This presentation gives an overview of etiology, pathophysiology and management of acid base disorders.

1. Metabolic
Acid-Base Disorders
(An overview of etiology, pathophysiology and treatment.)
By:
Omaid Hayat Khan
Pharm-D, MS (Clinical Pharmacy)
Universiti Sains Malaysia.

2. An Overview of Kidney
 Regulates fluid volume and acid base balance of the plasma (pH 7.4)
 Excrete nitrogenous waste
 Synthesize erythropoietin, 1,25-dihydroxycholecalceferol & Renin
 Drug metabolism
 Is a target organ for both Parathormone (PTH) & Aldosterone.

3. Renal Corpuscular Region of a Nephron
A – Renal corpuscle
B – Proximal tubule
C – Distal convoluted tubule
D – Juxtaglomerular apparatus
1. Basement membrane (Basal lamina)
2. Bowman's capsule – parietal layer
3. Bowman's capsule – visceral layer
3a. Pedicels (Foot processes from
podocytes)
3b. Podocyte
4. Bowman's space (urinary space)
5a. Mesangium – Intraglomerular cell
5b. Mesangium – Extraglomerular cell
6. Granular cells (Juxtaglomerular cells)
7. Macula densa
8. Myocytes (smooth muscle)
9. Afferent arteriole
10. Glomerulus Capillaries
11. Efferent arteriole

7. Classification of Acid Base Disorder
ACIDOSIS ALKALOSIS
7.4
7.35 – 7.45
• -emia refers to a pH in blood
• -osis refers to an abnormal condition or process

8. Plasma Buffer System
H+ + HCO3
-
H2CO3 CO2 + H2O
(Volatile Acid)
• Resisting to change in pH is very crucial for normal body
functioning.
• Buffering refers to ability of solution to MAINTAIN / RESIST
CHANGE in pH after addition of strong acid/alkali.
• Three general mechanism work together:
1. Chemical buffering
• HCO3 in ECF
• Proteins & phosphate buffers in ICF
2. Alveolar ventilation (maintaining PaCO2)
3. Renal H+ handling
• HCO3 reabsorption
• Excretion of titratable acid (H2PO4-) and NH4+

9. Plasma Buffer System
H+ + HCO3
-
H2CO3 CO2 + H2O
(Volatile Acid)
• Body’s principle extracellular buffer system is the carbonic
acid/ bicarbonate system (H2CO3/HCO3
-
) system.
• Ratio of HCO3/H2CO3 is 20:1 which is constant at normal
pH.
• Body’s main Acid = CO2
• If 1 HCO3 is lost from body 1 H+ stay behind, the net result
is addition of 1 free H+ into the ECF.
• Conversely, if H+ is lost 1 HCO3 is added to the body.

10. Normal Ranges
Blood Gas Arterial Blood
pH 7.40 (7.35 – 7.45)
PaO2 80-100 mmHg
SaO2 95%
PCO2 35 – 45 mmHg
HCO3- 22 – 26 mEq/L (22-26 mmol/L)
WHEN TO ORDER ABGs???
• Any serious illness
• Multi-organ Failure
• Respiratory Failure
• Cardiac Failure
• Uncontrolled DM (DKA)
• Poisoning (Barbiturates, Ethylene glycol)

11. Classification of Acid/Base Disorders
Acidosis
(Fall in pH)
• Respiratory
acidosis
• Metabolic
Acidosis
Alkalosis
(Rise in pH)
• Respiratory
acidosis
• Metabolic
alkalosis
Can occur individually or together as compensatory response.

