ACIDS AND BASES

pH Review

• ECF pH = 7.4• Tightly regulated

– Fatal if pH 7.25 > pH > 7.55– Nec for proper enzyme activity

• May change protein shape (enzymes) • Enzymes catalyze rxns by holding substrates

properly for rxn to occur at active site of certain shape

• pH change cell death

pH Review – cont’d

• pH = - log [H+] – High [H+] = acidic sol’n = low pH (1-6)– Low [H+] = basic (alkaline) sol’n = high pH

(8-14)– pH = 7 = neutral solution

Acids• H+ donors

– Body acids classified as:• Volatile (eliminated from the body as CO2)

– Most impt -- carbonic acid (H2CO3)– Gives up H+ by reaction:

H2CO3 CO2 + H2O

• Nonvolatile (eliminated through kidney tubules)– Ex: lactic acid, phosphoric acid, etc

Acids – cont’d• Another classification of acids: weak/strong

– Strong – easily gives up H+ from molecular structure• Ex: HCl mostly (H+ + Cl-)

Note: there are few strong acids in the body– Weak – most physiological acids – may or may not

easily give up H+ in solution• Dissociation depends on molecular structure and

conditions of solution

Carbonic Acid Important

• CO2 + H2O H2CO3 H+ + HCO3-(carbon (water) (carbonic (hydrogen (bicarbonate)dioxide) acid) ion)

Both reversible reactions catalyzed by enzyme carbonic anhydrase

Bases, Buffers

• Bases -- H+ acceptors– Overall negative (-) charge (ex: OH-)– Can also be weak or strong

• Buffer – system of weak acid + conjugate base– Pairs of related molecules – Conjugate base – what’s left of a weak acid molecule,

once H+ dissociated– React with either added base or added acid no

significant change in pH• Blood buffers -- first responders to changes in blood

pH

Buffers – cont’d• Four important body buffers:

– Bicarbonate/carbonic acid• Weak acid = carbonic acid• Conjugate base = bicarbonate ion

– Hb/oxy-Hb

– Phosphate system – works inside cells

– Protein system – important in ISF

Bicarbonate/Carbonic Acid Buffer System

• Henderson-Hasselbach equation (for any buffer):– pH = pKa + log [conjugate base]/[weak acid],

where• pH can be measured• pKa is constant for any weak acid

– If pKa is known, concentration of conjugate base and weak acid can be calculated

• For carbonic acid buffer system:– pH = pKa + log [HCO3-]/[H2CO3]

Bicarb/Carbonic Acid Buffer – cont’d• Blood concentrations of base, acid in proper

blood buffer (REMEMBER 20:1)– Substitute into H-H eq’n

(pH = pKa + log [base]/[acid]):– Normal blood pH = 7.4– pKa for carbonic acid = 6.1

• Solve for [base]/[acid] ratio:– [HCO3-]/[H2CO3] = 20 / 1

• For every 1 carbonic acid molecule in bloodstream, body strives to maintain 20 bicarbonate molecules

• Actual concentrations in healthy blood: [HCO3-]=24 mEq/L, [H2CO3]=1.2 mEq/L

Bicarb/Carbonic Acid Buffer – cont’d• Respiratory component

– From overall carbonic acid rxn• CO2 + H2O H2CO3 H+ + HCO3-

– Resp component is left side of equation:• CO2 + H2O H2CO3

– H2CO3 dependent on CO2, which is expired through lung

• Lung can rapidly decrease [H2CO3] in blood by excreting CO2

• Body uses respiratory system to maintain H2CO3 at proper amounts to maintain 20:1 buffer ratio

– Fast mechanism• Minutes to hours

Bicarb/Carbonic Acid Buffer – cont’d

• Respiratory component – cont’d– Acid/base disorders identified

• Incr’d blood [H2CO3] decr’d blood pH– Respiratory acidosis– Due to retained CO2

• Decr’d blood [H2CO3] incr’d blood pH– Called respiratory alkalosis– Due to too little CO2 in blood

• Note: respiratory component disorders are based on the amount of one of the blood buffer components (H2CO3).

Bicarb/Carbonic Acid Buffer – cont’d

• Renal component– HCO3

- regulated by kidney, w/ H+ secreted to urine– From overall carbonic acid rxn

• CO2 + H2O H2CO3 H+ + HCO3-– Renal component is right side of equation

• H2CO3 H+ + HCO3-– Kidneys control excr’n H+ and HCO3- from blood

• Body uses renal system to manipulate HCO3- part buffer system to maintain the 20:1 buffer ratio

– Slow• Hours to days (so not sufficient in acute dysfunction or

disease)

Bicarb/Carbonic Acid Buffer – cont’d

• Renal component – cont’d– Acid/base disorders identified

• Incr’d blood [HCO3-] incr’d blood pH– Metabolic alkalosis

• Decr’d blood [HCO3-] decr’d blood pH– Metabolic acidosis

• Note: metabolic dysfunctions focus on amount of conjugate base part of the buffer system (HCO3-)

Importance of K+ -- It Can Exchange for H+• If blood acidosis (high concentration of

