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WATER AND ACID BASE BALANCE

WATER

1. Give an account of water distribution and its balance in the body.2. Water toxicity.3. Describe the rennin-angitensin - aldosterone system and its importance. Pon. May 201Water distribution

1. Body maintains a nearly constant amount of water that is approximately 50% to 60% of body weight in adults and 75% of body weight in children.

2. 60% of the total body water is intracellular and 40% extracellular.3. The extracellular water includes the fluid in plasma (blood after the cells have been removed) and

interstitial water (the fluid in the tissue spaces, lying between cells). 4. Transcellular includes gastrointestinal secretions, urine, sweat, and fluid that has leaked through

capillary walls because increased hydrostatic pressure or inflammation.Water Balance:Intake: 2500 ml/day

1. Exogenous water: Ingested water and beverages, water content of solid foods constitute the exogenous source of water.

2. Endogenous water: The metabolic water produced within the body is the endogenous water. This water (300-350 ml/day) is derived from the oxidation of foodstuffs. On an average/ about 125 ml of water is generated for 1,000 Cal consumed by the body.

Output: 2500 ml/day1. Urine : In a healthy individual, the urine output is about l-2 l/day2. Lung: During respiration about 400 ml/day is lost through the expired air. 3. Skin: About 450 ml/dayis lost through skin as sweat. The loss of water by perspiration (via skin) and

respiration (via lungs) is collectively referred to as insensible water loss.4. Fecal: A bout 150 ml/day is lost through feces in a healthy individual

Water toxicity: Overhydration1. Overhydration or water intoxication is caused by excessive retention of water in the body. 2. This may occur due to excessive intake of large volumes of salt free fluids, renal failure, overproduction of

ADH etc. Overhydration is observed after major trauma or operation, lung infections etc.3. Water intoxication is associated with dilution of ECF and ICF with a decrease in osmolality. The clinical

symptoms include headache, lethargy and convulsions. The treatment advocated is stoppage of water

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intake and administration of hypertonic saline.

ACID BASE BALANCEQuestions:

1. What is the normal pH? How is regulated? Write in detail about the Renal Mechanism of regulation of pH. Pon May 2009

2. What is the normal pH of the blood? Explain how kidney regulates acid base balance. Write a note on metabolic acidosis. Pon Nov 2010

3. What is the normal pH of blood? Explain the different mechanisms involved in the maintenance of acid base balance. Pon Nov 2011

4. Describe the different mechanisms by which human body regulates pH of blood. Pon May 20135. What is normal pH of blood? Explain the various a mechanism by which normal pH of blood is maintained. Feb

20056. What is normal blood pH? Write a note on blood buffers. What is the acid base status respiratory acidosis and

how it is compensated by the buffers. April 1999.7. Write in detail diagrammatically the reaction mechanisms by which HCO3 is reclaimed and regenerated in

kidneys. What is meant by metabolic acidosis and how it is compensated: March 20028. Write how acid base balance is maintained in the body. Mention causes and biochemical alterations of

metabolic acidosis. Oct 20039. Discuss the regulation of blood pH. April 199410. Write in detail diagrammatically the reaction mechanisms by which HCO3 is reclaimed and regenerated in

kidneys. What is meant by metabolic acidosis and how it is compensated? March 200211. Write how acid base balance is maintained in the body. Mention causes and biochemical alterations of

metabolic acidosis. Oct 200312. What is normal blood pH? Write a note on blood buffers. What is the acid base status in respiratory acidosis

and how it is compensated by the buffers? April 1999Short notes:

1. Lactic acidosis - Nov 19932. Metabolic acidosis- Nov 1994; April 1995; Feb 2006; Aug 2007; April 2001; April 1998; April 20003. Respiratory acidosis- Nov 19954. Anion gap and its diagnostic importance. August 20055. Role of kidneys in acid base balance – April 20016. Write the difference between metabolic and respiratory acidosis. April 20007. S.N: Write briefly on maintenance of pH of blood. Oct 998. S.N: Definition, expression and significance of Km value. Oct 20039. Discuss the role of kidney in acid base balance. Pon Nov 2007

Introduction:1. Normal pH of blood is 7.4 (7.35 to 7.45); the pH of interstitial fluid is 0.5 units below that of plasma.

