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Acid – Base Disturbances

Acid–base imbalance is an abnormality of the human body's normal balance of acids and bases that

causes the plasma pH to deviate out of the normal range (7.35 to 7.45).

Ordinarily, chemical and physiological buffer systems maintain the hydrogen ion concentration of body

fluids within very narrow pH ranges. Abnormal conditions may disturb the acid-base balance. For

example:

The pH of arterial blood is normally 7.35-7.45.

A pH value below 7.35 produces Acidosis.

A pH above 7.45 produces Alkalosis.

Such shifts in the pH of body fluids may be life threatening. In fact, a person usually cannot survive if the

pH drops to 6.8 or rises to 8.0 for more than a few hours.

ACIDOSIS

Acidosis results from an accumulation of acids or a loss of bases, both of which cause abnormal increases

in the hydrogen ion concentrations of body fluids.

ALKALOSIS

Alkalosis results from a loss of acids or an accumulation of bases accompanied by a decrease in hydrogen

ion concentrations.

TYPES OF DISTRUBANCES

There Are Four Basic Types of Imbalance/Disturbances:

1. Respiratory Acidosis 2. Respiratory Alkalosis 3. Metabolic Acidosis 4. Metabolic Alkalosis

If PaCO2 primarily ↑, pH tends to be ↓— Respiratory Acidosis

If PaCO2 primarily ↓, pH tends to be ↑— Respiratory Alkalosis

If [HCO3-] primarily ↓, pH tends to be ↓— Metabolic Acidosis

If [HCO3-] primarily ↑, pH tends to be ↑— Metabolic Alkalosis

Respiratory Acidosis

Respiratory acidosis is a condition in which a build-up of carbon dioxide in the blood produces a shift in the body's pH balance and causes the body's system to become more acidic.

This condition is brought about by a problem either involving the lungs and respiratory system or signals from the brain that control breathing.

There is primary increase in Pco2 with compensatory increase in HCO3 −; pH usually low but may be near normal. (Ventilatory failure; Respiratory failure; Acidosis – respiratory)

Mechanism:

Carbon dioxide is produced constantly as the body burns energy, and this CO2 will accumulate

rapidly if the lungs do not adequately dispel it through alveolar ventilation.

Alveolar hypoventilation thus leads to an increased PaCO2 (called Hypercapnia). The increase in PaCO2 in turn decreases the HCO3−/PaCO2 ratio and decreases pH resulting respiratory acidosis.

Types of Respiratory Acidosis:

1- Acute Respiratory Acidosis

2- Chronic Respiratory Acidosis

1. Acute Respiratory Acidosis:

Acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range

(over 6.3 kPa or 47 mm Hg) with an accompanying Acidemia (pH <7.35).

Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by:

Depression of the central respiratory center by cerebral disease or drugs. Inability to ventilate adequately due to neuromuscular disease (e.g., myasthenia

gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, muscular dystrophy). Airway obstruction related to asthma or chronic obstructive pulmonary disease

(COPD) exacerbation.

2. Chronic Respiratory Acidosis:

Chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference

range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO3− >30 mm Hg).

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves multiple mechanisms, including

Decreased responsiveness to hypoxia and Hypercapnia Increased ventilation-perfusion mismatch leading to increased dead space ventilation Decreased diaphragm function secondary to fatigue and hyperinflatio

Chronic respiratory acidosis also may be secondary to: Obesity hypoventilation syndrome (i.e., Pickwickian syndrome) Neuromuscular disorders such as amyotrophic lateral sclerosis Severe restrictive ventilatory defects as observed in interstitial fibrosis and thoracic

deformities

Causes:

Hypoventilation

Diseases of the airways (such as asthma and chronic obstructive lung disease), which send air

into and out of the lungs

Diseases of the chest (such as scoliosis), which make the lungs less efficient at filling and

emptying

Diseases affecting the nerves and muscles that "signal" the lungs to inflate or deflate

Drugs that suppress breathing (including powerful pain medicines, such as narcotics, and

"downers," such as benzodiazepines), especially when combined with alcohol

Severe obesity, which restricts how many the lungs, can expand.

Signs and Symptoms:

Sign And Symptoms of Respiratory Acidosis

Central Nervous System Respiratory System Cardiovascular System

Mild and moderate Hypercapnia

Cerebral Vasodilatation

Increased Intracranial Pressure

Headache Confusion Hallucinations Transient Psychosis Myoclonic Jerks Flapping Tremor

Severe Hypercapnia Stupor Coma Constricted Pupils Depressed Tendon

Reflexes Extensor Plantar

Response Seizures

Breathlessness Central and Peripheral

Cyanosis Pulmonary Hypertension

Mild to moderate Hypercapnia Warm and Flushed

skin Bounding Pulse Well maintained

Cardiac output and blood pressure

Diaphoresis Severe Hypercapnia

Cor Pulmonale Decreased Cardiac

output Systemic Hypotension Cardiac Arrhythmias Pre-renal Azotemia Peripheral Edema

Papilledema

Compensation:

Problem: Increase pCO2 and these results in a decrease blood pH (high H+) [H+] stimulates kidney to generate and retain bicarbonate

Respiratory acidosis is compensated for by the development of a metabolic alkalosis

Compensation is complete ([HCO3] levels out) in 2-4 days

Final HCO3 can be calculated from the following equation: HCO3 mmol/L = 0.44 X pCO2 mmHg + 7.6 (+/-2).

