Homeostasis

Section 2: Acid-Base Balance

• Acid-base balance (H+ production = loss)– Normal plasma pH: 7.35–7.45– H+ gains: many metabolic activities produce

acids• CO2 (to carbonic acid) from aerobic respiration• Lactic acid from glycolysis

– H+ losses and storage• Respiratory system eliminates CO2

• H+ excretion from kidneys• Buffers temporarily store H+

Figure 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.

Section 2: Acid-Base Balance

• Classes of acids– Fixed acids• Do not leave solution

– Remain in body fluids until kidney excretion• Examples: sulfuric and phosphoric acid

– Generated during catabolism of amino acids, phospholipids, and nucleic acids

– Organic acids• Part of cellular metabolism

– Examples: lactic acid and ketones• Most metabolized rapidly so no accumulation

Section 2: Acid-Base Balance

• Classes of acids (continued)– Volatile acids• Can leave body by external respiration• Example: carbonic acid (H2CO3)

Module 24.5: Buffer systems

• pH imbalance– ECH pH normally between 7.35 and 7.45• Acidemia (plasma pH <7.35): acidosis (physiological state)

– More common due to acid-producing metabolic activities– Effects

» CNS function deteriorates, may cause coma» Cardiac contractions grow weak and irregular» Peripheral vasodilation causes BP drop

• Alkalemia (plasma pH >7.45): alkalosis (physiological state)– Can be dangerous but relatively rare

Figure 24.5 1

Figure 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

Module 24.5: Buffer systems

• CO2 partial pressure effects on pH– Most important factor affecting body pH– H2O + CO2 H2CO3 H+ + HCO3

–

• Reversible reaction that can buffer body pH

– Adjustments in respiratory rate can affect body pH

Figure 24.5 3

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

When the PCO2 falls, the reaction runs in reverse, and

carbonic acid dissociates into carbon dioxide andwater. This removes H ions from solution andincreases the pH.

If PCO2 rises If PCO2

falls

PCO2

40–45mm Hg

pH7.35–7.45

The inverse relationship between the PCO2 and pH

HOMEOSTASIS

H2O CO2 H2CO3 H HCO3 H HCO3

H2CO3 H2O CO2

PCO2

PCO2pH

pH

Module 24.5: Buffer systems

• Buffer – Substance that opposes changes to pH by removing

or adding H+

– Generally consists of: • Weak acid (HY)• Anion released by its dissociation (Y–)• HY H+ + Y– and H+ + Y– HY

Figure 24.5 4

The reactions that occur when pH buffer systems function

HY H YH Y

H

H HYH HY

H

H Y

A buffer system in body fluids generallyconsists of a combination of a weak acid (HY)and the anion (Y) released by its dissociation.The anion functions as a weak base. In solution,molecules of the weak acid exist in equilibriumwith its dissociation products.

Adding H to thesolution upsets the equilibrium and resultsin the formation ofadditional molecules ofthe weak acid.

Removing H from thesolution also upsets theequilibrium and results in the dissociation ofadditional molecules ofHY. This releases H.

Module 24.5 Review

a. Define acidemia and alkalemia.

b. What is the most important factor affecting the pH of the ECF?

c. Summarize the relationship between CO2 levels and pH.

Module 24.6: Major body buffer systems

• Three major body buffer systems– All can only temporarily affect pH (H+ not eliminated)

1. Phosphate buffer system• Buffers pH of ICF and urine

2. Carbonic acid–bicarbonate buffer system• Most important in ECF• Fully reversible• Bicarbonate reserves (from NaHCO3 in ECF) contribute

Module 24.6: Major body buffer systems

• Three major body buffer systems (continued)3. Protein buffer systems (in ICF and ECF)• Usually operate under acid conditions (bind H+)

– Binding to carboxyl group (COOH–) and amino group (—NH2)• Examples:

– Hemoglobin buffer system» CO2 + H2O H2CO3 HCO3

– + Hb-H+

» Only intracellular system with immediate effects– Amino acid buffers (all proteins)– Plasma proteins

Figure 24.6 1

The body’s three major buffer systems

Buffer Systems

Intracellular fluid (ICF) Extracellular fluid (ECF)

occur in

Phosphate BufferSystem

Protein Buffer Systems Carbonic Acid–Bicarbonate Buffer System

Has an importantrole in buffering thepH of the ICF andof urine

Contribute to the regulation of pH in the ECF and ICF;interact extensively with the other two buffer systems

Is most important in theECF

Hemoglobinbuffer system

(RBCs only)

