1 ACID BASE BALANCE OR Homeostasis of Blood pH OR Regulation of Blood pH Dr Anissa Atif Mirza

2 Synopsis Introduction Sources of Acids and Bases in bodyWhat is Acid Base Balance? Mechanisms Regulating Blood pH. Significance of Maintaining Acid Base Balance Acid Base Imbalance and their conditions. Diagnostic Tests

3 Introduction Acid Base Balance is a physiological and biochemical mechanism associated to body/blood pH.

4 What Is pH? pH is a Hydrogen ion concentration. pH = - log [H+] Different compartment of human body has specific pH. pH has role in Enzyme activity.

5 Why blood pH is Altered?

6 Addition of various acids or alkalies by metabolic activities alters body/blood pH.

7 Sources and Types of Acids and Alkalies Added During Metabolic Life Processes

8 Acids are H+ donors. Bases are H+ acceptors, or give up OH- in solution.

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10 Acids and Bases can be strong or weak:A strong acid or base is one that dissociates completely in a solution - HCl, NaOH, and H2SO4 A weak acid or base is one that dissociates partially in a solution -H2CO3, C3H6O3, and CH2O, Lactate.

11 Acidic Substances of body:Carbonic acid(H2CO3) Phosphoric acid( H3PO4) Sulphuric acid (H2SO4) Organic Acids: Lactate, Acetoactate, Pyruvate Alkaline Substances of body: Citrate Bicarbonates.

12 What is Acid Base Balance?

13 Homeostatic Mechanisms That Regulate Blood/Body pH

14 Acid Base balance is a homeostatic mechanismCarried out to regulate the altered pH of blood and other body compartments to its normal constant range.

15 Maintenance of Acid Base balanceIs a prime requisite to maintain normal healthy and active life.

16 Acid-Base Balance It is the regulation of HYDROGEN ions.(The more Hydrogen ions, the more acidic the solution and the LOWER the pH) The acidity or alkalinity of a solution is measured as pH 16

17 Acid Base Balance Regulates pH Why it is Very Essential To Regulate pH?

18 pH of blood and other body compartments are precisely regulated.pH is always tried to be maintained to its normal constant range.

19 Acid Base Balance maintains the blood pH at normal constant narrow range of 7.35-7.45.

20 pH of the medium directly affects the enzyme activitiesOptimum pH is an essential requisite for enzyme activities and normal metabolism.

21 It is prerequisite for regulating blood/body pH:To maintain normal/optimal Enzyme activities Normal metabolism Normal Coordination Normal Health

22 Factors Regulating Acid Base Balance

23 Acid Base Balance is Regulated ByFirst Line of Defense Blood Buffer System Second Line of Defense Respiratory Mechanism Third Line of Defense Renal Mechanism

24 Chemical Buffers React very rapidly (less than a second) 2) Respiratory Regulation Reacts rapidly (seconds to minutes) 3) Renal Regulation Reacts slowly (minutes to hours)

25 Role of Blood Buffer SystemFirst line of defense in mechanism of Acid Base Balance. Acids (H+) added are neutralized by the salt part of buffer.

26 Extracellular BuffersBicarbonate Buffer NaHCO3/H2CO3 (20:1 at 7.4 pH) Phosphate Buffer Na2HPO4/NaH2PO4 (4:1 at 7.4 pH) Protein Buffer Na-Protein/H-Protein

27 Intracellular BuffersBicarbonate Buffer KHCO3/H2CO3 Phosphate Buffer K2HPO4/KH2PO4 Protein Buffer K-Hb/H-Protein

28 Mechanism Action of Buffer SystemsBuffers mixture of weak acids and its salts Resist change in pH of blood when small amount of acids or alkalis added to the medium.

29 Buffers act quickly but not permanently

30 Bicarbonate Buffer System Respiratory Buffer SystemAcid - Base balance is primarily concerned with Bicarbonate Buffer mechanism : H2CO3/ Hydrogen (H+) Bicarbonate (HCO3- ) (Alkali Reserve) H+ HCO3-

31 Bicarbonate Buffer Bicarbonate Buffer- Chief Buffer system of Blood.NaHCO3 the salt part of buffer neutralizes the strong and non volatile acids added to blood. It constitutes Alkali reserve(HCO3-)

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33 Bicarbonate Buffer HCl + NaHCO3 ↔ H2CO3 + NaClSodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) Maintain a 20:1 ratio : HCO3- : H2CO3 HCl + NaHCO3 ↔ H2CO3 + NaCl NaOH + H2CO3 ↔ NaHCO3 + H2O

34 Action of Bicarbonate (NaHCO3) converts strong dissociable acid into weak non dissociable acid (H2CO3) and a neutral salt without altering the pH.