1. <7.3 is acidosis; <7 is incompatible with life.2. >7.5 is alkalosis and >7.8 is incompatible with life.

2. Functions of hydrogen ions:1. Difference in H+ concentration acts as a driving force for oxidative phosphorylation in

mitochondria2. Provides Surface charge and structure of proteins 3. Helps ionization of week acids and facilitates their physiological functions.

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3. Normal Acid and base production during metabolic activities:

Acid Source

H2Co3 Cellular oxidation.

Sulphuric acid Oxidation of sulphur of ingested proteins

Phosphoric acid Oxidation of phosphorus of ingested proteins, nucleoproteins and phospholipids.

Lactate and keto acids Normal metabolic activities

Basic substances food which is alkaline in nature

4. Definitions:1. Acids: proton donors; an acid is defined as any compound, which forms hydrogen ions in

solution.2. Base: Proton acceptors; A base is a compound that combines with hydrogen ions in solution.3. Week acid and base: ionize incompletely in solutions4. Strong acid and base: ionize completely in solutions5. Dissociation constant (Ka): the ratio between dissociated (H+ and A-) and un dissociated

substance (HA) is a constant at equilibrium. The pH at which the acid is half ionized is called pKa.

a. Ka = [H+] [A-] i. [HA]

6. pH is the negative of the logarithm of hydrogen ion concentration: 7 is neutral pH.1. pH = 1

7. log [H+]8. Henderson – Hasselbalch equation:

pH = pKa + log [base] [acid]

REGULATION OF BLOOD PHNormal pH

1. The normal pH of the blood is maintained in the narrow range of 7,35-7.45, i.e. slightly alkaline. 2. <7.3 is acidosis; <7 is incompatible with life. >7.5 is alkalosis and >7.8 is incompatible with life.

Buffers:The body has developed three lines of defense to regulate the body's acid-base balance and maintain the blood pH (around 7.4).

(1) Blood buffers(2) Respiratory mechanism(3) Renal mechanism.

BLOOD BUFFERS:1) A buffer may be defined as a solution of a weak acid (HA) and its salt (BA) with a strong base. The buffer

resists the change in pH by the addition of acid or alkali and the buffering capacity is dependent on the

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absolute concentration of salt and acid.2) The blood contains 3 buffer systems.

(1) Bicarbonate buffer(2) Phosphate buffer(3) Protein buffer

Bicarbonate buffer system: (1) Sodium bicarbonate and carbonica cid (NaHCO3- H2CO3) is the most predominant huffer system of

the extracellular fluid, particularly the plasma. Carbonic acid dissociates into hydrogen and bicarbonate ions.

H2Co3 H+ + HCo3-

(2) Henderson-Hasselbalch equation for bicarbonate buffer is:

(3) As per this equation, pH is dependent on ratio of the concentration of the base, HCO3 to acid H2CO3. (a) The plasma bicarbonate (HCO3) conceritration is around24 mmol. Carbonic acid is a solution of

CO2 in water. (b) lts concentratioins given by the product of pco2 (arterial partial pressure of CO2 = 49 mm Hg) and

the solubility constant of CO2 (0.03). Thus H2CO3 = 40 x 0.03 = 1.2 mmol/L. (c) Substituting the values (blood p H = 7.4; pKa for H2CO3 = 6.1; HCO3 = 24 mmol/l; H2CO3 = 1.2

mmol/L, in the above equation7.4 = 6.1 + log 24 1.2 = 6.1 + log 20

= 6.1 + 1.3 = 7.4

(4) lt is evident that at a blood pH 7.4, the ratio of bicarbonate to carbonic acid is 20 : 1. Thus, the bicarbonate concentration is much higher (20 times) than carbonic acid in the blood. This is referred to as alkali reserve and is responsible for the effective buffering of H+ ions, generated in the body.

Phosphate buffer system: 1. Sodium dihydrogen phosphate and disodium hydrogen phosphate ( NaH2POa- Na2HPOa)

constitute the phosphate buffer. lt is mostly an intracellular buffer and is of less importance in plasma due to its low concentration.

