This document discusses acid-base physiology and disorders. It begins by explaining how carbon dioxide and volatile and non-volatile acids are produced daily through metabolism. It then defines volatile and non-volatile acids. The document goes on to discuss various calculations used to interpret acid-base disorders, including anion gap, delta ratio, osmolal gap, and urine anion gap. It explains the causes and characteristics of metabolic acidosis and alkalosis, including mixed disorders. Throughout, it provides examples of how to approach and diagnose complex acid-base imbalances.

1. Dr Mohammed
IMO
Ward 14
Chittagong Medical College Hospital

2. • About 20,000 moles of C02 are produced each
day by the metabolism of CHO & fat.
•Non volatile acid is produced each day by the
metabolism of protein (50-100 mmol /day)
• If 1 HCO¯³ is lost from the body 1 H+ stay
behind, the net result is addition of 1 free H+ into
the body.
•Conversely if H+ is lost 1 HCO¯³ is added to the
body.

3.  Volatile Acids:
 carbonic acids
 Non Volatile Acids:
 HCl, H2SO4, H3PO4, Lactic acid & Ketoacids.

4.  Calculations
 There are various calculations that are
commonly used diagnostically in interpreting
acid base disorders and distinguishing
between different causes of acid base
disorders.
 Calculating the anion gap is an approach
that must be taken in all cases of metabolic
acidosis.
 Other calculations such as osmolal gap and
urinary anion gap, delta gap, osmolarity &
urinary electrolytes.

5.  Acidaemia causes increase ammoniagenesis
 Alkalaemia causes descrease ammoniagenesis
 Hypokalaemia causes increase
ammoniagenesis
 Hyperkalaemia causes decrease
ammoniagenesis
 Facilitate non volatile acid secretion at the level
of collecting tubule

6.  The anion gap is estimated by subtracting the
sum of Cl- and HCO3- concentrations from
the plasma Na concentration.
 Na + Unmeasured cations = Cl- + HCO3- +
Unmeasured anions

 Anion gap = [Na] – ([Cl-] +
[HCO3-])

7.  The major unmeasured cations are calcium,
magnesium, gamma globulins and potassium.
The major unmeasured anions are negatively
charged plasma proteins (albumin), sulphate,
phosphates, lactate and other organic anions.
 The anion gap is defined as the quantity of
anions not balanced by cations.
 This is usually equal to 12 ± 4 meq/L and is
usually due to the negatively charged plasma
proteins as the charges of the other
unmeasured cations and anions tend to balance
out.

8.  If the anion of the acid added to plasma is Cl- ,
the anion gap will be normal (i.e., the decrease
in [HCO3-] is matched by an increase in [Cl-]).
For example:
HCl + NaHCO3 → NaCl + H2CO3 → CO2
+ H2O
 In this setting, there is a meq. for meq.
replacement of extracellular HCO3- by Cl- ;
thus, there is no change in the anion gap, since
the sum of Cl-] + [HCO3-] remains constant.

9.  This disorder is called a hyperchloremic
acidosis, because of the associated increase in
the Cl- concentration.
 GI or renal loss of HCO3- produces the same
effect as adding HCl as the kidney in its effort
to preserve the ECV will retain NaCl leading to
a net exchange of lost HCO3- for Cl-.

10.  In contrast, if the anion of the acid is not Cl-
(e.g. lactate, β-hydroxybutyrate), the anion gap
will increase (i.e. the decrease in [HCO3-] is not
matched by an increase in the [Cl-] but rather
by an increase in the [unmeasured anion]:
HA + NaHCO3 → NaA + H2CO3 → CO2
+ H2O, where A- is the unmeasured anion.

11.  Causes of elevated Anion gap acidosis is best
remembered by the mnemonic KULT or the
popular MUDPILES
 K = Ketoacidosis
 (DKA,alcoholic ketoacidosis, starvation)
U = Uremia (Renal Failure)
L =Lactic acidosis
T = Toxins
 (Ethylene glycol, methanol, paraldehyde,
 salicylate)

12.  M = Methanol
U = Uremia
D = DKA (also AKA and starvation)
P = Paraldehyde
I = INH
L = Lactic acidosis
E = Ethylene Glycol
S = Salycilate

13.  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 add 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).

