assessment disorders acidbase sarah curtis

8/11/2019 Assessment Disorders Acidbase Sarah Curtis

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Aims of the lecture

• Understand measurements used to

describe acid-base biochemistry

• Develop a logical approach to assessment

of acid-base disorders

• Apply knowledge to clinical cases



Let’s take a look at the

Henderson-Hasselbalch equation…

pH = pKa + Log10 [A-]

[AH]

Where has it come from?

Panic!

Panic!

Panic!

Panic!

Panic!

Panic!

What am I supposed to do with it?

Panic!

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You may previously have seen two different ‘logs’ used:

Base ‘10’ (Log10 often just written Log)

We are only concerned with Log10

Base ‘e’ (Loge or Ln)

and the reverse of this, ‘antilog’, 10x



The logarithm of 1000 to base 10 is 3…

Log10 1000 = 3

The logarithm of a number is the exponent by which another fixed

value, the base, has to be raised to produce that number.

????????

And in reverse… the ‘antilog’ of 3 to base 10 is 1000

Antilog 3 = 103 = 1000

…because 1000 is 103

1000 = 103 = 10 × 10 × 10



Enough maths, time for

some Chemistry…



Acid Equilibria

Acids reversibly dissociate to release protons (H+)

AH A- H+

acid conjugate

base (salt)

proton



Acid Dissociation Constant

Ka = [A-] x [H+]

[AH]

Strong acids (e.g. HCl) are more favourably dissociated: Ka large

Weak acids (e.g. ethanol) are poorly dissociated: Ka small

Describes the readiness with which an acid will dissociate

HCl Cl- H+

HCl Cl-Cl-

Cl-H+

H+

H+

H+Cl-

EtOH EtO-H+

EtO-

H+EtOHEtOH

EtOH

EtOH



Bringing in the logarithms…

We all love ‘pH’, but what does it mean?

Even for strong acids, [H+] is still very small…

Logarithms make the numbers manageable (pre electronic calculators!)

pH = -Log10[H+]

[H+]Blood = 40 nmol/L

Blood pH = -Log10[0.00000040]

= 0.00000040 mol/L

= pH 7.0

The same trick is used for the rather less popular ‘pKa’

pKa = -Log10[Ka]



Deep breath…

pKa = -Log10 [Ka] Substituting for Ka

Since LogXY = LogX + LogY

pH = pKa + Log10 [A-][AH]

= -Log10 [A-] [H+][AH]

= -Log10 [A-

] - Log10 [H+

][AH]

= -Log10 [A-] + pH

[AH]

pKa = -Log10 [Ka]Ka = [A-] [H+][AH]

We know:

Substituting for -Log10[H+]

Rearranging to put pH at the beginning

pH = -Log10 [H+]

= -Log10 [A-] x [H+]

[AH]

Henderson-Hasselbalch



Let’s take another look at the

Henderson-Hasselbalch equation…

pH = pKa + Log10 [A-

][AH]

Conjugate base (salt)

Acid

In blood there is a bicarbonate buffering system

Describes the relationship between pH and a buffering system

weak acid and its conjugate base (salt)

HCO3

-H2CO3 + H+



Henderson-Hasselbalch

and the blood

pH = pKa + Log10 [HCO3-

][H2CO3]

Conjugate base (salt)

Acid

The lungs

excrete CO2,

increasing

the buffering

capacity

Bicarbonate buffering in

blood has a pKa’ = 6.1

H2O + CO2

Carbonic

anhydrase

As H2CO3 is in equilibrium with CO2 we can replace this with PCO2 (kPa)

multiplied by a solubility factor 0.225

HCO3

-H2CO3 + H+

6.10.225 x PCO2



How does this relate to laboratory

assessment of acid-base Biochemistry?

pH = 6.1 + Log10 [HCO3- ]

0.225 x PCO2

Normal blood pH = 7.35-7.45

[H+] > 45 nmol/L = acidaemia

[H+] < 35 nmol/L = alkalaemia

Normal [H+] = 35-45 nmol/L

What is the prevailing [H

+

]?

