ACID-BASE BALANCE

AND DISODERS
Dr Tawari Patricia Erebi

Chemical Pathology
Objectives
• What are acids/Bases
• What are buffers/ types
• Understand importance of maintaining acid-base balance.
• Understand different ways the body maintains this balance.
• Disorders of acid-base balance
• Compensatory mechanisms
• Develop differential diagnoses based on the acid-base disorder.
• Calculation of anion gap.

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 Definition
 Hydrogen ion [H+]: a single free proton released from a hydrogen atom.

 Acid: molecules that release H+ in solutions

 Base: Molecules that accepts H+

 Strong acid: Molecule that rapidly dissociates releases large amounts of H+ in solution

 Weak acids: less tendency to dissociate their ions

 Strong Base: reacts rapidly and strongly with H+

 Weak base: binds weakly with H+

 pH = log 1/[H+] = - Log[H+].

• Acids are H+ donors.

• Bases are H+ acceptors, or give up OH- in solution.

• Acids and bases can be:

• Strong – dissociate completely in solution

• HCl, NaOH
• Weak – dissociate only partially in solution
• Lactic acid, carbonic acid

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 INTRODUCTION
• Hydrogen bonding is a key force that maintains the structural integrity of biologic
molecules. So, H+ concentration must be maintained within tight limits not to
disrupt cellular function.

• pH represents a convenient scale of expressing H+ concentration (pH=-log[H+]).

• Normal metabolism is associated with continuous production of hydrogen ions

(H+) and carbon dioxide (CO2), both of which tend to reduce pH.

• Thus mechanisms are put in place to maintain normal blood pH (i.e. preserve acid-
base homeostasis). This systems involves chemical buffers in blood, the red cells
(erythrocytes), which circulate in blood, and the function of three organs: lungs,
kidneys and brain.
 pH review

• Normal [H+] is 40nEq/L (0.000000004Eq/L)

pH = - log (0.00000004)

Normal pH = 7.4

 pH is inversely relate to [H+], therefore

low pH corresponds to high H+ concentration
high pH corresponds to low H+ concentration
pH Review contd
• pH = - log [H+]

• H+ is a proton

• Range is from 0 – 14

• If [H+] is high, the solution is acidic; pH < 7

• If [H+] is low, the solution is basic or alkaline ; pH > 7

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 Acids
• An acid is a substance which releases hydrogen ions (H+) on dissociation in
solution.
• For example: Hydrochloric acid (HCl) dissociates to hydrogen ions and
chloride ions
HCl → H+ + Cl-
• Carbonic acid (H2CO3) dissociates to hydrogen ions and bicarbonate ions
H2CO3 H+ + HCO3–

• HCl is a strong acid while H2CO3 is a weak acid. The difference is that
strong acids dissociate more than weak acids. Consequently the hydrogen
ion concentration of a strong acid is much higher than that of a weak acid.
Base
• A base is a substance which in solution accepts hydrogen ions.

• For example, the base bicarbonate (HCO3–) accepts hydrogen ions to

form carbonic acid:
HCO3– + H+ → H2CO3
 Buffers
• Buffers are chemicals in solution which minimize the change in pH which occurs
when acids/bases are added by ‘mopping up’ or ‘release’ hydrogen ions.

• A buffer is a solution of a weak acid and its conjugate base.

• In blood, the principle buffer system is the weak acid, carbonic acid (H 2CO3) and its
conjugate base, bicarbonate (HCO3–).

• If we add a strong acid, e.g. HCl, to the bicarbonate buffer, The acid will dissociate,
releasing hydrogen ions:
HCl → H+ + Cl–
• The bicarbonate buffer then ‘absorbs’ the hydrogen ions, forming carbonic acid in
the process:
HCO3– + H+ → H2CO3 (carbonic acid)
• Normal cell metabolism depends on the maintenance of blood pH within very
narrow limits (7.35-7.45).

