Deaths related to alcohol

Sebastian Lucas

Issues

• Is acute alcohol toxicity different from chronic alcohol toxicity?
• Yes – the former [acute] has to have an Inquest, the latter does not

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• How many alcohol-related fatal pathologies and scenarios do you know?

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• How do you sort them out at autopsy?

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Alcohol-related pathology

• A combination of:

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• The given clinical history
• Gross appearances
• Histopathology
• Biochemical (toxicology) indices in blood, urine and vitreous

Detail from MoJ Coroners Statistics 2022

Personal observations – descending frequency

Common

• Acute alcohol toxicity
• SUDAM
• Ketoacidosis (post-binge) syndrome
• Portal hypertension and GI bleed
• Traumatic death (fall etc)
• Drowning

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• Decomposed ?pathogenesis

Occasional

• Fire
• Fat embolism syndrome
• Combined with morphine – multidrug toxicity
• Withdrawal seizure
• Phlegmonous enteritis, bacterial peritonitis

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• Homelessness
• precipitate cardiac death
• Hypertension, ischaemic heart

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Case

• Known alcohol dependent male, and illicit drug abuse.
• Previous right hip surgery and previous bone fractures.

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• Found dead at home, decomposing. Police: ‘not suspicious’
• Autopsy – negative, apart from Liver histology:
• micronodular cirrhosis,
• steatosis with Mallory hyaline
• steatohepatitis
• No myoglobin casts in renal tubules [not crush injury]

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• Toxicology results:
• Blood: ethanol 11mg/dL; small amount of desmethyldiazepam; no morphine or other illicit drugs detected.
• Urine ethanol 38mg/dL

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Liver micronodular cirrhosis

Classic alcohol micronodular cirrhosis

Usual ethanol levels and outcome: -�commentary from forensic toxicology labs

• 80mg/dL = UK drink-drive limit
• 100-200 = drunk
• 200-300 = very drunk
• 300-400 = coma
• >400 = dead

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• Much latitude re tolerance
• General rule: over 24 hours, blood alcohol metabolised to zero.

General rule

• Blood & urine ethanol ~10mg/dL
• Regarded as post-mortem decomposition

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• In exceptional cases, levels up to 100mg/dL could be decomposition, not prior alcohol intake
• Moorgate underground train crash 1975
• High ambient temperature

Case

• Cause of death:

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• 1a. Acute on chronic alcohol toxicity
• 2. -

• Query from coroner:
• is this ‘acute’ or ‘chronic’ alcohol toxicity? – need to know re holding an inquest.

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• Pathology evidence:
• Chronic = cirrhosis
• Acute = Mallory hyaline + steatohepatitis
• Both can take days/weeks to resolve

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Basic alcohol-related pathology taxonomy:��5 separable clinical pathology scenarios��Acute = hours/days�Chronic = weeks/months/years�

1. acute metabolic events
2. acute organ damage – direct
3. acute organ damage – indirect
4. chronic organ damage – direct
5. chronic organ damage - indirect

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Acute metabolic events

• Acute ethanol toxicity – blood & urine ethanol >400mg/dL
• Note half life of alcohol in blood

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• Post-binge scenarios – more anon:
• Ketoacidosis (KAS) and MOF
• Ill-understood abnormality affecting
• Heart – SUDAM
• Brain – SUDEP, seizures

Acute organ damage – direct

• Liver – steatosis, hepatitis, cholestasis

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• Pancreas – acute pancreatitis

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• Brain – central pontine myelinolysis

Macrovesicular steatosis - severe

WARNING

Diabetes can produce

similarly severe steatosis

Alcohol steatosis variants?

