Assessment Disorders Acidbase Sarah Curtis
Transcript of 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
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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
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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
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Enough maths, time for
some Chemistry…
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Acid Equilibria
Acids reversibly dissociate to release protons (H+)
AH A- H+
acid conjugate
base (salt)
proton
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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
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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]
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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
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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+
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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
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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
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How does this relate to laboratory
assessment of acid-base Biochemistry?
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
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How does this relate to laboratory
assessment of acid-base Biochemistry?
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)
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How does this relate to laboratory
assessment of acid-base Biochemistry?
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
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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
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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)
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Disorders of Hydrogen Ion
Homeostasis
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Metabolic Acidosis
pH [H+] PCO2 HCO3- PO2
N /
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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?
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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
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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
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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
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Respiratory Acidosis
pH [H+] PaCO2 HCO3-
N /
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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
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Respiratory Acidosis – Response
Buffering
Limited buffering by haemoglobin
Intracellular buffers important in chronic acidosis
Respiratory Compensation
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
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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
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Metabolic Alkalosis
pH [H+] PaCO2 HCO3- K+
N /
(not > 8kPa)
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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
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Metabolic Alkalosis – Response
Buffering
Release of buffered H+, with HCO3-
Respiratory Compensation
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+
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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)
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Respiratory Alkalosis
pH [H+] PaCO2 HCO3- K+ Phos
N /
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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
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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)
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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
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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
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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