Limit of compensation is a HCO3 of 45 mmol/L

Alteration of Metabolism and Function:

• Also include dysfunction of cardiovascular system and CNS.

• Respiratory acidosis usually has more profound impacts on CNS than metabolic acidosis with the

same plasma pH

– CO2 readily across blood-brain-barrier, and elevated level of CO2 can make

vasodilatation of cerebral blood vessel→↑ cerebral blood volume and intracranial

pressure

– HCO3- is water-soluble, and cannot pass through blood-brain-barrier as easy as CO2→ the

pH value of cerebrospinal fluid in respiratory acidosis is usually lower than that of

metabolic acidosis

RESPIRATORY ALKALOSIS

Respiratory alkalosis is a condition where the amount of carbon dioxide found in the blood drops to a

level below normal range. This condition produces a shift in the body's pH balance and causes the body's

system to become more alkaline (basic). This condition is brought on by rapid, deep breathing called

hyperventilation. There is a primary decrease in Pco2 with or without compensatory decrease in HCO3 −

pH high or near normal. (Alkalosis – respiratory)

Mechanism:

Respiratory alkalosis generally occurs when some stimulus makes a person hyperventilate. The increased

breathing produces increased alveolar respiration, expelling CO2 from the circulation. This alters the

dynamic chemical equilibrium of carbon dioxide in the circulatory system, and the system reacts

according to Le Chatelier's principle. Circulating hydrogen ions and bicarbonate are shifted through the

carbonic acid (H2CO3) intermediate to make more CO2 via the enzyme carbonic anhydrase .The net

result of this is decreased circulating hydrogen ion concentration, and thus increased pH (alkalosis). There

is also a decrease in ionized blood calcium concentration.

Types of Respiratory Alkalosis:

1. Acute Respiratory Alkalosis: It occurs rapidly. During acute respiratory alkalosis, the person may lose consciousness where the rate of

ventilation will resume to normal.

2. Chronic Respiratory Alkalosis: It is a more long-standing condition. For every 10 mM drop in pCO2 in blood, there is a corresponding 5 mM of bicarbonate

ion drop. The drop of 5 mM of bicarbonate ion is a compensation effect which reduces the alkalosis effect of the drop in pCO2 in blood. This is termed metabolic compensation.

Causes:

Hyperventilation

Intracerebral hemorrhage, meningitis, stroke Salicylate and Progesterone drug usage Anxiety, hysteria, stress and pain Cirrhosis of the liver Sepsis Elevated body temperature sexual activity, which may induce excessive breathing due to excitation Hypoxia

Any lung disease that leads to shortness of breath can also cause respiratory alkalosis.

Sign and Symptoms:

SIGN AND SYMPTOMS OF RESPIRATORY ALKALOSIS

Central Nervous System Cardiovascular System Neuromuscular System

Cerebral vasoconstriction Reduction in intracranial

pressure Light-headedness Confusion Increased deep tendon

reflexes Generalized seizures

Chest oppression Angina pectoris Ischemic

electrocardiographic changes Normal or decreased blood

pressure Cardiac arrhythmias Peripheral vasoconstriction

Numbness and paresthesias

of the extremities Circumoral numbness Laryngeal spasm Manifestations of tetany

Muscle cramps Carpopedal spasm Trousseau’s sign

Chvostek’s sign

Compensation:

Problem: decrease pCO2 causing increase blood pH (low H+) Increase pH stimulates the kidney to excrete bicarbonate

o respiratory alkalosis is compensated for by the development of a metabolic acidosis If the condition has been present for 7 days or more full compensation may occur. Compensation is complete ([HCO3] levels out) in 7-10 days. The limit of compensation is a HCO3 of 12 mmol/L

Alteration of Metabolism and Function:

• Similar to that of metabolic alkalosis

• Respiratory alkalosis usually has more profound impacts on CNS than metabolic alkalosis with the same plasma pH

– The decrease in CO2 content of blood causes constriction of cerebral blood vessel→↓

cerebral blood volume and regional cerebral ischemia

METABOLIC ACIDOSIS

Metabolic acidosis results from all conditions that decrease the pH of the body fluids below 7.35, with the exception of conditions resulting from altered function of the respiratory system.

