ACID BASE DISTURBANCE

by
Assoc. Prof. Dr. Subashini C. Thambiah

MPATH I INTENSIVE COURSE

30/01/2019
 SCOPE OF LECTURE
• Introduction:
– Normal acid base physiology

• Acid base Disorders:

– Metabolic Acidosis (Non-Respiratory Acidosis)
– Respiratory Acidosis
– Metabolic Alkalosis (Non-Respiratory Alkalosis)
– Respiratory Alkalosis

• Questions

• Summary
 INTRODUCTION
• Normal process of metabolism results in net formation of 40-80mmol/L of H+
ions /24h

• As H+ ions generated, they are buffered  limit ↑ [H+]

• Buffer System weak acid & conjugate base

H+ + HCO-3  H2CO3 Eqn 1

• HCO-3 most important buffer system in ECF  enhanced as carbonic acid can
readily be formed from carbon dioxide or disposed by conversion into carbon
dioxide and water

CO2 + H2O  H2CO3 Eqn 2

• From the Eqns 1 & 2:

[H+] = K PCO2 Eqn 3
[HCO-3]
where K is a dissociation constant
 INTRODUCTION

H+ + HCO-3  H2CO3  CO2 + H2O

• For every H+ buffered by HCO-3, a HCO-3 is consumed

• To maintain capacity of buffer system, HCO-3 MUST be regenerated

• Yet when HCO-3 is formed from H2CO3 (indirectly from CO2 & H2O), equimolar
amounts of H+ are formed simultaneously

• HCO-3 formation can only continue if H+ removed

• This process occurs in renal tubular cells, where H+ secreted into urine while
HCO-3 generated and retained in the body

• Other buffer systems  proteins, PO-4

REABSORPTION OF FILTERED BICARBONATE BY
RENAL TUBULAR CELLS (PCT)

HCO-3 cannot be
reabsorbed directly.

H+ and HCO-3 are

generated in renal tubular
cells and the H+ are
secreted in exchange for
Na+ into tubular lumen
where they combine with
filtered HCO-3 to form CO2
and H2O.

HCO-3 diffuse with Na+ from

the tubular cells into the
interstitial fluid and then
into the plasma
RENAL HYDROGEN ION EXCRETION (DCT)

H+ and HCO-3 are

generated in renal tubular
cells from CO2 and H2O by
the reversal of the buffering
reaction.

The H+ are excreted in the

urine buffered by phosphate
and ammonia while HCO-3
the enters the ECF,
replacing that which was
consumed in buffering.
 HENDERSON-HASSELBACH EQUATION
pH = pK + log (base) / (acid)

pH  HCO-3
H2CO3

In plasma, H2CO3 is directly related to PCO2

pH  HCO-3
PCO2

↑ pH  alkalosis
↓ pH  acidosis

Normal range pH: 7.35 – 7.45

 DISORDERS OF H+ HOMEOSTASIS
• 4 components in pathophysiology of H+ disorders:
– Generation
– Buffering
– Compensation
– Correction

pH  HCO-3
• Acid base disorders can be classified as: PCO2
– Acidosis ([H+] above normal or pH below normal)
– Alkalosis ([H+] below normal or pH above normal)

• Which is further classified as:

– Respiratory (primary change in PCO2)
– Metabolic (primary change in [HCO-3])
 METABOLIC ACIDOSIS
H+ + HCO-3  H2C03  CO2 + H20
• Excess [H+] buffered by HC0-3 & other buffers

• H2C03 forms & dissociates and the C02 is lost in the expired air

• This buffering limits the potential rise in [H+] at the expense of a reduction in
[HC0-3]

• Compensation by hyperventilation (direct stimulation of respiratory centre by

increased [H+]  increases removal of C02 and lowers PC02  PC02 / HC0-3
ratio falls  reduce [H+]
[H+] = K PC02
[HC0-3]
• In a healthy person  hyperventilation produces respiratory alkalosis

• If renal function normal  excess [H+] excreted by kidneys

 Increased H+ formation:
- Ketoacidosis (diabetes (DKA), alcoholic)
- lactic acidosis (LA) (causes next slide)
- Poisoning eg ethanol, methanol, ethylene glycol,salicylate
- Inherited organic acidoses

Acid ingestion:
Loss of HCO-3 :
- Acid poisoning
- Diarrhoea Causes of
Metabolic - Excessive parenteral
- Pancreatic,
Acidosis admin’n of amino
intestinal and biliary
acids eg arginine,
fistulae and drainage
lysine & histidine