35 Weak acid H2CO3 formed during buffering action of Bicarbonate buffer is then expired out by Lungs.Thus Bicarbonate buffer is connected to the respiratory system Bicarbonate buffer is also termed as Respiratory buffer.

36 Alkali reserve is represented by the concentration of NaHCO3 in the blood.Alkali reserve concentration(HCO3-) determines the strength of buffering action towards added H+ ions by acids. More the concentration of Alkali reserve ,more is the buffering action and vice a versa.

37 The blood buffers are effective as long asThe acid load added is not very high and The alkali reserve (HCO3 -) is not exhausted.

38 Phosphate Buffer/Urine BufferNa2HPO4/NaH2PO4 (4:1 at 7.4 pH) H+ + HPO42- ↔ H2PO4- OH- + H2PO4- ↔ H2O + H2PO42-

39 Phosphate Buffer MechanismWhen H+ ions added they are neutralized/fixed by Na2HPO4 (Alkaline Phosphate) and converted to NaH2PO4 (Acid Phosphates). These acid phosphates then excreted out through kidneys as acidic urine.

40 Thus Phosphate Buffer is connected to Excretory system .Phosphate Buffer also termed as Urine Buffer.

41 When an alkali enters it is buffered by the acid phosphate NaH2PO4 which converted to Na2HPO4 alkaline phosphate. Excreted in urine making it alkaline urine.

42 Protein Buffers Includes hemoglobin, work in blood. Carboxyl group gives up H+ Amino Group accepts H+ The Imidazole group of Histidine present in Hb structure has buffering capacity.

43 Role of Respiratory MechanismsRespiratory system plays second line of defense mechanism of Acid Base Balance. Role of respiration in acid base balance is short term regulatory process.

44 H2CO3 formed from Bicarbonate Buffer, is exhaled out through respiratory system.Increased H2CO3 stimulates the respiratory centre in Medulla Oblongata. This in turn stimulates hyperventilation which promptly removes H2CO3 from blood by expiration.

45 Exhalation of H2CO3 is as carbon dioxide by activity of enzyme Carbonic Anhydrase of Lungs.H+ + HCO3- ↔ H2CO3 ↔ CO2 + H20

46 Respiratory mechanism is powerful, but only works with volatile acids.Doesn’t affect fixed acids like lactic acid.

47 Blood pH can be adjusted through respiratory mechanismBy changing rate and depth of breathing.

48 Low H2CO3 concentration in blood depresses respiratory centre ,causes hypoventilation i.e slow and shallow respiration. This retains H2CO3 in blood.

49 If Nervous centre / Respiratory system fails.Acid Base Balance fails.

50 Generation of bicarbonate by RBCLACK OF AEROBIC ACTIVITY,DIFFUSION OF CARBONDIOXIDE,H+ BUFFERED BY HHb.

51 Events in lungs and tissueHCO3- HCO3- HHb HHb O2 O2 H+ H+ H2CO3 HbO2 HbO2 H2CO3 H2O CO2 H2O CO2 Isohydric transport of co2 EXPIRED AIR METABOLISM

52 Role of Renal MechanismRenal mechanism is the third line of defense mechanism. Role of renal mechanism is long term regulatory process.

53 The acid and alkaline phosphates formed during phosphate buffering mechanism are filtered from blood and excreted out through urine. Thus the phosphate buffer system is directly connected to renal mechanism.

54 Renal mechanism conserve and produce Bicarbonate ions ( Alkali reserve).Renal Mechanism is the most effective regulator of blood pH. If kidneys fail, pH balance fails.

