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