• Even relatively mild excursions outside this normal pH range can have
deleterious effects, including reduced oxygen delivery to tissues, electrolyte
disturbances and changes in heart muscle contractility; survival is rare if blood
pH falls below 6.8 or rises above 7.8.

• Since normal metabolism results in production of H+ and CO2 which tends to

reduce pH, buffer tries to maintain this homeostasis.

• Although a buffer greatly minimizes pH change, it does not eliminate it

because even a weak acid (like carbonic acid) dissociates to some extent.
• Major extracellular buffers in the human body include
bicarbonate (HCO3-), haemoglobin (Hgb) and certain
proteins, and phosphates.

• Intracellular buffering involves H+ entering the cell in

exchange for potassium and sodium

• This relationship, known as the Henderson-Hasselbalch

equation, shows that pH is governed by the ratio of base
(HCO3–) concentration to acid (H2CO3) concentration.
 Henderson-Hasselbalch equation
pH = pKa + log [base]
[acid]
Base is bicarbonate HCO3- and the acid is carbonic acid H2CO3.
Measuring the H2CO3 is difficult, however there is an equilibrium between
dissolved CO2 and partial pressure of C02 (PCO2).
Therefore the concentration of H2CO3 is measured by derivation
pH = pKa + log [HCO3-]
PCO2 x S
S is solubility constant of CO2 =0.23, pKa of bicarbonate system =6.1

pH = 6.1 + log [HCO3-] pH= 6.1 + log 24mmol/L pH = 6.1 +log 24mmol/L
PCO2 x 0.23 40mmHg x 0.03 1.2mmol

•pH = 6.1 + log 20 , therefore pH =7.40

Buffer System and Role in pH Regulation

Buffers resist change in pH when a strong acid or base is added.

• 1. Bicarbonate/carbonic acid buffer system

• 2. Phosphate buffer system

• 3. Plasma protein and haemoglobin buffer system

Bicarbonate/carbonic acid buffer system

It consists of a weak acid H2CO3 and a bicarbonate salt such as NaHCO3

H2CO3 is formed by the reaction of CO2 and H2O

CO2 + H2O H2CO3 H+ + HCO3-
carbonic anhydrase
CA is abundant in the walls of the lung alveoli where CO2 is released, in
the epithelial of the renal tubules

This is the most important buffer of plasma, it is also present in

erythrocytes but a lower concentration.
• As hydrogen ions are added to the bicarbonate buffer:
H+ + HCO3– → H2CO3
• bicarbonate (base) is consumed (concentration decreases) and carbonic acid is
produced (concentration increases). If hydrogen ions continue to be added, all
bicarbonate would eventually be consumed (converted to carbonic acid) and
there would be no buffering effect – pH would then fall sharply if more acid were
added.

• However, if carbonic acid could be continuously removed from the system and
bicarbonate constantly regenerated, then the buffering capacity and therefore pH
could be maintained despite continued addition of hydrogen ions.

• This is where the lungs and kidney comes to play cause the lungs ensure removal
of carbonic acid (as carbon dioxide) and the kidneys ensure continuous
regeneration of bicarbonate.
Phosphate buffer system
• Plays major role as an intracellular buffer. Consists of
H2PO4_ and HPO42-.
• At pH 7.4 most of the phosphate in plasma is
monohydgrogen phosphate HPO42- which can accept
H+ to become dihydgrogen phosphate H2PO4-.

• On addition of a strong acid such as HCl, the HCl is

replaced by a weak acid which decreases the pH.

HCl + NaHPO4- → NaH2PO4 + NaCl

Lungs role in acid- base homeostasis
• This role of the lungs is dependent on a singular characteristic of the
bicarbonate buffering system and that is the ability of carbonic acid to
be converted to carbon dioxide and water.

