ACIDOSIS AND ALKALOSIS

DR. A Dandare
Department of Biochemistry & Molecular Biology
Usmanu Danfodiyo University, Sokoto
ACIDOSIS AND ALKALOSIS

COURSE CONTENT
➢Review of acid, bases and buffer solution

➢Meaning of acidosis and alkalosis

➢Types of acidosis and alkalosis

➢Differences between metabolic and

respiratory acidosis and alkalosis

➢Causes of acidosis and alkalosis

 Acids and Bases
Acids: are substances that donate protons (H⁺ ions) in an aqueous solution.
▪ Acids increase the concentration of H⁺ ions in the solution.
▪ It has pH below 7.0

1. Strong acids: these are acids that dissociate or ionize completely in water.
Examples include mineral acids
such as HCl, H2SO4, HNO3 etc

2. Weak acids: these are acids that do not dissociate or ionize completely in
water. Examples include organic acids such as acetic acid, lactic acid, citric acid,
succinic acid, oxalic acid etc..

Weak acids are of paramount importance in biochemistry because of their role in

influencing the [H+] of an aqueous environment
 Acids and Bases
Bases: are substances that accept protons or release hydroxide ions (OH⁻)
in an aqueous solution.
▪ They reduce the concentration of H⁺ ions in the solution.
▪ It has pH greater than 7.0

▪ Examples: Ammonia (NH₃): A weak base involved in nitrogen metabolism.

▪ Bicarbonate Ion (HCO₃⁻): Acts as a buffer in blood plasma.
 The pH scale
▪ pH is a measure of the hydrogen ion concentration ([H⁺]) in a solution.
▪ The pH scale, which ranges from 0 to 14, measures how acidic or basic (alkaline) a
solution is.
▪ The human body normally maintains a tightly regulated blood pH of approximately
7.35 to 7.45.

▪ Range:0-14, where 7 is neutral.< 7 is acidic; > 7 is basic.

▪ A change in 1 pH unit reflects a tenfold change in H⁺ ion concentration.
▪ Cells and tissues maintain specific pH ranges to ensure proper enzymatic reactions
and metabolic function.

▪ Any deviation from this range can impair cellular function and metabolic processes.
 Buffers
Buffers: are solutions that resist changes in pH upon the addition of small
amounts of acid or base.

▪ They are typically composed of a weak acid and its conjugate base or a weak
base and its conjugate acid.

▪ When an acid is added, the conjugate base in the buffer neutralizes it, and vice
versa.
 Physiological Acid-Base Balance
The physiological acid-base balance is maintained through several control
mechanisms that prevent deviations from normal pH levels.

Disruptions in this balance can lead to acid-base disorders, which may be detrimental
to the body's normal functioning.

Acids-Base Balance is Acids-Base Balance

Controlled by: Disrupted by:
✓Lungs ✓Vomiting
✓Diarrhea
✓Kidneys
✓Respiratory Failure
✓Buffers
✓Kidney Failure
✓Infections and
✓Drugs ingestion
7
 Physiological Acid-Base Balance
1. Role of the Lungs: Carbon dioxide, which is mildly acidic, is a waste product of cellular
metabolic processes as such, is constantly produced by cells.
▪ Carbon dioxide in the blood reacts with water to form carbonic acid (H2CO3), catalyzed carbonic
anhydrase

▪ Carbonic acid is unstable and quickly dissociates into bicarbonate and hydrogen ions.

▪ One mechanism the body uses to control blood pH is the release of CO2 from the lungs.

▪ As carbon dioxide accumulates in the blood, the pH of the blood decreases (acidity increases).

▪ The brain regulates the amount of CO2 that is exhaled by controlling the speed and depth of
breathing (ventilation).

▪ CO2 exhaled, & consequently the blood pH, increases as breathing becomes faster and deeper.

▪ By adjusting the speed and depth of breathing, the brain and lungs are able to regulate the blood
pH minute by minute.
 Physiological Acid-Base Balance
2. Role of the kidneys
• The renal system can also adjust blood pH through the excretion of hydrogen ions
(H+) and the conservation of bicarbonate, but this process takes hours to days to
have an effect.
3. Buffer systems
▪ Yet another mechanism for controlling blood pH involves the use of chemical
buffer systems, which guard against sudden shifts in acidity and alkalinity.
▪ Buffer systems are combinations of the body's own naturally occurring weak acids
and weak bases.
▪ The buffer systems work chemically to minimize changes in the pH of a solution by
adjusting the proportion of acid and base.
▪ When an acid is added to a buffer, the conjugate base in the buffer neutralizes it.
Conversely, when a base is added, the weak acid in the buffer neutralizes the it.
 Physiological Acid-Base Balance
The body uses several buffer systems to maintain pH homeostasis:

a. Bicarbonate Buffer System:

