This document provides an overview of acid-base abnormalities and their management. It defines key terms, outlines regulatory mechanisms like buffers and respiration, and describes different acid-base disorders including their causes and treatments. An example case is presented of a patient with metabolic and respiratory acidosis on admission, resolving to metabolic acidosis and respiratory alkalosis after treatment. Overall it reviews acid-base physiology and the approach to diagnosing and managing common acid-base imbalances.

1. ACID BASE ABNOMALITIES
AND
MANAGEMENT
(causes and treatment)
Presenter: Dr PASHI
Moderator: Dr Sergii Yakubiuk
Date: 29-11-2016

2. OUTLINE
• Introduction
• Definitions
• Regulatory Mechanisms
• Anion gap
• Acid Base Disorders
• Causes
• Treatment

3. Introduction
• Daily acid production: 15,000 mmol of CO2 and 50-
100 meq of non-volatile acid (mostly sulfuric acid
from metabolism of amino acids)
• Balance maintained by renal and pulmonary
excretion
• Renal excretion: combination of H+ with titratable
acids, mainly phosphate and ammonia

4. Introduction
• Balance assessed in terms of bicarbonate-carbon
dioxide buffer system, Henderson-Hasselbalch
equation
– pH = 6.10 x log ([HCO3] / [0.03 x pCO2])
• Acid-base homeostasis critically affects tissue and
organ performance
• Both acidosis and alkalosis can have severe
and life threatening consequences
• It is the nature of the responsible condition
that determines the prognosis

5. Definitions
• An acid is a substance that can release or
donate H+;
• A base is a substance that can combine with
or accept H.
• Acid base balance : maintenance of normal pH
within the body systems.
• Normal body pH : 7.35 - 7.45
• Acidosis < 7.35 alkalosis >7.45

6. Definitions
• Base Excess refer to an excess or deficit,
respectively, in the amount of base present in
the blood. Reference range is – 2 to +2 mEq/L
• Normal pH is accomplished by regulation of
hydrogen ion balance.
• When an acid (HA) is added to water, it
dissociates reversibly ,
HA H+ + A- ;
yielding a free H+ and its conjugate base, A-.

7. Definitions
• At equilibrium, the rate of dissociation of an
acid , and the rate of association of H+ and A-
to form HA, are equal. the acid dissociation
constant, (Ka), is
• Ka = [H+]x[A-]
[HA]
pKa = -log10Ka (logarithmic expression of Ka)
• The higher Ka the more an acid dissociates
and the stronger the acid

8. Definitions
• pH is a logarithmic measure of hydrogen ion
concentration.
pH= -log10 [H+]
• pH is inversely proportional to [H+] . Each
whole number on the pH scale represents a
10fold (logarithmic) change in acidity.

9. Definitions
• The pH of a solution is determined by the pKa
of the acid and the ratio of the concentration
of the conjugate base to acid.
pH= pKa + log [A-]
[HA]
(Henderson-Hasselbalch equation)

10. Definitions
• Most enzymes function only within narrow pH
ranges
• Acid base balance can also affect electrolytes
• Can also affect hormones

11. Regulatory Mechanisms
• Buffer system
• Respiratory
• Renal

12. Buffer system
• Take up H+ or release H+ as conditions
change
• Buffer pairs – weak acid and a base
• Exchange a strong acid or base for a weak
one
• Results in a much smaller pH change
• In the ECF, the main chemical buffers are
bicarbonate, inorganic phosphate and
plasma proteins.

13. Bicarbonate buffer
• Sodium Bicarbonate (NaHCO3) and carbonic
acid (H2CO3)
• Maintain a 20:1 ratio : HCO3
- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
• It is in very high concentration and is the main
buffer pair
• It is controlled both by lungs and kidneys

14. Phosphate Buffer
• Major intracellular buffer
• H+ + HPO4
2- ↔ H2PO4-
• OH- + H2PO4
- ↔ H2O + H2PO4
2-

15. Protein Buffers
• Includes hemoglobin, work in blood
• Carboxyl group gives up H+
• Amino Group accepts H+
• Side chains that can buffer H+ are present on
27 amino acids.

