COMPENSATORY MECHANISM OF ACID - BASE BALANCE

By

Dr KHALED SALEH ALGARIRI

2014

Alkalosis refers to excess removal of H+ from the body fluids

Acidosis refers to excess addition of H+

Acidosis- a decline in blood pH ↓Metabolic acidosis: due to a decrease in

bicarbonate. ↓Respiratory acidosis: due to an increase in

carbonic acid. ↑Alkalosis- a rise in blood pH ↑

Metabolic alkalosis: due to an increase in bicarbonate.↑

Respiratory alkalosis : due to a decrease in carbonic acid. ↓

4

pH

Acidosis Alkalosis

respiretory

[HCO3-]

↓[HCO3

-]↑

PaCO2↑ PaCO2

↓

metabolicmetabolic respiretory

HCO3－

5

Affect all body systems

Particularly nervous and cardiovascular

systems

Both are dangerous But acidosis is more common Because normal cellular activities generate

acids

Acidosis and Alkalosis

Types of Acids in the Body

1. Fixed acids

2. Organic acids

3. Volatile acids

The body produces more acids than bases

Acids take in with foods.Cellular metabolism produces CO2.Acids produced by metabolism of lipids

and proteins.

Volatile acid

H2CO3 CO2+ H2O

CO2

CO2 CO2

Fixed acid

H2SO4 H3PO4

Uric acidLactic acid

Ketone body(H+ < 0.05 –0.10 mol /d)

(H+ 15 –20 mol /d)

F 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

The Basic Relationship between PCO2 and Plasma pH

pH

PCO2

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

carbonic acid dissociates into carbon dioxide and water.This removes H ions from solution and increases thepH.

pH

7.35–7.45HOMEOSTASIS

If PCO2 falls

H HCO3 H2CO3 H2O CO2

pH< 7.35: Acidosis

pH > 7.45: Alkalosis

The body response to acid-base imbalance

is called compensationThe body gears up its homeostatic

mechanism and makes every attempt to restore the pH to normal level.

May be complete if brought back within normal limits

Partial compensation if range is still outside norms.

Defenses against changes in hydrogen ion concentration

There are three primary systems that regulate the H+ concentration in the body fluids to prevent acidosis or alkalosis:

(1) the chemical acid-base buffer systems of the body fluids

(2) the respiratory center(3) the kidneys, which can excrete either

acid or alkaline urine, thereby readjusting the extracellular fluid H+ concentration toward normal during acidosis or alkalosis

Buffer system

A chemical substance that minimizes changes in pH by releasing or binding hydrogen ions

Buffer SystemMost buffers composed of weak acid and

weak baseThe purpose of the buffer is to help the

body maintain pHThree important buffer system: 1. H2CO3/HCO3 buffer system (Most important in ECF)

2. H2PO4-/HPO4-2 buffer system (Buffers pH of ICF and urine)

3. Protein buffers (plasma proteins and hemoglobin)

The Carbonic Acid–Bicarbonate Buffer SystemCarbon dioxide

Most body cells constantly generate carbon dioxide Most carbon dioxide is converted to carbonic acid,

which dissociates into H+ and a bicarbonate ion

Is formed by carbonic acid and its dissociation products

Prevents changes in pH caused by organic acids and fixed acids in ECF

The Carbonic Acid–Bicarbonate

Buffer System 1. Cannot protect ECF from changes in pH

that result from elevated or depressed

levels of CO2

2. Functions only when respiratory system

and respiratory control centers are

working normally

3. Ability to buffer acids is limited by

availability of bicarbonate ions

The Phosphate Buffer System Consists of anion H2PO4

– (a weak acid)

Works like the carbonic acid–bicarbonate

buffer system

Is important in buffering pH of ICF

Protein Buffer Systems Depend on amino acids

Respond to pH changes by accepting or

releasing H+

If pH rises:Carboxyl group of amino acid

dissociatesActing as weak acid, releasing a

hydrogen ionCarboxyl group becomes carboxylate ion

Protein Buffer Systems At normal pH (7.35–7.45)