The main buffer in extracellular fluid, it involves the reversible reaction:

This system can quickly neutralize excess H⁺ or OH⁻ to maintain pH.

b. Phosphate Buffer System: Operates in the intracellular fluid and kidneys: this buffer
consists of dihydrogen phosphate (H₂PO₄⁻) and hydrogen phosphate (HPO₄²⁻).

c. Protein Buffer System: Proteins, especially albumin, can act as buffers by binding to H⁺
or releasing it, particularly in the blood.

d. Hemoglobin Buffer System: In red blood cells, hemoglobin binds to CO₂ (forming
carbamino hemoglobin) and H⁺ (buffering the blood as it releases oxygen in tissues
Meaning of Acidosis and Alkalosis

▪ Acidemia: serum pH < 7.35

▪ Alkalemia: serum pH > 7.45

▪ Acidosis: pathologic process that lowers [HCO3-] or

raises PCO2

▪ Alkalosis: pathologic process that raises [HCO3-] or

lowers PCO2

11
 Types of Acid-Base Balance Disorders
Acids base balance disorders are
categorized into four main types based
on the underlying cause of the
disturbance in the blood's pH.

1. Respiratory acidosis

2. Metabolic acidosis

3. Respiratory alkalosis

4. Metabolic alkalosis
 Types of Acid-Base Balance Disorders
1. Respiratory Acidosis: This occurs when there is an excess of CO₂ in the
blood, leading to an increase in carbonic acid and a decrease in blood pH
(acidosis), resulting from impaired lungs function or hypoventilation condition such
as chronic obstructive pulmonary disease (COPD), severe asthma, or respiratory
muscle. weakness.

Symptoms: include shortness of breath, confusion or lethargy, headache,

cyanosis (bluish color of the skin due to lack of oxygen).

Diagnosis: Blood gas analysis shows low pH, elevated CO₂, and possibly a
compensatory increase in bicarbonate (HCO₃⁻) if chronic.

Treatment: Addressing the underlying cause (e.g., improving ventilation, treating

respiratory conditions). In acute cases, supplemental oxygen or mechanical
ventilation might be needed.
 Types of Acid-Base Disorders
2. Metabolic Acidosis: Metabolic acidosis occurs when there is an excess of
hydrogen ions (H⁺) or a loss of bicarbonate (HCO₃⁻) in the blood, leading to a
decrease in blood pH (acidosis). Caused by
i. increased acid production: due to Lactic Acidosis (caused by shock, or severe
hypoxia), Ketoacidosis (Seen in uncontrolled diabetes or in starvation), Renal
Failure (Kidneys fail to excrete acids properly).
ii. Loss of Bicarbonate: due to Diarrhea (Loss of bicarbonate-rich intestinal fluids),
Renal Tubular Acidosis (Kidneys fail to reabsorb bicarbonate effectively)
Symptoms: Include rapid breathing (as compensatory response to hyperventilation),
fatigue or weakness, confusion, nausea and vomiting
Diagnosis: Blood gas analysis shows low pH, low bicarbonate (HCO₃⁻), and a
compensatory decrease in CO₂ if chronic.
Treatment:
▪ Addressing the underlying cause: For example, insulin for diabetic ketoacidosis
▪ Administration of bicarbonate:
Causes of Metabolic Acidosis Due to Gain of Acid
Endogenous hydrogen ion production ▪ Lactic acidosis: Characterized by
▪ Ketoacidosis: resulted from starvation a buildup of L-lactate in the body,
with formation of extremely low pH
diabetes mellitus in the bloodstream.
Beta oxidation
Glucose
TCA
Acetyl CoA Glycolysis
Cycle
Acetoacetyl CoA

Acetoacetate
Ketone
β-hydroxybutyrate Acetone bodies

Ketone bodies ionizes to contribute to severe metabolic

acidosis
 Metabolic Acidosis Due to Metabolism of Toxins
Metabolic acidosis can occur due to the metabolism of certain toxins that produce
acidic metabolites, increase the production of endogenous acids, or impair the
body's ability to excrete acid.
▪ Salicylate overdose: Salicylates stimulate the metabolic rate, which leads
to increased production of organic acids, such as lactic acid and keto-acids.
▪ Salicylates interfere with the mitochondrial energy production by uncoupling
oxidative phosphorylation.
▪ This leads to inefficient ATP production and increased anaerobic metabolism,
resulting in the production of lactate and other acidic intermediates.

➢ Methanol and Ethylene Glycol: These are metabolized to formic acid and
glycolic acid/oxalic acid, respectively.

