This document provides an overview of metabolic acidosis. It defines metabolic acidosis as a process that increases hydrogen ions or decreases pH due to accumulation of acid in the body. The main causes discussed are diabetic ketoacidosis, lactic acidosis, renal failure, methanol poisoning, diarrhea, and renal tubular acidosis. Compensation and treatment methods such as sodium bicarbonate administration are also reviewed. Blood gas analysis is described as a key tool to identify the primary acid-base disturbance, compensatory responses, and calculate the anion gap to help diagnose the specific cause of metabolic acidosis.

2. Metabolic Acidosis
Dr. Muhammad Usama Azhar
Post Graduation Resident
Internal Medicine

3. Objectives
We will learn the following topics:
O Metabolic Acidosis
O Definition
O Causes
O Investigations
O Management
O Interpretation of Blood Gas Analysis
O Simple and Mixed Acid-Base Disorders

4. O What is Acidosis?

5. Acidemia vs Acidosis
O Acidemia: when blood pH <7.35
O Acidosis: is a process that increases [H+]
or process which tends to ↓pH
(accumulation of acid in body)

7. O Mechanism:
O gain of H+
O loss of HCO3
O Results in:
O ↓pH (7.35)
O ↓HCO3- (<22mEq/L)
O pCO2 depends on compensation

8. Compensation in
Metabolic Acidosis
O Hyper-ventilation to ↓ PaCO2= Kasmaul
Breathing
O The maximal compensation takes 12 to 24
hours
O The increase in ventilation usually starts
within minutes, usually well advances at 2
hours of onset, but maximal compensation
may take 12 to 24 hours to develop.
O Compensation can never normalize pH, it
can improve it.

10. Anion Gap
O Anion gap = ([Na+] ) − ( [Cl−] + [HCO3−])
O As sodium is the main extracellular cation,
and chloride and bicarbonate are the main
anions, the result should reflect the
remaining anions.

12. O Normally, this concentration is about 8-16
mmol/l (12±4).
O An elevated anion gap (i.e. > 16 mmol/l)
can indicate particular types of metabolic
acidosis, particularly certain poisons,
lactate acidosis and ketoacidosis.

14. Classfication
O Metabolic Acidosis can be divide into 2
groups:
O Raised anion gap acidosis
O Normal anion gap acidosis

15. High Anion Gap
Metabolic Acidosis
O M-Methanol
O U-Uremia (chronic kidney failure)
O D-Diabetic ketoacidosis
O P-Propylene glycol
O I- Infection, Iron, Isoniazid, Inborn errors
of metabolism
O L-Lactic acidosis
O E-Ethylene glycol

16. High Anion Gap
Metabolic Acidosis
O Endogenous
O Ketoacidosis
O Diabetic
O Alcoholic
O Starvation
O Lactic acidosis
O Uremia
O Exogenous
O Methanol
Ingesion
O Ethanol
O Ethylene glycol
O Isoniazid
O Salicylates
poisoning

17. Normal Anion Gap
Metabolic Acidosis
O Bicarbonate loss through Gut
O Diarrhea
O Pancreatic fistula
O Uretero-sigmoidostomy
O Bicarbonate loss through Kidney
O Renal tubular acidosis
O Carbonic anhydrase inhibtors
O Post-hypocapnea

18. Diabetic Ketoacidosis
O Due to the overproduction of ketone bodies
(Ketosis) leading to accumulation of ketones
in plasma (Ketonemia) and urine (Ketonuria).
O In starvation states where plasma glucose
levels are low or in states of low plasma
insulin where uptake of glucose by cells is
diminished, fatty acids will be mobilized and
transported to tissues (brain, skeletal muscle,
heart) for fatty acid oxidation and energy
production.

19. Diabetic Ketoacidosis
O Acetyl CoA from fatty acid oxidation can
not be oxidized and is instead converted
to the generation of ketone bodies.
(acetoacetate and β-hydroxybutyrate)
which serve as a source of fuel.

