Clinical Biochem Flashcards
What are the causes of respiratory acidosis?
- COPD
- Obesity Hypoventillation syndrome
- Neuromuscular disease
- Sedative drugs e.g. benzodiazepine, opiate overdose
- Decompensation as a consequence of respiratory conditions e.g. severe asthma attacks, type 2 resp failure secondary to COPD, pulmonary oedema
What are the causes of respiratory alkalosis?
- Altitude
- Pregnancy high progesterone stimulates the respiratory centre in the brain stem.
- Hyperventillation panic attacks, anxiety
- Pulmonary embolism lack of perfusion high CO2 stimulates medullary chemoreceptors stimulates respiratory drive increased total minute ventilation respiratory alkalosis
- Overdose salicylate poisoning initially respiratory alkalosis as it stimulates the respiratory centre, but later the patient develops metabolic acidosis.
- CNS disorders e..g stroke, subarachnoid haemorrhage, encephalitis
What is meant by the anion gap? Why is it important?
- Serum is electrically neutral amount of positive charge = amount of negative charge.
- We only measure potassium, sodium, chloride and bicarbonate ions when looking at the anion gap equation.
- As we don’t measure all of the anions e.g. organic anions, plasma protein anions, there is a gap (unmeasured).
Why might anion gap increase?
- Increase in the number of organic anions e.g. lactate ions, salicylate ions, ketones, methanol
- Since these organic anions have a proton associated with it, which becomes buffered by HCO3-, the proportion of HCO3- decreases. As a consequence, the organic anions then start to represent a larger proportion of the anions available in the serum hence the term raised anion gap.
What causes metabolic acidosis due to a high anion gap?
- Lactic acidosis: shock, sepsis, hypoxia
- Ketone acidosis : diabetic ketoacidosis, alcoholic ketoacidosis.
- Urate: Renal failure
- Acid poisoning: salicylates, methanol
When can anion gap be normal but the patient is still sick?
- When there is a loss of bicarbonate, but the level of anions is compensated by an increase in the amount of chloride ions.
- Since there is a reduction in the amount of bicarbonate ions available to buffer the protons in the serum, it leads to acidosis.
- Also called normal anion gap/hyperchloraemic metabolic acidosis.
What are the causes of metabolic acidosis due to normal anion gap?
- Diarrhoea is one of the biggest reasons for bicarbonate anion loss.
- Other reasons include:
o Gastrointestinal bicarbonate loss: diarrhoea ; uterosigmoidostomy, fistula
o Renal tubular acidosis
o Drugs e.g. acetazolamide works by inhibiting carbonic anhydrase increase availability of bicarbonate ions in the blood reduction in bicarbonate ion absorption in the kidneys reduction in bicarbonate ions in serum metabolic acidosis.
o Ammonium chloride injection
o Addison’s disease reduction in aldosterone level reduction in secretion of H+ ions metabolic acidosis
Describe the RAAS?
- Liver produces angiotensinogen
- Angiotensiongen - Angiotensin I (renin secreted by kidneys) angiotensin IIi (angiotensin converting enzyme as produced by the lungs).
- Angiotensin II has a number of effects on the body.
o Increases sympathetic activity of the body
o Causes adrenal glands to secrete aldosterone aldosterone increases the reabsorption of Na+/Cl-/H2O and excretion of K+.
o Causes vasoconstriction of the arterioles increase TPR increase BP
o Stimulates the pituitary gland to release ADH increase reabsorption of water from the DCT increase BV and BP by increasing the cardiac output of the heart.
What is the HPA axis?
CRH (hypothalamus) –> ACTH (pituitary gland) –> Cortisol/Aldosterone (adrenal glands)
What is diabetic ketoacidosis? Features? Management?
Complication of type 1 diabetes]
- Lack of glucose entry into cells due to lack of insulin –> cells become energy starved and so carry out lipolysis (adipose tissue) and proteolysis (muscle tissue). Lipolysis in adipose tissue leads to ketone production. Ketoacids increase the acidity of the blood.
Features
- Kussmall Breathing –> remove CO2 from the body (Respiratory compensation)
- Hyperkalaemia (lack of insulin mediated potassium entry into cells; due to buffering excess H+ in exchange for excretion of K+).
- High anion gap (ketoacidosis)
- Glycosuria, Polyuria, Polydypsia,
- Nausea, vomitting, changes in the mental state, cerebral oedema
- Fruity breath –> Ketones are removed from the body by conversion into acetones, which is removed by breathing. Acetones have a nice fruity smell (pear smell).
Treatment
- Fluids for dehydration
- Insulin to help lower blood glucose levels
- Potassium –> when given insulin, patients become hypokalaemic –> resolve via potassium.
What is Salicylate Poisoning? Features? Management
- Overdose of aspirin
- Mixed respiratory alkalosis and metabolic acidosis (later). In children, the metabolic acidosis is more predominant.
