Acid-Base Disorders

Prof. Nafiu Amidu

nafamidu@[Link]
 Objectives
• Discuss the normal physiology of acid-base
balance, including the importance of normal pH
and usual compensatory mechanism
• Describe the role of the kidney in maintaining A-
B balance
• Describe the role of the lung in gas exchange and
maintaining of A-B balance
• Explain the importance of carbonic
acid/bicarbonate buffer system and the role of
other buffer system
 Objectives cont.
• List the 4 simple A-B disorders, their
important cause and accompanying lab. Test
result
• Evaluate a patient’s A-B status, given the
clinical presentation and lab. Results
• In a case study, use the results of ABGs and
serum [bicarbonate] to assess A-B disorder,
ventilation and oxygenation
 WHY ASSESSING ACID-BASE
• STATUS?
Normal pH is required for normal health
• Cellular metabolism produces acid that must be excreted
• Lung, kidney, complex system of buffer maintain homeostasis
• Assessment of the type of acid base disorder requires at a
minimum 2 of the following:
1) Arterial pH
2) pCO2
3) plasma HCO3-

• Complete analysis of an ABG requires:

 pH 6. BE/BD
 pO2 7. Anion Gap (AG)
 pCO2 8.  AG
 9.
HCO3-  HCO3-
 O2 Sat
Overview of Acid-Base Physiology
ACID PRODUCTION
• Volatile Acids – metabolism produces 15,000-20,000 mmol
of CO2 per day.
Henderson Hasselbach Equation
pH = pK + log base
acid
pH = 6.1 + log HCO3-
H2CO3
pH = 6.1 + log HCO3-
0.03 pCO2
H+ = 24 x pCO2
HCO3-
• Non-Volatile Acids – 50-100 meq/day of
non-volatile acids produced daily.
1. The primary source is from metabolism of
sulfur containing amino acids (cystine,
methionine) and resultant formation of
sulfuric acid.
2. Other sources are non metabolized
organic acids, phosphoric acid and other
acids
Range of ECF [H+] variation very small

pH Vs. [H+]
pH nanoeq
[H+]/L
7.00-7.38 Acidemia 100-44
7.38-7.44 Normal 44-36
7.44-7.80 Alkalemia 36-16

Relationship between pH and [H] at physiologic pH

pH 7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70
[H+] (nM) 100 79 63 50 40 32 25 20
 Importance of pH Control
• pH (intracellular and ECF including blood) maintained
in narrow range to preserve normal cell, tissue and
organ function

Intracellular pH (pHi)
• Maintained at  7.2:
1. To keep imp metabolic intermediates in ionized state
and limit tendency to move out of cell
2. Most intracellular enzymes taking part in cellular
metabolism have pH optimum close to this value
3. DNA, RNA & Protein synthesis  at slightly higher pH

• Maintained with help of plasma membrane H+/base

transporters (activated in response to acidemia)
Blood pH
• Maintained at  7.4:
1. To keep pHi in optimal range
2. Enable optimal binding of hormones to receptors
3. Enable optimal activity of enzymes present in blood
 Regulation of arterial pH
1. BUFFERS – presence of buffer systems minimize the
change in pH resulting from production of acid and provide
immediate protection from acid load. Main buffer system in humans
is HCO3-
HCO3- + H+  H2CO3  H2O + CO2

2. ROLE OF THE RESPIRATORY SYSTEM –

elimination  of volatile acid -- CO2.
a. Respiratory centers (Chemoreceptors) in the brain
respond  to changes in pH of CSF and blood to  affect ventilatory
rate.
b. Ventilation directly controls the elimination of CO2.
 3. ROLE OF THE KIDNEY - To retain and regenerate
HCO3- thereby regenerating the body buffer with the net effect
of eliminating the non-volatile acid load
a. H+ secretion
1. Free urinary H+ - minimal contribution
2. Ammonia
3. Phosphorus

b. HCO3- reabsorption
1. Proximal tubule – 90%
2. Distal tubule

Factors affecting H+ secretion/reabsorption HCO3-

a. CO2 concentration, pH
b. Aldosterone d. Potassium concentration
c. ECF volume e. Chloride
 Anion Gap
• AG traditionally used to assess acid-base status
•  AG &  HCO3- used to assess mixed acid-base disorders