16. Respiratory Mechanism
• Exhalation of carbon dioxide
• Powerful, but only works with volatile acids
• Doesn’t affect fixed acids like lactic acid
• CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3
-
• Body pH can be adjusted by changing rate and
depth of breathing

17. Respiratory Mechanisms
• Arterial PCO2 stimulates chemorecptors in the
medulla oblongata
• An elevated arterial blood PCO2 is a stimulus
to increase ventilation leading to increased
expiration of CO2 hence increase blood pH
• Conversely, a drop in blood PCO2 inhibits
ventilation; the consequent rise in blood
[H2CO3] reduces the alkaline shift in blood pH

18. Renal Mechanisms
• Can eliminate large amounts of acid
• Can also excrete base
• Can conserve and produce bicarb ions
• Most effective regulator of pH
• If kidneys fail, pH balance fails

19. Renal Mechanisms
• Acidification of the glomerular ultrafiltrate as
the H+ is secreted into the lumen by a Na+/H+
exchanger and H+-ATPase in the brush border
membrane.
• At the end of the tubule the pH would have
dropped from 7.4 to 6.7
• The H+ is buffered by the HCO3- and H2PO4-
(present in filtrate) and NH3 (from epith cells)

20. Renal Excretion of Acid, Sodium/Hydrogen
Ion Exchange and Formation of Ammonia

21. Renal Reclamation of Bicarbonate

22. Rates of Correction
• Buffers function almost instantaneously
• Respiratory mechanisms take several minutes
to hours
• Renal mechanisms may take several hours to
days

23. 23

24. Acid Base Disorders
• Respiratory acidosis
• Respiratory alkalosis
• Metabolic acidosis
• Metabolic alkalosis

25. Respiratory Acidosis
• Acute increase in pCO2
• Buffered primarily by intracellular buffers
Chronic state:
• Kidneys compensation:
- Increase net acid excretion, (48 hours for full
development)
Underlying cause:
• Central nervous system disease,
• lung (COPD)and heart disease,
• sedatives and opiates depressing the respiratory
center
• Hypercapnic encephalopathy can develop

26. Respiratory Acidosis
• Treatment
- Restore ventilation
- IV lactate solution
- Nabicarb IV ( mmol = kg * 0.3 * BE )
- Treat underlying dysfunction or disease

27. 27

28. Respiratory Alkalosis
• Carbonic acid deficit
• pCO2 less than 35 mm Hg (hypocapnea)
• Most common acid-base imbalance
• Primary cause is hyperventilation

29. Respiratory Alkalosis
pCO2 , pH  due to:
Hypoxia (compensatory hyperventilation)
• Acute: pulmonary edema or emboli, pneumonia,
• Chronic: severe anemia, high altitude,
hypotension
Respiratory center stimulation
• Pregnancy, Anxiety, Fever, heat stroke, sepsis,
salisylate intox., cerebral disease, hepatic
cirrhosis,
Increased mechanical ventilation

30. Respiratory Alkalosis
Treatment
• Treat underlying cause
• Reduce ventilation, increase dead space
• Breathe into a paper bag
• IV Chloride containing solution – Cl- ions
replace lost bicarbonate ions

31. 31

32. Metabolic Acidosis
• Hallmark is [HCO3
-]
• Acid production  net acid intake 
above net renal excretion
(ketoacidosis, lactic acidosis, ammonium chloride
loading)
• failure of renal net excretion
(chronic renal failure, renal tubular acidosis)
• Bicarbonate loss via the gastroinestinal tract
(diarrhea, gastrointestinal fistula)
• Nonbicarbonate solutions added to ECF
(dilutional acidosis)

