Acidosis and Alkalosis

(MBBS Students)

Hassan Yankuzo, MBBS, MSc, PhD.

Senior Lecturer,
Department of Medical Biochemistry,
Usmanu Danfodiyo University, Sokoto
 Learning Objectives

 Review of acid, bases and buffer solution

 Understanding the acid-base balance

 Meaning of acidosis and alkalosis

 Types of acidosis and alkalosis

 Differences between metabolic and respiratory

acidosis and alkalosis
 Causes of acidosis and alkalosis
 Acids, Bases and Buffer solution
• Acids: Proton (H+)donors
• Bases: Proton Acceptors
• Weak acids: dissociate partially in
solution (Organic Acids)
• pH = -log[H+]; degree of acidity or
alkalinity of solutions
 Biological Molecules

• Proteins • Nucleic • Lipids

Acids
Carboxylic and Phosphoric
Fatty acids
Amino groups acids

Undergo acid base reactions

Many properties are dictated by the acidity of solutions they are
subjected to.
Many other molecules of biological importance are either acids or
bases and behave as such
 [H+] M
100 A strong acid
pH
10-1 • Most living cells have a very
10-2
narrow range of tolerance for
10-3
10-4
pH, i.e. [H+].
10-5 • [H+] is controlled in all
10-6 biological organisms, and in
10-7 virtually all biochemical
10-8 processes.
10-9
• Each pH unit represents a
10-10
factor of 10 difference in [H+].
10-11
10-12
10-13 A strong base

10-14

The pH scale goes from 0 to 14—because [H+][OH-] = 10-14 5

 Weak acids, their conjugate
bases, and buffers…
 Weak acids have only a partial tendency to shed their
protons

 The corresponding negatively charged anion is a willing

proton acceptor, and is called the conjugate base.

 The properties of a buffer rely on a balance between a

weak acid and its conjugate base.

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 Buffer Solution
 A buffer is a solution of a weak acid (proton
donor) and its conjugate base (proton acceptor)
that resists changes in pH upon addition of small
amount of acid (H+) or base (OH-)

 A buffer works best in the middle of its range,

where the amount of undissociated acid is almost
equal to the amount of the conjugate base

 Precisely when pH = pKa + 1.0

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Disturbances of Acid Base balance
• Acid base disorders are of two categories
Respiratory
Primary defect is in ventilation affecting Pco2
Metabolic
The defects include production of fixed acids (or
ingestion of substances that generate them) in excess of
kidneys ability to excrete them, or loss of H+ from the
body, or loss or retention of HCO3-
Each of these is subdivided into two
Acidosis (decreased pH due to acidemia)
Alkalosis (increased pH due to alkalemia)
 Disturbances of Acid Base balance
The disorders are best understood from the basis of Carbonic anhydrase
(CA) catalysed reaction
CA CA
• CO2 + H2O H2CO3 H+ + HCO3-

• H2CO3 is source of H+ ions in the body

• Normal ratio of base (HCO3-) to acid (H2CO3 ) is 20:1 at physiological pH

of 7.4

• Deviations from this ratio are used to identify Acid-Base imbalances

Disturbances of Acid Base balance

• The primary disturbances are usually

accompanied by compensatory physiological
changes which tend to correct the plasma [H+]
towards normal
 Principles of Acid-Base Disorders

 Metabolic acid-base disorders and

alter [HCO3-]
 secondary metabolic compensation

 Respiratory acid-base disorders and

alter (PCO2)
 secondary respiratory compensation

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 Reference ranges and points
Parameters Reference range Reference point
Na+ 135-147 mmol/L
K+ 3.5-5.0 mmol/L
Cl- 95-105 mmol/L
CO2, total 24-30 mmol/L
pH 7.35-7.45 7.40
PCO2 33-44 mm Hg 40 mm Hg
PO2 75-105 mm Hg
HCO3- 22-28 mmol/L 24 (27) mEq/L
Anion gap 8-16 mEq/L 12 mEq/L
 Meaning of Acidosis and Alkalosis
• Acidosis: pathologic process that lowers
[HCO3-] or raises PCO2 in the blood resulting
in a decrease serum pH < 7.35.

• Alkalosis: pathologic process that raises

[HCO3-] or lowers PCO2 in the blood
resulting in an increase serum pH > 7.45.