AG based on principle of electroneutrality:

• Total Serum Cations = Total Serum Anions

• Na + (K + Ca + Mg) = HCO3 + Cl + (PO4 + SO4 + Protein + Organic

Acids)

• Na + UC = HCO3 + Cl + UA

• Na – (HCO3 + Cl) = UA – UC

• Na – (HCO3 + Cl) = AG
Unmeasured anion normally exceed unmeasured cation
Revised N value AG = 8 +/- 4 meq/L
 LIMITING FACTORS FOR AG
•HYPOALBUMINEMIA - Pts with low S. albumin
can have high AG acidosis, but measured AG may be N
because albumin has many -ve surface charges &
accounts for a significant proportion of AG. Severe
hypoalbuminemia may exhibit N AG as low as 4.
Therefore in severe hypoalbuminemia if AG is normal,
one must suspect an additional metabolic cause for
increased AG

•ALKALOSIS-Alkalemic patients with pH > 7.5, AG

may be  due to met alkalosis per se & not because of
additional met acidosis. Reasons proposed for the same
include:
1. Surface charges on albumin become more -ve in
alkalemic conditions (due to loss of protons) --> 
unmeasured anions
2. Assoc vol contraction --> hyperproteinemia
3. Induction of glycolysis and resultant hyperlactatemia

• HYPERCALCEMIA - Fall in AG as expected ( UC) except

in paraneoplastic hypercalcemia for unknown reasons
• DRUGS - Lithium and polymyxin cause fall in AG ( UC)
because they are +ve charge while carbenicillin,
mezlocillin, azlocillin and piperacillin cause  in AG (act
as UA)

• HYPERLIPIDEAMIA – decrease AG because they occupy

space in plasma volume and by interfering with the lab.
Assay for chloride
Conditions Invalidating or Modifying ABG
Results

•DELAYED ANALYSIS - Consumption of O2 &

Production of CO2 continues after blood drawn into
syringe

Iced Sample maintains values for 1-2 hours

Uniced sample quickly becomes invalid

PaCO2  3-10 mmHg/hour and PaO2  at a rate

related to initial value & dependent on Hb Sat
EFFECT OF TEMP ON RATE OF CHANGE
IN ABG VALUES

Parameter 37 C (Change 4 C (Change

every 10 min) every 10 min)
 pH 0.01 0.001

 PCO2 1 mm Hg 0.1 mm Hg

 PO2 0.1 vol % 0.01 vol %

•EXCESSIVE HEPARIN
Dilutional effect on results  HCO3- & PaCO2
Syringe be emptied of heparin after flushing

Risk of alteration of results  with:

1. size of syringe/needle
2. volume of sample
25% lower values if 1ml sample taken in 10 ml syringe
(0.25 ml heparin in needle)
Syringes must be > 50% full with blood sample

•HYPERVENTILATION OR BREATH HOLDING May lead to

erroneous lab results
• AIR BUBBLES
1. PO2 150 mmHg & PCO2 0 mm Hg in air bubble(R.A.)
2. Mixing with sample lead to  PaO2 &  PaCO2
3. Mixing/Agitation  S.A. for diffusion  more erroneous
results
4. Discard sample if excessive air bubbles
5. Seal with cork/cap immediatly after taking sample

• FEVER OR HYPOTHERMIA
1. Most ABG analyzers report data at N body temp

2. If severe hyper/hypothermia, values of pH & PCO2 at 37 C

can be significantly diff from pt’s actual values

3. Changes in PO2 values with temp predictable

 DEFINITIONS AND TERMINOLOGY
3 Component Terminology –
1. Compensated/Uncompensated
2. Respiratory/Metabolic
3. Acidosis/Alkalosis