H+ + HCO3– ↔ H2CO3 ↔ H2O + CO2

• It is important to note that the reactions are reversible. Direction is

dependent on the relative concentration of each element. So that, for
example, a rise in carbon dioxide concentration forces reaction to the
left with increased formation of carbonic acid and ultimately
hydrogen ions.
 Lung function, transport of CO2 and acid-base balance
• A constant amount of CO2 in blood is essential for normal acid-base balance. This
reflects a balance between that produced as a result of tissue cell metabolism and
that excreted by the lungs in expired air.

• By varying the rate at which carbon dioxide is excreted, the lungs regulate the
carbon dioxide content of blood.

• Carbon dioxide diffuses out of tissue cells to surrounding capillary blood. A small
proportion dissolves in blood plasma and is transported to the lungs unchanged.

• But most diffuses into red cells where it combines with water to form carbonic
acid. The acid dissociates with production of hydrogen ions and bicarbonate.
Hydrogen ions combine with deoxygenated hemoglobin (hemoglobin is acting as
a buffer here), preventing a dangerous fall in cellular pH, and bicarbonate diffuses
along a concentration gradient from red cell to plasma.
• Thus most of the carbon dioxide produced in the tissues is
transported to the lungs as bicarbonate in blood plasma.

CO2 produced in tissues converted to bicarbonate for transport to lungs.

 Alveoli of the Lungs
• At the alveoli in the lungs the process is reversed (Fig. below). Hydrogen ions
are displaced from hemoglobin as it takes up oxygen from inspired air. The
hydrogen ions are now buffered by bicarbonate which diffuses from plasma
back into red cell, and carbonic acid is formed.

• As the concentration of this rises, it is converted to water and carbon dioxide.

Finally, carbon dioxide diffuses down a concentration gradient from red cell to
alveoli for excretion in expired air.

• Respiratory chemoreceptors in the brain stem respond to changes in the

concentration of carbon dioxide in blood, causing increased ventilation
(breathing) if carbon dioxide concentration rises and decreased ventilation if
carbon dioxide falls.
• O2 oxygen • H+ hydrogen ion CO2
carbon dioxide Hb hemoglobin
• H2CO3 carbonic acid H+Hb reduced hemoglobin
• HCO3- bicarbonate ions (hemoglobin acting as a
buffer)
• O2 - Hb oxyhemoglobin

At the lungs bicarbonate converted back to CO2 and eliminated by the lungs.
 Kidneys and acid-base balance
• Elimination of hydrogen ions and regeneration of bicarbonate, are accomplished by
the kidneys. Renal tubule cells are rich in the enzyme carbonic anhydrase, which
facilitates formation of carbonic acid from carbon dioxide and water.

• Carbonic acid dissociates to bicarbonate and hydrogen ions. The bicarbonate is

reabsorbed into blood and the hydrogen ions pass into the lumen of the tubule and
are eliminated from the body in urine.

• This urinary elimination is dependent on the presence in urine of buffers, principally

phosphate and ammonia ions.

• The kidneys regulate plasma HCO3- by 3 processes: reabsorption of filtered HCO3-,

formation of titratable acid and excretion of NH4+ in urine.
 Bicarbonate generation
• The Carbonate dehydratase system
• HCO3- is produced by the dissociation of carbonic acid formed from CO2 and
H2O, catalysed by carbonic anhydrase/carbonate dehydratase(CD) which is
present in high concentration in the RBC and renal tubular cells.
CD
H2O + CO2↔ H2CO3↔H+ + HCO3–
• HCO3- generation is accelerated whenever
CO2 rises
HCO3- falls
H+ falls (buffered by erythrocytes or excreted by the renal tubular cells
 HCO3- Generation by RBC
• RBC lacks aerobic pathways and so little CO2 is produced by them. However,
plasma CO2 diffuses along its concentration gradient into RBCs where CD
catalyses its reaction with H2O to form carbonic acid which dissociates to H+
(buffered by Hb) and HCO3-

• To maintain electronic neutrality Cl- diffuses in the opposite direction. This

movement is which called the chloride shift.
HCO3- Generation by RBC

Cl-
HHb
HCO3- + H+

CD Hb

CO2 + H2O
 Bicarbonate reclamation by the kidney
• Normal urine is HCO3- free because an equivalent amount being filtered is returned to the tubular cells.