[H+] can’t be neutralized by blood buffer base)– H+ can leave IVF ISF– If ISF [H+] high enough, H+ will enter the cell cell with too high + charge– To maintain neutral ICF charge, K+ leaves cell,

enters ISF

K+ Exchange – cont’d

• Opposite in alkalosis: – Too little H+ in ECF H+ from cell moves

into ECF– To maintain charge neutrality, ECF K+ moves

into cell from ECF in exchange ECF hypokalemia

Acid/Base Imbalances (Figs.4-10 – 4-13)

• Respiratory Acidosis– Decr’d ventilation (breathing or gas exchange) incr’d PaCO2

(arterial pressure CO2)• Lung dysfunction CO2 improperly excr’d Build-up of CO2 in bloodstream• Increased PaCO2 = hypercapnia

– Due to:• Chronic conditions

– Depression of resp center of brain that controls breathing rate– Paralysis of respiratory or chest muscles

• Acute conditions– Adult Respiratory Distress Syndrome (ARDS)

» Occurs with trauma, acute infection high amts biochems impt to inflammatory response severe impact on the lungs inhibited breathing

– Pneumothorax (or collapsed lung)

Acid/Base Imbalances – cont’d• Respiratory acidosis – cont’d

– Causes differ for chronic/acute• Acute – airway obstruction• Chronic – chronic pulmonary disease

– Compensation differs for chronic/acute• Acute – compensation difficult

– Can’t use resp system to adjust acid/base levels– Renal component too slow to accommodate acute difficulty

• Chronic – renal mechanism compensates – Body senses increased [CO2] in IVF Stim’n kidney to increase reabsorption HCO3- from renal tubules – Also incr’d [CO2] sensed stimulates kidney to incr excr’n of H+ into urine

• Taken together, blood now will have less H+ (so will be less acidic) and more HCO3- (neutralizes any excess H+ remaining)

Acid/Base Imbalances – cont’d

• Respiratory acidosis – cont’d– Clinical

• Neurological effects: if acidity increases enough, cerebrospinal fluid becomes acidic tremors, coma

– Treatment• Restore ventilation• Treat any underlying cause of chronic dysfunctions

or diseases

Acid/Base Imbalances – cont’d• Respiratory Alkalosis

– Most common acid/base imbalance– Primarily caused by hyperventilation decr’d PaCO2

(hypocapnia) – Due to:

• Pulmonary diseases• Congestive heart failure

– Both hypoxia sensed at chemoreceptors in vasculature– Chemoreceptors send signals to brain (respiratory center) incr’d breathing to bring in more oxygen– BUT incr’d breathing incr’d CO2 excr’n so decr’d PaCO2

» Now less CO2 + H2O H2CO3, and too little acid defines alkalosis

• Acute: anxiety hyperventilation

Acid/Base Imbalances – cont’d

– Clinical• Frequent yawning• Deep respirations

– Treatment• Eliminate underlying disease• Breathe into a paper bag (to decrease CO2 lost with

breathing)

Acid/Base Imbalances – cont’d

• Metabolic acidosis – Due to:

• Incr’d metabolic acids accumulating in blood– With metabolic disorders– With hypoxia

• Greatly incr’d ingested acids• Decr’d excreted acids

– With renal dysfunction• Decr’d [HCO3-] in blood

– With chronic diarrhea

Acid/Base Imbalances – cont’d

• Metabolic acidosis – cont’d – Compensation - incr'd serum [HCO3-]; K+ exch.

• Resp system responds to decr’d [H2CO3] in blood by decreasing CO2 in blood (or increasing excr’n CO2)

– So hyperventilation

• Renal system must respond to incr’d excr’n H+ if possible

• K+ exchanges with excess H+ in ECF– So K+ moves out of the cells into ECF as H+ moves out of ECF

into the cells

Acid/Base Imbalances – cont’d

• Metabolic acidosis – cont’d– Clinical

• Headache, lethargy• CNS depression• Deep, rapid respirations• Dysrhythmias

– Treatment• Treat underlying cause• Lactate solution IV

– In liver, lactate converted to HCO3-– So incr’s base available to bring buffer system ratio back to

normal

Acid/Base Imbalances – cont’d

• Metabolic alkalosis – Increased relative [HCO3-] in the blood– Due to

• Chronic vomiting, g.i. suction, diuresis– H+ lost to body fluids along with other electrolytes– Problematic if concurrent renal dysfunction that allows

incr’d HCO3- reabsorption

• Heavy ingestion of antiacids

Acid/Base Imbalances – cont’d

• Metabolic alkalosis – cont’d– Compensation

• Renal compensation difficult (HCO3- reabs'd)– Most commonly occurs with renal dysfunction, so patient can’t

count on kidney to compensate

• Resp. compensation difficult (limited hypovent'n)– Body needs to increase PaCO2 ( increased [H2CO3])

– Patient must hypoventilate (to decrease excretion of CO2)– BUT hypoventilation is only temporary (through breathing

reflex at resp center)– So the patient can’t count on the respiratory system to

compensate

Acid/Base Imbalances – cont’d

• Metabolic alkalosis – cont’d– Clinical

• Respirations slow, shallow• Symptoms often related to depletion of electrolytes

(if cause is vomiting, etc.)– Atrial tachycardia– Dysrhythmias

– Treatment• Electrolytes to replace those lost• Treat underlying renal disorder if possible