ACIDEMIA – reduction in arterial pH    (pH<7.35)

ALKALEMIA – increase in arterial pH (pH>7.45)
ACIDOSIS – presence of a process which tends to
 pH by virtue of gain of H +  or loss of HCO3-
ALKALOSIS – presence of a process which tends to
 pH by virtue of loss of H+ or gain of HCO3-
RESPIRATORY VS METABOLIC
• Respiratory – processes which lead to acidosis or
alkalosis through a primary alteration in
ventilation and resultant excessive elimination or
 retention of CO2

• Metabolic – processes which lead to acidosis

or alkalosis through their effects on kidneys and
the consequent disruption of H + and HCO3-
control
COMPENSATION – The normal response of the
 respiratory system or kidneys to change in pH
induced by a primary acid-base disorder

SIMPLE VS. MIXED ACID-BASE DISORDER

Simple acid-base disorder – a single primary
process  of acidosis or alkalosis

Mixed acid-base disorder – presence of more than

one acid base disorder simultaneously
 Compensation
• In the presence of acidosis or alkalosis, regulatory
mechanisms occur which attempt to maintain the arterial pH
in the physiologic range. These processes result in the return
of pH towards, but generally just outside the normal range
• Disturbances in HCO3- (metabolic acidosis or alkalosis) result
in respiratory compensation while changes in CO2
(respiratory acidosis/alkalosis) are counteracted by renal
compensation
a. Renal compensation – kidneys adapt to alterations in pH
by changing the amount of HCO3- generated/excreted. Full
renal compensation takes 2-5 days
b. Respiratory compensation – alteration in ventilation allow
immediate compensation for metabolic acid-base disorders
RENAL & RESPIRATORY COMPENSATIONS TO  ACID-
BASE DISTURBANCES
Disorder Compensatory response
Metabolic acidosis PCO2  1.2 mmHg per 1.0 meq/L  HCO3-

Metabolic alkalosis PCO2  0.7 mmHg per 1.0 meq/L HCO3-

Respiratory acidosis [HCO3-] 

Acute 1.0 meq/L per 10 mmHg  Pco2
Chronic 3.5 meq/L per 10 mmHg  Pco2

Respiratory alkalosis [HCO3-] 

Acute 2.0 meq/L per 10 mmHg  Pco2
Chronic 4.0 meq/L per 10 mmHg  Pco2
 STEPWISE APPROACH TO ABG ANALYSIS
• Determine whether patient is alkalemic
or acidemic using the arterial pH measurement
• Determine whether the acid-base disorder is a
primary respiratory or metabolic disturbance
based on the pCO2 and serum HCO3- level
• If a primary respiratory disorder is present,
determine whether it is chronic or acute
• In metabolic disorders, determine if there
is adequate compensation of the respiratory
system
• In respiratory disorders, determine if there
is adequate compensation of the metabolic system
 Interpretation: pH
•Normal arterial pH = 7.36 to 7.44
•Determine Acidosis versus Akalosis
–1. pH <7.35: Acidosis
–2. pH >7.45: Alkalosis
•Metabolic Conditions are suggested if
–pH changes in the same direction as pCO2/HCO3-
–pH is abnormal but pCO2 remains unchanged
Respiratory Conditions are suggested if:
–pH changes in the opp direction as pCO2/HCO3-
–pH is abnormal but HCO3- remains unchanged
 Resp and/or
 Acidemia Met Acidosis
Resp Acidosis
and
Met Alkalosis
pH N No acidemia
No A-B Dis
/alkalemia
Met Acidosis
and
Resp Alkalosis

