Lecture 8a: Pathobiology of Forensic Pathology

“Golden Triangle” of any Death Investigation

History, scene, postmortem findings

• History/scene: Context of death (from warrant) determines approach

• External examination: Skin colour, bruising, etc.

• Internal examination: Injury/disease

• Ancilallry tests: Blood cultures, tox screen, DNA analysis, etc.

• Medico-legal opinion: Cause of death determination ± court appearance

Somatic Death

Irreversible complete cessation of all vital functions including circulation and respiration

May be preceded by neurological death

Neurological Death

Irreversible loss of capacity for consciousness and all brainstem functions including capacity to breathe

Generally determined in 2 separate tests by 2 different physicians

Criteria for Neurological Deeath

Proof of etiology capable of causing neurological death

Absence of reversible causes of coma or confounding factors

• Resuscitated shock

• Low body temperature (<34 celcius, 36 celcius for newborns)

• Treatable metabolic/endocrine/electrolyte disturbances (hypernatremia, hypoglycemia, severe hypophosphatemia, liver/renal dysunction)

• Peripheral nerve/muscle dysfunction due to disease/neuromuscular blocking agents (pancuronium, succinylcholine)

• CNS depressants/drug intoxication (EtOH, barbiturates, sedatives)

Absence of brain stem reflexes (blinking, coughing, light reflexes)/absence of bilateral movement, spontaneous and in response to stimulation

• Spinal reflexes exempt

• Deep pain testing must include all extermities and above clavicles

Absence of respiratory effort (apnea testing)

Postmortem Changes

Rigor mortis: Actin-myosin filaments unable to unbind (lack of ATP)

• Plateau of variable duration based on activity before death, temperature

• Naturally breaks after ~3 days from tissue autolysis

Liver mortis: Gravity-dependent pooling of blood

• Vessels where body touching surface compressed (eventually settle)

Algor mortis: Thermodynamics → cooling at specific theoretical rate

• Dependent on temperature before death, body fat, clothing worn

Autolysis: Endogenous pH changesand enzyme release (beginning in pancreas)

Putrefactive decomposition: Microorganism anaerobic hydrolysis of fat in damp anaerobic environment > saponification to oleic/palmitic/stearic acids

Skeletonization: End stage of multiple decomposition pathways (anthropology)

Postmortem predation: INsects, rodents, carnivores, deer

Vitreous fluid biochemical changes: Cell lysis, increased vitreous K⁺, decreased Na⁺, Cl^-

• Can no longer conduct biochemical blood analysis after 3 days

Postmortem redistribution: Substances may settle in different locations

ADME

Absorption, distribution, metabolism, excretion

Postmortem Redistribution

Basic, lipophilic drugs with high V_d most susceptible

Changes in pH drive weakly acidic/basic drug movement — 7.4 → 5.6

Spontaneous hydrolysis (cocaine has no metabolites)

Residual endogenous metabolism by enzymes/microbes

Passive diffusion throughout blood or parenchyma (transparietal)

• High concentrations → organs and tissue (stomach, heart, liver, lungs, fat)

• Peripheral tissues often give more accurate results

Cellular Physiology of PMR

Anoxic microenvironment → anaerobic glycolysis → increased lactic acid → decreased pH → intracellular increase of basic drug

Anaerobic metabolism failure → decreased ATP → Na⁺/K⁺ pump stops → Increased Na⁺ inside cell → increased H₂O in cells → swelling disrupts ribosomes/lysosomes → lysosomes degrade cell

Release of basic drugs to ECM → redistribution to lung (often volatile substances), luminal Gi tract, liver, heart

PMR from Myocardium

Numerous cardiac drugs sequestered: CCB, quinidine, morphine, amphetamine, methamphetamine, prophoxyphene, imipramine, amitripryline, doxepine, metoprolol

Rapid redistribution into heart +/i venous blood up to subclavian vein

• Digoxin concentration after death ≠ living blood concentration

PMR to Adipose

Volatiles and anaesthetics not known to reach steady state antemortem

Postmortem, will continue to distribute from blood into adipose tissue

Putrefactive Processes

Generally, enzymatic transformations from parent → metabolite do not occur postmortem, but some plasma/hepatic enzymes function shortly after death

• Plasma cholinesterase activity inhibited by addition of fluouride

EtOH production: 58 bacteria, 17 yeasts (eg. E. coli, C. albicans)

• Increased glucidic compounds in liver, skeletal muscle, lung, myocardium → increased postmortem EtOH production

• Vitrous humor relatively protected, desirable matrix for EtOH

Bacterial metabolism of EtOH, nitrobenzodiazepines (clonazepam, nitrazepam, flunitrazepam), cyanide

Injury Dating

General timeframes for inflammatory reactions, infiltration by macrophages, hemosiderin formation, bony repair processes

• No formula to account for differences (eg. diabetes, chronic malnutrition) → requires estimation and expert opinion

• Potential determination of chronic repeated injury: Abuse, activity

No reaction if injury after death

At time of death: Bruising, blood outside vessels

Hours before death: Bruising, neutrophils

Days before death: Green/yellow bruising, macrophages