Acid-Base Disorders

S. Kadiri
Introduction
Acids from metabolism

Fixed or volatile

Buffered or excreted to maintain pH
Buffer is a substance which limits the change in pH when acid or base is
added

70-100 mEq acid eliminated daily

Kidneys and lungs

Liver metabolism

Buffers
CO
2
-HCO
3
-quickest

Haemoglobin

Protein
-most abundant intracellular

Phosphate
pH = - log
10
[H
+
]

pH = base/acid = HCO
3
/CO
2

Normal 7.35-7.45

Introduction (cont)
H
+
= 24 pCO
2
/HCO
3
-pCO
2
and HCO
3
change in line to stabilize H+
- pCO
2
by CNS and lungs
- HCO
3
by kidneys
-response never returns H
+
to normal in pure ABDs

Base excess = 0.93 x [HCO
3
-24.4 + 14.8(pH-7.4)]
normal = +/-2
1 ATM = 101.9 kPa
mmHg/7.5 = kPa


pH
Normal
Acidaemia pH<7.35
Alkalaemia pH>7.45

Acidaemia more common
Metabolic acidosis perhaps most important
Definition

Buffer base the sum of HCO
3
-
and the nonvolatile weak acid buffers (A
-
)


Base excess (BE) the amount of acid or base that must be added to a
sample of whole blood in vitro to restore the pH of the sample to 7.40 while
the P
CO2
is held at 40 mmHg
-negative in acidaemia
-positive in alkalaemia


Standard base excess
-base excess at reference of Hb 5g/dL
- Hb buffers plasma and much larger extracellular fluid.




Compensation
Kidneys slow: 1-2 days and full in 3-5 days
Lungs can be fast: within mins, full in 1-2 days
Changes in C0
2
, no change in H
+
With well functioning organs

pCO
2
changes not caused by overproduction

Metabolic acidosis or alkalosis features of
acute met disturbance or chronic lung disease
- not acute lung disease


Steps to Interpretation
Note pH : normal, acid, alkaline
pCO
2
serum HCO
3
Compensation
Anion gap may be the only abnormality
Mixed disorders
Acute or chronic
Severity of disorder


Interpreting ABGs (Identifying
Imbalances)
1. Look at pH first. Is it normal, acidotic or alkalotic?


2. Look at pCO
2
next. Is it normal, high (acidotic) or low
(alkalotic)?
***If pCO
2
is inverse with pH, its a respiratory problem.


3. Look at HCO
3
-
next. Is it normal, low (acidotic) or high
(alkalotic).
***If HCO
3
-
is direct with pH, its a metabolic problem.
pH CO2 HCO3 2
nd
ary Responses

RAc < 7.4 > 40 > 24 increased renal acid excretion
(increased HCO3, rarely > 32 mEq/L)




R Alk > 7.4 < 40 < 24 Decreased renal acid excretion
(decreased HCO3, rarely <16 mEq/L)




MAc < 7.4 < 40 < 24 Hyperventilate




M Alk > 7.4 > 40 > 24 Hypoventilate
(pCO2 usually < 55 mmHg)
Respiratory acidosis - compensation
Problem high pCO
2
High H
+
, low pH
H
+
stimulates kidney to retain HCO
3
Complete in 2-4 days
Limit of compensation 45
Expected HCO
3
= 0.44 x pCO
2
+ 7.6 +/- 2

Respiratory alkalosis - compensation
Problem low pCO
2
Low H
+
, high pH
Stimulates kidneys to excrete HCO
3
Complete in 7-10 days
Limit is 12 mmol/L
Metabolic acidosis - compensation
Problem low HCO
3
High H
+
. Low pH
Stimulates respiration
Complete in 12-24 hrs
Expected pCO
2
= 1.5 x HCO
3
+ 8..+/-2
Limit 10 mmHg
Metabolic alkalosis - compensation
Problem high HCO
3
Low H
+
, high pH
Suppresses respiration which raises pCO
2
Complete in 12-24 hrs
Expected CO
2
= 0.9 x HCO
3
+ 9 ..+/- 2
Limit is 60
Mixed acid-base disorders
Plasma HCO
3
and CO
2
change in different
directions

Appropriate secondary responses not present

Secondary responses fully correct or overshoot
pH

Severity and worse outcomes with disorders that
enhance pH change
pCO2 respiratory component
pCO
2
inverse to pH respiratory cause

If HCO
3
also low combined resp & met
acidosis

If pCO
2
direct to pH not resp
low pCO
2
resp compensation for met acid

HCO
3
/SBE metabolic component
pH direct with HCO
3
/SBE metabolic

If pCO
2
also high combined met & resp acid

If SBE/HCO
3
inverse to pH not metabolic
HCO
3
/SBE high compensation


In Metabolic acidosis
If there is a metabolic acidosis (pH<7.4 and
HCO
3
-
< 24), what should the pCO
2
be?
Winters formula: ONLY IN METABOLIC
ACIDOSIS
Predicts the compensation of pCO
2
pCO
2exp
=[ [HCO
3
-
] x 1.5] + 8 + 2
NONE OF THE OTHER RULES WORK.