14. pH = pK + log {[ acid ] / [ base ]}
H+ + HCO3- ═ H2CO3 ═ CO2 + H20
“The Buffer system” :
Extracellular- Hb,Proteins, HCO3-
Intracellular- Proteins, H2PO4-
Urine- NH3, H2PO4- , HCO3-

15.  The three main causes of normal anion gap
acidosis are:
 Loss of HCO3- from Gastrointestinal tract
(diarrhea)
 Loss of HCO3- from the Kidneys (RTAs)
 Administration of acid

16.  Distinguishing between the above 3 groups of
causes is usually clinically obvious, but
occasionally it may be useful to have an extra
aid to help in deciding between a loss of base
via the kidneys or the bowel.
 Calculation of the urine anion gap may
be helpful diagnostically in these cases

17.  The measured cations and anions in the urine
are Na+, K+, and Cl- ; thus the urine anion gap
is equal to:
 Urine anion gap
 =
 [Na+] + [K+] - [Cl-]
 Urine anion gap =
 unmeasured anions – unmeasured cations

18.  In normal subjects, the urine anion gap is usually
near zero or is positive.
 In metabolic acidosis, the excretion of the NH4+
(which is excreted with Cl- ) should increase
markedly if renal acidification is intact.
 Because of the rise in urinary Cl- , the urine anion
gap which is also called the urinary net charge,
becomes negative, ranging from -20 to more than -
50 meq/L.
 The negative value occurs because the Cl-
concentration now exceeds the sum total of Na+
and K+.

19.  If one molecule of metabolic acid (HA) is
added to the ECF and dissociates, the one H+
released will react with one molecule of HCO3-
to produce CO2 and H2O.
 This is the process of buffering.
 The net effect will be an increase in
unmeasured anions by the one acid anion A-
(ie anion gap increases by one) and a decrease
in the bicarbonate by one meq

20.  As a memory aid, remember ‘neGUTive’ -
negative UAG in bowel causes.
 Remember that in most cases the diagnosis
may be clinically obvious
 Causes of Renal tubular Acidosis
 (RTA Type-1, 2 and 4)

21.  The delta ratio is sometimes used in the
assessment of elevated anion gap metabolic
acidosis to determine if a mixed acid base
disorder is present.
 Delta ratio = ∆ Anion gap/∆ [HCO3-]
 or ↑anion gap/ ↓ [HCO3-

22.  Now, if all the acid dissociated in the ECF and
all the buffering was by bicarbonate, then the
increase in the AG should be equal to the
decrease in bicarbonate so the ratio between
these two changes (which we call the delta
ratio)
 should be equal to one.

23.  As described previously, more than 50% of excess
acid is buffered intracellularly and by bone, not by
HCO3- .
 In contrast, most of the excess anions remain in the
ECF, because anions cannot easily cross the lipid
bilayer of the cell membrane
 In lactic acidosis, for example, the ∆/∆ ratio
averages 1.6:1
 On the other hand, although the same principle
applies to ketoacidosis, the ratio is usually close
to 1:1 in this disorder because the loss of ketoacids
anions (ketones) lowers the anion gap and tends to
balance the effect of intracellular buffering.

24.  A delta-delta value below 1:1 indicates a
greater fall in [HCO3-] than one would expect
given the increase in the anion gap.
 This can be explained by a mixed metabolic
acidosis, i.e a combined elevated anion gap
acidosis and a normal anion gap acidosis, as
might occur when lactic acidosis is
superimposed on severe diarrhea.
 In this situation, the additional fall in HCO3- is due
to further buffering of an acid that does not
contribute to the anion gap.
 (i.e addition of HCl to the body as a result of
diarrhea)

25.  Delta Ratio <0.4=Hyperchloremic normal
anion gap acidosis
 Delta Ratio <1= High and normal anion gap
acidosis
 Delta ratio 1 to 2 = Pure anion gap acidosis
 Delta ratio 1.6:1 =lactic acidosis
 Delta ratio >2= High anion gap acidosis with
concurrent metabolic acidosis.

26.  The Osmolar Gap is another important
diagnostic tool that can be used in
differentiating the causes of elevated anion gap
metabolic acidosis.
 The major osmotic particles in plasma are Na+ ,
Cl- , HCO3-, urea and glucose and as such,
plasma osmolarity can be estimated as follows
 Plasma osmolarity = 2(Na) +
glucose/18 + BUN/2.8

27.  The normal osmolar gap is
 10-15 mmol/L H20 .
 The osmolar gap is increased in the presence of
low molecular weight substances that are not
included in the formula for calculating plasma
osmolarity.
 Common substances that increase the osmolar
gap are
 Ethanol, ethylene glycol, methanol, acetone,
isopropyl ethanol and propylene glycol.