55 Renal System maintains Acid Base Balance through:Reabsorption of Bicarbonate (HCO3-) ions. Excretion of H+ ions Excretion of titrable acids(Acid Phosphates) Excretion of Ammonium ions (Glutaminase activity)

56 REABSORPTION OF BICARBONATE~Conservation of Bicarbonate ~Urine is free of HCO3- ~Simultaneous excretion of H+

57 EXCRETION OF TITRABLE ACIDS~measure of acid excreated by kidney ~no. of millilitres of N/10 NaOH required to titrate 1 litre of urine to pH 7.4 ~role of phosphate buffer

58 Excretion Of H+ ions ~Elimination of nonvolatile acid ~Excretion of H+~Occurs in PCT ~Regeneration of bicarbonate ~H+ combine with non carbonate base and excreated

59 EXCRETION OF AMMONIUM IONNH3 is obtained from Deamination of Glutamine NH4+ cant diffuse back 2/3 of body acid load liberated in the form of NH4+

60 Rates of correction Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days

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64 MECHANISM FOR REGULATION OF ACID BASE BALANCEBuffer system: temporary solution Respiratory mechanism provide short time regulation Renal mechanism : permanent solution Urine pH < plasma pH , Eliminate nonvolatile acid, buffered by cation (principally Na+) Maintain alkali reserve

65 Acid Base Imbalance OR Conditions Of Acid Base Disturbances

66 The Body and pH Homeostasis of blood pH is tightly controlled by mechanisms of Acid Base Balance. Extracellular fluid = 7.4 Blood pH regulated to = 7.35 – 7.45

67 Occurrence of Acid Base ImbalanceWhen Factors involved in homeostatic mechanisms to regulate Acid Base Balance fails to work efficiently. Does not maintain the altered pH of blood to normal constant range. Results into Acid Base Imbalance.

68 Two major disturbances in Acid-Base balance Acidosis Alkalosis

69 Conditions Of Acid Base ImbalanceAcidosis /Acidemia ( Decreased pH/Increased H+ ions) Alkalosis/Alkalemia (Increased pH/Decreased H+ ions)

70 Acidosis (Acidemia) below 7.35Alkalosis (Alkalemia) above 7.45 Blood pH < 6.8 or > 8.0 death occurs

71 ACIDOSIS / ALKALOSIS AlkalosisA condition in which the blood has too much acid (or too little base), frequently resulting in a decrease in blood pH. Alkalosis A condition in which the blood has too much base (or too little acid), occasionally resulting in an increase in blood pH.

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75 Effect of Altered pH Altered pH may seriously disturbs the vital processes. Might lead to fatality.

76 Most enzymes function only with narrow pH ranges.Extremes of pH affects the enzymatic action by protonation or deprotonation at the active sites of Enzymes. Makes Enzymes inactive.

77 Inactivated Enzymes affect metabolic reactions and metabolic pathways.Metabolism gets deranged . Leads to metabolic syndromes.

78 pH Excitability pH ExcitabilitypH also affect excitability of Nerve and Muscle cells pH Excitability pH Excitability

79 ACID-BASE REGULATION Enzymes, Hormones and ion distribution are all affected by Hydrogen ion concentrations

80 ACIDOSIS / ALKALOSIS pH changes have dramatic effects on normal cell function 1) Changes in excitability of nerve and muscle cells 2) Influences Enzyme activity 3) Influences K+ levels/Retention of K+

81 CHANGES IN CELL EXCITABILITYpH decrease (more acidic) depresses the central nervous system Can lead to loss of consciousness pH increase (more basic)causes over excitability of nervous system. Tingling sensations, nervousness, muscle twitches

82 INFLUENCES ON ENZYME ACTIVITYpH increases or decreases can alter the shape of the enzyme rendering it non-functional Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell

83 INFLUENCES ON K+ LEVELSIf H+ concentrations are high (acidosis) than H+ is secreted in greater amounts This leaves less K+ than usual excreted. The resultant K+ retention can affect cardiac function and other systems K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+ Na+ H+ H+ H+ H+ H+ H+ H+

84 Small changes in pH can produce major disturbancesAcid-base balance can also affect Electrolytes (Na+, K+, Cl-) Can also affect Hormones

85 ACID-BASE IMBALANCE Derangements of Hydrogen/Carbonic acid (H+/H2CO3)Bicarbonate (HCO3-) concentrations In body fluids are common in conditions of Acid Base Imbalance