33. Metabolic Acidosis
Treatment
- IV lactate solution
- Nabicarb IV
- Treat underlying cause

34. 34

35. 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

36. Metabolic Alkalosis
• Alkalosis most commonly occurs with renal
dysfunction, so can not count on kidneys
• Respiratory compensation difficult –
hypoventilation limited by hypoxia

37. Metabolic Alkalosis
• Respiration slow and shallow
• Hyperactive reflexes ; tetany
• Often related to depletion of electrolytes
• Atrial tachycardia
• Dysrhythmias

38. Metabolic alkalosis
Treatment
- Electrolytes to replace those lost
- Ascorbic acid, tranexamic acid
- IV chloride containing solution
- Treat underlying disorder

39. 39

40. Anion Gap
• The anion gap is the difference in the
measured cations (positively charged ions)
and the measured anions (negatively charged
ions) in serum or urine.
• It is calculated as :
([Na+] + [K+]) − ([Cl−] + [HCO3−])
• Anion gap is calculated when attempting to
identify the cause of metabolic acidosis.

41. Anion Gap
• The anion gap is influenced by changes of the
unmeasured ions.
• The most frequent change is an increase of the
anion gap, indicating acidosis due to
accumulation of acid metabolites.
• Less frequently a decrease of the anion gap is
seen, which may be due to hypoproteinemia, the
presence of a cationic paraprotein as in multiple
myeloma, or an increase in calcium or
magnesium (“undetermined cations”).

42. Causes of Increased Anion Gap
• Ketoacidosis (diabetic, alcoholic, starvation)
caused by acetoacetate and β-hydroxybutyrate
• Renal failure (accumulation of organic acids,
sulfuric acid, phosphoric acid)
• Lactic acidosis
• Treatment with substances that are unmeasured
anions at physiological pH, e.g. citrate, lactate,
carbenicillin, penicillin
• Poisonings (all yield unmeasured anions) ◦Aspirin,
salicylic acid, and other organic acids

43. Causes of Decreased Anion Gap
•Hypoalbuminemia (decrease in negative
charge)
•Hemodilution
◦Normal anion gap: (140 + 4) - (100 + 25) =
144 - 125 = 19
◦But with 20% dilution: (112 + 3.2) - (80 + 20)
= 115.2 - 100 = 15.2

44. Causes of Acid Base Disorders
Metabolic
Acidosis Anion
Gap
“MUDPILERS”
Metabolic
Acidosis Non-
Gap
“HARDUPS”
Acute Resp.
Acidosis
“anything
causing
hypoventilation”
Metabolic
Alkalosis
“CLEVERPD”
Respiratory
Alkalosis
“CHAMPS”
•Methanol
•Uremia
•DKA/Alcoholic
ketoacidosis
•Paraldehyde
•Isoniazid
•Lactic acidosis
•Ethanol
•Renal
failure/Rhabdo
•Salicylates
•Hyperalimentation
•Acetazolamide
•Renal Tubular
Acidosis
•Diarrhea
•Uretero-Pelvic
shunt
•Post-hypocapnia
•Spironolactone
•CNS depression
•Airway
obstruction
•Pulmonary
edema
•Pneumonia
•Hemo/Pneumo
thorax
•Neuromuscular
•Contraction
•Licorice
•Endocrine
(Conn/Cushing
/Bartters)
•Vomiting
•Excess alkali
•Refeeding
•Post-
hypercapnia
•Diuretics
•CNS disease
•Hypocapnia
•Anxiety
•Mech. Ventilation
•Progesterone
•Salicylates
•Sepsis

45. Diagnosis of acid Base Disorder
1. Determine the primary disturbance:
– Acidemia or Alkalemia: look at the pH
< 7.40 = acidemia
> 7.40 = alkalemia
– Respiratory or Metabolic: look at HCO3 and CO2
HCO3 = primary metabolic acidosis
pCO2 = primary respiratory acidosis
and vice versa for alkalosis