20. Lactic Acidosis
O Dead-end product of glycolysis
O Occurs when the body must regenerate ATP
without oxygen
O Normal lactic level is maintained at 0.7-1.3
mEq/L
O Eliminated in liver (50%), kidneys (25%), heart
and skeletal muscles
O Normal Lactate/Pyruvate ratio suggest that
the cause is not related to anaerobic
metabolism or anoxia

21. Lactic Acidosis
O Serum lactate > 5 mEq/L
O Typte1 hypoxia+peripheral generation of
Lactate in patient with circulatory failure+
shock.
O Type2 impaired metabolism of lactate in
liver disease and drug+toxin inhibit lactate
metabolism(eg:metformin)

22. Metabolic Acidosis in Renal
Failure
O Normal AG acidosis results from failure of
the kidney to generate new HCO3- from a
reduced rate of synthesis and excretion of
NH4+ (usually GFR 20-50ml/min)
O Increased AG acidosis results from the
reduced GFR, with accumulation of
sulfates, urates and phosphates. (usually
GFR <15-20ml/min)

23. Methanol Poisoning
O Methanol is metabolized by alcohol
dehydrogenase to formaldehyde and then
to formic acid
O High AG: formic acid, lactic acid, and
ketoacid
O Formaldehyde: optic nerve and CNS
toxicity
O Retinal edema, CNS depression, and
unexplained metabolic acidosis with high
anion and osmolar gaps

24. Normal Anion Gap
Metabolic Acidosis
O Two main causes
O 1. Renal
O 2. Extra-renal
Urinary Anion Gap= Na+ + K+ – Cl- = 0
If positive = Renal
If negative = Extra-renal

25. Metabolic Acidosis in
Severe Diarrhea
O It is when the bowel movement occurs
more than 5 times a day.
O The person loses a great amount of
bicarbonate ions in the stool and therefore
the amount of anions decreases.
O Bicarbonate ions are important for the
blood buffer system.
O Due loss of these ions the buffer system
cannot work properly thus making the
blood acidic.

26. Renal Tubular Acidosis
O •Inability of the kidney to reabsorb the
filtered HCO3
O Inability of the kidney to excrete NH4+

27. Types of RTA
O Type 1 RTA: Distal RTA
O Type 2 RTA: Proximal RTA
O Type 4 RTA: Hyperkalemic

29. Type 1 (distal) RTA
O Defective H+ ion secretion by
α-intercalated cells in late DCT &
CT → ↑H+ ions (acidemia)
O Nephrolithiasis (calcium phosphate
stones) is frequently associated with
untreated type 1 RTA.
O Causes:
O Sjogren’s syndrome, SLE, liver
cirrhosis, and toxins (e.g. amphotericin
B, lithium)

30. Type 2 (proximal) RTA
O Impaired HCO3– reabsorption in PCT →
↑ HCO3– loss in urine → ↑ Blood acidity
O Associated with:
O Multiple myeloma, Fanconi syndrome,
and toxins (e.g. Acetazolamide,
outdated tetracycline)

31. Type 4 (hyperkalemic) RTA
O Aldosterone deficiency/resistance in
Collecting Tubules
O Cause:
O Addison’s disease, diabetic
nephropathy, sickle cell disease, and
drugs (e.g. trimethoprim, NSAIDs, ACE
inhibitors, spironolactone).

33. Consequences of Acidemia on
various Organ System
O Cardiovascular System:
O ↓ contractility
O Arterial vasodilatation
O ↓MAP
O ↓CO
O ↓ response to Catecholamine
O ↑ risk of arrhythmias

34. Consequences of Acidemia on
various Organ System
O Respiratory System:
O Hyperventilation(compensatory)
O ↓ Respiratory Muscle Strength
O Neurological:
O Cerebral Vasodilation → ↑ ICP

35. Consequences of Acidemia on
various Organ System
O Metabolic:
O ↑ Potassium (Due to H+/K+ pump
exchanging excess H+ with Intracellular
K+)
O ↑ Bone resoprtion (In chronic cases)
O ↑ Phosphate concentration in extracellular
fluid

36. Sign & Symptoms
O Neurological:
O Headache
O Drowsiness
O Comatose
O Seizures
O Cardiovascular:
O Tachycardia
O Arrythmia
O Hypotension

37. Sign & Symptoms
O Respiratory:
O Shortness of breath
O Deep and rapid breathing
O Coughing
O Gastric:
O Nausea
O Vomiting
O Diarrhea

38. Sign & Symptoms
O Muscular:
O Cramps
O Seizures
O Generalzied Weakness

40. Investigations
O Blood Gas Analysis (VBGs or ABGs)
O Blood Glucose Level
O Serum Electrolytes
O Serum Ketones (or Urine Ketones)
O Serum Lactates
O Urea and Creatinine
O ECG

42. Management
O Emergency Management
O Treat Underlying Cause
O Replace Losses
O Specific Therapy

43. Management
O Emergency Management:
O Intubation and ventilation for airway or
ventilatory control;
O Cardiopulmonary resuscitation; severe
hyperkalaemia
O Treat Undelying Cause:
O Treat the underlying disorder as the primary
therapeutic goal.
O Consequently,accurate diagnosis of the cause
of the metabolic acidosis is very important.