86 Acid-Base Imbalances pH< 7.35 Acidosis pH > 7.45 Alkalosis

87 4 Types of Primary Acid-Base DisordersAcid Base Imbalances Biochemical Change Respiratory Acidosis Increased H2CO3 Respiratory Alkalosis Decreased H2CO3 Metabolic Acidosis Metabolic Alkalosis

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90 RESPIRATORY ACIDOSIS

91 Primary Carbonic acid excess Increased H2CO3/Increased pCO2 Respiratory Acidosis Primary Carbonic acid excess Increased H2CO3/Increased pCO2 Defect in respiratory centre of brain Defect in respiratory organ system Decreased elimination of H2CO3 by the lungs. Hypoventilation

92 Increased blood levels of CO2 above 45 mm Hg.Hypercapnia – high levels of pCO2 in blood

93 RESPIRATORY ACIDOSIS Respiratory acidosis develops when the lungs don't expel CO2 adequately. This can happen in diseases that severely affect the lungs.

94 Chronic conditions: Depression of respiratory center in brain that controls breathing rate – drugs or head trauma Paralysis of respiratory or chest muscles Emphysema Asthma Pneumonia Pulmonary edema Obstruction of respiratory tract Congestive Cardiac Failure

95 HYPOVENTILATION Causes Respiratory AcidosisHypo = “Under” Elimination of CO2 H+ pH

96 : RESPIRATORY ACIDOSIS 2 20CO2 CO2 HCO3- CO2 CO2 H2CO3 : 2 20 breathing is suppressed holding CO2 in body pH = 7.1

97 RESPIRATORY ACIDOSIS 1) Obstruction of air passagesVomit, Anaphylaxis, Tracheal Cancer

98 RESPIRATORY ACIDOSIS Drug overdose 2) Decreased RespirationShallow, slow breathing Depression of the respiratory centers in the brain which control breathing rates Drug overdose

99 RESPIRATORY ACIDOSIS Left lung collapsed 4) Collapse of lungCompression injury, open thoracic wound Left lung collapsed

100 Respiratory Acidosis Acute conditions: Adult Respiratory Distress Syndrome Pulmonary edema Pneumothorax

101 Compensation for Respiratory AcidosisKidneys eliminate hydrogen ion and retain bicarbonate ions.

102 Signs and Symptoms of Respiratory AcidosisBreathlessness Restlessness Lethargy and disorientation Tremors, convulsions, coma Respiratory rate rapid, then gradually depressed Skin warm and flushed due to vasodilation caused by excess CO2

103 Treatment of Respiratory AcidosisRestore ventilation IV lactate solution Treat underlying dysfunction or disease

104 RESPIRATORY ALKALOSIS

105 Respiratory AlkalosisPrimary Carbonic acid deficit Decreased H2CO3 pCO2 less than 35 mm Hg (hypocapnea) Most common acid-base imbalance Primary cause is hyperventilation Washes out excessive quantity of H2CO3 through expiration process of lungs.

106 Stimulation of respiratory centre in brainHyperventilation

107 Respiratory AlkalosisConditions that stimulate respiratory center: Oxygen deficiency at high altitudes Pulmonary disease and Congestive heart failure – caused by hypoxia Respiratory center lesions Acute anxiety Fever, anemia Early salicylate intoxication Cirrhosis Gram-negative sepsis/Meningitis

108 RESPIRATORY ALKALOSISAnxiety is an emotional disturbance The most common cause of hyperventilation, and thus respiratory alkalosis, is noted in anxiety

109 RESPIRATORY ALKALOSISRespiratory center lesions Damage to brain centers responsible for monitoring breathing rates Tumors Strokes

110 RESPIRATORY ALKALOSISHigh Altitude Low concentrations of O2 in the arterial blood reflexly stimulates ventilation in an attempt to obtain more O2 Too much CO2 is “blown off” in the process

111 RESPIRATORY ALKALOSISFever Rapid shallow breathing blows off too much CO2

112 RESPIRATORY ALKALOSISSalicylate poisoning (Aspirin overdose) Ventilation is stimulated without regard to the status of O2, CO2 or H+ in the body fluids

113 RESPIRATORY ALKALOSISKidneys compensate by: Retaining hydrogen ions Increasing bicarbonate excretion HCO3- HCO3- H+ H+ HCO3- HCO3- H+ H+ H+ HCO3- H+ HCO3- HCO3- H+ HCO3- H+ HCO3- H+ H+ HCO3- H+