12. RESPIRATORY DISTURBANCES
Caused by:
 Altered alveolar ventilation
 Producing changes in arterial PaCO2 tension
Main culprit is CARBON DIOXIDE.
Increase in PaCO2 = Acidosis
Decrease in PaCO2 = Alkalosis

13. METABOLIC DISTURBANCES
Caused by:
 Kidney Failure
 DKA
 Lactic acidosis
 Diarrhea/ Vomiting
 Starvation
 Poisoning
 Hypokalemia etc.
Main Culprit is BICARBONATE
Increase in HCO3 = Alkalosis
Decrease in HCO3 = Acidosis

15. METABOLIC ACIDOSIS
Decrease in pH…………..Decrease in HCO3-
 Causes:
 Adding organic acid to ECF (Lactic acids, Keto Acids etc)
 Loss of HCO3- Stores (Diarrhea)
 Accumulation of endogenous acids due to impaired renal function. (eg.
Phosphates and sulphates)
 Serum ANION GAP (SAG) used to calculate the cause.
 Elevated AG acidosis
 Normal AG acidosis
 Primary Compensatory mechanism:
 Decreasing PaCO2 via hyperventilation (Kussmaul respiration as in DKA)
 Clinical Presentation:
 Bone demineralization (rickets, osteomalacia, osteopenia)
 Acute manifestations of acute disease invlove CVS, Respo & CNS.

18. ANION GAP
 “Quantity of anions not balanced by cations.”
 Measurable Ions:
 Major cation is Na+ and K+
 Major Anions are HCO3- & Cl-
 Unmeasurable Ions:
 Major cations are Ca++, Mg++, gamma globulins and K+
 Major anions are Albumins, sulphate, phosphate,lactate and other organic
anions.
 Normal physiology: number of anion = number of cations
 So,
 [Na] + [K] + Unmeasured cations = [Cl-] + [HCO3-] + Unmeasured anions
 ([Na] + [K] + Unmeasured cations ) – ([Cl-] + [HCO3-] + Unmeasured anions) = 0
 But actual value is 12 mEq/L = WHY???
 Hence there is a GAP and it is ANIONIC…. Why??
 Practically Calculated as:
ANION GAP = [Na+] – ( [Cl-] + [HCO3-] )
Normal Value
12 ± 4 mEq/L

19. Interpretation of ANION GAP

20. Interpretation of ANION GAP
 Case 1:
HCl + NaHCO3 → NaCl + H2CO3 → CO2 + H2O
 Case 2:
HA + NaHCO3 → NaA + H2CO3 → CO2 + H2O,
where A- is the unmeasured anion.

21. Interpretation of ANION GAP
 Causes of ELEVATED Anion Gap:
 remembered by the mnemonic KULT or the popular MUDPILERS
M = Methanol
U = Uremia
D = DKA (also AKA and starvation)
P = Paraldehyde
I = INH
L = Lactic acidosis
E = Ethylene Glycol
R = Rhabdomyolysis / Renal failure
S = Salycilates
K = Ketoacidosis (DKA,alcoholic
ketoacidosis, starvation)
U = Uremia (Renal Failure)
L =Lactic acidosis
T = Toxins (Ethylene glycol, methanol,
paraldehyde, salicylate)

22. Interpretation of ANION GAP
 Because, negatively charged plasma proteins account for the
normal anion gap, the normal values should be adjusted
downward for patients with hypoalbuminemia.
 The approximate correction is a reduction in the normal anion gap
of 2.5 meq/l for every 1g/dl decline in the plasma albumin
concentration (normal value = 4 g/dl).

23. Interpretation of ANION GAP
 EXAMPLE:
 A 60 year old homeless man presents with nausea, vomiting and
poor oral intake 2 days prior to admission. The patient reports a 3
day history of binge drinking prior to symptoms.
 Does the patient have an abnormal anion gap?
LABs Value Normal LABs Value Normal
Na 132 135 – 145 BUN 25 10 – 25
K 5 3.5 – 5 Cr 1.3 1.2 – 1.5
Cl 104 95 – 105 Glu 75 60 – 100
HCO3 16 22 – 26 pH 7.30 7.35 – 7.45
pCO2 29 35 – 45 PO2 92 80 – 100
Albumin 1.0 3.5 – 5