2. With a pK of 6.8, the phosphate buffer would have been more effective, had it been present in high concentration. lt is estimated that the ratio of base to acid for phosphate buffer is 4 compared to 20 for bicarbonate buffer.

Protein buffer system: 1) The plasma proteins and hemoglobin together constitute the protein buffer system of the blood. The

buffering capacity of proteins is dependent on the pK of ionizable groups of amino acids. The imidazole group of histidine (pK = 6.7) is the most effective contributor of protein buffers. The plasma proteins account for about 2% of the total buffering capacity of the plasma.

2) Hemoglobin of RBC is also an important buffer. lt mainly buffers the fixed acids, besides being involved in the transport of gases (O2 and CO2).

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RESPIRATORY MECHANISM FOR PH REGULATION:1) Respiratory system provides a rapid mechanism for the maintenance of acid-base balance. This is

achieved by regulating the concentration of carbonic acid (H2CO3) in the blood i.e. the denominator in the bicarbonate buffer system.

2) The large volumes of CO2 produced by the cellular metabolic activity endanger the acid base equilibrium of the body. But in normal circumstances, all of this CO2 is eliminated from the body in the expired air via the lungs, as summarized below.

Carbonica nhydraseH2CO3 --------------------- CO2+ H2O.

3) The rate of respiration (or the rate of removal of CO2) is controlled by a respiratory centre, located in the medulla of the brain. This centre is highly sensitive to changes in the pH of blood. Any decrease in blood pH causes hyperventilation to blow off CO2, thereby reducing the H2CO3 concentration. Simultaneously the H+ ions are eliminated as H20. Respiratory control of blood pH is rapid but only a short term regulatory process, since hyperventilation cannot proceed for long.

4) Hemoglobin as a buffer : a. Hemoglobin is also important in the respiratory regulation of pH. At the tissue level,

hemoglobin binds to H+ ions and helps to transport CO2 as HCO2 with a minimum change in pH (referred to as isohydric transport).

b. ln the lungs, as hemoglobin combines with 02, H+ ions are removed which combine with HCO3 to form H2CO3.The latter dissociates to release CO2 to be exhaled. The plasma CO2 diffuses into the RBC along the concentration gradient where it combines with water to form H2CO3. This reaction is catalysed by carbonic anhydrase (alsocalled carbonate dehydratase).

c. In the RBC, H2CO3 dissociates to produce H+ and HCO3 . The H+ ions are trapped and buffered by hemoglobin. As the concentration of HCO3 increases in the RBC, it diffuses into plasma along with the concentration gradient, in exchange for Cl- ions, to maintain electrical neutrality. This phenomenon, referred to as chloride shift, helps to generate HCO3.

RENAL MECHANISM FOR PH REGULATION:1. The renal mechanism tries to provide a permanent solution to the acid-base disturbances. This is in

contrast to a short term respiratory mechanism. 2. The kidneys regulate the blood pH by maintaining the alkali reserve, besides excreting or reabsorbing

the acidic or basic substances.3. The pH of urine is acidic (-6.0). The H+ ions generated in the body are eliminated by acidified urine.

Carbonic anhydrase and renal regulation of pH: 1. The enzyme carbonic anhydrase is of central importance in the renal regulation of pH which occurs by

the following mechanisms.i. Excret ion of H+ ions

ii. Reabsorption of bicarbonateiii. Excretion of titratable acidiv. Excretion of ammonium ions.

2. Excretion of H+ ions: Carbonic anhydrase catalyses the production of carbonic acid (H2CO3) from CO2 and H2O in the renal tubular cell. H2CO3 then dissociates to H+ and HCO3. The H+ ions are secreted into the tubular lumen in exchange for Na+. The Na+ in association with HCO3 is reabsorbed into the blood. This is an effective mechanism to eliminate acids (H+) from the body with a simultaneous

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generation of HCO3.3. Reabsorption of bicarbonate: Bicarbonate freely diffuses from the plasma into the tubular lumen.

Here HCO3 combines with H+, secreted by tubular cells, to form H2CO3. H2CO3 is then cleaved by carbonic anhydrase (of tubular cell membrane) to form CO2 and H2O. CO2 diffuses into the tubular cells along the concentration gradient. In the tubular cell, CO2 again combines with H2O to form H2CO3 which then dissociates into H+ and HCO3. The H+ is secreted into the lumen in exchangef or Na+. The HCO3 is reabsorbed into plasma in association with Na+.