44. Management
O Replace Losses:
O Replace losses (e.g. of fluids and
electrolytes) where appropriate.Other
supportive care (oxygen administration)
is useful.
O In most cases, IV sodium bicarbonate
is NOT necessary, NOT helpful, and
may even be harmful so is not
generally recommended.

45. Management
O Specific Treatment:
There are often specific problems or
complications associated with specific
causes or specific cases which require
specific management. For example:
O Ethanol blocking treatment with methanol
ingestion;
O Insulin for diabetic ketoacidosis
O Haemodialysis can remove some toxins

46. Management
O Alkali Therapy: Indicated in
O Normal AG Metabolic Acidosis
O Raised AG Metabolic Acidosis due to non-
metabolizable anions
HCO3
- Deficit= 0.5 x Weight (24-[HCO3
-])
O Severe Acidemia pH <7.0 in case of Raised AG
Metabolic Acidosis (50-100mEq IV NaHCO3
-
over 30-45 minutes)
Reference:
Harrison’s Principles of Internal Medicine

47. Management of DKA
O Correction of fluid loss with intravenous fluids
O Correction of hyperglycemia with insulin
O Correction of electrolyte disturbances,
particularly potassium loss
O Correction of acid-base balance
O Treatment of concurrent infection, if present

48. Management of Lactic
Acidosis
O Intravenous fluid to promote circulation
O Oxygen, delivered with a face mask or
another way
O Positive pressure ventilation to deliver oxygen
to the lungs
O Hemodialysis with bicarbonate
O Individuals who experience lactic acidosis
while exercising can stop what they are doing,
rehydrate by drinking water, and rest.

49. Management of RTA
O Type 1 RTA: NaHCO3 (1-3mEq/kg/d)
O Type 2 RTA: NaHCO3 or KHCO3
(10-15mEq/kg/d)
Thiazide diuretics
O Type 4 RTA: Fludrocortisone
(0.1-0.5mg/d)
Dietary restriction
Furosemide (40-160mg/d)

50. Scenario
O 20 year young male diabetic patient presented
with fever and vomiting for 1 day. He was
drowsy and taking deep and rapid breaths.
ABGs showed following findings:
O pH 7.18
O PaCO2 30mmHg
O PaO2 55mmHg
O HCO3
- 10mmol/L
O Na+ 140mEq/L
O Cl- 90meq/L
O What is the interpretation of ABGs?

51. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH-------- acidemia or alkalemia
O HCO3- & pCO2 analysis---primary
disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

52. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH-------- acidemia or alkalemia
O HCO3- & pCO2 analysis---primary
disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

53. History taking and physical
examination
O Comprehensive history taking and
physical examination can often give clues
as to the underlying acid-base disorder

54. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

55. Identify the Primary Disorder
O Is there alkalemia or acidemia present?
pH < 7.35 acidemia
pH > 7.45 alkalemia
O This is usually the primary disorder
O Remember: an acidosis or alkalosis may be
present even if the pH is in the normal range
(7.35 – 7.45)
O You will need to check the PaCO2, HCO3- and
anion gap

56. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

57. Identify the Primary Disorder
O Is the disturbance respiratory or
metabolic?
O What is the relationship between the
direction of change in the pH and the
direction of change in the PaCO2?
O In primary respiratory disorders, the pH
and PaCO2 change in opposite directions;
in metabolic disorders the pH and
PaCO2 change in the same direction.

58. Identify the Primary Disorder
Acidosis Respiratory pH ↓ PaCO2 ↑
Acidosis Metabolic pH ↓ PaCO2 ↓
Alkalosis Respiratory pH ↑ PaCO2 ↓
Alkalosis Metabolic pH ↑ PaCO2 ↑

59. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

60. Compensatory Response
O Is there appropriate compensation for the
primary disturbance?
O Usually, compensation does not return the
pH to normal (7.35 – 7.45).