28.  In a patient suspected of poisoning, a high
osmolar gap (particularly if ≥ 25)

 with an otherwise unexplained high anion gap
metabolic acidosis is suggestive of either
methanol or ethylene glycol intoxication

30.  Metabolic acidosis + Respiratory acidosis
 Metabolic acidosis + Metabolic alkalosis
 Metabolic acidosis + Respiratory alkalosis
 Metabolic alkalosis + Respiratory acidosis
 Metabolic alkalosis + Respiratory alkalosis

31.  WHO IS THE PRIMARY CULPRIT ?
 WHO IS TRYING TO COMPENSATE ?
 HOW TO TRACE THE MIXED ACID BASE
DISTURBANCES ?
 IS THERE AN OTHER DISORDER NOT
APPARENT IN THE ABG SLIP ?
TO REMEMBER
“ A NORMAL ABG DOES NOT RULE OUT AN
ACID BASE DISTURBANCE “

32.  STEP I - Catch The Primary Disorder
 STEP 2- Is the compensation adequate ?
 STEP 3- The 4 “Gaps”
 STEP 4- Don’t forget the electrolytes !
 STEP 5- Approach to each of the disorder

33.  pH= 7.35 -7.45
 HCO3- = 22-26 mEq/l
 pCO2 = 35- 45 mmHg
 ANION GAP = 9 -16 meq /l
 Na+ = 135 -145 meq/l
 K+ = 3.5 – 5.0 meq/l
 Cl- = 101-112 meq/l
 Se.osmolality = 275 -293 meq/l

34.  pH < 7.35 – ACIDOSIS ↓ HCO3- ↑Pco2
 pH > 7.45 – ALKALOSIS ↓ Pco2 ↑ HCO3

35.  Various formulae available
 To remember-
*Respiratory compensation (lungs)
occurs fast
*Metabolic compensation (kidneys)
occurs slow

39.  Serum Anion gap
 Urine anion gap
 The Delta gap
 Osmolar gap
 Correction for albumin

40.  For every 1 g/dl fall of albumin, anion gap falls
by 2.5 meq/l
 Hence, need to add 2.5 to anion gap for every 1
g/dl fall of albumin

41.  Tracing the “pattern”
 Egs-
1.Low Na,High K, N. AG Met. acidosis and
hypotension  Addison’s Disease
2.Hypertension,hypokalemia,metabolic
alkalosis Cushing’s Disease
3.Low Na, Low K, Low Cl, Met.Alkalosis in a
hypertensive pt.- Probable diuretic usage
4.Low K, High Cl, renal stones, Normal anion gap
Met.AcidosisRenal Tubular Acidosis

42.  Approach to each of the disorder

43.  ↑ ANION GAP ( k.u.s.m.a.l )
 NORMAL ANION GAP
+ URINE ANION GAP = R.T.A
- URINE ANION GAP = G.I bicarbonate
losses,Drugs,Addison’s

44.  CHLORIDE RESPONSIVE
• Urine Cl < 15 meq/l , ECV contracted
• G.I losses, diuretics, post hypercapnia,
• Post acidotic states, admin. of non reabs.
Anions (drugs )
 CHLORIDE NON RESPONSIVE
• Urine Cl > 25 meq/l ,hypervolemia, HTN
• Low K, Low Mg, Bartter’s syn.

45.  CAUSES OF HYPOVENTILATION
Respiratory problems, neurogenic poblems,
neuromuscular,drugs

46. Causes of hyperventilation
• CNS stimulation ( pain, anxiety , fever, trauma,
tumor, infection )
• Drugs ( progesterone, salicylates )
• Hypoxemia ( pneumonia, ARDS )
• Chest receptor stimulation ( PE , LVF )
• Septicemia , Hepatic failure

47.  A patient with AG=12,
Serum HCO3 24mEq/L
In ABG pH=7.40, [HCO3]=24, PCO2=40,
Then patient develop lactic acidosis AG rises from
12 to 32 HCO3 doesn’t fall it is still in 24 mEq/l
pH remains =40 PCO2= 40
What happened?

48.  Step 1: Everythings look normal
 Step 2: PCO2 & HCO3 normal no respiratory
disorder
 Step 3:AG is incresed by 20. there is incresed
AG but HCO3 is normal
 So change in HCO3= AG/1.5=13.3mEq/l
 HCO3 level should be (24-13.3)=10.7
 But HCO3 level is in 24 ,so there must be
something that pushing the HCO3 level to 24

49.  It is a metabolic alkalosis. The severe anion gap
acidosis is masked by metabolic alkalosis.
 If we don’t calculate the anion gap we can miss
this mixed metabolic acidosis.

50.  A pts pH=7.65,
 PCO2=30,
 HCO3=32,
 AG=30
Temperature is 102 degree
& BP=80/50. the urine analysis shows numerous
WBC & urinary deep stick is negative .

51.  Step 1: pH is up & HCO3 is up so Metabolic
alkalosis.
 Step 2: Compensated PCO2 in this case of
metabolic alkalosis
 PCO2=40+0.7(32-24)=45.6
 But PCO2 is 30 so respiratory alkalosis is also
present.
 Step 3: AG is 30 so high anion gap acidosis is
present this is due to lactic acidosis.
 So Ans is Metabolic alkalosis with respiratory
alkalosis with severe high anion gap metabolic
acidosis