➢ These metabolites are highly toxic and contribute to severe metabolic acidosis.
Metabolic Acidosis Due to Metabolism of Toxins

➢ Ethanol: Excessive consumption leads to an increase in the production of

acetic acid.
➢ Chronic alcohol consumption can also lead to a state of ketoacidosis,
particularly in malnourished individuals.
➢ Carbon Monoxide: It binds to hemoglobin with a higher affinity than oxygen,
leading to tissue hypoxia. Cells resort to anaerobic metabolism, increasing
lactic acid production.

➢ Metformin: Though generally safe, in overdose or in patients with renal

insufficiency, metformin can lead to lactic acidosis due to the inhibition of
gluconeogenesis and mitochondrial respiration
➢ Cyanide: Cyanide inhibits cellular respiration by binding to cytochrome c
oxidase in the electron transport chain, leading to anaerobic metabolism and
lactic acid production.
 Types of Acid-Base Disorders
3. Respiratory Alkalosis: is a condition in which there is a decrease in CO₂ levels in
the blood, leading to a decrease in carbonic acid and an increase in blood pH
(alkalosis), resulted from hyperventilation often due to anxiety, pain, stress, lower
atmospheric CO₂ levels, or fever
Symptoms: include Light-headedness or dizziness, tingling in the fingers and toes,
muscle cramps or spasms, palpitations
Diagnosis: Blood gas analysis shows high pH, low CO₂, and possibly a
compensatory decrease in bicarbonate if chronic.
Treatment: Addressing the underlying cause (e.g., managing anxiety, treating fever).
▪ Breathing into a paper bag can sometimes help to increase CO₂ levels
temporarily.
 Types of Acid-Base Disorders
4. Metabolic Alkalosis: Is a condition that occurs when there is an excess of
bicarbonate (HCO₃⁻) or a loss of hydrogen ions (H⁺) in the blood, leading to an
increase in blood pH (alkalosis),
Metabolic alkalosis is caused by increased bicarbonate (excessive use of
bicarbonate-containing antacids., Primary hyperaldosteronism) or loss of hydrogen
ions (by vomiting, diuretic use etc).

Symptoms: muscle cramps, dizziness, tingling or numbness, confusion etc

Diagnosis: Blood gas analysis shows high pH, high bicarbonate (HCO₃⁻), and a
compensatory increase in CO₂ if chronic.
Treatment:
▪ Address the underlying cause
▪ Correct electrolyte imbalances
▪ Hydration.
 Compensatory Responses in Acidosis
• 1. Respiratory Acidosis Compensation:
• Renal Compensation: The kidneys respond by increasing the excretion of
hydrogen ions (H⁺) and reabsorbing bicarbonate (HCO₃⁻) from the urine. This
process helps to buffer the excess acidity in the blood.
• Renal compensation is a slower process, taking hours to days to fully develop.
2. Metabolic Acidosis Compensation:
• Respiratory Compensation: The respiratory system compensates by increasing
the rate and depth of breathing (hyperventilation) to expel more CO₂.
• This reduces the concentration of carbonic acid in the blood, thereby decreasing
the H⁺ concentration.

Respiratory compensation occurs rapidly, within minutes to hours.

 Compensatory Responses in Alkalosis
3. Respiratory Alkalosis Compensation:
Renal Compensation: The kidneys respond by decreasing the excretion of H⁺
and decreasing the reabsorption of bicarbonate, allowing bicarbonate to be
excreted in the urine. This helps increase the acidity of the blood, thereby reducing
the pH.
Renal compensation for respiratory alkalosis is slower, taking hours to days.
4. Metabolic Alkalosis Compensation:
Respiratory Compensation: The respiratory system compensates by reducing
the rate and depth of breathing (hypoventilation) to retain CO₂.
This increases the concentration of carbonic acid in the blood, thereby increasing
the H⁺ conc.
Respiratory compensation occurs rapidly, within minutes to hours.
Compensatory Responses in Acidosis & Alkalosis
Primary pH HCO3- PCO2 Compensation
Disturbance
Respiratory <7.35 Compensatory Primary Kidney will increase the removal of H+ :
acidosis increase increase [HCO3-] will increase further

Respiratory >7.45 Compensatory Primary Kidney will decrease the removal of H+ :

alkalosis decrease decrease [HCO3-] will decrease further

Metabolic <7.35 Primary Compensatory Lungs increase the removal of CO2,

acidosis decrease decrease bicarbonate ion decrease further

Metabolic >7.45 Primary Compensatory Lungs decrease the removal of CO2,

alkalosis increase increase bicarbonate ion increase further