NB: presence of each, suggest an underlying metabolic abnormality

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 Metabolic Acidosis
• HCO3- excretion is controlled by the kidney
• H+ excretion is controlled by the kidney
• One H+ buffers one HCO3-

– So, metabolic acidosis always characterized by

increased production of H+ ions and a reduction in
plasma HCO3-

• Gain of H+
Decrease in pH
• Loss of HCO3-
Causes of metabolic acidosis due to gain of acid
 Endogenous hydrogen ion production:
 Ketoacidosis
 Starvation or as a result of diabetes mellitus

Beta oxidation

Acetyl CoA TCA Cycle

Acetoacetyl CoA

Acetoacetate

Ketone bodies

β-hydroxybutyrate Acetone
Ketone bodies are overproduced in severe
diabetes and starvation
• Starvation and untreated diabetes mellitus lead to
overproduction of ketone bodies, with several
associated medical problems
• During starvation, gluconeogenesis depletes citric
acid cycle intermediates, diverting acetyl-CoA to
ketone body production
• In untreated diabetes, when the insulin level is
insufficient, extrahepatic tissues cannot take up
glucose efficiently from the blood, either for fuel or
for conversion to fat.
 Ketone bodies are overproduced in severe
diabetes and starvation
• Under these conditions, levels of malonyl-CoA fall, relieving
the inhibition of carnitine acyltransferase I, and fatty acids
enter mitochondria to be degraded to acetyl-CoA—which
cannot pass through the citric acid cycle because cycle
intermediates have been drawn off for use as substrates in
gluconeogenesis.
• Accumulation of acetyl-CoA leads to overproduction of the
ketone bodies (acetoacetate and B-hydroxybutyrate), which
cannot be used by extrahepatic tissues as fast as they are
made in the liver
• acetone, which results from the spontaneous decarboxylation of
acetoacetate
 Ketoacidosis
• Higher than normal quantities of ketone bodies present
in the blood or urine constitute ketonemia
(hyperketonemia) or ketonuria, respectively. The
overall condition is called ketosis.
• The ketone bodies are carboxylic acids, which ionize to
release protons. In uncontrolled diabetes this acid
production can overwhelm the capacity of the blood's
bicarbonate buffering system and produce a lowering
of blood pH called acidosis or, in combination with
ketosis, ketoacidosis, a potentially life-threatening
condition
Ketoacidosis
Ketoacidosis
 Lactic Acidosis
When animal tissues cannot be supplied with sufficient
oxygen to support oxidation of the pyruvate and NADH
produced in glycolysis, NAD+ is regenerated from NADH by
the reduction of pyruvate to lactate
 Lactic Acidosis
Lactic acidosis is characterized by a buildup
of Lactate in the body, with consequent
generation of low pH in the blood
Glucose

Pyruvate
NADH
LDH
NAD+

Lactate

• salicylate overdose
 METABOLIC ACIDOSIS

0.5 10
 Other causes of metabolic acidosis
 Metabolism of toxins
 Methanol (wood alcohol)
 ethylene glycol (antifreeze solution)
 Salicylate overdose
 Decreased renal excretion of acids
 Uremia (as seen in renal failure)
 renal tubular acidosis (type 1) distal
 Loss of Bicarbonate
 Renal tubular acidosis type II (proximal)
 GI loss (e.g. in severe diarrhea as well as prolonged vomitting)
 Disease conditions from abnormal metabolism
e.g. Diabetes Mellitus
 Strenuous exercise resulting into accumulation of Lactic Acid
 Metabolic Acidosis
• Treatment
– Treat the underlying condition and the pH will
gradually normalize. For e.g. control of diabetes
with Insulin, adequate hydration with IV Fluids in
mild cases of acidosis, and dialysis for extreme
cases of renal insufficiency.

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 Metabolic Alkalosis
 Alkalemia due to loss of acid [H+] or gain of base [HCO3-],
resulting in the Plasma HCO3- level is

 The loss of H+ causes H2CO3 to dissociate into HCO3- and

H+
 Since the primary disturbance is of non respiratory origin,
PCO2 remains normal even though H+ falls and HCO3- rises.

• Respiratory Compensation is usually in form of

hypoventilation to increase PCO2 in response to fall in H+,
while the kidneys increase the retention of H+

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 Metabolic Alkalosis
 Causes (organized in 2 ways)
 Ingestion of alkaline substances as remedy for gastric
hyperacidity, e.g. use of antacids, or baking soda
(NaHCO3), which dissociates into Na+ and HCO3- .
HCO3- neutralizes heart burn, and binds free H+ to raise
the pH level in the plasma.