In Metabolic Acidosis
Example: if the HCO
3
-
is 12
pCO
2exp
= [12 x 1.5] +8 + 2 = 26 +2
Using this example, it is a simple disorder if the
pCO
2
is 24-28
If the pCO
2
< 24, then it is too far: therefore, a
primary respiratory alkalosis
If the pCO
2
> 28, not far enough, therefore, a
primary respiratory acidosis




additional tips

Expected pCO
2
= last 2 digits of blood pH

If inadequate, additional respiratory acidosis

If excessive, additional respiratory alkalosis
Acid-base rules
The compensating partner has five choices:
1. Change in the proper direction, but too far.
2. Change in the proper direction, just right.
3. Change in the proper direction but not far enough.
4. Not change at all.
5. Change in the other direction.
6. Only one of this is a simple disorder with appropriate
compensation: #2.
7. All of the others have a second primary disorder
Acute or chronic ?
Respiratory compensation fast
Renal compensation slow
Ac. R Ac - 10mmHg increase in CO
2
, HCO
3
up by 1
Ch. R Ac - 10mmHg increase in CO
2
, HCO
3
up by 4
Ac. R Al decrease of 10, HCO
3
drop by 2
Ch. R Al decrease of 10, HCO
3
drops by 5
severity

Adjective
PCO
2

mmHg
SBE
mEq/L
Alkalosis
Severe > 18 > 13
Marked 18 to 25 13 to 9
Moderate 25 to 30 9 to 6
Mild 30 to 34 6 to 4
Minimal 34 to 37 4 to 2
Normal Normal 37 to 43 2 to -2
Acidosis
Minimal 43 to 46 -2 to -4
Mild 46 to 50 -4 to -6
Moderate 50 to 55 -6 to -9
Marked 55 to 62 -9 to -13
Severe > 62 to < -13
Acid-case patterns observed in humans
Acid excretion
Origin of acidosis
Addition of acid
endogenous
exogenous

Reduced excretion of acid

Loss of bicarbonate
Renal excretion of acid

Secretion of ammonia

Titratable acidity

Reabsorption of bicarbonate
Excretion of ammonia

Produced in tubular cells
Captures H
+
in lumen
Excretion of NH
4
-
salts
Facilitated by acidaemia and hypokalaemia
Inhibited by alkalaemia and hyperkalaemia
Titratable acidity

Definition

Mainly P0
4
-
and SO
4
-


Capture H
+
in lumen
Bicarbonate reabsorption
80-90% in PCT

Brush border carbonic anhydrase

10-20% in distal segments

Daily filtered about 4500 mEq

Metabolic acidosis


Classification
High and Normal anion gap MA

[Na] [HCO
3
-
- Cl
-
}

Owing to serum albumin, unmeasured anions

Normal 4-12
Limitations of AG
Potassium level (K
+
) ignored when 4 mEq/L
Normal values for AG in most laboratories
12 +/- 4 if K
+
is considered
8 +/- 6 if K
+
is not considered
Doubt of AG reliance on normal albumin and
phosphate which are changed by pH


At pH 7.4, 1 g/dL of albumin has charge of 2.8 mEq/L
at pH 7.0, the charge is 2.3 mEq/L
at pH 7.6, the charge is 3.0 mEq/L

Low anion gap - causes

Hypoalbuminaemia
Hyperlipidaemia
Hyperviscosity
Paraproteinaemia
Increased cations
Causes of metabolic acidosis
Normal AG

Renal acidification defects
Proximal renal tubular acidosis
Classic distal tubular acidosis
Hyperkalemic distal tubular acidosis
Early renal failure

Gastrointestinal loss of bicarbonate
Diarrhea
Small bowel losses
Ureteral diversions
Anion exchange resins
Ingestion of CaCl2

Acid infusion
HCl
Arginine HCl
Lysine HCl
Increased AG

Endogenous acid load
Ketoacidosis
-Diabetes mellitus
-Alcoholism
-Starvation
Uremia
Lactic acidosis

Exogenous toxins
Osmolar gap present
-Methanol
-Ethylene glycol
Osmolar gap absent
-Salicylates
-Paraldehyde
Renal failure
Impaired secretion of NH
3
-maybe NAG at this stage