Normal liver

Microvesicular steatosis

Cholestasis

Perls stain

Pancreatitis

Acute organ damage – indirect

• Accidents
• Fights [forensic]
• Brain injuries – trauma, fracture, contusions, haemorrhage
• General fractures
• Fat embolism syndrome
• Drowning

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• Aspiration pneumonia
• Vomiting: Mallory-Weiss tear of oesophagus, perforation and mediastinitis

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Oesophagus

• Mallory-Weiss tear from vomiting
• Bleeding and tear
• Perforation and mediastinitis

Acute organ damage – indirect

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• Hypothermia

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• Kidney injury
• Crush injury – myoglobin casts
• KAS fat accumulation in proximal tubules

Kidney – indirect damage to tubules

Ketoacidosis – fat accumulation in proximal tubules

Myoglobin casts – crush injury

Kidney tubules fat vacuolation in KAS

Chronic organ damage – direct

• Heart – dilated cardiomyopathy (DCM) – fibrosis, irregular myofiber hypertrophy

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• Liver – cirrhosis, usually micronodular (=<3mm nodule diameter)

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• Pancreas – chronic fibrosing pancreatitis

Chronic duct obstruction pancreatitis

Chronic organ damage - indirect

• Liver cirrhosis
• Portal hypertension
• Variceal bleeding
• Splenomegaly
• Hepatic encephalopathy

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• Hepatocarcinoma

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• Primary bacterial peritonitis
• Phlegmonous colitis
• The same entity?

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• Increased all-cause mortality
• Sepsis
• Perioperative

• Pancreas damage
• diabetes mellitus
• bile duct compression by fibrotic pancreas

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• Bone marrow
• Erythroid dysplasia
• Ring sideroblasts

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• Brain – see later

Portal hypertension, bleeding oesphageal varices

Bleeding,

Banded,

Ulcerated,

Perforated,

Re-bleeding

Varix.

Died of massive

G-I haemorrhage

Phlegmonous colitis & ileitis – associated with cirrhosis

Gram-ve bacterial infection

of submucosa and muscularis, with acute inflammation.

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Can grossly mimic Crohns (oedematous mucosa) and ischaemic bowel

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Is this the pathogenesis of bacterial peritonitis in cirrhotics without a perforation lesion?

Phlegmonous colitis

Critical histopathology at autopsy

• LIVER – steatosis (macrovesicular and microvesicular), steatohepatitis, portal and central fibrosis (6 stage score), hepatocyte necrosis, cholestasis, Mallory hyaline, Cu-associated protein (Wilson disease), giant mitochondria, dysplasia and carcinoma, siderosis, ground glass cytoplasm.

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• KIDNEY – myoglobin casts in tubules (IHC+)

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• LUNGS – aspiration pneumonia, fat embolism

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• HEART – normal (SUDAM); dilated cardiomyopathy (DCM)

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• PANCREAS – normal, necroses, pancreatitis, acute and chronic, fibrosis

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• BRAIN – traumatic injuries

Critical toxicology at autopsy

• Blood
• Urine
• Vitreous

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• For alcohol, ketone/acetone/Beta OH butyrate

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• ?general drug screen, depending on scenario of death

Brain pathology and alcohol – thanks to Greenfield ‘Neuropathology’, [2015] vol 1

• General malnutrition
• Thiamine deficiency – Wernicke encephalopathy (WKS)

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• Alcohol-related brain damage (ARBD)
• Atrophy – reduced white matter
• Neuronal loss – superior frontal cortex and deep nuclei, cerebellum

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• Central pontine myelinosis (CPM)

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• Marchiafava-Bignami disease (MBD) – atrophy of corpus callosum

Wernicke’s encephalopathy

Brain pathology and alcohol – thanks to Greenfield ‘Neuropathology’, vol 1

• Hepatic encephalopathy (HE)
• Acute liver failure
• Oedema, swelling of perivascular astrocytes

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• Chronic HE – porto-systemic shunting
• Alzheimer type 2 astrocyte change – doublets, in grey matter

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In reality, only CNS experts can confidently identify such lesions?