4. Ex cr et io n

of titratable acid:Titratable acidity refers to the number of milliliters of N/ l0 NaOH required to titrate 1 liter of urine to pH 7.4. Titratable acidity reflects the H+ ions excreted into urine which resulted in a fall of pH from 7.4 (that of blood). The excreted H+ ions are actually buffered in the urine by phosphate buffer.

5. Excretion of ammonium ions: This is another mechanism to buffer H+ ions secreted into the tubular fluid. The H+ ion combines with NH3 to form ammonium ion (NH4+). The renal tubular cells deaminate glutamine to glutamate and NH3. This reaction is catalysed by the enzyme glutaminase. The NH3, liberated in this reaction, diffuses into the tubular lumen where it combines with H+ to form NH4. Ammonium ions cannot diffuse back into tubular cells and, therefore, are excreted into urine. Renal regulation via NH4, excretion is very effective to eliminate large quantities of acids produced in the body.

6. Carbon dioxide-the central molecule of ph regulation: CO2 is of central importance in the acid-base balance of the body. lt has the ability to combine with H2O to from H2CO3 which can dissociate to HCO3 and H+.

Buffers of intracellular fluids: The H+ ions generated in the cells are exchanged for Na+ and K+ ions. This is particularly observed in skeletal muscle which reduces the potential danger of H+ accumulation in the cells.

ACID BASE DISTURBANCES (Acidosis and alkalosis)

1. Body maintains pH in a very range around 7.4 and life is impossible beyond the range of 7 to 7.6. 2. Classification of acid base disturbances:

a. Acidosis-a decline in blood pH

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i. Metabolic acidosis-due to a decrease in bicarbonate.ii. Respiratory acidosis-due to an increase in carbonic acid.

b. Alkalosis-a rise in blood pHi. Metabolic alkalosis-due to an increase in bicarbonate.

ii. Respiratory alkalosis-due to a decrease in carbonic acid.c. Mixed type of disordersd. Compensated states: in real clinical conditions a person will be in different states of

compensation by altering pCo2 and bicarbonate levels through various mechanisms.i. uncompensated

ii. partially compensatediii. Fully compensated

3. The terms acidemia and alkalemia, respectively, refer to an increase or a decrease in H+ ion concentration in blood. They are not commonly used.

4. ANION GAPa. The total concentration of cations and anions (expressed as mEq/l) is equal in the body fluids. This

is required to maintain electrical neutrality. b. The commonly measured electrolytes in the plasma are Na+, K+, Cl- and HCO3. Na+ and K+

together constitute about 95% of the plasma cations. Cl- and HCO3 are the major anions, contributing to about 80% of the plasma anions.

c. The remaining 20% of plasma anions (not normally measured in the laboratory) include proteins, phosphate, sulfate, urate and organic acids.

d. Anion gap is defined as the difference between the total concentration of measured cations (Na+ and K+) and that of measured anion (Cl- and HCOj).

e. The anion gap (A-) represents the unmeasured anions in the plasma which may be calculated by substituting the normal concentration of electrolytes (mEq/l).

Na++ K+ = Cl- + HCO- + A- (anion gap) 136+4 = 100+25 + A- (15 mEq/l)

f. The anion gap in a healthy individual is around 15 meq/l (range 8-18 meo/l). Acid-base disorders are often associated with alterations in the anion gap.

g. Metabolic acidosis may exist with high or normal anion gap depending on clinical state. Classification by Anion Gap

a. 'High anion gap metabolic acidosis'b. 'Normal anion gap metabolic acidosis'

METABOLIC ACIDOSIS: 1. Definition: It refers to primary deficit of bicarbonate due to accumulation of acid metabolites or

depletion of bicarbonate due to buffering.2. Causes:

1. Diabetes mellitus (ketoacidosis)a. Renal failureb. Lactic acidosisc. Severe diarrhead. Renal tubular acidosis

2. Metabolic acidosis is due to an excessive production of organic acids which combine with NaHCO3 and deplete the alkali reserve.