Measured using pH electrode on blood gas machine

pH1st





pH = 6.1 + Log10 [HCO3-

]0.225 x PCO2

Normal blood PCO2 = 4.7-6.0 kPa

PCO2 > 6.0 kPa = metabolic

PCO2 < 4.7 kPa = respiratory

2nd

PCO2 > 6.0 kPa = respiratory

PCO2 < 4.7 kPa = metabolic

Alkalosis Acidosis

Is the primary disorder metabolic or respiratory?

Measured using CO2 electrode on blood gas machine

PCO2





pH = 6.1 + Log10 [HCO3- ]

0.225 x PCO2

Normal blood standard HCO3- = 22-26 mmol/L

3rd

Is there any compensation?

Derived by blood gas machine (Van Slyke equation) using pH, PCO2 & Hb

Normal [HCO3-]standard = all respiratory

Abnormal [HCO3

-]standard

= metabolic component

‘Standard’ bicarbonate is one corrected for respiratory contribution (normalise PCO2 )

a - 24.4 = - (2.3 ± b + 7.7) ± (c - 7.40) + d /(1 - 0.023 ± b )

a = bicarbonate concentration in plasma (mmol/L)

b = haemoglobin concentration in blood (mmol/L)

c = pH of plasma at 37 °C

d = base excess concentration in blood (mmol/L)





pH = 6.1 + Log10 [HCO3- ]

0.225 x PCO2

Normal Total CO2 (‘bicarbonate’) = 22-33 mmol/L

Measured enzymatically or derived by gas machine from Henderson-Hasselbalch

‘Total CO2 ’ is approximation of bicarbonate = HCO3- + CO2 + H 2 CO3 + CO3

-

TCO2 = Metabolic acidosis / Respiratory alkalosis

TCO2 = Metabolic alkalosis / Respiratory acidosis



Base Excess

CO2 cannot be buffered by bicarbonate…

Respiratoryalkalosis

relative base deficit

HPr

Pr - H+

Pr -

HPr

H+

Equilibration of CO2 requires non-bicarbonate buffers

relative base excess

H2O + CO2Carbonic

anhydrase

HCO3-H2CO3 + H+

/ negative base excess

Derived by blood gas machine using pH, PCO2 & Hb

Amount of strong acid/alkali needed to titrate whole blood to pH 7.4 at normal PCO2

BE = (HCO3- - 24.4 + [2.3 × Hb + 7.7] × [pH - 7.4]) × (1 - 0.023 × Hb)

Respiratory

acidosis



Anion Gap

‘Unmeasured’ Anions • Proteins

• -Hydroxybutyrate

• Acetoacetate

• Lactate

• Sulphates

• Phosphates• Formate

• Glycolate

• Oxalate

• Hippurate

• Salicylate

‘Unmeasured’ Cations • Calcium

• Magnesium

• (Lithium)

• (Cationic Igs)

Difference between sum of measured anions and cationsAnion gap = [Na+] + [K+] – [Cl-] – [HCO3

-]

Normal individuals have excess measured cations, hence anion ‘gap’

Increased

anion gap inmetabolic

acidosis

(HCO3-)

Absent gap is rare phenomenon

• Increased unmeasured cations

• Hypoalbuminaemia

• Bromide toxicity (spurious Cl-)

• Nitrates

(Osmolar gap indicates uncharged species)



Disorders of Hydrogen Ion

Homeostasis



Metabolic Acidosis

pH [H+] PCO2 HCO3- PO2

N /



Metabolic Acidosis - Causes

Increased Acid FormationKetoacidosis: diabetic, alcoholic, starvation

Lactic acidosis

Type A: tissue hypoxia

Type B: drugs, liver disease, IEMs

D-lactic acidosis

Poisoning: salicyate, alcohols

Inherited organic acidoses

Decreased Acid ExcretionUraemia

Distal renal tubular acidosis (1/4)

Acid IngestionStrong acid

Ammonium chloride

I.V. feeding with cationic amino acids

Loss Of BaseGastrointestinal: diarrhoea, fistula

Renal

Proximal renal tubular acidosis (2)

Acetazolamide

Ureteroenterostomy

Which of these increase the anion gap?