Alkalemia Resp and/or

 Met Alkalosis
 pCO2 , HCO3  Resp + Met Alkalosis

pCO2 , HCO3 N Uncomp Resp Alkalosis

pH 
pCO2 N, HCO3  Uncomp Met Alkalosis

pCO2 , HCO3  Comp(F/P) Met Alkalosis

pCO2 , HCO3  Comp(F/P) Resp Alkalosis

 pCO2 , HCO3  Resp + Met Acidosis

pCO2 , HCO3 N Uncomp Resp Acidosis

pH 
pCO2 N, HCO3  Uncomp Met Acidosis

pCO2 , HCO3  Comp(F/P) Resp Acidosis

pCO2 , HCO3  Comp(F/P) Met Acidosis

 Comp(F) Resp Acidosis
pCO2 , HCO3 
Comp(F) Met Alkalosis
Resp Acidosis
+
Met Alkalosis
N
pH or pCO2 N, HCO3 N N Acid Base Homeostasis
N

Comp(F) Met Acidosis

Comp(F) Resp Alkalosis

pCO2 , HCO3  Met acidosis

+
Resp alkalosis
 RESPIRATORY ACID BASE DISORDERS
• Respiratory alkalosis most common of all
the 4 acid base disorders (23-46%) -followed
by met alkalosis –

• Resp acidosis seen in 14-22% of pts

• Attention to possibility of hypoxemia and its

correction always assumes priority in
analysis of pts with a possible respiratory
acid-base disorder
RESPIRATORY ALKALOSIS
 Common cause of RA
• Hypoxemia
• Lung disease
• Pneumonia
• Pulmonary embolism

• CNS-respiratory stimulation
• Cerebrovascular accident
• Fever
• Liver disease
• Anxiety-hyperventilation syndrome
• Pregnancy
• Progesterone derivatives
• Salicylate intoxication
 Manifestations of Resp Alkalosis
1. Lightheadedness
2. Confusion
3. Decreased intellectual function
4. Syncope
5. Seizures
6. Paraesthesias (circumoral, extremities)
7. Muscle twitching, cramps, tetany
8. Hyperreflexia
9. Strokes in pts with sickle cell disease

• BIOCHEMICAL ABNORMALITIES:
 tCO2 PO43-
Cl-  Ca2+
 Homeostatic Response to Resp Alkalosis
• In ac resp alkalosis, imm response to fall in CO2 (&
H2CO3)  release of H+ by blood and tissue buffers 
react with HCO3-  fall in HCO3- (usually not less than
18) and fall in pH
• Cellular uptake of HCO3- in exchange for Cl-
• Steady state in 15 min - persists for 6 hrs
• After 6 hrs kidneys increase excretion of HCO3- (usually
not less than 12-14)
• Steady state reached in 11/2 to 3 days.
• Timing of onset of hypocapnia usually not known except
for pts on MV. Hence progression to subac and ch resp
alkalosis indistinct in clinical practice
RESPIRATORY ACIDOSIS
 Causes of Respiratory Acidosis
• CNS disorder
– Cerebralvascular accident
– Tumor
– Sleep apnea
– Drug (eg. Opiods, sedative)

• Lung disorder
– Airway obstruction
– Asthma
– Chronic obstructive pulmonary disease eg. Bronchitis
– Pulmonary edema

• Neuromascular disorder
– Myasthenia gravis
– Hypokalemia
– Hypophosphateamia
– Neuromuscular blocking drug
 Manifestations of Resp Acidosis
1. Anxiety
2. Asterixis
3. Lethargy, Stupor, Coma
4. Delirium
5. Seizures
6. Headache
7. Papilledema
8. Focal Paresis
9. Tremors, myoclonus

