acidemia and its clinical effects

1. ACIDOSI
S
Dr NOOR UL AIN
PGR ANESTHESIA , SMCH

2. CONTENTS
– ACIDEMIA
– PHYSIOLOGICAL EFFECTS OF ACIDEMIA
– TYPES OF ACIDOSIS
METABOLIC ACIDOSIS :
1. ANION GAP
2. HIGH ANION GAP METABOLIC ACIDOSIS
3.NORMAL ANION GAP METABOLIC ACIDOSIS
4.TREATMENT
RESPIRATORY ACIDOSIS:
CAUSES
ACUTE AND CHRONIC TYPES
TREATMENT
ANESTHETIC CONSIDERATIONS

3. ACIDEMIA &ACIDOSIS
The term acidemia describes the state of low
blood ph (< 7.35)
Acidosis is used to describe the processes
that increases H+ and compensatory
physiological responses on arterial blood ph

5. Physiological effects of acidemia
Direct effect
1. H+ competitively
inhibits Ca2+ combine
with troponin in
myocardial excitation
contraction coupling
process
2. Inhibit Ca2+ influx
across membrane
3. Inhibit Ca2+ release
from SR
Inc. K = increases
depol & shortens
repol

6. Rapid , gasping and
very deep type of
labored breathing

8. THE EFFECT OF LOW PH ( INCREASED H+) ON HB
IS TO STABILIZE THE DEOXYGENATED FORM,
DECREASING ITS AFFINITY FOR OXYGEN
AS SOON AS OXYHAEMOGLOBIN RELEASES ITS OXYGEN CARGO ,THE PRESENCE OF A LOW PH LOCKS ITS IN AN
UNRECEPTIVE STATE PREVENTING IT FROM BINDING OXYGEN MOLECULES .
Histidine 146
Histidine 122
Salt
bridge
At physiological ph there is no bond
formation as there is no
protonation of side chain , if there is
no +ve charge obviously there can
be no interaction .

9. METABOLIC
THEORY OF
INTRINSIC
REGULATION OF
BLOOD FLOW
By local responses
from metabolites (
like lactic acid , H+,
CO2 ) these All
cause vasodilation .

13. Plasma K+
increases
0.6mEq/l
for each
0.10 dec
in ph
CO2 narcosis

17. METABOLIC ACIDOSIS
– Metabolic acidosis is defined as primary decrease in HCO3-
– A fall in plasma HCO3- without a proportionate reduction in PaCO2 decreases
arterial pH
– MECHANISMS:
1. consumption of HCO3- by a strong non volatile acid
2.renal or gastrointestinal wasting of bicarbonate
3.rapid dilution of extracellular fluid compartment with a bicarbonate free fluid

18. THE ANION GAP
– It is defined as
– Calculations : anion gap=(Na+)-(cl +HCO3-)
(140)-(104+24) = 12 mEq/l
Normal range =7-14 mEq/l
“The difference between the major measured
cations and the measured anions “
Anion gap= major plasma cations –major plasma
anions

19. Principle of electroneutrality
Therefore in reality, an anion gap cannot exist !
So,
anion gap= unmeasured anions –unmeasured cations
“ the sum of all the
anions must be equal
to the sum of all the
cations “
Unmeasured
cations
K+
Ca2+
Mg2+
+ Unmeasured
anions
Plasma
proteins
Phosphates
sulfates
-

20. – Plasma albumin normally accounts for the largest fraction of anion gap
=11mEq/l
– The anion gap decreases by 2.5 mEq/l for every 1g/dl reduction in plasma
albumin concentration
Increased anion gap
• Increase unmeasured anions
• Decrease unmeasured cations
Decreased anion gap
• Decrease unmeasured anions
• Increase unmeasured cations

21. – Other causes of changes in anion gap
High anion gap
Metabolic
alkalosis
Extracellular
volume
depletion
Increase
charge on
albumin
Compensatory
increase in
lactate
Low anion gap
Hypoalbuminemia
Bromide
/lithium
intoxication
Multiple
myeloma

22. CAUSES OF METABOLIC
ACIDOSIS
Increased anion gap
•Increased production of non volatile acids
•Ketoacidosis
•Lactic acidosis
•Non ketotic hyperosmolar coma
•Alcoholic
• decrease excretion of non volatile acid
•Renal failure
•Inborn error of metabolism
•Rhabdomyolysis
•Ingestion of toxins
Normal anion gap (hyperchloremic)
• Increase git loss of HCO3
• Diarrhea
• Fistula
• Increase renal loss of HCO3
• RTA
• Hypoaldosteronism
• Carbonic anhydrase inhibitors
• Dilutional
• TPN
• Large amout of bicarbonate free fluid
• Increase intake of chloride containing acids