Metabolic Acidosis – Response

Buffering Acute H+ resisted by bicarbonate buffering causing HCO3

-

Tissue proteins and bone important in chronic acidosis

Respiratory Compensation

Peripheral chemoreceptors and respiratory centre stimulated – hyperventiliation

Self-limiting as generates additional CO2 – lower limit for PCO2 is 1.6 kPa

Develops rapidly but several hours to become maximal

Renal CompensationUrine H+ excretion maximised (pH 4.2)

Glutaminase induced in chronic acidosis

Increased renal gluconeogenesis

Increased rate of regeneration of bicarbonateGlutamine Glutamate

NH3 H2O



Systemic Effects Of Acidosis

Cardiovascular

Negative inotropic effect

Arteriolar vasodilaton

Constriction of peripheral veins

Oxygen Delivery

Immediate right shift (Bohr) in oxyHb dissociation curve

Slow left shift in oxyHb dissociation curve (synthesis breakdown 2,3-BPG)

Potassium

K+ movement from ICF to ECF causing hyperkalaemia

Decreased renal excretion

Frequently K-depleted; hypokalaemia common with correction

Bone

Decalcification with negative calcium balance

Osteodystrophy



Metabolic Acidosis - Management

Identify and treat cause

Administration of i.v. sodium bicarbonate (alkali)

Usually only given if [H+] > 100 nmol/L (pH 7.0)

Oral bicarbonate

CKD, RTA types 1 & 2

Rapid correction impairs O2 delivery (until 2,3-BPG normal)

Rebound alkalosis possible



Respiratory Acidosis

pH [H+] PaCO2 HCO3-

N /



Respiratory Acidosis - Causes

Defective Control Of RespirationCNS depression

Anaesthetics

Narcotics

Severe hypoxia

CNS disease

TraumaStroke

Neurological disease

Spinal cord lesions

Poliomyelitis

Guillan-Barre syndrome

Motor neurone diseaseNeurotoxins

Defective Respiratory FunctionMechanical

Myasthenic syndrome

Myopathies

Thoracic tumours and deformities

Pneumothorax

Pleural effusion Airway disease

Restrictive defects

Fibrosis

Pulmonary oedema

Infiltrative tumours

Obstructive defectsChronic bronchitis

Emphysema

Severe asthma

Laryngospasm

Impaired perfusion

Massive pulmonary embolism



Respiratory Acidosis – Response

Buffering

Limited buffering by haemoglobin

Intracellular buffers important in chronic acidosis


PCO2 stimulates respiratory centre but disease prevents adequate response

Renal Compensation

Maximal bicarbonate reabsorption

Almost all phosphate excreted as H2PO4-

Marked increase in urinary ammonium



Respiratory Acidosis – Systemic Effects

Hypoxaemia:

Breathlessness, cyanosis, drowsiness

Hypercapnia:

Neurological, headache, papilloedema, extensor plantar responses, myoclonus

Effects of acidosis (as for metabolic)

Respiratory Acidosis – Management

Treat underlying cause if possible

Maintain adequate arterial PO2, avoid loss of hypoxic stimulus to respiration Avoid rapid correction as risk of alkalosis due to persistence of compensation



Metabolic Alkalosis

pH [H+] PaCO2 HCO3- K+

N /

(not > 8kPa)



Metabolic Alkalosis - Causes

Saline-Responsive

Gastrointestinal

Vomiting

Gastric drainageCongenital Cl-losing diarrhoea

Exogenous alkali administration

Sodium bicarbonate

Lactate

Acetate (especially if GFR)

