releases acids

Ingestion of acids Acetylsalicylic acid (aspirin) Methyl alcohol (forms acid when metabolized)


Metabolic Alkalosis Is caused by elevated HCO3

– concentrations Bicarbonate ions interact with H+ in solution

Forming H2CO3

Reduced H+ causes alkalosis Typical causes are:

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

reabsorbed


The responses to metabolic acidosis Additionof H

Start

CO2 CO2 H2O H2CO3

(carbonic acid)H HCO3

Lungs(bicarbonate ion)

HCO3 Na NaHCO3

(sodium bicarbonate)

Generationof HCO3

CARBONIC ACID–BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE

Respiratory Responseto Acidosis

Renal Response to Acidosis

Otherbuffer

systemsabsorb H

KIDNEYS

Secretionof H

Increased respiratoryrate lowers PCO2

,effectively convertingcarbonic acid moleculesto water.

Kidney tubules respond by (1) secreting H

ions, (2) removing CO2, and (3) reabsorbingHCO3

to help replenish the bicarbonatereserve.


The responses to metabolic alkalosisStart

Lungs

Removalof H

CO2 H2O H HCO3H2CO3

(carbonic acid)HCO3

Na NaHCO3

(sodium bicarbonate)(bicarbonate ion)

CARBONIC ACID–BICARBONATE BUFFER SYSTEM BICARBONATE RESERVE

Generationof H KIDNEYS

Secretionof HCO3

Otherbuffer

systemsrelease H

Respiratory Responseto Alkalosis

Renal Response to AlkalosisDecreased respiratoryrate elevates PCO2

,effectively convertingCO2 molecules tocarbonic acid.

Kidney tubules respond byconserving H ions and secreting HCO3

.


Table 27-4 Changes in Blood Chemistry Associated with the Major Classes of Acid–Base Disorders


Acid-Base Balance

Table 20-2


The response to acidosis caused by the addition of H

Additionof H

Start

(carbonic acid) (bicarbonate ion)H

Otherbuffer

systemsabsorb H

KIDNEYS

Increased respiratoryrate lowers PCO2

,

effectively convertingcarbonic acidmolecules to water.

LungsCO2 CO2 H2O

Respiratory Responseto Acidosis

Secretionof H

H2CO3 HCO3 HCO3

Na

BICARBONATE RESERVE

NaHCO3

Generationof HCO3

Renal Response to Acidosis


Kidney tubules respond by (1) secreting H

ions, (2) removing CO2, and (3) reabsorbing

HCO3 to help replenish the bicarbonate

reserve.

CARBONIC ACID-BICARBONATE BUFFER SYSTEM


BICARBONATE RESERVE

Removalof H

H

(carbonic acid) (bicarbonate ion)H2CO3 HCO3

Otherbuffer

systemsrelease H

Generationof H

Secretionof HCO3

KIDNEYS

H2OCO2 Lungs

Respiratory Responseto Alkalosis

Decreased respiratoryrate elevates PCO2

,

effectively convertingCO2 molecules tocarbonic acid.

Renal Response to Alkalosis

HCO3 NaHCO3Na


Kidney tubules respond byconserving H ions andsecreting HCO3

.

The response to alkalosis caused by the removal of H

Start

CARBONIC ACID-BICARBONATE BUFFER SYSTEM

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummingshttp://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummingshttp://www.mhhe.com/biosci/esp/2002_general/Esp/default.htm

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Table 27-3 A Review of Important Terms Relating to Acid–Base Balance

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