• The luminal surfaces of renal tubular cells are impermeable to HCO3-, thus HCO3- is only returned to the
body if first converted to CO2 in the tubular lumina and then to HCO3- within the tubular cells (catalysed
by CD).

• Filtered HCO3- combines with H+ secreted by tubular cells to form H2CO3 which dissociates to form CO2
and H2O. (Proximal tubules catalysed by CD, distal tubules dissociates spontaneously).

• As luminal PCO2 increases, CO2 diffuses into tubular cells along its concentration gradient, CD catalyses
its combination with H2O to form H2CO3 which dissociates to form HCO3- and H+.

• H+ are then secreted into the tubular lumina in exchange for Na+
Proximal Tubular Bicarbonate
Reclamation Process (90 %)
 HCO3 Generation by Kidney
-

• Tubular cells generation of HCO3- is similar to HCO3- reabsorption, however

there is a net loss of H+ from the body and a net gain of HCO3- .

• This usually occur when urinary buffers such as ammonia or the phosphate
buffer are present.
Distal tubular mechanism of net H+
excretion.
Bicarbonate reclamation in the proximal renal tubule.
Buffer Systems in Body Fluids
33
Anion Gap
• Anion Gap is the difference between the total concentration of
measure cations (Na+ and K+) and measured anion (Cl- and
monohydgrogen phospahate H2CO3-.

• Estimates unmeasured anions in plasma (albumin)

• [Na+ ][K+] = [Cl-] +[HCO3-] +[ AG]

• AG = ([Na+ ][K+]) - ([Cl-] +[HCO3-])

=(140mmol + 4mmol) – (103mmol +25mmol)
=16mmol/L
• AG will be used in mixed disorders
 Anion Gap:
• Anion gap represents unmeasured anions in plasma. In practise [K+] is
neglected
AG = [Na+ ] - ([Cl-] +[HCO3-]) = 12mmol/L
Normal AG = 10 -16 mmol/L, HCO3- represents total CO2

• The unmeasured anions include–Anionic proteins, Phosphate, Sulphate

and organic anions.

• An increase in AG is due to increase in unmeasured anions and less

commonly due to decrease in unmeasured cations (Ca++, Mg++, K+). The
AG may increase with an increase in anionic albumin, either due to
increased albumin concentration or alkalosis which alters albumin
charge.
DISORDERS OF ACID-BASE
BALANCE
The Body and pH
• Homeostasis of pH is tightly controlled
• Extracellular fluid = 7.4
• Blood = 7.35 – 7.45
• < 6.8 or > 8.0 death occurs

• Acidosis (acidemia) below 7.35

• Alkalosis (alkalemia) above 7.45

• If plasma levels fall below 7.35 (acidemia), acidosis results
• If plasma levels rise above 7.45 (alkalemia), alkalosis results
• Alteration outside these boundaries affects all body systems
• Can result in coma, cardiac failure, and circulatory collapse
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 Disturbances of acid-base balance
Most acid-base disturbances result from disease or damage to organs
(kidney, lungs, brain) whose normal function is necessary for acid-base
homeostasis

Disease which causes abnormally increased production of metabolic acids

such that homeostatic mechanisms are overwhelmed

 Medical intervention (e.g. mechanical ventilation, some drugs)

 Types of Disorders
Arterial blood gases are the blood test used to identify and monitor acid-
base disturbances.

Three parameters measured during blood gas analysis, arterial blood pH

(pH), partial pressure of carbon dioxide in arterial blood (pCO2) and
concentration of bicarbonate (HCO3–) are of crucial importance

Results of these three allow classification of acid-base disturbance to one

of four etiological categories:
1. Respiratory acidosis
2. Respiratory alkalosis
3. Metabolic acidosis
4. Metabolic alkalosis
 Respiratory acidosis – (raised pCO2, reduced pH)
• Respiratory acidosis occurs when the blood is overly acidic due to an excess of
carbonic acid, resulting from too much CO2 in the blood.

