acids and bases. ph review ecf ph = 7.4 tightly regulated –fatal if ph 7.25 > ph > 7.55...
TRANSCRIPT
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