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NaHCO3 + Organic acids --- Na salts of organic acids + CO23. Metabolic acidosis is commonly seen in severe uncontrolled diabetes mellitus which is

associated with excessive production of acetoacetic acid and b-hydroxybutyric acid (both are organic acids).

4. Anion gap and metabolic acidosis : a. Increased production and accumulation of organic acids causes an elevation in the anion gap.

This type of picture is seen in metabolic acidosis associated with diabetes (ketoacidosis). b. High Anion Gap Metabolic Acidosis:

i. Renal failure: The excretion of H+ as well as generation of bicarbonate are both deficient.

ii. Diabetic ketoacidosisiii. Alcoholic ketoacidosis iv. Starvation ketoacidosisv. Lactic acidosis: Normal lactic acid content in plasma is less than 2 mmol/L. It is

increased in tissue hypoxia, circulatory failure, and intake of biguanides. Lactic acidosis causes a raised anion gap.

c. Normal Anion Gap Metabolic Acidosis:vi. When there is a loss of both anions and cations, the anion gap is normal, but

acidosis may prevail.vii. Diarrhea: Loss of intestinal secretions lead to acidosis. Bicarbonate, sodium and

potassiumare lost.viii. Renal tubular acidosis may be due to failure to excrete acid or reabsorb

bicarbonate.d. Decreased Anion Gap is Seen in

ix. Hypoalbuminemiax. Multiple myeloma (paraproteinemia)

xi. Bromide intoxicationxii. Hypercalcemia

5. Major Effects of a Metabolic Acidosis1. Respiratory Effects

1. Hyperventilation ( Kussmaul respirations) - this is the compensatory response2. Shift of oxyhaemoglobin dissociation curve (ODC) to the right3. Decreased 2,3 DPG levels in red cells (shifting the ODC back to the left)

2. Cardiovascular Effects1. Depression of myocardial contractility2. Sympathetic over activity 3. Peripheral arteriolar vasodilatation4. Effects of hyperkalaemia on heart

3. Other Effectsa. Increased bone resorption (chronic acidosis only)b. Shift of K+ out of cells causing hyperkalaemia

6. Compensation:1. Respiratory:

i) Compensation for a metabolic acidosis is hyperventilation to decrease the arterial pCO2.called Kussmaul’s respiration.

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ii) Maximal compensation takes in 12 to 24 hours2. Renal:

i) In metabolic acidosis renal compensation occurs slowly by excreting NH4+ ions and generation of new bicarbonate; This usually occurs as a consequence of an increase in ammonium excretion.

7. Laboratory values:Stage pH HCO3 PaCO2 RatioMetabolic acidosis Low Low N <20Uncompensated Low Low N <20Partially compensated Low Low Low <20Fully compensated N Low Low 205. Treatment: This is done by giving bicarbonate which is calculated on the basis of deficit:

Sodium bicarbonate in mEq= body wt in Kg X 0.2 – base excess in mEq/L

METABOLIC ALKALOSIS:1. When acid is lost or base is gained bicarbonate level increases and this is called metabolic

alkalosis.2. Causes of loss of acid:

a. Loss of HCL from stomach leading to hypochloremic alkalosis in :a. Severe vomiting when gastric HCL is lost; b. Gastric aspiration for therapeutic reasons

b. hyperaldosteronisma. There is retention of sodium and loss of potassium leadind to

hypokalemia. b. The increased aldosterone levels lead to increased distal tubular Na+

reabsorption and increased K+ & H+ losses. c. The increased H+ loss is matched by increased amounts of renal

reabsorption of HCO3- . d. The net result is metabolic alkalosis with hypochloraemia and

hypokalaemia. e. Due to excess in H+ in urine the pH of urine remains acidic(Paradoxic

acidosis)c. Intake of alkali (milk alkali syndrome)d. Diuretic therapy

3. Types of Metabolic alkalosis:1. Chloride responsive: urinary chloride level is less than 10 mmol/l (as seen in vomiting ,

gastric aspiration and diuretic therapy) and responds to NaCl infusion.2. Choride resistant: urinary chloride level is more than 10 mmol / l (as seen in

hyperaldosteronism and hypertension) and does not respond to NaCl infusion.4. Complications:

1. decreased myocardial contractility 2. arrhythmias 3. decreased cerebral blood flow 4. confusion 5. mental obtundation

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6. neuromuscular excitability 5. Compensatory mechanisms:

1. Alkalosis depresses respiratory centre and the will be hypoventilation and retention of CO2 which will increase carbonic acid.