Decreased H+ excretion:
- Renal tubular acidoses
- Chronic renal failure (CRF)
- Carbonic dehydratase inhibitors
 METABOLIC ACIDOSIS:
CAUSES OF LACTIC ACIDOSIS
• Type A - Tissue hypoxia:
– Decreased perfusion
– Reduced arterial P02

• Type B – other causes:

– Drugs, etc:
• Ethanol, methanol
• Phenformin
• Fructose, sorbitol

– Congenital:
• Glucose 6-phosphatase deficiency
• Other inherited diseases with defective gluconeogenesis or
pyruvate oxidation
 ANION GAP IN METABOLIC ACIDOSIS
• The difference between the sum of [ ] of the principal cations (Na+ and K+) & of the
principal anions (Cl- and HC0-3 ) is known as the ANION GAP:

ANION GAP = ([Na+] + [K+]) – ([Cl-] + [HC0-3 ])

• In health, anion gap is 14 – 18 mmol/L

• When [HC0-3 ] falls, electrochemical neutrality must be maintained by other anions

• If Acidosis is due to:

– Excess generation of acids eg. acetoacetate & -hydroxybutyrate in DKA &

lactate in LA (increase in anions other than Cl-) Anion Gap is HIGH (HAGMA)
because HC0-3 consumed in buffering these acids

– loss of HC0-3 eg. diarrhoea  Anion Gap is NORMAL (NAGMA) because loss of
HC0-3 is replaced by increased renal Cl- retention (↑ Cl-) and therefore anion gap
is unaffected

• Thus, anion gap can be useful in the Dx of metabolic acidosis

 METABOLIC ACIDOSIS
Characteristic biochemical changes: [H+] = K PC02
[HC0-3]

pH  HC0-3 / PC02
Analyte Changes

↓[HC0-3 ] [H+] ↑

↓ pH pH ↓

Stimulates respiratory centre PC02 ↓

(respiratory
(hyperventilation) compensation)

↓PC02 [HC0-3 ] ↓↓

Normalises pH
 RESPIRATORY ACIDOSIS

• Associated with increase in PC02

• For every H+ produced, a HCO-3 generated

• H+ buffered by intracellular buffers particularly Haemoglobin

• Acute respiratory acidosis  HCO-3 may increase but usually

within reference range

• Chronic respiratory acidosis  HCO-3 clearly elevated due to

renal compensation
 Depression of respiratory
Airway obstruction:
centre:
• Chronic obstructive • anaesthetics
airway disease eg • sedatives
bronchitis, emphysema • cerebral trauma
• Bronchospasm eg asthma • tumours
• Aspiration
Causes of
Respiratory
Acidosis
Pulmonary disease:
• pulmonary fibrosis
Neuromuscular disease: • severe pneumonia
• poliomyelitis • respiratory distress syndrome
• Guillain-Barre syndrome
• motor neuron disease
• tetanus, botulism
• neurotoxins, curare Extrapulmonary thoracic disease:
• flail chest
• severe kyphoscoliosis
 RESPIRATORY ACIDOSIS
• Characteristic biochemical changes:
H+ + HCO-3  H2C03  CO2 + H20
pH  HC0-3 / PC02
↑PC02
Analyte Acute Changes Chronic Changes

[H+] ↑ Slight ↑ or
↑ HC0-3 high-normal

pH ↓ Slight ↓ or
low-normal
Acute Chronic
1st 10mins 7 days PC02 ↑ ↑
↑2-4mmol/L ↑ 45mmol/L
Site: RBC Site: Kidney [HC0-3 ] Slight ↑ ↑
(renal
compensation)

Normalises pH
 METABOLIC ALKALOSIS
H+ + HCO-3  H2C03  CO2 + H20

• Characterised by primary increase in the ECF [HC0-3], with a

consequent reduction in [H+]

• In a normal person, an increase in HC0-3 leads to incomplete

renal tubular reabsorption and excretion of HC0-3 in urine

• A low arterial [H+] inhibits the respiratory centre 

hypoventilation  increase PC02  increase ratio PC02 / HC0-3
 increase H+
[H+] = K PC02
[HC0-3]
 Causes of Metabolic Alkalosis

Loss of unbuffered H+:

Gastrointestinal:
- Gastric aspiration
- Vomiting with pyloric stenosis
-Congenital chloride-losing
diarrhoea Administration of alkali:
- Inappropriate treatment
Renal: of acidotic states
Mineralocorticoid excess: -Chronic alkali ingestion
- Cushing’s syndrome
- Conn’s syndrome
Drugs with mineralocorticoid activity
eg carbenoxolone
Diuretic therapy (not K+ sparing)
Rapid correction of chronically raised
PC02
K+ depletion
 METABOLIC ALKALOSIS
Characteristic biochemical changes: [H+] = K PC02
[HC0-3]

pH  HC0-3 / PC02
Analyte Changes
↑ [HC0-3 ]
[H+] ↓

↑ pH
pH ↑

Inhibits respiratory centre PC02 ↑

(hypoventilation) (respiratory
compensation)