46. Diagnosis of acid Base Disorder
2. Determine acute or chronic for Respiratory
Disturbance:
o Compensation attempts to normalize pH but can be
present with an abnormal pH
o Expected change in pCO2 best used for primary
metabolic disturbance and expected change in HCO3
for primary respiratory disturbance

47. Diagnosis of acid Base Disorder
3. Primary Metabolic Disturbance:
o Calculate anion gap : Na – (Cl + HCO3)
o Normal = 12 +/- 2
o If gap is >20 then there is primary metabolic
acidosis regardless of pH or bicarb.
o Helps narrow differential with a anion gap or non-
anion gap metabolic acidosis

48. Diagnosis of acid Base Disorder
4. Assess appropriate respiratory compensation
for metabolic disorder:
o Respiratory compensation is fast
o Winters formula:
Expected pCO2 = (1.5 * HCO3) + 8 (+/-2)
o If measured pCO2 is
< expected then co-existing resp. alkalosis
> expected then co-existing resp. acidosis

49. Diagnosis of acid Base Disorder
5. Determine if other metabolic disturbances co-
exist with AG metabolic acidosis:
o Delta gap – accounts for increase in anion gap and
shows any variation in HCO3
o If no other disorder is present then the calculation
should be 24
Corrected HCO3 = measured HCO3 + (AG - 12)
o So if corrected HCO3
>24 then metabolic alkalosis co-exists
<24 then non-anion gap metabolic acidosis co-exists

50. Normal values
pH 7.35 – 7.45
PCO2 35 – 45mmHg
PO2 80 -100mmHg
K+ 3.5 – 5.0meq/l
Na+ 135 -145meq/l
Cl- 98 – 108mmol/l
HCO3- 22 – 26meq/l
Anion gap 9 - 16

51. 51

52. Example
55 yo man collapsed in a bar and was brought to the
ER. He was unresponsive, no BP was obtainable,
a sinus tachycardia was present and he had
peritoneal signs.
pH 6.86 pCO2 81 HCO3 14 Na 139 Cl 84
K 3.9 HCO3 16
He was intubated, started on pressors and treated
with HCO3
pH 7.04 pCO2 34 HCO3 9 Na 148 Cl 93
K 4.5 HCO3 10

53. On Admission
• pH: 6.85 low, acidosis
• pCO2: 81 high, respiratory acidosis
• HCO3: 16 low, metabolic acidosis
• Anion Gap: 139 – (84 + 16) = 39
• Winter’s equation (expected pCO2): (16 x 1.5 = 24) + 8 =
32 (lower than observed, 81)
• Delta change HCO3: (39-12 = 27 )+16 (observed) = 43
• Answer:
– anion gap metabolic acidosis
– respiratory acidosis
– metabolic alkalosis

54. After Intubation
• pH: 7.04 low, acidosis
• pCO2: 34 low, respiratory alkalosis
• HCO3:10 low, metabolic acidosis
• Anion Gap: 148 – (93 + 10) = 45 (increasing)
• Winter’s equation(expected pCO2): (10 x 1.5 = 15) +
8 = 23 (lower than observed, 34)
• Delta change HCO3: (45-12 + 33)+10(observed) = 43
• Answer:
– anion gap metabolic acidosis (lactate was 24)
– respiratory alkalosis
– metabolic alkalosis

55. References
• Alpern RJ: Renal acidification mechanisms. In Brenner BM
(ed):The Kidney, 6th ed. Philadelphia: WB Saunders, 2000,
pp 455-519.
• Capasso G, Unwin R, Rizzo M, et al: Bicarbonate transport
along the loop of Henle: molecular mechanisms and
regulation J Nephrol 15(Suppl 5):S88, 2002.
• Decoursey TE: Voltage-gated proton channels and other
proton transfer pathways. Physiol Rev 83:475, 2003.
• Gennari FJ, Maddox DA: Renal regulation of acid-base
homeostasis.
• Seldin DW, Giebisch G (eds): The Kidney—Physiology and
Pathophysiology, 3rd ed. New York: Raven Press, 2000, pp
2015-2054.