Carboxyl groups of most amino acids have already given up their H+

If pH drops: Carboxylate ion and amino group act as weak

bases Accept H+

Form carboxyl group and amino ion

Protein Buffer Systems Carboxyl and amino groups in peptide bonds

cannot function as buffers

Other proteins contribute to buffering

capabilities Plasma proteins Proteins in interstitial fluid Proteins in ICF

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

The Hemoglobin Buffer System

CO2 diffuses across RBC membrane

No transport mechanism required

As carbonic acid dissociates: Bicarbonate ions diffuse into plasma In exchange for chloride ions (chloride shift)

Hydrogen ions are buffered by hemoglobin

molecules

Figure 23-24 A Summary of the Primary Gas Transport Mechanisms

Systemiccapillary

Cells inperipheral

tissues

Chlorideshift

CO2 pickup

Figure 23-24 A Summary of the Primary Gas Transport Mechanisms

Alveolarair space

Pulmonarycapillary

CO2 delivery

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

Respiratory and Renal Mechanisms Support buffer systems by:

1. Secreting or absorbing H+

2. Controlling excretion of acids and bases

3. Generating additional buffers

Respiratory control of pH

Within body fluids, CO2 and H2O coming together to form H2CO2 which breaks down into HCO3- and H+

HCO3- and H+ are constantly forming H2CO3 which can split apart to form CO2 and H2O

Respiratory control of pHWhen we breathe more quickly, more

CO2 leaves the body

When we breathe more slowly, less CO2 leaves the body

Renal control of pH

The kidneys control acid-base balance by excreting either an acidic or a basic urine

Excreting an acidic urine reduces the amount of acid in the extracellular fluids

Excreting a basic urine removes base from the extracellular fluids

Under normal conditions, almost all HCO3- are reabsorbed from the tubules, thereby conserving the buffer system of the extracellular fluid

This reabsorption of HCO3- are accomplished through the process of H+ secretion by the tubules

Renal control of acid base balanceThe kidneys regulate extracellular fluid H+

concentration through three mechanisms:

1. Secretion of H+2. Reabsorption of filtered HCO3-3. Production of new HCO3-

About 80 to 90 per cent of the bicarbonate reabsorption (and H+ secretion) occurs in the proximal tubule

In the thick ascending loop of Henle, another 10 per cent of the filtered bicarbonate is reabsorbed

The remainder of the reabsorption takes place in the distal tubule and collecting duct

Secretion of Hydrogen Ions 1. CO2 arrive at the kidney

tubules cells 2. Within tubular cells, CO2

combine with H2O to form H2CO3 by carbonic anahydrase

3. Then H2CO3 split to HCO3 and H+

4. The H+ is secreted from the cell into the tubular lumen by Na-H counter transport

5. The HCO3- generated in the cell moves into the peritubular capillary blood

6. The epithelial cells in PCT, thick ascending limb and DCT all secrete H+ into the tubular lumen

Reabsorption of HCO3- from filtrate 1. HCO3- that is filtered by

the glomerulus combines with H+ to form H2CO3 which eventually becomes CO2 and H2O

2. The H2CO3 formed dissociate into CO2 and H2O

3. CO2 diffuses into tubular cell where it recombine with H2O under the influence of CA to generate H2CO3

4. Then H2CO3 split to HCO3 and H+

5. The HCO3- generated in the cell moves into the renal interstitial fluid and the peritubular capillary blood

Generating new HCO3-

H+ combined with HCO3- in the tubular fluid which results in reabsorption of HCO3-

If high H+ (as in acidosis), the kidneys generate new HCO3- by phosphate and ammonia buffers mechanisms

Phosphate buffer system carries excess H+ into the urine and generate new bicarbonate

Phosphate buffer composed of HPO4= and H2PO4-

Excess H+ can combine with HPO4=

After H+ combines with HPO4= to form H2PO4 , it can be excreted as a NaH2PO4 carrying with it the excess H+

Excretion of excess H+ and generation of new HCO3- by ammonia buffer system

The glutamine delivered to the kidneys is transported into the epithelial cells of the proximal tubules, thick ascending loop of Henle, and distal tubulesGlutamine is metabolized to form two NH4+ and two HCO3-

The HCO3 is transported across the basolateral membrane along with reabsorbed Na+ into the peritubular capillariesIn chronic acidosis the dominant mechanism by which acid is eliminated is excretion of NH4+

The Detection of Acidosis and

Alkalosis

Includes blood tests for pH, PCO2’

and HCO3– levels

Recognition of acidosis or

alkalosisClassification as respiratory or

metabolic

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