↑PC02
[HC0-3 ] ↑↑

Normalises pH
 RESPIRATORY ALKALOSIS

• Characterised by fall in PC02, which reduces the ratio of

PC02/HC0-3

• The fall in PC02 causes a small decrease in [HC0-3] by

Haemoglobin buffer system in RBC

• Compensation occurs through a reduction in renal H+ excretion

 further decreases plasma [HC0-3] (less HC0-3 regenerated)

• Renal compensation in respiratory alkalosis develops slowly, as

it does in respiratory acidosis
 Mechanical Hypoxia:
overventilation
- High
Causes of altitude
Respiratory - Severe
Alkalosis anaemia
- Pulmonary
disease
Increased respiratory drive:
- Respiratory stimulants, eg
salicylates
Pulmonary disease:
- Cerebral disturbances, eg
trauma, infection & tumours - Pulmonary
oedema
- Hepatic failure
- Pulmonary
- Gram negative septicaemia embolism
- Primary hyperventilation
syndrome
- Voluntary hyperventilation
 RESPIRATORY ALKALOSIS
• Characteristic biochemical changes:
H+ + HCO-3  H2C03  CO2 + H20
pH  HC0-3 / PC02
↓PC02
Analyte Acute Changes Chronic
Changes
[H+] ↓ Slight ↓ or
↓ HC0-3 low-normal

pH ↑ Slight ↑ or
high-normal
Acute Chronic
1st 10mins 7 days
PC02 ↓ ↓
↓2-4mmol/L ↓ 12-14mmol/L
Site: RBC Site: Kidney [HC0-3 ] Slight ↓ ↓
(renal
compensation)

Normalises pH
 SUMMARY
pH  HC0-3
PC02

Acid-Base Plasma pH Primary disturbance Compensation

Imbalance
Metabolic acidosis ↓ ↓ HC0-3 Hyperventilation 
Low PC02

Metabolic alkalosis ↑ ↑ HC0-3 Hypoventilation 

High PC02

Respiratory alkalosis ↑ ↓ PC02 Decreased renal H+

excretion 
decrease serum HC0-3

Respiratory acidosis ↓ ↑ PC02 Increased renal H+

excretion 
increase serum HC0-3
SUMMARY
• 70-year-old man presented with haematemesis and malaena with past history of
oesophageal varices secondary to liver cirrhosis. No history of medication
intake.
• On examination, patient was tachypnoeic, tachycardic and hypotensive.
Investigations as below:

Plasma Results Reference

range
Sodium 139 mmol/L 135 – 145
Potassium 4.8 mmol/L 3.6 – 4.8
Chloride 98 mmol/L 98 – 108
Bicarbonate 6 mmol/L 23 – 33
Urea 24 mmol/L 3.3 – 6.7
Creatinine 0.24 mmol/L 0.06 – 0.12
pH 7.13 7.35 – 7.45
PC02 22mmHg 35 – 45

• Further blood tests revealed:

• Glucose 5.6 mmol/L (2.8 – 6.0mmol/L)
• Hb 5.5g/dL (14 – 17)
• Lactate 28mmol/L (< 2)
A 25-year-old man with no previous medical illness was admitted
unconscious following a head injury. CT-scan revealed extensive cerebral
contusions. The respiratory rate was increased, at 39 breaths/minute. The
following are his arterial blood gas results.

Plasma Results Reference range

pH 7.47 7.35 – 7.45
PCO2 29 35 – 45 mmHg
HCO3- 21 23 – 26 mmol/L

Select the best explanation for his PCO2 result.

a) Due to chronic respiratory alkalosis.

b) Due to hyperventilation in respiratory alkalosis.
c) Presence of mixed acid base imbalance.
d) Respiratory compensation for metabolic acidosis.
Causes of respiratory acidosis include

a) severe asthma.
b) flail chest.
c) liver failure.
d) acute renal failure.
e) alcoholic ketoacidosis.
7-year-old girl started hyperventilating prior to her
ballet performance. She complained of tingling of
her fingers and toes and was unable to dance. She
was rushed to the hospital. Investigations as below:

Plasma Results Reference

range
pH 7.53 7.35 – 7.45
PC02 29 mmHg 35 – 45
Bicarbonate 20 mmol/L 23 – 33

1. State the acid base disorder.

2. Explain your answer in (1).

3. Explain briefly the cause of her tingling extremities.