• Respiratory acidosis is characterized by increased pCO2 due to inadequate alveolar

ventilation (hypoventilation) and consequent reduced elimination of CO2 from the
blood.

• Respiratory acidosis can result from anything that interferes with respiration, such
as pneumonia, emphysema, congestive heart failure, bronchopneumonia, asthma
and chronic obstructive airways disease.

• Some drugs (e.g. morphine and barbiturates) can cause respiratory acidosis by
depressing the respiratory center in the brain. Damage or trauma to the chest wall
and the musculature involved in the mechanics of respiration may reduce
ventilation rate.
 Causes
Airway obstruction
Severe pneumonia
Pulmonary embolism
Foreign object inhalation
Obstructive Pulmonary diseases

Neuromuscular
Brainstem injury
High spinal cord injury
Cardiac arrest
Signs and Symptoms of Respiratory Acidosis
• Breathlessness

• Headache

• Restlessness

• Lethargy and disorientation

• Tremors, convulsions, coma

• Respiratory rate rapid, then gradually depressed

• Skin warm and flushed due to vasodilation caused by excess CO 2

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Biochemical changes in Respiratory Acidosis
 Reduced pH

pCO2 is high

HCO3- is high
Treatment of Respiratory Acidosis
• Restore ventilation (Mechanical ventilation)
• IV lactate solution
• Treat underlying dysfunction or disease

• Compensation for Respiratory Acidosis

• Kidneys eliminate hydrogen ion and retain bicarbonate ion

44
 Respiratory alkalosis – (reduced pCO2, increased
pH)
• Respiratory alkalosis occurs when the blood is overly alkaline due to a deficiency in
carbonic acid and CO2 levels in the blood.

• Respiratory alkalosis is characterized by decreased pCO2 due to excessive alveolar

ventilation and resulting excessive elimination of CO 2 from blood. This condition
usually occurs when too much CO 2 is exhaled from the lungs, as occurs in
hyperventilation, which is breathing that is deeper or more frequent than normal.

• An elevated respiratory rate leading to hyperventilation can be due to severe anemia,

extreme emotional upset or fear, fever, infections, hypoxia, or abnormally high levels
of catecholamines, such as epinephrine and norepinephrine.

• One of the less welcome properties of salicylate (aspirin) is its stimulatory effect on
the respiratory center. This effect accounts for the respiratory alkalosis that occurs
following salicylate overdose.
Major causes
• Head trauma
• Brain tumour/ vascular accidents
• Anemia,
• Extreme emotional upset or fear,
• Fever,
• Infections,
• Hypoxia
• Altitude
• salicylate (aspirin)
• Abnormally high levels of catecholamines, such as epinephrine and
norepinephrine.
Clinical signs and symptoms

• Hyperventilation

• Muscle cramps

• Cardiac arrhythmias

• Seizures

• Tachypnea
Biochemical changes in respiratory alkalosis
 high pH

pCO2 is low

HCO3- is low
 Metabolic acidosis – (decreased HCO3–, decreased
pH)
• Metabolic acidosis occurs when the blood is too acidic (pH below 7.35) due
to too little bicarbonate, a condition called primary bicarbonate deficiency.

• The most common cause of metabolic acidosis is the presence of organic

acids or excessive ketones in the blood. 

• Reduced bicarbonate is always a feature of metabolic acidosis. This occurs

for one of two reasons: increased use of bicarbonate in buffering an
abnormal acid load or increased losses of bicarbonate from the body.
Diabetic ketoacidosis and lactic acidosis are two conditions characterized
by overproduction of metabolic acids and consequent exhaustion of
bicarbonate.
 Diabetic ketoacidosis Increased ketones
Strenuous exercise Lactic acid
Methanol Formic acid*
Paraldehyde β-Hydroxybutyric acid*
Isopropanol Propionic acid*
Ethylene glycol Glycolic acid, and some oxalic and formic acids*
Salicylate/aspirin Sulfasalicylic acid (SSA)*

• Metabolic acidosis can also result from uremia, which is the retention of urea and uric
acid.