- Features include:
> Hyperventillation –> stimulate the resp centre to mediate respiratory compensation through the removal of CO2
> Tinnitus –> one of the earliest symptoms of salicylic acid poisoning
> Sweating/pyrexia –> salicylates stimulate uncoupling oxidative phosphorylation which causes heat production. Increased glucose and fat utilisation –> leads to metabolic acidosis as well.
> Hypoglycaemia/hyperglycaemia
> Seizures
>Coma
Treatments include
> ABCs
> Activated Charcoal within 1 hour of poisoning
> Urinary alkalisation to remove aspirin from the blood
> Haemodylasis
Metabolite of methanol? What is methanol poisoning? Features? Abnormal ranges of methanol in child and adults?
Management?
Methanol is a highly toxic alcohol.
Methanol is converted into formaldehyde and formic acid. It is these metabolic products that are responsible for the most serious toxic features e.g. metabolic acidosis, blindness and cerebral oedema.
> Formic acid accumulation leading to high anion gap metabolic acidosis.
> Formaldehyde is toxic to the retina and causes blindness, cerebral oedema.
Child - 10mL of pure methanol is fatal Adult - 30mL of pure methanol is fatal - ingestion of 10mL of methanol causes blindness
Mx
Need to reduce conversion of methanol to toxic metabolites
Methanol –> formaldehyde –> formic acid
Ethanol infusion (need to keep levels to 200mg/dL to compete with methanol for metabolism by alcohol dehydrogenase.
If methanol levels > 200mg/dL (6.2 mmol/L) –> consider haemodyalysis.
OR
Fomepizole (injection every 12 hours) – newer treatment – inhibits alcohol dehydrogenase.
Cofactor therapy with folinic acid to reduce any opthamological complications.
What is ethylene glycol? What is ethylene glycol poisoning? Features? Ix? Fatal doses? Management?
- Ethylene glycol is a type of alcohol used as a coolant and an anti-freeze.
The features of ethylene toxicity can be divided into 3 stages:
1) Stage 1: symptoms similar to alcohol intoxication: confused, slurred speech, dizziness.
2) Metabolic acidosis with high anion gap and high osmolar gap. Also, tachycardia and hypertensive.
3) Acute kidney injury.
Ix
- ABG, urine analysis
- Calculate anion gap –> marked high anion gap
- Calculate osmoality gap > high osmolality gap
- Measure serum ethanol to see if it accounts for the anion gap.
- serum calcium and renal function.
Fatal doses
- Fatal dose for a 70kg adult is approximately 100g of ethylene glycol (90ml of pure ethylene glycol).
Concentrations of ethylene glycol vary depending on the commercial product
- Anti-freeze : 60-100%
- Screen wash: 0-30%
Ethylene glycol is rapidly absorbed from the gut. Peak concentrations occur 1-4 hours after ingestion. If untreated, death from multiple organ failure will occur 24-36 hours after ingestion.
Management
- Ethanol was previously used for many years. It worked by competing with ethylene glycol for the enzyme alcohol dehydrogenase which would limit the formation of toxic metabolic such as glycoaldehyde and glycolic acid which were responsible for the features of the poisoning.
- Fomepizole- an inhibitor of alcohol dehydrogenase, is used as first line for ethylene glycol toxicity.
- Haemodyalsis may also be used in some cases.
What is metabolic alkalosis due to?
Causes of metabolic alkalosis?
- Excessive vomiting/aspiration (e.g. peptic ulcer leading to pyrloic stenosis; nasogastric suction).
o Excessive removal of gastric acid through vomiting or aspiration.
o Excessive vomiting leads to excessive depletion of the extracellular fluid. This activates the RAAS. This causes an increase in aldosterone levels. Aldosterone causes reabsorption of Na+ in exchange for H+ becoming excreted out in the DCT. This causes excessive loss of H+ ions, leading to metabolic alkalosis.
- Diuretics (loop diuretics)
o Can lead to excessive depletion of the ECF activates RAAS increase in aldosterone levels - increase in reabsorption of Na+ in exchange for H+ becoming excreted metabolic alkalosis.
- Liquorice, carbenoxolone
- Hypokalaemia
o K+ shifts from the cells into the extracellular space to increase K+ levels. To maintain electrical neutrality, H+ is shifted into the cells. This causes metabolic alkalosis.
- Primary hyperaldosteronism
o High levels of aldosterone excessive absorption of Na+ in exchange for H+ becoming excreted metabolic alkalosis.
- Cushing’s syndrome
o Cushing’s syndrome causes hypokalaemia and associated metabolic alkalosis.
- Bartter’s syndrome
o Kidneys unable to reasorb salt and therefore water depletion of ECF activation of RAAS high aldosterone metabolic alkalosis.
Treatment of metabolic alkalosis due to excessive vomitting?
- IV fluids (to prevent excessive activation of the RAAS).
- Potassium resupplementation
- Anti-emetic to stop the vomitting