114 HYPERVENTILATION Causes Respiratory AlkalosisHyper = “Over” Elimination of CO2 H+ pH

115 Compensation of Respiratory AlkalosisIf kidneys are functioning normal The conditions of respiratory acidosis or alkalosis are compensated. Kidneys conserve hydrogen ion Excrete bicarbonate ion

116 Treatment of Respiratory AlkalosisTreat underlying cause Breathe into a paper bag IV Chloride containing solution Cl- ions replace lost bicarbonate ions

117 METABOLIC ACIDOSIS

118 Metabolic Acidosis Primary Alkali deficitBicarbonate deficit - blood concentrations of bicarbonate drop below 22mEq/L Causes: Loss of bicarbonate through diarrhea or renal dysfunction. Overproduction production of acids (lactic acid or ketones) Failure of kidneys to excrete H+

119 = 7.4 = 7.4 : : METABOLIC ACIDOSIS 1 20 1 10Occurs when there is a decrease in the normal 20:1 ratio Decrease in blood pH and bicarbonate level Excessive H+ or decreased HCO3- H2CO3 HCO3- 1 20 : = 7.4 H2CO3 HCO3- 1 10 : = 7.4

120 METABOLIC ACIDOSIS Any acid-base imbalance not attributable to CO2 is classified as metabolic Metabolic production of Acids Or loss of Bases

121 METABOLIC ACIDOSIS The causes of metabolic acidosis can be grouped into five major categories 1) Ingesting an acid or a substance that is metabolized to acid 2) Abnormal Metabolism 3) Kidney Insufficiencies 4) Strenuous Exercise 5) Severe Diarrhea

122 METABOLIC ACIDOSIS 1) Ingesting An AcidMost substances that cause acidosis when ingested are considered poisonous Examples include wood alcohol (methanol) and antifreeze (ethylene glycol) However, even an overdose of aspirin (acetylsalicylic acid) can cause metabolic acidosis

123 METABOLIC ACIDOSIS 2) Abnormal MetabolismThe body can produce excess acid as a result of several diseases Ketoacidosis Type I Diabetes Mellitus Uncontrolled Diabetes mellitus Prolonged Starvation Lacticacidosis Shock Haemorrhage Violent Exercise-

124 METABOLIC ACIDOSIS Unregulated diabetes mellitus causes ketoacidosisBody metabolizes fat rather than glucose Accumulations of metabolic acids (Keto Acids) cause an increase in plasma H+

125 METABOLIC ACIDOSIS 3) Kidney InsufficienciesThis type of kidney malfunction is called renal tubular acidosis or uremic acidosis and may occur in people with kidney failure or with abnormalities that affect the kidneys' ability to excrete acid

126 METABOLIC ACIDOSIS 3) Kidney InsufficienciesKidneys may be unable to rid the plasma of even the normal amounts of H+ generated from metabolic acids Kidneys may be also unable to conserve an adequate amount of HCO3- to buffer the normal acid load

127 METABOLIC ACIDOSIS C6H12O6 2C3H6O3 + ATP (energy)4) Strenuous Exercise Muscles resort to anaerobic glycolysis during strenuous exercise Anaerobic respiration leads to the production of large amounts of lactic acid Enzymes C6H12O6 2C3H6O3 + ATP (energy) Lactic Acid

128 METABOLIC ACIDOSIS 5) Severe DiarrheaFluids rich in HCO3- are released and reabsorbed during the digestive process During diarrhea this HCO3- is lost from the body rather than reabsorbed

129 METABOLIC ACIDOSIS 5) Severe DiarrheaThe loss of HCO3- without a corresponding loss of H+ lowers the pH Less HCO3- is available for buffering H+ Prolonged deep (from duodenum) vomiting can result in the same situation

130 Symptoms of Metabolic AcidosisHeadache, lethargy Nausea, vomiting, diarrhea Coma Death

131 Compensation for Metabolic AcidosisIncreased ventilation. Renal excretion of hydrogen ions if possible. K+ exchanges with excess H+ in ECF. H+ into cells, K+ out of cells.