• Other causes of metabolic acidosis are a decrease in the excretion of hydrogen ions,
which inhibits the conservation of bicarbonate ions, and excessive loss of bicarbonate
ions through the gastrointestinal tract due to diarrhea.
Metabolic acidosis normal anion gap
• Renal bicarbonate depletion
• Renal insufficiency

• Ingestion of ammonium chloride

• Gastrointestinal causes
• Diarrhoea
• Fistula
 Increased anion gap
Metabolic acidosis
• Ketoacidosis (diabetic)
• Uremia (renal failure)
• Salicylate intoxication
• Starvation
• Methanol intoxication
• Alcohol ketoacidosis
• Unmeasured osmoles (intoxication)
• Lactic acidosis
Increased anion gap Metabolic acidosis
• A useful mnemonic to help remember some causes of acidosis with high
anion gap metabolic acids is DR MAPLES

• D= Diabetic Ketoacidosis (diabetic)

• R = renal failure (Uremia)
• M = Methanol intoxication
• A =Alcohol ketoacidosis
• P =Paracetamol
• L = Lactic acidosis
• E = Ethylene glycol
• S = Salicylate intoxication
 Metabolic Acidosis
Bicarbonate deficit - blood concentrations of bicarb drop below 22mEq/L

Causes:
Loss of bicarbonate through diarrhea or renal dysfunction
Accumulation of acids (lactic acid or ketones)/Production of large numbers
of fixed / organic acids
Failure of kidneys to excrete H+ Depletion of bicarbonate reserve
Bicarbonate loss due to chronic diarrhea

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Symptoms of Metabolic Acidosis
Headache, lethargy
Hypotension
Shock
Tinnitus
Oliguria
Fruity breath odour
Nausea, vomiting, diarrhea
Coma

55
Biochemical changes in Metabolic Acidosis
 low pH

pCO2 is low

HCO3- is low
Compensation for Metabolic Acidosis

Increased ventilation

Renal excretion of hydrogen ions if possible

K+ exchanges with excess H+ in ECF

( H+ into cells, K+ out of cells)

Treatment of Metabolic Acidosis
• Treat underlying dysfunction or disease
Renal disturbances – dialysis
Cases of over dose dialysis can also be done

• In severe metabolic acidosis pH < 7.1 sodium bicarbonate can be

administered but with caution to prevent hypernatraemia, volume
overload and lead to alkalosis

58
Metabolic alkalosis – (increased HCO3– , increased pH)

• Bicarbonate is always raised in metabolic alkalosis. Rarely, excessive

administration of bicarbonate or ingestion of bicarbonate in antacid
preparation can cause metabolic alkalosis, but this is usually
transient.

• Abnormal loss of hydrogen ions from the body can be the primary
problem. The projectile vomiting of gastric juice, for example,
explains the metabolic alkalosis that can occur in patients with pyloric
stenosis.
Metabolic Alkalosis
• Bicarbonate excess - concentration in blood is greater than 26
mEq/L
• Causes:
• Excess vomiting = loss of stomach acid
• Excessive use of alkaline drugs
• Certain diuretics
• Endocrine disorders
• Heavy ingestion of antacids
• Severe dehydration

60
Biochemical changes in metabolic alkalosis
 high pH

pCO2 is high

HCO3- is high
Compensation for Metabolic Alkalosis
• Alkalosis most commonly occurs with renal dysfunction, so can’t
count on kidneys
• Respiratory compensation difficult – hypoventilation limited by
hypoxia

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Symptoms of Metabolic Alkalosis
• Respiration slow and shallow
• Hyperactive reflexes ; tetany
• Often related to depletion of electrolytes
• Atrial tachycardia
• Dysrhythmias

63
Treatment of Metabolic Alkalosis
• Electrolytes to replace those lost
• IV chloride containing solution
• Treat underlying disorder

64
 Maintenance of acid- base homeostasis: COMPENSATORY
MECHANISMS

• It is vital for life that pH does not waiver too far from normal, and the
body will always attempt to return an abnormal pH towards normal
when acid-base balance is disturbed.