24. HIGH ANION GAP METABOLIC
ACIDOSIS
– Metabolic acidosis with an increased anion gap (>30 mEq/l) is characterized by
an increase in relatively strong nonvolatile acids
Non volatile acids
Dissociate into H+ &
respective anion
H+ consume HCO3
to form CO2
Anions accumulate
and take HCO3 place
Increased anion gap

25. – 1. failure to excrete endogenous non volatile acids
- These are eliminated by the kidneys in the urine
- GFR below 20 ml /min ( renal failure ) results in accumulation of these acids
2. Increased endogenous non volatile acid production
- Lactic acidosis
- Ketoacidosis
- Inborn errors of metabolism

26. LACTIC ACIDOSIS
– Lactic acid accumulates in body causing acidosis
– Lactic acid is the end product of anerobic metabolism of glucose (glycolysis)
– Lactate Level normally is 0.3-1.3 m Eq/l

27. KETOACIDOSIS
– CAUSES :
– 1. lack of insulin resulting in hyperglycemia
– 2. accumulation of beta hydroxybutyric & acetoacetic acid
– 3. starvation
– 4. alcoholic binges
– 5.NKHOC

30. INBORN ERRORS OF
METABOLISM
– 1. MAPLE SYRUP URINE DISEASE
– 2. METHYMALONIC ACIDURIA
– 3. PROPIONIC ACIDEMIA
– 4. ISOVALERIC ACIDEMIA

31. – 3. INGESTION OF EXOGENOUS NONVOLATILE ACIDS
– salicylic acid & other acid intermediates
1 . They rapidly accumulate& produce a high anion gap acidosis
2. they produce direct respiratory stimulation
3 . most adults develop mixed metabolic acidosis with superimposed respiratory
alkalosis
– Methyl alcohol
– Methanol formic acid
Alcohol
dehdrogenase

32. – It causes visual disturbance ( retinitis)
– Ethylene glycol :
Ethylene glycol glycolic acid
oxalic acid
deposited in the renal tubule
renal failure
Alcohol
dehydrogenase

33. NORMAL ANION GAP
METABOLIC ACIDOSIS
– Metabolic acidosis associated with a normal anion gap is typically characterized
by hyperchloremia.
Plasma Cl- increases to take place of HCO3- which is lost
Calculation :
Urine anion gap= (Na+K) – CL-
Normally urine anion gap is positive or close to zero
1.Principal unmeasured
urinary cation =NH4
2.NH4 increases along
with Cl ( negative urinary
anion gap)
3. Impairment of NH4
secretion causes +ve gap

34. INCREASED GIT LOSS OF
HCO3
– 1. diarrhea : diarrheal fluid contains 20-50 mEq/l of HCO3
– Small bowel ,biliary , pancreatic fluids are rich . Loss of these fluids lead to
hyperchloremic metabolic acidosis
– 2. ureterosigmoidostomies & ileal loops obstruction also leads to
hyperchloremic metabolic acidosis
– 3. ingestion of chloride containing anion exchange resins (cholestyramin). They
bind bicarbonate ions
– 4. large amount of calcium or magnesium chloride result in absorption of Cl
and loss of bicarbonate ions .they form insoluble salts with bicarbonate ion .

35. Increased renal loss of HCO3
– Faiure to reabsorb HCO3 or to secrete adequate amount of H in the form of
titrable acid orammonium ion
– This can be present in
– 1. due to carbonic anhydrase inhibitor ; acetazolamide
– 2. renal tubular acidosis
– RENAL TUBULAR ACIDOSIS
It comprises of a groupof nonazotemic defects of H+
secretion by the renal tubules resulting in urinary ph
too high for systemic acidemia

36. – These defects may be due to
– 1. primary renal defect
– 2. secondary to a systemic disorder
– Site : it may be
– 1. distal renal tube – type 1
– 2. proximal renal tbule – type 2
– Type 4 renal tubular acisosis = hyporeninemic hypoaldosteronism

37. TYPE 1 DISTAL RTA
-The defect occurs at a site after most of the
HCO3 has been reclaimed
-- failure to acidify urine
-The net acid excretion is less than the net
production
-Associated with :
-1. hypokalemia
-2. demineralization of bone
-3. nephrolithiasis
-4. nephrocalcinosis
-Treatment = alkali therapy NaHCO3 1-3
mEq/kg/d
TYPE 2 PROXMIAL RTA
-Less common type
-Defective H + secretion result in massive
wasting od HCO3
-Defect in reabsorption of other substances
also occur
-1. glucose
-2. amino acids
-3. phosphates
-It results in volume depletion and
hypokalemia
-Treatment = alkali 10-25 mEq/kg/day
-Pottasium supplements