Amino acidbuffers

(All proteins)

Plasmaproteinbuffers

Figure 24.6 4

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 24.6 2

The events involved in the functioning of the hemoglobin buffer system

Tissuecells

Plasma Plasma Lungs

Red blood cells Red blood cells Releasedwith

exhalation

CO2

H2O

H2CO3 HCO3 Hb H H HCO3

Hb H2CO3

H2O

CO2

Figure 24.6 3

The mechanism by free amino acids function inprotein buffer systemsStart

Normal pH(7.35–7.45)

Increasing acidity (decreasing pH)

At the normal pH ofbody fluids (7.35–7.45), the carboxylgroups of most aminoacids have releasedtheir hydrogen ions.

If pH drops, the carboxylate ion (COO)and the amino group (—NH2) of a freeamino acid can act as weak bases andaccept additional hydrogen ions, forming acarboxyl group (—COOH) and an aminoion (—NH3

), respectively. Many of theR-groups can also accept hydrogen ions,forming RH.

Module 24.6: Major body buffer systems

• Disorders– Metabolic acid-base disorders• Production or loss of excessive amounts of fixed or

organic acids• Carbonic acid–bicarbonate system works to counter

– Respiratory acid-base disorders• Imbalance of CO2 generation and elimination• Must be corrected by depth and rate of respiration

changes

Module 24.6 Review

a. Identify the body’s three major buffer systems.

b. Describe the carbonic acid–bicarbonate buffer system.

c. Describe the roles of the phosphate buffer system.

Module 24.7: Metabolic acid-base disorders

• Metabolic acid-base disorders– Metabolic acidosis

• Develops when large numbers of H+ are released by organic or fixed acids

• Accommodated by respiratory and renal responses– Respiratory response

» Increased respiratory rate lowers PCO2

» H+ + HCO3– H2CO3 H2O + CO2

– Renal response» Occurs in PCT, DCT, and collecting system» H2O + CO2 H2CO3 H+ + HCO3

–

H+ secreted into urine HCO3

– reabsorbed into ECF

Figure 24.7 1

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.

Figure 24.7 2

The activity of renaltubule cells in CO2

removal and HCO3

production

Tubularfluid

Renal tubule cells ECF

H

H

H

H

Na

Na

CO2 CO2

HCO3

HCO3

H2CO3

HCO3

CO2

H2O

Cl

Cl

Carbonicanhydrase

CO2 generated by the tubulecell is added to the CO2

diffusing into the cell fromthe urine and from the ECF.

Steps in CO2 removal andHCO3

production

Carbonic anhydraseconverts CO2 and water tocarbonic acid, which then dissociates.

The chloride ions exchangedfor bicarbonate ions areexcreted in the tubular fluid.

Bicarbonate ions andsodium ions are transportedinto the ECF, adding to thebicarbonate reserve.

Module 24.7: Metabolic acid-base disorders

• Metabolic alkalosis– Develops when large numbers of H+ are removed

from body fluids– Rate of kidney H+ secretion declines– Tubular cells do not reclaim bicarbonate– Collecting system transports bicarbonate into urine and retains

acid (HCl) in ECF

Module 24.7: Metabolic acid-base disorders

• Metabolic alkalosis (continued)– Accommodated by respiratory and renal responses• Respiratory response

– Decreased respiratory rate raises PCO2

– H2O + CO2 H2CO3 H+ + HCO3–

• Renal response– Occurs in PCT, DCT, and collecting system– H2O + CO2 H2CO3 H+ + HCO3

–

» HCO3– secreted into urine (in exchange for Cl–)

» H+ actively reabsorbed into ECF

Figure 24.7 3

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

.

Figure 24.7 4

The events in thesecretion of bicarbonateions into the tubularfluid along the PCT, DCT,and collecting system

Tubularfluid

Renal tubule cells ECF

H2CO3

CO2

H2OCarbonicanhydrase

H

CO2

HCO3 HHCO3

CO2

Cl Cl

CO2 generated by the tubulecell is added to the CO2

diffusing into the cell from thetubular fluid and from the ECF.

Carbonic anyhydrase convertsCO2 and water to carbonic acid, which then dissociates.

The hydrogen ions are activelytransported into the ECF,accompanied by the diffusionof chloride ions.

HCO3 is pumped into the

tubular fluid in exchange forchloride ions that will diffuseinto the ECF.

Module 24.7 Review

a. Describe metabolic acidosis.

b. Describe metabolic alkalosis.

c. lf the kidneys are conserving HCO3– and

eliminating H+ in acidic urine, which is occurring: metabolic alkalosis or metabolic acidosis?