• Compensation is the name given to this life-preserving process. To

understand compensation, it is important to recall that pH is governed
by the ratio [HCO3–] : pCO2 (20:1). So long as the ratio is normal, pH will
be normal.
 RESPIRATORY COMPENSATION

• Respiratory compensation for metabolic acidosis increases the

respiratory rate to drive off CO2 and readjust the bicarbonate to carbonic
acid ratio to the 20:1 level. This adjustment can occur within minutes.

• Consider a patient with metabolic acidosis whose pH is low because

bicarbonate [HCO3–] is low. To compensate for the low [HCO3–] and
restore the ratio towards normal the patient must lower his pCO2.

• Chemoreceptors in the respiratory center of the brain respond to a rising

hydrogen ion concentration (low pH), causing increased ventilation
(hyperventilation) and thereby increased elimination of carbon dioxide;
the pCO2(a) falls and the ratio [HCO3–] : pCO2 returns towards normal.
METABOLIC COMPENSATION

• Metabolic and renal compensation for respiratory diseases that can

create acidosis revolves around the conservation of bicarbonate ions.

• In cases of respiratory acidosis, the kidney increases the conservation of

bicarbonate and secretion of H+ through the exchange mechanism
(HCO3– regeneration and reclamation) . These processes increase the
concentration of bicarbonate in the blood, reestablishing the proper
relative concentrations of bicarbonate and carbonic acid.

• In cases of respiratory alkalosis, the kidneys decrease the production of

bicarbonate and reabsorb H+ from the tubular fluid. These processes can
be limited by the exchange of potassium by the renal cells, which use a
K+-H+ exchange mechanism (antiporter).
DIAGNOSING ACIDOSIS AND
ALKALOSIS
Types of Acidosis and Alkalosis
  pH pCO2 Total HCO3–
Metabolic acidosis ↓ N, then ↓ ↓
Respiratory acidosis ↓ ↑ N, then ↑
Metabolic alkalosis ↑ N, then↑ ↑
Respiratory alkalosis ↑ ↓ N, then ↓
Simple decompensated
Acid-base Disorders

• Acid Base Dis.: pH pCO2 HCO3-

• Metabolic acidosis

• Respiratory acidosis

• Metabolic alkalosis

• Respiratory alkalosis
 Acid-Base Disorders
• Respiratory acid base disorders
• Result when abnormal respiratory function causes rise or fall in CO2 in ECF

• Metabolic acid-base disorders

• Generation of organic or fixed acids
• Anything affecting concentration of bicarbonate ions in ECF
Compensation
• If underlying problem is metabolic, hyperventilation or
hypoventilation can help : respiratory compensation.

• If problem is respiratory, renal mechanisms can bring about

metabolic compensation.

71
Figure 27.12 Respiratory Acid-Base
Regulation

Figure 27.12a
 Mixed or combined acid-base balance
• Mixed acid-base disorders are complex conditions where 2 primary
disturbances occurs simultaneously in same patient.

• For example, A patient with diabetic ketoacidosis (metabolic acidosis) may

develop an independent respiratory problem leading to respiratory acidosis
or alkalosis

• Patients who have ingested an overdose of drug combinations such as

sedatives and salicylates may have mixed disturbances as a result of the acid-
base response to the individual drugs (metabolic acidosis mixed with
respiratory acidosis or respiratory alkalosis, respectively).
Diagnosis of Acid-Base Imbalances
1. Note whether the pH is low (acidosis) or high (alkalosis)
2. Decide which value, pCO2 or HCO3- , is outside the normal range
and could be the cause of the problem. If the cause is a change in
pCO2, the problem is respiratory. If the cause is HCO3- the problem
is metabolic.
3. Look at the value that doesn’t correspond to the observed pH
change. If it is inside the normal range, there is no compensation
occurring. If it is outside the normal range, the body is partially
compensating for the problem.