Urinary

Poorly reabsorpable anion therapy

Diuretic administration post PCO2

Saline-Unresponsive

Association with hypertension

Primary hyperaldosteronism

Secondary hyperaldosteronism

Not usually associated with HT

Barter’s syndrome

Refeeding syndrome

Severe potassium depletion

Magnesium deficiency

Excessive loss / increased generation of H+

, exogenous alkali



Metabolic Alkalosis – Response

Buffering

Release of buffered H+, with HCO3-


Decreased stimulation of chemoreceptors but self-limiting as PCO2 stimulates

Hypoxic stimulus also overrides H+

Renal Compensation

Inappropriate reabsorption of HCO3- due to GFR and increased tubular function

If ECF volume associated with Cl- deficiency, obligatory HCO3- reabsorption

Potassium deficiency contributes to persistence of alkalosis

Increased mineralocorticoid activity promotes distal tubular Na+



Metabolic Alkalosis – Systemic Effects

Generally opposite to those of acidosis

Less pronounced CV effects, poor O2 delivery, no apparent bone effects

Potassium depletion, which sustains alkalosis

Neuromuscular hyperexcitability: parasthesia, muscle cramps, tetany, convulsions

( Binding of H+ to albumin increases Ca2+ binding, lowering ionised calcium)

Metabolic Alkalosis – Management

Treat underlying cause

Treat factors that sustain alkalosisDo not give saline if saline-unresponsive cause

(e.g. sodium excess)



Respiratory Alkalosis

pH [H+] PaCO2 HCO3- K+ Phos

N /



Respiratory Alkalosis - Causes

Rate of excretion of CO2 exceeds rate of production Voluntary hyperventiliation

Mechanical hyperventilation

Reflex hyperventilationPulmonary compliance

Disease affecting chest wall

Irritative lesions of the air passages

Respiratory stimulation

Cortical influences : pain, fever, anxietyLocal disease: trauma, tumours

Toxins: salicylate, hepatic failure

Hypoxaemia: high altitude, right-to-left shunts, pulmonary disease, CO

Recovery from metabolic acidosis



Respiratory Alkalosis – Response

Buffering

Release of H+ from non-bicarbonate buffers

New steady state achieved within 6 hours

Respiratory CompensationInhibitory effect of PCO2 overwhelmed by primary cause

Renal Compensation

Decreased renal generation of bicarbonate (CO2 is substrate)



Respiratory Alkalosis – Systemic Effects

Manifestations of underlying disease predominate

Acute hypocapnia decreases cerebral blood flow

Ionised calcium: perioral and peripheral parasthesia

Cardiovascular: increased heart rate, tightening of chest, angina

Mild hypokalaemia

Marked hypophosphataemia

Respiratory Alkalosis – Management

Treat underlying cause

Rapid symptomatic relief by re-breathing

Sedation or prevention of hyperventilation

by mechanical hyperventilation



Mixed Acid-Base DisordersMixed primary disorders are quite common if you look for them

Some examples of double disorders… triple etc. also occur!

Metabolic Acidosis Metabolic Alkalosis

Respiratory Acidosis Respiratory failure

Cardiac arrest

Ethanol

Methanol

Diuretics + COPD

Vomiting + COPD

Severe K+ depletion

Respiratory Alkalosis Salicylate

Septicaemia

Fulminant hepatic failure

Ketoacidosis + pneumonia

Vomiting + CCF

Diuretics + pneumonia

Metabolic Alkalosis Vomiting + renal failure

Diuretics + DKA

Severe vomiting in ketoacidosis

Counterbalancing Additive



Conclusions

• Henderson-Hasselbalch is our friend!

• Respiratory disorders are compensated by

metabolic processes

• Metabolic disorders are compensated by

respiratory processes

• Over-compensation does not occur

assessment disorders acidbase sarah curtis

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