24. Interpretation of ANION GAP
 Is patient Acedemic Or Alkalemic?
 Acidemic. With low HCO3 and low pH. Hence METABOLIC ACIDOSIS.
 Which type?
 Normal Anion gap OR Elevated Anion gap(Lactic or Ketoacidosis) ??
 To find out calculate AG
 Anion gap = (Na-(Cl +HCO3-) = 132 -(104 +16) = 12
 Lactic acidosis appears unlikely!!
 However, note patient is severe hypoalbumenic. What is your inference?
 False anion gap which needs to be adjusted.
 Therefore in this scenario, AG should be:
 Decline in albumin = 4 – 1 = 3 g/dL
 Reduction in normal anioin gap = 3 x 2.5 = 7.5
 Adjusted anion gap = 12 -7.5 = 4.5
 So what is your assessment now??
 Patients has an elevated anion gap metabolic acidosis which may be due to lactic or
ketoacidosis.
LABs Value Normal LABs Value Normal
Na 132 135 – 145 BUN 25 10 – 25
K 5 3.5 – 5 Cr 1.3 1.2 – 1.5
Cl 104 95 – 105 Glu 75 60 – 100
HCO3 16 22 – 26 pH 7.30 7.35 – 7.45
pCO2 29 35 – 45 PO2 92 80 – 100
Albumin 1.0 3.5 – 5

25. HIGH ANION GAP
METABOLIC ACIDOSIS
Decreased
acid secretion
• Renal Failure
Increased acid
production
• Lactic acidosis
• Ketoacidosis
Toxicity
• Salicylate
• Methanol

26. NORMAL ANION GAP
METABOLIC ACIDOSIS
OR
HYPERCHLOREMIC ANION GAP
Loss of HCO3
and Cations
• Diarrhoea
Impaired
acidification of
urine
• RTA Type 1, 2 &
4

27. Difference in RTA types

28. Getting Rid of H+ (Acid Load)
by Kidneys
 Hydrogen ion secretion
 In form of non-volatile acids (as NH4 or titratable acids like H2PO4)
 Normally, kidneys reabsorb all the filtered bicarbonate which is vitally
important to maintain acid/base balance.
 Bicarb. Reabsorption mainly occurs in proximal tubule (90%).
 Remaining occurs in thick ascending limb and collecting tubule.
1
2
3
45
6 7
Aldosterone

29. Getting Rid of H+ (Acid Load)
by Kidneys
 Excretion of titratable acids is dependent on the quantity of phosphate
filtered and excreted by the kidneys, which is dependent on one's diet,
and also PTH levels.
 As such, the excretion of titratable acids is not regulated by acid base
balance and cannot be easily increased to excrete the daily acid load.
 Ammonium production can however be regulated to respond to acid
base status
Getting rid of H+
1) NH4 production
2) Phosphate buffer
• 2 possible mechanisms.
• Depends on acid/base balance
• Further produces HCO3 ions.
• Independent of acid base balance
• Depends on ones diet and PTH

30. Ammonium Excretion
 3 steps.
1. Ammonium Formation (ammoniagenesis) (proximal tubule)
2. Ammonium Reabsorption (Medullary Recycling)(thick ascending loop)
3. Ammonium Trapping (collecting tubule)

31. Note that this process is primarily dependent on acidification of the urine in the
collecting tubule as a result of hydrogen secretion by intercalated cells.
In states of alkalosis, the process is appropriately hindered as a result of the
alkalemic urine.