Mechanism:

As hydrogen ions accumulate in the body fluids, buffers first resist a decline in pH. If the buffers cannot compensate for the increase in hydrogen ions, the respiratory center helps regulate the body fluid pH. The reduced pH stimulates the respiratory center, which causes hyperventilation. During hyperventilation, carbon dioxide is eliminated at a greater rate. The elimination of carbon dioxide also eliminates excess hydrogen ions and helps maintain the pH of the body fluids within a normal range.

If metabolic acidosis persists for many hours and if the kidneys are functional, the kidneys can also help compensate for metabolic acidosis. They begin to secrete hydrogen ions at a greater rate and increase the rate of bicarbonate ion reabsorption. Symptoms of metabolic acidosis appear if the respiratory and renal systems are not able to maintain the pH of the body fluids within its normal range.

Causes:

• Central change: ↓ [HCO3-]

1. Direct excessive loss of HCO3- :

i. Diarrhea, intestinal suction or intestinal or biliary fistula ii. Proximal renal tubular acidosis

a. caused by impaired reabsorption of HCO3- in the proximal tubule

iii. Treatment with carbonic anhydrase inhibitor 2. Indirect loss of HCO3

- for buffering increased nonvolatile acid i. Excessive intake of nonvolatile acid:

a. acetylsalicylic acid (aspirin) b. Methanol c. Ammonium chloride

ii. Excessive production of nonvolatile acid: a. Lactic acidosis

Hypoxia Shock, cardiac arrest, severe anemia, pulmonary edema, carbon

monoxide poisoning Severe liver dysfunction

b. Ketoacidosis Diabetes alcoholism Fasting and starvation

iii. Decreased renal excretion of acid: a. Renal dysfunction b. Distal renal tubular acidosis caused by reduced H+ secretion in the distal nephron

Types of Metabolic Acidosis:

1. Increased AG type Caused by increased nonvolatile acids, but the fixed acids containing chloride are

excluded.

2. Normal AG type Direct loss of HCO3-

Excessive intake of acidic salt containing chloride

Sign And Symptoms:

SIGNS AND SYMPTOMS OF METABOLIC ACIDOSIS

Respiratory

System

Cardiovascular

System

Metabolism Central

Nervous

System

Skeleton

Respiratory distress and dyspnea

Decreased strength of respiratory muscles and promotion of muscle fatigue

Impairment of cardiac contractility, arteriolar dilation, vasoconstriction

Reductions in cardiac output, arterial blood pressure, and hepatic and renal blood flow

Sensitization to reentrant arrhythmias and reduction in threshold for ventricular fibrillation

Increased sympathetic discharge but attenuation of cardiovascular responsiveness to catecholamines

Increased metabolic demands

Insulin resistance

Inhibition of anaerobic glycolysis

Reduction in adenosine triphosphate synthesis

Hyperkalemia Increased

protein degradation

Impaired metabolism

Inhibition of cell volume regulation

Progressive obtundation

Coma

Osteomalacia Fractures

Compensation: Blood buffering:

Increased H+ is combined immediately by the base salt of bicarbonate and non-bicarbonate buffer system

H++HCO3-→H2CO3→CO2+H2O

Respiratory regulation: ↑[H+] → stimulate peripheral chemoreceptor in carotid and aortic body → respiratory center

excitation → hyperpnea →↑CO2 elimination and ↓PaCO2 → [HCO3-] /[H2CO3] near 20/1 → pH

is maintained i.e. pH 7.4→7.0,

o alveolar ventilation 4L/min→30L/min

Intracellular buffering: ↑ [H+] in ECF→ H+ move in cells through H+-K+ exchange and K+ move out of cells→

hyperkalemia is resulted in

Renal regulation: ↑ [H+] in ECF→ ↑activity of carbonic anhydrase, H+-ATPase and glutaminase

– ↑Renal tubular secretion of H+ – ↑Renal tubular reaborption of HCO3

- – ↑Renal tubular secretion of ammonia (3-5days)

Alteration of Metabolism and Function:

1. Cardiovascular System: Effects of acidosis on myocardial contractility:

a. H+ inhibits cardiac contractility i. Competitively inhibits Ca2+ combine with troponin in myocardial excitation-

contraction coupling process ii. Inhibits Ca2+ influx across the cell membrane

b. When pH = 7.2, above two opposite effect nearly equal→ no marked change of myocardial contractility

c. When pH < 7.2, the heart less responsive to catecholamine →↓myocardial contractility

Effect of acidosis on vascular system: a. H+ dilates capacitance and resistance vasculature, plus the impaired cardiac

contractility, hypotension commonly occurs. Arrhythmia

2. CNS: Depression Manifestation: weakness, Conscious disturbance, stupor, lethargy and even coma. Mechanism:

i. Acidosis make elevated activity of glutamate decarboxylase→↑gamma-amino butyric acid (GABA) production, an inhibitive neurotransmitter

ii. Acidosis makes decreased activity of biological oxidases in

mitochondria→↓ATP production in brain.