CLINICAL MODULE 24.8: Respiratory acid-base disorders

• Respiratory acid-base disorders– Respiratory acidosis

• CO2 generation outpaces rate of CO2 elimination at lungs• Shifts bicarbonate buffer system toward generating more carbonic

acid• H2O + CO2 H2CO3 H+ + HCO3

–

– HCO3– goes into bicarbonate reserve

– H+ must be neutralized by any of the buffer systems» Respiratory (increased respiratory rate)» Renal (H+ secreted and HCO3

– reabsorbed)» Proteins (bind free H+)

Figure 24.8 1

The events in respiratory acidosis

CARBONIC ACID–BICARBONATEBUFFER SYSTEM BICARBONATE RESERVE

Lungs

CO2 CO2 H2O H2CO2

(carbonic acid)H HCO3

(bicarbonate ion)HCO3

Na NaHCO3

(sodium bicarbonate)

When respiratory activity does not keeppace with the rate of CO2 generation,alveolar and plasma PCO2

increases.

This upsets the equilibrium and drivesthe reaction to the right, generatingadditional H2CO3, which releases H

and lowers plasma pH.

As bicarbonate ions and hydrogen ionsare released through the dissociation ofcarbonic acid, the excess bicarbonateions become part of the bicarbonatereserve.

To limit the pH effects ofrespiratory acidosis, the excess H must either be tied up byother buffer systems or excreted at the kidneys. The underlyingproblem, however, cannot beeliminated without an increase inthe respiratory rate.

Figure 24.8 2

The integrated homeostatic responsesto respiratory acidosis

IncreasedPCO2

Elevated PCO2 results

in a fall in plasma pH

Respiratory Acidosis

Responses to Acidosis

Combined Effects

Respiratory compensation

Renal compensation

Decreased PCO2

Decreased H andincreased HCO3

Stimulation of arterial and CSFchemoreceptors results inincreased respiratory rate.

H ions are secreted andHCO3

ions are generated.

Buffer systems other than thecarbonic acid–bicarbonatesystem accept H ions.

HOMEOSTASISDISTURBED

HOMEOSTASISRESTORED

Hypoventilationcausing increased PCO2

Plasma pHreturns to normalStart

Normal acid-base balance

HOMEOSTASIS

CLINICAL MODULE 24.8: Respiratory acid-base disorders

• Respiratory alkalosis– CO2 elimination at lungs outpaces CO2 generation rate – Shifts bicarbonate buffer system toward generating more carbonic

acid– H+ + HCO3

– H2CO3 H2O + CO2 • H+ removed as CO2 exhaled and water formed

– Buffer system responses– Respiratory (decreased respiratory rate)– Renal (HCO3

– secreted and H+ reabsorbed)– Proteins (release free H+)

Figure 24.8 3

The events in respiratory alkalosis

If respiratory activity exceeds the rate of CO2 generation, alveolar and plasma PCO2

decline,

and this disturbs the equilibrium and drivesthe reactions to the left, removing H and elevating plasma pH.

CO2 CO2 H2O H2CO2

(carbonic acid)H HCO3

(bicarbonate ion)HCO3

Na NaHCO3

(sodium bicarbonate)Lungs

CARBONIC ACID–BICARBONATEBUFFER SYSTEM BICARBONATE RESERVE

As bicarbonate ions and hydrogenions are removed in the formation ofcarbonic acid, the bicarbonate ions—but not the hydrogen ions—arereplaced by the bicarbonate reserve.

Figure 24.8 4

The integrated homeostatic responses torespiratory alkalosis

StartNormal acid-base balance

HOMEOSTASIS

DecreasedPCO2

Lower PCO2 results

in a rise in plasma pH

Respiratory Alkalosis

HOMEOSTASISDISTURBED

Hyperventilationcausing decreased PCO2

Plasma pHreturns to normal

HOMEOSTASISRESTORED

Increased PCO2

Combined Effects

Increased H anddecreased HCO3

Responses to Alkalosis

Respiratory compensation

Renal compensation

Inhibition of arterial and CSFchemoreceptors results in adecreased respiratory rate.

H ions are generated and HCO3

ions are secreted.

Buffer systems other than thecarbonic acid–bicarbonate systemrelease H ions.

CLINICAL MODULE 24.8 Review

a. Define respiratory acidosis and respiratory alkalosis.

b. What would happen to the plasma PCO2 of a patient who has an airway obstruction?

c. How would a decrease in the pH of body fluids affect the respiratory rate?