132 Treatment of Metabolic AcidosisIV lactate solution

133 METABOLIC ALKALOSIS

134 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 Cushings Syndrome Prolonged exposure to x rays and UV rays

135 7.4 METABOLIC ALKALOSIS Elevation of pH due to an increased 20:1 ratioMay be caused by: An increase of bicarbonate A decrease in hydrogen ions Imbalance again cannot be due to CO2 Increase in pH which has a non-respiratory origin 7.4

136 METABOLIC ALKALOSIS Can be the result of:1) Ingestion of Alkaline Substances 2) Vomiting ( loss of HCl )

137 METABOLIC ALKALOSIS Baking soda (NaHCO3) often used as a remedy for gastric hyperacidity NaHCO3 dissociates to Na+ and HCO3-

138 Compensation for Metabolic AlkalosisAlkalosis most commonly occurs with renal dysfunction, so can’t count on kidneys. Respiratory compensation difficult – hypoventilation limited by hypoxia.

139 Symptoms of Metabolic AlkalosisRespiration slow and shallow Hyperactive reflexes ; tetany Often related to depletion of electrolytes Atrial tachycardia Dysrhythmias

140 Treatment of Metabolic AlkalosisElectrolytes to replace those lost IV chloride containing solution Treat underlying disorder

141 Severe acidosis causesPrincipal effect of acidosis is depression of the CNS through ↓ in synaptic transmission. Generalized weakness Deranged CNS function the greatest threat Severe acidosis causes Disorientation Coma Death

142 Severe Alkalosis causes :Alkalosis causes over excitability of the central and peripheral nervous systems. Numbness Light headedness Severe Alkalosis causes : Nervousness muscle spasms or Tetany Convulsions Loss of consciousness Death

143 Compensation Of Acid Base ImbalanceThe body response to acid-base imbalance is called compensation May be complete compensation if altered pH brought back within normal limits Partial compensation if pH range is still outside norms. Uncompensated if pH range is very out from norms.

144 If underlying problem is respiratory, renal mechanisms can bring about metabolic compensation.If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation.

145 ACIDOSIS respiratory acidosis metabolic acidosis decreased removal ofCO2 from lungs failure of kidneys to excrete acids metabolic acid production of keto acids absorption of metabolic acids from GI tract prolonged diarrhea accumulation of CO2 in blood accumulation of CO2 in blood accumulation of acid in blood accumulation of acid in blood excessive loss of NaHCO3 from blood excessive loss of NaHCO3 from blood deep vomiting from GI tract respiratory acidosis metabolic acidosis increase in plasma H+ concentration kidney disease (uremia) depression of nervous system

146 ALKALOSIS metabolic respiratory alkalosis alkalosis anxiety overdoseof certain drugs high altitudes prolonged vomiting ingestion of excessive alkaline drugs excess aldosterone hyperventilation loss of CO2 and H2CO2 from blood hyperventilation loss of CO2 and H2CO2 from blood loss of acid loss of acid accumulation of base accumulation of base metabolic alkalosis respiratory alkalosis decrease in plasma H+ concentration overexcitability of nervous system

147 Organ dysfunction And Acid Base ImbalanceCNS – respiratory acidosis (suppression) and alkalosis (stimulation) Pulmonary – respiratory acidosis (COPD) and alkalosis (hypoxia, pulmonary embolism) Cardiac – respiratory alkalosis, respiratory acidosis, metabolic acidosis (pulmonary edema) GIT – metabolic alkalosis (vomiting) and acidosis (diarrhea) Liver – respiratory alkalosis, metabolic acidosis (liver failure) Kidney – metabolic acidosis (RTA) and alkalosis (1st Aldosterone)

148 Organ Dysfunction Endocrine Drugs/toxinsDiabetes mellitus – metabolic acidosis Addisons Disease/Adrenal insufficiency – metabolic acidosis.(Decreased H+ ions excretion) Cushing’s Syndrome – metabolic alkalosis (Increased Cortisol- Increased H+ ions excretion) Primary aldosteronism – metabolic alkalosis Drugs/toxins Toxic alcohols – metabolic acidosis ASA/Aspirin – metabolic acidosis and respiratory alkalosis( Causes Hyperventilation) Theophylline overdose – respiratory alkalosis

149 ACID – BASE DISORDERS Clinical State Acid-Base DisorderPulmonary Embolus Respiratory Alkalosis Cirrhosis Pregnancy Diuretic Use Metabolic Alkalosis Vomiting Chronic Obstructive Pulmonary Disease Respiratory Acidosis Shock Metabolic Acidosis Severe Diarrhea Renal Failure Sepsis (Bloodstream Infection) Respiratory Alkalosis, Metabolic Acidosis

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151 Anion Gap

152 Sum of anion and cations is always equalSodium and Potassium accounts for 95% of cations Chloride and bicarbonate accounts for 68% of anions There is difference between measured anion and cation The unmeasured anions constitute the ANION GAP.