METABOLIC ALKOLOSIS

Metabolic alkalosis refers to primary increase in plasma HCO3- concentration, the pH tends to be

increased.

Causes:

Central change: ↑ [HCO3-]:

• Excessive gain of HCO3- :

Excessive ingestion of NaHCO3 Infusion of large amounts of stocked blood (full of citrate)

• Excessive loss of H+ : excessive loss of H+ via stomach

o Vomiting, gastric suction excessive loss of H+ via kidney

o Aldosteronism(↑ADS), cushing’s syndrome (↑glucocorticoid) o Thiazide and loop diuretics

hypokalemia

• Volume contraction: Volume contraction→plasma HCO3

- concentrated → contraction alkalosis Loss of body fluid Diuretic therapy

Sign and Symptoms:

SIGNS AND SYMPTOMS OF METABOLIC

Central

Nervous System

Headache, Lethargy, Stupor Delirium, Tetany, Seizures Potentiation of hepatic encephalopathy

Cardiovascular System

Supraventricular and ventricular arrhythmias Potentiation of digitalis toxicity Positive inotropic ventricular effect

Respiratory System Hypoventilation with attendant Hypercapnia and hypoxemia

Neuromuscular System

Chvostek’s sign, Trousseau’s sign Weakness (severity depends on degree of potassium depletion)

Metabolic Effects

Increased organic acid and ammonia production Hypokalemia, Hypocalcemia, Hypomagnesemia Hypophosphatemia

Renal (Associated Potassium Depletion)

Polyuria, Polydipsia Urinary concentration defect Cortical and medullary renal cysts

Compensation:

• Blood buffering – During metabolic alkalosis, ↓[H+]ECF and ↑ [OH-]ECF→ OH- can be buffered by weak

acids, such as H2CO3→↑ [HCO3-]

• Ion exchange between intra- and extra-cell – In alkalosis, ↓[H+]ECF →through H+- K+ exchange, H+ shift out of cells and K+shift into

cells→hypokalemia

• Respiratory regulation – ↓[H+] →inhibition of respiratory center →↓alveolar ventilation→ ↑PaCO2 or [H2CO3] →

[HCO3-]/ [H2CO3] approach 20/1

– Respiratory regulation is limited and seldom make complete compensation • ↓Alveolar ventilation → ↑ PaCO2 →but when PaCO2 >60mmHg, respiratory

center is excited→respiration deepen and quicken→↑CO2 expiration

so compensatory limit of secondary increase of PaCO2 is 55mmHg

• Renal regulation – ↓[H+] → ↓the activity of carbonic anhydrase and glutaminase in renal tubular cell → ↓

renal secretion of H+ and ammonia, ↓renal reabsorption of HCO3- →↓ [HCO3- ] in plasma→ [HCO3

-]/ [H2CO3] approach 20/1 – The increased renal excretion of HCO3- peaks at 3-5 days, so this regulation is not useful

for acute metabolic alkalosis.

Alteration of Metabolism and Function:

• Mild metabolic alkalosis—asymptomatic or manifestation unrelated with alkalosis • Severe metabolic alkalosis—many alterations of metabolism and function

1. Dysfunction of CNS: Hyperexcitability Manifestation: Dysphoria, mental confusion Mechanism:

– ↑pH→↑the activity of gamma-aminobutyric acid transaminase (↑decomposition of GABA) and ↓the activity of glutamate decarboxylase (↓production of GABA)→↓GABA( a inhibitory neurotransmitter) → hyperexcitability of CNS

– ↑pH→ left-shift of oxygen-Hb dissociation→cerebral hypoxia

2. Left-shift of oxygen-Hb dissociation: Left-shift of oxygen-Hb dissociation curve→ O2 saturation of Hb increase at

the same PaO2→releasing of O2 bound by Hb in tissue decrease → tissue hypoxia is resulted in.

3. Hypocalcemia:

Manifestation: tetany, carpopedal spasm, convulsion Mechnism:

o Free Ca2++ abumin combined ca2+ 4. Hypokalemia:

Mechanism o alkalosis→H+ shift out of cells and K+ shift into cells through H+-K+

exchange o alkalosis→↓renal excretion of H+ and ↑renal excretion of K+

References:

1- http://www.mhhe.com/biosci/ap/foxhumphys/student/olc/u-reading5.html

2- http://www.authorstream.com/Presentation/ADahal-400878-respiratory-acidosis-alkalosis-

education-ppt-powerpoint/ 3- file:///C:/Users/Nayyab/Downloads/Documents/adk1_06.pdf