2. Kidneys conserve more H+ and excretes more HCO3- 3. Complete correction of acidosis will be effective only if hypokalemia is corrected and the

cause is treated.6. Management:

1. Correct cause 2. Correct the deficiency which is impairing renal bicarbonate excretion (ie give chloride, water

and K+)3. Expand ECF Volume with N/saline 4. Supportive measures: e.g. give O2 in view of hypoventilation; 5. Avoid hyperventilation as this worsens the alkalaemia

RESPIRATORY ACIDOSIS:1. Respiratory acidosis refers to primary increase in carbonic acid; arterial pCO2 is raised2. At onset, the acidosis is designated as an 'acute respiratory acidosis'. The body's initial

compensatory response is limited during this phase. 3. As the body's renal compensatory response increases over the next few days, the pH returns

towards the normal value and the condition is now a 'chronic respiratory acidosis'. 4. The differentiation between acute and chronic is determined by time but occurs because of the

renal compensatory response Causes of Respiratory Acidosis

1. Inadequate Alveolar Ventilation1. Central Respiratory Depression

a. CNS trauma,b. infarct,c. haemorrhage d. tumour

2. Drug depression of resp. centre a. opiates, b. sedatives,c. anaesthetics

3. Poliomyelitis4. Tetanus5. Cardiac arrest with cerebral hypoxia

2. Nerve or Muscle Disorders1. Guillain-Barre syndrome2. Myasthenia gravis3. Muscle relaxant drugs4. Toxins e.g. organophosphates, snake venom5. Various myopathies

3. Lung 1. Pulmonary oedema

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2. Adult respiratory distress syndrome4. Airway Disorders

1. Upper Airway obstruction2. Bronchospasm/Asthma

5. Over-production of Carbon Dioxide1. Malignant Hyperthermia

6. Increased Intake of Carbon Dioxide Compensation:

1. The compensatory response is a rise in the bicarbonate level (acute)1. immediate component which raises the bicarbonate slightly.2. delayed component where a further rise in plasma bicarbonate due to enhanced renal

retention of bicarbonate. (chronic)Buffering in Acute Respiratory Acidosis:

1. The compensatory response to an acute respiratory acidosis is limited to buffering. 2. Ninety-nine percent of the buffering of an acute respiratory acidosis occurs intracellularly.3. Proteins (especially haemoglobin in red cells) and phosphates are the most important

buffers 4. These take up the H+ produced from the dissociation of H2CO3.

Buffering in Chronic Respiratory Acidosis: 1. With continuation of the acidosis, the kidneys respond by retaining bicarbonate.2. The renal response in underway by 6 to 12 hours with a maximal effect reached by 3 to 4 days. 3. The response occurs because increased of intracellular pCO2 in proximal tubular cells and this

causes increased H+ secretion from the PCT cells into the tubular lumen.4. This results in:

1. increased HCO3 production 2. increased Na+ reabsorption 3. increased 'NH3' production to 'buffer' the H+ in the tubular lumen4. so urinary excretion of NH4Cl increases

1. In summary, the compensation for hypercapnia is: Acute: Buffering only and predominantly intracellular (99%) Chronic: Renal retention of bicarbonate (in addition to buffering) The pCO2 rapidly returns to normal with restoration of adequate alveolar ventilation

Treatment:1. Ventilation and O2 therapy2. Treat aetiology.

RESPIRATORY ALKALOSIS:Definition:

A respiratory alkalosis is a primary acid-base disorder in which arterial pCO2 falls to a level lower than expected.