61. Disorder Expected compensation
Metabolic acidosis PaCO2 = 1.5x[HCO3
-
] + 8 ± 2
Metabolic alkalosis
PaCO2 = 0.9x[HCO3
-
] + 16 ± 2
Acute respiratory acidosis [HCO3
-
] = 24 + 𝐏 𝐚
𝐂𝐎 𝟐
−𝟒𝟎
𝟏𝟎
x 1
Chronic respiratory acidosis [HCO3
-
] = 24 + 𝐏 𝐚
𝐂𝐎 𝟐
−𝟒𝟎
𝟏𝟎
x 4
Acute respiratory alkalosis [HCO3
-
] = 24 - 𝟒𝟎−𝐏𝐚𝐂𝐎𝟐
𝟏𝟎
x 2
Chronic respiratory alkalosis [HCO3
-
] = 24 - 𝟒𝟎−𝐏𝐚𝐂𝐎𝟐
𝟏𝟎
x 5

62. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

63. Anion Gap
O Calculate the anion gap
O AG= [Na+]-( [Cl-] + [HCO3-] )=12 ± 2
O A normal anion gap is approximately 12
meq/L.

64. Anion Gap
O It is important to remember what the
expected “normal” anion gap for your
patient should be, by adjusting for
hypoalbuminemia.
O Calculate corrected sodium before
measurement of anion gap.

65. Corrected Anion Gap for
Hypoalbuminemia
O Normal Anion Gap is 12±2 mmol/L (at
Serum Albumin level 4g/dL)
O Corrected AG = AG + (2.5 x (4-albumin)
expressed in g/dL
O Every 1g/dL decrease in serum albumin
will decrease 2.5mmol/L of anion gap.

66. Corrected Sodium for
Hyperglycemia
O Corrected Na+ =
measured Na++[1.6(glucose–100)/100]
O Glucose is taken in mg/dL.
O This forumla is according to Katz,1973;
correction factor is 2.4 according to
Hillier,1999.

67. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Urine anion gap
O Formulate acid-base diagnosis

68. Delta Ratio
O If an increased anion gap is present,
assess the relationship between the
increase in the anion gap and the
decrease in [HCO3-].
O Assess the ratio of the change in the
anion gap (∆AG ) to the change
in [HCO3-] (∆[HCO3-]): ∆AG/∆[HCO3-]

69. Delta Ratio
O Delta ratio = ∆ Anion gap/∆ [HCO3-]
= (AG-12)/(24 - [HCO3-])
Let’s suppose AG=30, [HCO3-]= 6, Then
Delta ratio = 30-12/24-6
Delta ratio = 18/18 = 1

70. Delta Ratio
O This ratio should be between 1.0 and 2.0 if an
uncomplicated anion gap metabolic acidosis is
present.
O If this ratio falls outside of this range, then another
metabolic disorder is present:
O If ∆AG/∆[HCO3-] < 1.0, then a concurrent non-anion
gap metabolic acidosis is likely to be present.
O If ∆AG/∆[HCO3-] > 2.0, then a concurrent metabolic
alkalosis is likely to be present.

71. Scenario
O 20 year young male diabetic patient presented
with fever and vomiting for 1 day. He was
drowsy and taking deep and rapid breaths.
ABGs showed following findings:
O pH 7.18
O PaCO2 30mmHg
O PaO2 55mmHg
O HCO3
- 10mmol/L
O Na+ 140mEq/L
O Cl- 90meq/L
O What is the interpretation of ABGs?

72. Blood Gas Analysis
O History taking and physical examination
O Identify the primary disturbance
O Check pH: acidemia or alkalemia
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Calculate Anion Gap
O Assess delta ratio
O Formulate acid-base diagnosis

73. Blood Gas Analysis
O History= Suspected DKA
O Identify the primary disturbance
O Check pH: 7.2 (acidemia)
O HCO3- & pCO2 analysis: primary disorder
O Compensatory responses
O Predicted PaCO2 = 1.5x[HCO3
-] + 8 ± 2
O Predicted PaCO2 = 1.5x10 + 8 ± 2 = 23 ± 2
O Measure PaCO2 > Predicted PaCO2 =
Concomitant Respiratory Acidosis

74. Blood Gas Analysis
O Calculate Anion Gap
O AG= Na+ - (Cl- + HCO3
-)
O AG= 140 – (90+10) = 140-100= 40
O Assess delta ratio
O Delta ratio = ∆ Anion gap/∆ [HCO3-]
= (AG-12)/(24 - [HCO3-])
=40-12/24-10
=28/14
=2 ( Concomitant Met.Alkalosis)

75. Blood Gas Analysis
O PaO2 = 55mmHg which is <60mmHg
meaning Respiratory Failure
O Formulate acid-base diagnosis
Raised AG Metabolic Acidosis +
Metabolic Alkalosis +
Respiratory Acidosis and
Type II Respiratory Failure