74
Detection of acidosis and alkalosis
• Arterial blood specimen is preferable, heparin and specimen should be
properly mixed. (if Na heparin is used, do not estimate Na from the same
specimen). Air bubbles should be properly expelled before sample
collection.

• Diagnostic blood tests.

• Blood pH
• PCO2
• Bicarbonate levels

• Distinguish between respiratory and metabolic

 Stepwise Approaches
• History & physical examination
• Arterial blood gas for pH, pCO2, (HCO3)
• Serum Na, K, Cl, CO2 content/ HCO3
• Use CO2 content to calculate anion gap
• Calculate anion gap
• Anion gap = {Na - (Cl + CO2 content)}
• Determine appropriate compensation
• Determine the primary cause
 CO2 content

Low Normal High

Metabolic acidosis Normal Metabolic

alkalosis
Resp alkalosis Mixed Resp acidosis

A normal CO2 content + high anion gap = metabolic acidosis +

Metabolic alkalosis or metabolic ac + compensatory respiratory ac.
Case study 1
• A 27 years old woman presented to causality with panic attack. On
examination she was found to be hyperventilating. Her arterial blood
results were

 pH 7.61 (7.35 -7.45)

PC02 2.7kPa (4.6 -6.0)
P02 13.3kPa (9.3-13.3)
Bicarbonate 18mmol/L (24 -32)

Classify the acid-base disorder and how does compensation occur

Answer 1
• The patient presents with respiratory alkalosis. The panic attack
resulted in the hyperventilation. Compensation is by the kidney which
increases bicarbonate excretion and reduce acid excretion.
Case Study 2:
• Bob is a 64-year-old male admitted to the emergency room for
asthma.
His laboratory results are as follows:
pH 7.31, pCO2 higher than normal, and total HCO3– also higher than
normal.

Classify his acid-base balance as acidosis or alkalosis, and as metabolic

or respiratory. Is there evidence of compensation? Propose the
mechanism by which asthma contributed to the lab results seen.
Answer 2
• Respiratory acidosis is present as evidenced by the decreased pH and
increased pCO2, with some compensation as shown by the increased
total HCO3–.

• His asthma has compromised his respiratory functions, and excess

CO2 is being retained in his blood.
Case Study 3:
• Kim is a 38-year-old women admitted to the hospital for bulimia.
Her laboratory results are as follows: pH 7.48, pCO2 in the normal
range, and total HCO3– higher than normal.

Classify her acid-base balance as acidosis or alkalosis, and as metabolic

or respiratory. Is there evidence of compensation? Propose the
mechanism by which bulimia contributed to the lab results seen.
Answer 3
• Metabolic alkalosis is present as evidenced by the increased pH and
increased HCO3–, without compensation as seen in the normal pCO2.

• The bulimia has caused excessive loss of hydrochloric acid from the
stomach and a loss of hydrogen ions from the body, resulting in an
excess of bicarbonate ions in the blood.
 Case 4
A 26 year old woman, complains of weakness. She denies vomiting
or taking medications.

Serum Na 133mmol/L HCO3 32mmol/L

K 3.1mmol/L Cl 100mmol/L,
pH 7.48 (H+ 32).

Calculate her anion gap

Which of the following is characterized as metabolic
alkalosis?

a. increased pH, decreased pCO2, decreased HCO3–

b. increased pH, increased pCO2, increased HCO3–

c. decreased pH, decreased pCO2, decreased HCO3–

d. decreased pH, increased pCO2, increased HCO3–