32. Renal Acid Exretion; Take Home Points
1. The net quantity of H+ ions excreted in the urine is equal to the amount of H+ excreted
as titratable acidity and NH4+ minus any H+ added to the body because of urinary
HCO3- loss.
Net acid excretion(NAE) = titratable acidity + NH4
+ - urinary HCO3
-
Note that normally there is no urinary HCO3- and therefore:
Net acid excretion(NAE) = titratable acidity + NH4
+
2. Titratable acidity is dependent on the dietary intake of phosphate and cannot be
regulated to increase acid excretion
3. The kidney 's main response to an increased acid load is to increase ammonium
production and excretion
4. A very important feature of titrable acidity and ammonium excretion is the regeneration
of bicarbonate ions.
5. The kidney must reabsorb all filtered HCO3- in order to maintain acid base balance.
6. Hydrogen ion secretion in the collecting tubule is very important in maximally acidifying
the urine.
7. In states of acidosis, maximal acidification of the urine in the collecting tubule must
occur for adequate ammonium excretion.
8. In states of acidosis, ammonium excretion is increased by increasing ammonium
production and increased hydrogen ion secretion in the collecting duct.
9. Aldosterone stimulates secretion of hydrogen ion in the collecting duct .
10. Although the extracellular pH is the primary physiologic regulator of net acid excretion,
in pathophysiologic states, the effective circulating volume, Aldosterone, and the plasma
K+ concentration all can affect acid excretion, independent of the systemic pH.

34. METABOLIC ALKALOSIS
Increase in pH…………..Increase in HCO3-
 Causes:
 Loss of H+ from GIT (nasogastric suctioning, Vomiting)
 Transcellular H+ shift (Hypokalemia)
 Loss of H+ from kidneys
o Loop & thiazide Diuretics
o Mineralocorticoid excess (Cushing’s syndrome, Steroids)
 Gain of HCO3 (Admin. Of bicarb. , Lactate, or citrate, Antacids)
 Contraction Alkalosis (reduction in ECV)
 Fail to excrete excess HCO3 (Abnormal renal function)
 Hypokalemia
 Primary Compensatory mechanism:
 Increasing PaCO2 via hypoventilation.
 Increase excretion of HCO3 and conservation of H+ (Secondary)
 Clinical Presentation:
 Often accompanied by Hypochloremia and Hypokalemia.
 No signs and symptoms associated with mild to moderate metabolic alkalosis.
 Severe is associated with cardiac arrhythmias (probably secondary to hypokalemia)
and neuromuscular irritability.

35. METABOLIC ALKALOSIS

36. Interpretation of ANION GAP

37. MAINTAINANCE OF METABOLIC
ALKALOSIS
 Kidneys have a high rate of filtering / compensating excess HCO3
 So normally, alkalosis is quickly compensated unless there is
maintenance.
 CAUSE 1: Vomiting
 >> decrease in ECV >>Decreased GFR (less HCO3 filtered) >> Increase angiotensin
& aldosterone >> Increase Na & HCO3 reabsorption >> Increased H+ secretion (via
Na-H exchanger at proximal tubule) combined with filtered HCO3 leading to further
reabsorption >> Rise in plasma HCO3 >>Hypokalemic metabolic alkalosis
 Because Aldosterone primarily acts distally to increase H+ and K
secretion resulting in increased acid and potassium excretion.

38. MAINTAINANCE OF METABOLIC
ALKALOSIS
 CAUSE 2: Contraction Alkalosis
 Diuretics >> decrease ECV >> increase HCO3 >> compensation by release of H+
buffers >> Normalized.
 However, if ECV reduction by diuretics result in hypovolemia >> Angiotensin &
Aldosterone stimulated >> & so on.. Increase HCO3 absorption & increase H & K
secretion.>> Hypokalemia >> further maintains alkalosis.
 CAUSE 3: Hypokalemia
 Commonly associated due to 2 factors:
1. Common causes of alkalosis leads to increase in aldosterone & thus cause
hypokalemia
2. Hypokalemia itself is a cause of metabolic alkalosis.
 Hypokalemia cause alkalosis by 3 mechanisms:
1. Initially transcellular shifting throughout body
2. Transcellular shift in cells of proximal tubules
 Resulting in intracellular acidosis >> NH3 production >> Excretion
3. H+ secretion in proximal & distal tubules increase
 Leading to further reabsorption of HCO3
 The net effect is an increase in the net acid excretion.