Retention of PO
4
-
and SO
4
-
Bicarbonate wastage
-HAG at this stage
Acid and Cl- administration
HCl from parenteral nutrition

NaCl infusion and expansion acidosis

Fall in blood pH

Cl
-
keeps anion gap
Bicarbonate losses - GIT
Severe diarrhoea
Pancreatic fistula
Biliary drainage
Pancreas-bladder anastomosis
Urine diversion to colon or ileum

HCO
3
-
exchanged for Cl
-
in ileum and colon
Bicarbonate losses - kidneys

Proximal tubular disorder

Hypocapnia

Reduced bicarbonate reabsorption

Reduced H+ excretion

Type-1 renal tubular acidosis

Type-4 renal tubular acidosis
-hypoaldosteronism
Type-1 RTA
Impaired H
+
extrusion from -intercalated
cells
Urine pH > 5.3
K
+
excretion for Na
+
reabsorption
Hypokalaemia
Hyperkalaemic form may occur with
obstruction
Ca phosphate stones and nephrocalcinosis
Calcium phosphate stones
Calcium citrate more soluble than calcium
phosphate
Increased PT reabsorption of citrate
Hypokalaemia promotes hypocitraturia
Hypocitraturia promotes phosphate stones
Ca phosphate stones less soluble than citrate
stones
Type-4 RTA - causes

Diabetes mellitus
NSAID
Cyclosporin
ACEI, ARB
Heparin
Type-4 RTA
Impaired Na
+
reabsorption

Impaired K
+
secretion

Hyperkalaemia inhibits NH
3
production

Acidosis, urine pH < 5.3
Acidosis clinical features
Blood pH > 7.20
Counter regulatory hormones actives

Kussmauls respiration
Nausea, vomiting
Change in mental status

Blood pH < 7.20 -- Counter regulatory
hormones ineffective

Hypotension
Depressed myocardial
contractility,
vasodilatation
Reentrant arrhythmias
Ventricular fibrillation

reduced albumin
synthesis
Activation of
complement
Enhanced muscle
breakdown
Bone buffering and
resorption

Investigations
pH
HCO
3
-
pCO
2
H
+
Anion gap
Serum K
+
Increased anion gap
Due to unmeasured anions
-Deplete bicarbonate

Corrected HCO
3
= measured HCO
3
+ (anion gap 12)
Normal = 22-26

If reduced, additional metabolic acidosis
If elevated, additional metabolic alkalosis
Normal anion gap MAc
2 large groups renal/GI
Clinical differentiation
Urine anion gap
Positive UAG, renal cause
Negative UAG, GI cause
Urine anion gap

UAG= [Na
+
+ K
+
] [Cl
-
]

<0 in diarrhoea

>0 in type-1 RTA
Treatment
Of acidaemia

Of underlying disorder

Alkali

Dialysis
Alkali therapy

Serum HCO
3
-
< 12 mEq/L
Newer recommendations to keep level 20-25
0.5-1 mEq/Kg/day
0.3 x weight x BE
NaHCO
3
K citrate in type-1 RTA
Calculating BE
Van Slyke equation ~ Scan J Clin Lab Invest 977; 146:15-20


* Hb and HCO
-
3
expressed in mmol/L
BE changes slightly with changes in PCO
2
Modified hemoglobin on CO
2
titration



Still changes slightly as PCO
2
and assume normal A
TOT

BE = (HCO
3
-
- 24.4 + [ 2.3 x Hb + 7.7 ] x [ pH 7.4 ]) x (1 0.023 x Hb)
SBE = 0.9287 x (HCO
3
-
- 24.4 + 14.83 x [ pH 7.4 ])
Six Classical Acid-Base Disturbances
pH PCO
2
SBE Interpretation Compensation
Acid
Acid
Alk Resp. Acid. Comp
SBE Half way - Normal
Met. Comp.
Norm Resp. Acid. Pure
SBE Normal - No Met.
Comp
Alk Acid Met. Acid. Comp
PCO
2
Half way -
Normal Resp. Comp.
Alk
Alk
Acid Resp. Alk. Comp
SBE Half way - Normal
Met. Comp.
Norm Resp. Alk. Pure
SBE Normal - No Met.
Comp
Acid Alk Met. Alk. Comp
PCO
2
Half way -
Normal Resp. Comp
Four Other Acid-Base Disturbances
pH PCO
2
SBE Interpretation Compensation
Acid
Acid Acid
Combined
Acidosis
Not Applicable -
Both Acid
Norm Acid Met. Acid. Pure
PCO
2
Normal -
No Resp. Comp
Alk
Alk Alk
Combined
Alkalosis
Not Applicable -
Both
Components
Alkaline
Norm Alk Met. Alk. Pure
PCO
2
Normal -
No Resp. Comp