39. OTHER CAUSES
– 1. DILUTIONAL HYERCHLOREMIC ACIDOSIS
– It occurs when extracellular volume is rapidly expanded by administrating
bicarbonate free fluid –e.g NaCl
– The plasma HCO3 decreases in proportion to amount of fluid infused
– 2. PARENTERAL HYPERALIMENTATION
– Amino acid infusions contains organic cations in excess to orgnic anions
– They produce hyperchloremic acidosis because Cl is anion for cationic amino acids
– 3. EXCESSIVE QUANTITIES OF CHLORIDE CONTAINING ACIDS
– Ammonium choride
– Arginine hydrochloride

40. Treatment of metabolic acidosis
– 1.correction of respiratory component of acidemia
– Ventilation should be controlled
– Achieve paCO2 level to 30
– 2. alkali therapy NaHCO3 (7.5% solution ) if ph remains below than 7.2
Amount is decided
– 1. fixed dose = 1mEq/kg
– 2. derived from base excess ( bicarbonate space )

41. – NaHCO3 produces CO2 that readily enters cells and bicarbonate ions does not
so buffers which donot produce CO2 are preferable
– 1. carbicarb
– 2. tromethamine THAM
3. acute hemodialysis with a bicarbonate dialysate = in profound or refractory
acidemia

42. – Therapy fro DKA :
– 1. replacement of fluid deficit
– 2. replacement of insulin, potassium ,phosphate and magnesium
– THERAPY FOR LACTIC ACIDOSIS
– 1. adequate oxygenation and tissue perfusion
– Alkalinization of urine increases salicyclates excretion
– ETHANOL INTOXICATION :
– Ethanol infusion
– Fomepizole administration
– Hemodialysis /hemofiltration

43. BICARBONATE SPACE
– “it is defined as the volume to which HCO3- will distribute when it is given
intravenously “
– It should equal the extracellular fluid space but it is 25- 60 % of body weight
– Depends on:
– 1. severity of acidosis
– 2. duration of acidosis
– NaHCO3 = BD x bicarbonate space x body weight in l
– 50 % of the calculated dose is given only & blood gas is measured

45. RESPIRATORY ACIDOSIS
– It is defined as
– EQUATION :
– H2O + CO2 H2CO3 H+ + HCO3-
– Increase in PaCO2 increase in H+ decrease in arterial ph
– HCO3- is minimally affected
Primary increase in paCO2 levels

46. – Paco2 represents the balance between CO2 production and elimination
– PaCO2 = CO2 production / alveolar ventilation
– CO2 is byproduct of fat and carbohydrate metabolism
– Excess CO2 production is influenced by
– 1.muscle activity
– 2. body temperature
– 3. thyroid hormone activity

47. causes of respiratory acidosis

49. ACUTE RESPIRATORY
ACIDOSIS
– The compensatory response to acute (6-12 h)elevatios in paCO2 is limited
– Buffering is provided by :
– 1.haemoglobin
– 2. exchange of H+ forNa+ & K+from bone and intracellular fluid compartment
– The renal response is very limited
– Plasma bicarb increases 1mEq/l for each 10 mmhg increase in PaCO2 above 40
mmHg

50. CHRONIC RESPIRATORY
ACIDOSIS
– Renal compensation is appreciable only after 12- 24 h and may not peak until
3-5 days
Plasma HCO3 increases 4mEq/l for each 10mmHg increase in PaCO2 above 40
mmHG

51. TREATMENT
– It is treated by reversing the imbalance between CO2 production and alveolar ventilation
– 1. by increasing / improving alveolar ventilation :
– 1.bronchodilation
– 2. reversal of narcosis
– Diuresis
– 2, reducing CO2 :
– 1. DANTROLENE for malignant hyperthermia
– 2.muscle paralysis for tetanus
– 3.antithyroid medication for thyroid storm
– 4. reduced caloric intake while on TPN

52. – CO2 narcosis and respiratory muscle fatigue are indications of mechanical
ventilation
– An increased oxygen gas concentration is required too
– SODIUM BICARBONATE THERAPY :
– Unless ph <7.10 and HCO3 <15mEq/l ; IV NaHCO3 is not necessary
– NaHCO3 therapy transiently increases PaCO2
– H+ = HCO3 CO2+ H2O-

53. – Chronic resp acidosis require special considerations
– When such patient develop acute failure
– Goal therapy
– 1. return paCO2 to normal value
– 2. oxygen therapy must be very careful because in these patients the drive is oxygen
not CO2

54. ANESTHETIC
CONSIDERATIONS
– Acidemia can potentiate the depressant effects of agents
– 1. OPIOIDS :
– Opioids are weak bases so acidosis increase the nonionized form facilitates
penetraton in brain
– Increased sedation
– Increased depression of airway reflexes
– Predispose to pulmonary aspiration
– The agent that decreases smpathetic tone can potentiate circulatory depression

55. – Halothane is more arrythmogenic in presence of acidosis
– Suucinylcholine should be avoided as it increases plama k+