39. METABOLIC ALKALOSIS
TREATMENT
 Saline / Chloride responsive (Urine Cl <25 meq/L)
 Vomiting or nasogastric suction
 Diuretics
 Posthypercapnia
 Cystic Fibrosis
 Low chloride intake
 Saline / Chloride un-responsive (urine Cl > 40 meq/L)
 Primary Mineralocorticoid excess
 Exogenous alkali load
 Barrter’s or Gitelman’s syndrome
 Severe Hypokalemia (K < 2.0)
 Potassium must be repleted in all cases of Metabolic
Alkalosis.

40. MIXED ACID BASE
DISTURBANCES
Metabolic acidosis + Respiratory acidosis
Metabolic acidosis + Metabolic alkalosis
Metabolic acidosis + Respiratory alkalosis
Metabolic alkalosis + Respiratory acidosis
Metabolic alkalosis + Respiratory alkalosis

41. When to suspect a Mixed acid-base disorder???
1. The expected compensatory response does not occur
2. Compensatory response occurs, but level of compensation is inadequate
or too extreme
3. Whenever the PCO2 and [HCO3-] becomes abnormal in the opposite
direction. (i.e. one is elevated while the other is reduced). In simple acid
base disorders, the direction of the compensatory response is always the
same as the direction of the initial abnormal change.
4. pH is normal but PCO2 or HCO3- is abnormal
5. In anion gap metabolic acidosis, if the change in bicarbonate level is not
proportional to the change of the anion gap. More specifically, if the delta
ratio is greater than 2 or less than 1.
6. In simple acid base disorders, the compensatory response should never
return the pH to normal. If that happens, suspect a mixed disorder.

42. 6 STEPS FOR ACID BASE ANALYSIS
Step 1: Is there an Acidemia or Alkalemia?
Step 2: Is the primary process metabolic or
respiratory?
Step 3: If primary process is respiratory, is it acute or
chronic?
Step 4: Is there an Anion gap? Na+ - Cl- - HCO3- > 12
Step 5: Is the respiratory compensation adequate?
 Expected pCO2 range = [1.5(measured HCO3-)] + 8 +/- 2
Step 6: Are there any other metabolic disturbances?
 Corrected HCO3- = (Measured HCO3-) + (AG – 12)

43. CASE STUDY
 60 year old male presents to ED from a nursing home. You have no history
other than he has been breathing rapidly and is less responsive than usual.
 Labs are:
LABs Value Normal LABs Value Normal
Na 123 135 – 145 BUN 10 – 25
K 3.5 – 5 Cr 1.2 – 1.5
Cl 99 95 – 105 Glu 60 – 100
HCO3 5 22 – 26 pH 7.31 7.35 – 7.45
pCO2 10 35 – 45 PO2 80 – 100
Albumin 3.5 – 5

44. LABs Value Normal LABs Value Normal
Na 123 135 – 145 BUN 10 – 25
K 3.5 – 5 Cr 1.2 – 1.5
Cl 99 95 – 105 Glu 60 – 100
HCO3 5 22 – 26 pH 7.31 7.35 – 7.45
pCO2 10 35 – 45 PO2 80 – 100
Albumin 3.5 – 5
Step 1: Is there an Acidemia or Alkalemia?
Step 2: Is the primary process metabolic or respiratory?
Step 3: If primary process is respiratory, is it acute or
chronic?
Step 4: Is there an Anion gap? Na+ - Cl- - HCO3- > 12
Step 5: Is the respiratory compensation adequate?
Expected pCO2 range = [1.5(measured HCO3-)] + 8 +/- 2
Step 6: Are there any other metabolic disturbances?
Corrected HCO3- = (Measured HCO3-) + (AG – 12)

45. Thanks for your Patience!!