Alcoholic Ketoacidosis��KAS unqualified = keto-alcoholic syndrome��Differential diagnosis: hyperglycaemic diabetes and malnutrition��Important: no other cause of death evident�

Note: after death, vitreous glucose level drops; so ‘zero’ = normal or hypoglycaemia

SUDAM

• Sudden unexpected death in alcohol misuse

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• Chronic alcohol toxicity – usually cirrhosis, or steatosis

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• Acute alcohol toxicity and KAS excluded

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• No other obvious pathology and the heart is structurally normal, ie SADS/MNH

A new understanding for sudden cardiac death syndromes?

Diagnoses of exclusion

Case

• Cause of death:
• 1a. Acute on chronic alcohol toxicity

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• Pathogenetic possibilities:
• SUDAM
• Sudden death in alcohol misuse
• SUDEP
• Ketoacidosis (KAS)

• Query from coroner: is this ‘acute’ or ‘chronic’ alcohol toxicity – need to know re holding an inquest.

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• Contact tox lab: no acetone, so not KAS.

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• Acute: steatosis + Mallory
• Chronic: micronodular cirrhosis

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SUDEP

• Definition of SUDEP – sudden unexpected death in epilepsy

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• The textbook definition of SUDEP is: the sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy with or without evidence for a seizure, and excluding documented status epilepticus [seizures >30min duration], in which post-mortem examination does not reveal a structural or toxicological cause for death.

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• [There may be hippocampal sclerosis]

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Hippocampal sclerosis – post-hypoxic injury reaction

Case

• Cause of death:
• 1a. Acute on chronic alcohol toxicity

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• Pathogenetic possibilities:
• SUDAM
• Sudden death in alcohol misuse
• SUDEP
• Ketoacidosis (KAS)

• Query from coroner: is this ‘acute’ or ‘chronic’ alcohol toxicity – need to know re holding an inquest.

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• Contact tox lab: no acetone, so not KAS.
• Acute: steatosis + Mallory
• Chronic: micronodular cirrhosis

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• Both SUDAM and SUDEP more likely to be triggered by a binge than happen because of cirrhosis per se = acute event

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• Diagnosis stands.

Some recent cases

One learns all the time

Decomposed bodies?

Decomposed liver steatosis

• Cause of death
• 1a. Alcohol toxicity
• 2. -

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• Could be SUDAM or Acute toxicity – impossible to distinguish at autopsy

Homeless, pneumonia

• Liver – bright yellow
• Blood alcohol = 180mg/dL
• Beta OH butyrate = 160mg/L

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• Cause of death:
• 1a. Pneumococcal pneumonia
• 2. acute alcohol toxicity, homelessness

? Homicide, accident, or drunk?

• Female 60 – with new boyfriend
• Much drinking and sex
• Partner went to bathroom; returned to find her dead on the bed

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• Clear fluid pouring from larynx and trachea
• Red lesion on face ? Traumatic injury

Outcome

• The face lesion = BURN on histology, not blunt trauma – some time previously

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• Blood alcohol = 209mg/dL
• Vitreous alcohol = 237mg/dL
• Liver – minimal steatosis = very acute toxicity

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• 1a. Asphyxia
• 1b. Choking on inhaled fluid
• 1c. Acute alcohol toxicity
• 2. –

• Burn: coagulated degenerate epithelium and dilated dermal blood vessels

Summary of the main acute alcohol-related death scenarios

• Acute toxicity – high blood alcohol levels
• Liver may or may not be steatotic

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• Ketoacidosis (KAS) – low or zero blood alcohol
• Liver usually steatotic

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• SUDAM – sudden death, low/zero blood alcohol, no KAS
• Liver steatotic or cirrhotic

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• Epileptic seizure – post-binge withdrawal; blood alcohol and KAS variable
• Seizures witnessed
• Liver steatotic +/- cirrhosis

FAQs at alcohol inquests

• Q: Can you tell from the blood/urine alcohol level how much the person drank and when he/she did?
• A: NO

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• Q: she did not drink at all/much, so your conclusion from the cirrhosis is wrong!
• A: no viral hepatitis or autoimmune hepatitis, not Wilson’s disease, not diabetic, not obese;
• so – sorry – you are probably underestimating how much, & females more susceptible etc

Questions?