A respiratory alkalosis is due to increased alveolar ventilation Causes of Respiratory Alkalosis

1. Central Causes Head Injury Stroke

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Anxiety-hyperventilation syndrome Increased intra cranial pressure (e.g. Brain tumour; head injury) Brain stem injury Septicaemia; meningitis

2. Drugs: salicylate intoxication3. Iatrogenic

Excessive controlled ventilationCompensation:

Compensation in an ACUTE Respiratory Alkalosis 1. The buffering is predominantly by protein and occurs intracellularly; 2. There is a drop in HCO3-

Compensation in a CHRONIC Respiratory Alkalosis 1. Renal loss of bicarbonate causes a further fall in plasma bicarbonate

Complications: Acute hypocapnia causes a reduction of serum levels of potassium and phosphate secondary to increased intracellular shifts of these ions. A reduction in free serum calcium also occurs. Calcium reduction is secondary to increased binding of calcium to serum albumin. Many of the symptoms present in persons with respiratory alkalosis are related to the hypocalcaemia.

Management:1. Respiratory alkalosis itself is rarely life threatening. Therefore, emergent treatment is usually not

indicated unless the pH level is greater than 7.5. Because respiratory alkalosis usually occurs in response to some stimulus, treatment is usually unsuccessful unless the stimulus is controlled.

2. In hyperventilation syndrome, patients benefit from reassurance, re breathing into a paper bag during acute episodes, and treatment for underlying psychological stress.

NORMAL SERUM ELECTROLYTES:pH: 7.4Bicarbonate: 22 to 26 mmol/lChloride: 96 to 106 mmol/lK: 3.5 to 5 mmo/lSodium: 136 to 145 mmol/lpCo2: 35 to 45 mm HgpO2: 80 to 100 mm of Hg

Measurement of acid base parameters1. Blood gas analyser : for pco2 and o2 from arterial blood samples2. Venous blood by titration method ; bicarbonate is estimated at pH 7.4 and from other electrolytes

value anion gap is calculated.LACTIC ACIDOSIS :

1. Lactic acidosis is a common cause of metabolic acidosis.

2. Each day the body has an excess production of about 1500 m.mols of lactate which enters the blood stream and is subsequently metabolised mostly in the liver.

3. Lactate is produced from pyruvate in a reaction catalysed by lactate dehydrogenase: Pyruvate + NADH + H+ <=> Lactate + NAD+

4. Lactate is metabolised predominantly in the liver (60%) and kidney (30%)6.

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5. Half is converted to glucose (gluconeogenesis) and half is further metabolised to CO2 and water in the citric acid cycle.

6. The result is no net production of H+ (or of the lactate anion) for excretion from the body. 7. Other tissues can use lactate as a substrate and oxidise it to CO2 and water but it is only the liver

and kidney that have the enzymes that can convert lactate to glucose.8. Mechanisms involved in Lactic Acidosis : Lactic acidosis can occur due to:

1. excessive tissue lactate production2. impaired hepatic metabolism of lactate

9. Causes of Lactic Acidosis

Classification of Some Causes of Lactic Acidosis (Cohen & Woods, 1976)

Type A Lactic Acidosis : Clinical Evidence of Inadequate Tissue Oxygen Delivery

Anaerobic muscular activity generalised convulsions Tissue hypoperfusion

o septic shocko cardiogenic or hypovolaemic shockhypotension;o cardiac arrest;o acute heart failure;

Reduced tissue oxygen delivery or utilisationo hypoxaemia,o carbon monoxide poisoning,

Type B Lactic Acidosis: No Clinical Evidence of Inadequate Tissue Oxygen Delivery

type B1 : Associated with underlying diseaseso ketoacidosis,o leukaemia,o lymphoma,o AIDS

type B2: Assoc with drugs & toxinso phenformin,o cyanide,o methanolo ethanol intoxication in chronic alcoholics,o anti-retroviral drugs

type B3: Assoc with inborn errors of metabolismo congenital forms of lactic acidosis with various enzyme defects eg pyruvate

dehydrogenase deficiency

DiagnosisThe condition is often suspected on the history and examination (eg shock, heart failure) and is confirmed and quantified by measuring the blood lactate level.

ManagementThe principles of management of patients with lactic acidosis are:

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1. Diagnose and correct the underlying condition 2. Restore adequate tissue oxygen delivery; restore adequate perfusion3. Avoid sodium bicarbonate (except possibly for treatment of associated severe hyper kalaemia)4. When the circulation is restored, the liver can metabolise the circulating lactate. 5. If lactic acidosis is severe and the cause cannot be corrected, the mortality can be quite high.