153 They are protein anions ,sulphates ,phosphates and organic acid(Unmeasured Anions)AG can be calculated as (Na+ + K+)—(HCO3- + Cl-) High anion gap acidosis: renal failure, DM Normal anion gap acidosis: diarrhea Hyperchloremic acidosis

154 Calculation Of Anion GapNa ++ K+ = Cl- + HCO3 - + A- = A- = 15 mEq/L

155 Normal AG is typically 12 ± 4 mEq/L.If AG is calculated using K+, the normal AG is 16 ± 4 mEq/L

156 Significance of Anion Gap CalculationCalculation of Anion gap and its values help in diagnosing conditions of Acid Base Balance and Imbalance.

157 Diabetic Ketoacidosis Renal FailureThe anion gap is increased in conditions such as metabolic acidosis: That result from elevated levels of metabolic acids (metabolic acidosis) Lactic acidosis Diabetic Ketoacidosis Renal Failure

158 A low anion gap occurs in conditions that cause a fall in unmeasured anions(primarily albumin) OR a rise in unmeasured cations

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160 Calculate the Anion Gap1. Calculate the anion gap as described. 2. An anion gap ,over 25 suggests a severe metabolic acidosis. 3. Causes of an high anion gap: ethylene glycol, lactic acid, methanol, paraldehyde, aspirin, renal failure, ketoacidosis (diabetic or ethanol).

161 Anion Gap Acidosis: Anion gap >12 mmol/L; caused by a decrease in [HCO3 -] Balanced by an increase in an unmeasured acid ion from either endogenous production or exogenous ingestion (normochloremic acidosis).

162 Metabolic Acidosis and the Anion gap2. Increased gap 1. Normal gap 1.  Acid prod 2.  Acid elimination Renal “HCO3” losses 2. GI “HCO3” losses Lactate DKA Ketosis Toxins Alcohols Salicylates Iron Renal disease Proximal RTA Distal RTA Diarrhea

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164 Henderson Hasselbalch EquationpH= pka +log [HCO3-]/[H2CO3] At pH 7.4 the ratio of HCO3-/H2CO3 is 1:20. A buffer is most effective when pH=pKa When concentration of salt and acid are equal.

165 Significance of Henderson Hasselbalch EquationThe equation helps in calculating pH of Buffers. The equation helps in assessing status of Acid Base balance.

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

167 DIAGNOSTIC LAB VALUES & INTERPRETATION

168 Arterial Blood Gas(ABG )Analyzer determines Acid Base Balance and Imbalance.

169 Diagnosis of Acid-Base ImbalancesNote whether the pH is low (acidosis) or high (alkalosis) Decide which value, pCO2 or HCO3- , is outside the normal range If the cause is a change in pCO2,/H2CO3 the problem is respiratory. If the change is in HCO3- the problem is metabolic.

170 Normal Arterial Blood Gas (ABG) Lab Values:Arterial pH: 7.35 – 7.45 HCO3-: 22 – 26 mEq/L PCO2: 35 – 45 mmHg TCO2: 23 – 27 mmol/L PO2: 80 – 100 mmHg Base Excess: -2 to +2 Anion Gap: 12 – 14 mEq/L

171 Example A patient is in intensive care because he suffered a severe myocardial infarction 3 days ago. The lab reports the following values from an arterial blood sample: pH 7.3 HCO3- = 20 mEq / L ( ) pCO2 = 32 mm Hg ( )

172 Diagnosis Metabolic acidosis With compensation

173 Questions Long Essays. What is acid-base balance? Describe the homeostatic mechanism by which the blood pH is regulated. Short Notes Blood Buffer System. Role of Kidney in acid-base balance. Hb as Buffer system. Acid-Base imbalance. Metabolic Acidosis. Difference between acidosis & alkalosis. Anion Gap.

174 END ACID - BASE BALANCE THANKS

175 THANK YOU