 Loss of H+ from ECF via kidneys (diuretics) or gut

(vomiting). Normally, HCO3- is added to the plasma as
HCl is secreted by the gastric parietal cells. HCO3- gets
neutralized by HCl that was reabsorbed from the gut.
This process is abolished during vomiting due to loss of
H+ in form of HCl which increases plasma HCO3- and pH
level of the blood.
 METABOLIC ALKALOSIS

1.25 25
 Metabolic Alkalosis
• Treatment

– IV Fluids replacement (Na+, K+, & Cl-) is

administered while treating the underlying cause

– In severe cases, diluted acids in form of IV

ammonium chloride can be administered.

– A diuretic, e.g. acetazolamide may be used if the

patient is edematous, to increase HCO3- secretion

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 Respiratory acidosis
 Accumulation of PCO2 in ECF (i.e. hyperkapnia) due to
hypoventilation
 Caused by
 Depression of respiratory centre by drugs such as opiates, sedatives, anesthetics
 Obstruction of air passage by: Vomittus, tracheal tumor, anaphylaxis, etc
 Iseases that affect alveolar ventilation such as emphysema, pulmonary oedema

 Acute or chronic Causes

 excess CO2 in the inspired air
 decreased alveolar ventilation
(central respiratory depression & other CNS problems, nerve or muscle
disorders (e.g. myasthenia gravis), lung or chest wall defects,(e.g. lung
collapse), airway disorders (e.g. Asthma, chronic bronchitis, COPD)
 increased production of CO (hyper catabolic disorders e.g. malignancy)
 RESPIRATORY ACIDOSIS
• The rate and depth of breathing control the
amount of CO2 in the blood
• Normally when CO2 builds up, the pH of the
blood falls and the blood becomes acidic
• High levels of CO2 in the blood stimulate the
parts of the brain that regulate breathing, which
in turn stimulate faster and deeper breathing

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RESPIRATORY ACIDOSIS

32
Respiratory Acidosis: Renal compensation
• The renal compensation results in the
retention of HCO3- and excretion of H+
• Plasma [H+] thus decreased towards
normal while [HCO3-] increased further
• These changes occurs over 4 to 5 days
• After which a steady state is achieved
resulting in normalised H+ excretion
and retention of HCO3-
 Respiratory alkalosis
 Caused by hyperventilation (i.e. increased elimination of

CO2 from the lungs thereby reducing the PCO2.

 Hyperventilation may be due to anxiety, fever, salicylate

poisoning, hypoxemia at high altitudes, assisted respiration
 The reduced PCO results in reduction of both H+ and HCO3-
2

 If the condition persist, the kidneys will compensate by

increasing the excretion of HCO3- and retaining the H+

 Plasma H+ returns to normal and HCO3- decreases further
 In 3 to 4 days a new steady state is achieved
 RESPIRATORY
Decreased ALKALOSIS
CO2 in the lungs will eventually slow the
rate of breathing and permits a normal amount
of CO2 to be retained in the lung
RESPIRATORY ALKALOSIS
 ACIDOSIS

decreased failure of metabolic production absorption of prolonged

removal of kidneys to acid of keto acids metabolic acids diarrhea
CO2 from excrete from GI tract
lungs acids

accumulation accumulation excessive loss

of CO2 in blood of acid in blood of NaHCO3
from blood

deep
vomiting
from
respiratory metabolic GI tract
increase in
acidosis plasma H+ acidosis
concentration kidney
disease
(uremia)
depression of
nervous system 37
 ALKALOSIS
anxiety overdose high prolonged ingestion of excess
of certain altitudes vomiting excessive aldosterone
drugs alkaline drugs

hyperventilation loss of acid accumulation

loss of CO2 and of base
H2CO2 from
blood

respiratory metabolic
alkalosis alkalosis
decrease
in plasma H+
concentration

overexcitability
of nervous
system 38
 ACID – BASE DISORDERS
Clinical State Acid-Base Disorder
Pulmonary Embolus Respiratory Alkalosis

Cirrhosis Respiratory Alkalosis

Pregnancy Respiratory Alkalosis

Diuretic Use Metabolic Alkalosis

Vomiting Metabolic Alkalosis

Chronic Obstructive Pulmonary Disease Respiratory Acidosis

Shock Metabolic Acidosis

Severe Diarrhea Metabolic Acidosis

Renal Failure Metabolic Acidosis

Respiratory Alkalosis,
Sepsis (Bloodstream Infection)
Metabolic Acidosis
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