• BIOCHEMICAL ABNORMALITIES:
 tCO2  PO43-
 Cl-
HOMEOSTATIC RESPONSE TO RESPIRATORY ACIDOSIS
• Imm response to rise in CO2 (& H2CO3)  blood
and tissue buffers take up H+ ions, H2CO3
dissociates and HCO3- increases with rise in pH.
• Steady state reached in 10 min & lasts for 8
hours.
• PCO2 of CSF changes rapidly to match PaCO2.
• Hypercapnia that persists > few hours induces an
increase in CSF HCO3- that reaches max by 24 hr
and partly restores the CSF pH.
• After 8 hrs, kidneys generate HCO3-
• Steady state reached in 3-5 d
METABOLIC ACIDOSIS
 Cause of Met Acidosis (Check AG)
• ELEVATED AG
• Renal failure
• Ketoacidosis
» Diabetes mellitus
» Starvation
» Ethanol
• Lactic acidosis
» Shock-sepsis, cardiogenic, hypovolemic
» Severe hypoxemia
» CO poisoning
» Tonic-clonic seizures
» Liver disease
• Intoxications
» Methanol
» Ethylene glycol
» Salicylate
 Cause of Met Acidosis (Check AG)
• NORMAL AG
• Renal tubular acidosis
• Drug/toxins
– Carbonic anhydrase inhibitors (e.g. acetazolamide)
– Amphotericin B
– Lithium carbonate
– Lead
– Ammonium chloride
– Arginine hydrochloride
 Manifestations of Met Acidosis
• Cardiovascular
Impaired cardiac contractility
Arteriolar dilatation, venoconstriction, and
centralization of blood volume
Increased pul vascular resistance
Fall in C.O., ABP & hepatic and renal BF
Attenuation of cardiovascular responsiveness to catecholamines
• Respiratory
Hyperventilation
 strength of respiratory muscles & muscle fatigue
Dyspnea
• Metabolic
Increased metabolic demands
Insulin resistance
Inhibition of anaerobic glycolysis
Reduction in ATP synthesis
Hyperkalemia (secondary to cellular shifts)
Increased protein degradation
• Cerebral
Inhibition of metabolism and cell vol regulation
Mental status changes (somnolence, obtundation & coma)
• Cardiovascular
Impaired cardiac contractility
Arteriolar dilatation, venoconstriction, and centralization of blood volume
Increased pul vascular resistance
Fall in C.O., ABP & hepatic and renal BF
Attenuation of cardiovascular responsiveness to catecholamines
• Respiratory
Hyperventilation
 strength of respiratory muscles & muscle fatigue
Dyspnea
• Metabolic
Increased metabolic demands
Insulin resistance
Inhibition of anaerobic glycolysis
Reduction in ATP synthesis
Hyperkalemia (secondary to cellular shifts)
Increased protein degradation
• Cerebral
Inhibition of metabolism and cell vol regulation
Mental status changes (somnolence, obtundation & coma)
METABOLIC ALKALOSIS
 Common cause of Met Alkalosis
• Loss of gastric acid
» Vomiting
» Nasogastric suction

• Mineralocorticoid excess
» Hyperaldosteronism
» Exogenous mineralocorticoids

• Hypokalemia
• Alkali administration
» Oral
» Parentheral nutrition with excess acetate
» Exces administration of HCO3 in met. Acid.

• Diuretic therapy
» Loop diuretic (e.g. furosemide)
» Thiazide diuretic (e.g. hydrochlorothiazide)
 Manifestations of Met Alkalosis
Symp of met alkalosis per se difficult to separate from those of
Cl-/K+/Vol depletion  latter usually more apparent than those
directly attributable to alkalosis.
• Cardiovascular
Arteriolar constriction
Reduction in Coronary BF/Anginal threshold

•Respiratory - Hypoventilation (Compensatory) 

Hypercapnia/Hypoxemia
•Metabolic
Stimulation of anaerobic glycolysis & organic acid production
Reduction plasma ionized Calcium conc
Hypokalemia (secondary to cellular shifts)
Hypomagnesemia & Hypophosphatemia

•Cerebral
Reduction in Cerebral BF  mental status changes (stupor, lethargy & delirium)
N-M irritability (related to low ionized plasma Ca)
 Tetany, Hyperreflexia, Seizures