diagnostics and pathophysiology of alcohol abuse

Question 1

how to calculate osmolal gap

Answer 1

(2x Na + Urea + Glucose)

Question 2

how to calculate anion gap

Answer 2

(Na+ + K+) – (HCO3- + Cl-)

Question 3

what is alcoholic ketoacidosis

Answer 3

• tends to occur the day after a massive binge
• Lipolysis tends to be increased because of the increased levels of cortisol and catecholamines, caused by the extra stress placed on the patient’s body from the alcohol.
• Lipolysis contributes to an abundance of FFA, which in turn sees some diverted to ketone production (the three ketones you will see mentioned are acetoacetate, beta-hydroxybutyrate, and acetone – alcoholic ketoacidosis tends to involve excess beta-hydroxybutyrate) .

The excess alcohol to be metabolised drives NADH+ production, which in turn, drives the production of the ketone beta-hydroxybutryate.
Chronic alcohol misusers have depleted reserve. Ethanol will provide calorie intake, though glycogen stores will be depleted.
The metabolism of ethanol raises NADH/NAD which in turn impairs hepatic gluconeogenesis and the metabolism of lactate.
So the patient has impaired ability to make glucose, or metabolise lactate, driving the hypoglycaemia and acidosis.

Question 4

what does a deficiency in thiamine cause

Answer 4

build up of lactic acid, amongst other things (chronic alcohol misusers are prone to be deficient in as alcohol blocks duodenal uptake of thiamine and interferes with thiamine storage and conversion).

Question 5

thiamine deficiency and unexplained lactic acidosis

Answer 5

Lack of activity of alpha ketoglutarate dehydrogenase in particular has been linked to mitochondrial damage causing cellular necrosis, and triggering apoptosis (cell death) – cells in the cerebellum are particularly sensitive to this (hence the motor control issues).
Thiamine (or its I.V. formulation Pabrinex) has very little downside to administration (there is the very small chance of anaphylaxis) – if you ever see an unexplained lactic acidosis, give thiamine.
If you do not, and give glucose without it in the malnourished or thiamine deficient patient, you risk driving Wernicke’s Encephalopathy.

Question 6

alcoholic liver disease and LFTs

Answer 6

The metabolite of ethanol, acetaldehyde, is thought to be particularly toxic especially to hepatic proteins.

With Fatty Liver (alcoholic steatosis) – there is often a subclinical hyperbilirubinaemia and mild elevation of transaminases (AST/ALT). Gamma GT is elevated in a majority of patients.

With Alcoholic Hepatitis – a diversity of presentations from jaundice, anaemia, and leucocytosis. The hepatic enzymes tend to present in a ratio of AST: ALT >2 (should normally be <1).