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Gastrointestinal causes of sudden unexpected death: A review

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DOI: 10.1177/0025802417737001

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Review article

Medicine, Science and the Law

2018, Vol. 58(1) 5–15
Gastrointestinal causes of sudden ! The Author(s) 2017
Reprints and permissions:
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DOI: 10.1177/0025802417737001
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Ritesh G. Menezes1, Saba Ahmed2, Syed Bilal Pasha2,

Syed Ather Hussain2, Huda Fatima2, Magdy A. Kharoshah3
and Mohammed Madadin1

Abstract
Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions
such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal
conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each
condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we
aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are
diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned.
In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected
death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected
death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are
several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to
cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden
unexpected death.

Keywords
Sudden death, sudden unexpected death, gastrointestinal causes, autopsy

Introduction
Sudden unexpected death comprises one of the most
important and worthy investigation case profiles in
emergency medicine and forensic pathology.
The principal causes of sudden unexpected death vary
in different age groups.1 The predominant causes of
sudden unexpected death in adults and the elderly are
atherosclerotic coronary artery disease and hyperten-
sion.2 Sudden unexpected death in infancy is usually
caused by infections or sudden infant death syndrome.3
Gastrointestinal conditions1,2,4–63 are a less common
cause of sudden unexpected death compared to
various other conditions. This is because gastrointesti-
nal pathologies frequently present with symptoms
which immediately attract medical attention. On rare
occasions, they do present with less observable signs
and symptoms which might go unnoticed by the phy-
sician. Sometimes, gastrointestinal pathologies may
also remain untreated if the individual was living all
alone and did not get a chance to call for help or if
the individual refused medical help.
In the present review, we define ‘gastrointestinal’
causes as those either directly or indirectly related to
the stomach and intestines only, and we exclude all
other abdominal pathologies and oesophageal condi-
tions. Conditions related to the accessory organs of
digestion, the liver, gall bladder and pancreas are
excluded. Direct causes relate to the organs, the stom-
ach and intestines per se. Indirect causes relate predom-
inantly to the vasculature of the stomach and
intestines.
Gastrointestinal causes of sudden unexpected death
include various congenital abnormalities and acquired
conditions (Table 1). To our knowledge, currently, only
1
Forensic Medicine Division, Department of Pathology, College of
Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin
Faisal University, Dammam, Saudi Arabia (KSA)
2
Dow Medical College, Dow University of Health Sciences, Karachi,
Pakistan
3
Forensic Medicine Centre, Dammam, Saudi Arabia (KSA)
Corresponding author:
Ritesh G. Menezes, Imam Abdulrahman Bin Faisal University (Formerly,
University of Dammam), Dammam 31451, Saudi Arabia.
Email: mangalore971@yahoo.co.in; rgmenezes@iau.edu.sa
6 Medicine, Science and the Law 58(1)

Table 1. Gastrointestinal causes of sudden unexpected death. has been questioned many times, and the aetiology is
Congenital causes now considered to be much more complex because of
 Duodenal obstruction the increased association with other congenital anom-
 Mesenteric defects alies. Associated congenital anomalies have been dis-
 Meckel’s diverticulum covered in about 50% of the cases, and around 30% of
 Mesenterium commune these are associated with trisomy 21.4 There is an
 Duplications increased incidence of prenatal deaths, even in the pres-
 Gastric heterotopia
ence of a normal karyotype, indicating that duodenal
Congenital and acquired causes
obstruction is an extremely serious condition that can
 Abdominal hernias
䊊 Inguinal hernia
cause sudden death prenatally as well as postnatally.
䊊 Internal hernia The obstructions are most commonly found in the
䊊 Diaphragmatic hernia second and third parts of the duodenum and are locat-
 Volvulus ed in close proximity to the opening of the bile duct.4
 Aneurysm These obstructions may increase the level of foetal
Acquired causes serum bile acids. Primary bile salts such as taurochlo-
 Intussusception rate have been found to alter the rate and rhythm of
 Superior mesenteric artery thrombosis
cardiomyocytes and affect the foetal heart rate.4
 Dissection
 Aortoenteric fistula
Additionally, reflex vagal cardiac inhibition due to dis-
 Abdominal apoplexy tension of the upper gastrointestinal tract has also been
 Cocaine-induced haemorrhage described as another rapid cause of death due to duo-
 Perforation secondary to ulcers denal obstruction.4
 Gastric dilatation
 Tumours Mesenteric defects
 Varices
 Miscellaneous Although extremely rare, sudden death due to congen-
ital mesenteric defects has been described in the litera-
ture.6 These are mostly asymptomatic but may give rise
to symptoms if complications such as internal hernias
arise. Therefore, it is important to consider mesenteric
case reports and audit articles are available on the
defects as a differential diagnosis for a paediatric
topic, and no comprehensive review article describing
patient presenting with acute abdominal pain. These
the relevant pathologies has been previously published.
defects may arise in a variety of locations but are
This article discusses the various congenital and
most commonly found in the mesentery near the termi-
acquired gastrointestinal conditions1,2,4–63 that have
nal ileum.7 These are usually round or oval in shape
resulted in sudden unexpected death. The possible
and can have a diameter of >10 cm.6 The exact aetiol-
lethal mechanisms behind each condition, along with
ogy of these defects has not been determined. However,
any associated risk factors or secondary diseases, are
one theory suggests that these defects occur either due
described in detail. In addition, related fatal cases
to the expansion of a region of necrosis or because of
encountered occasionally in forensic/medico- an incomplete regression of the dorsal mesentery.8 Due
legal autopsy practice are also included in the present to peristaltic motility, intestinal loops can at times her-
review. niate through the defect, and as a result, fluid and air
can get trapped in the intestine. Death may ensue due
Congenital causes to ischaemia of the herniated part of the intestine if the
distention is severe or due to necrosis followed by septic
Duodenal obstruction complications.
Duodenal obstruction, which includes both stenosis
and atresia, has an incidence of 1 in 10,000 live births Meckel’s diverticulum
and is considered the most common intestinal obstruc- Meckel’s diverticulum is an uncommon cause of intes-
tion in neonates.4 Duodenal obstruction is just one tinal obstruction. However, it is the most common con-
example of a congenital condition of the gastrointesti- genital anomaly of the small bowel and occurs when
nal system that can cause sudden and rapid death. As the vitelline duct does not become completely atretic
suggested by Tandler, duodenal obstruction is caused during the fifth week of embryonic life. Meckel’s diver-
by failure of vacuolisation and recanalisation after the ticulum can be difficult to diagnose, as many of the
solid stage of duodenal development.5 However, this symptoms, such as abdominal tenderness, abdominal
Menezes et al.
pain and vomiting, can occur in several different con-
ditions. Most Meckel’s diverticulae are clinically silent,
and only about 4% of patients develop symptoms.9
They are mostly either discovered incidentally during
barium studies, laparotomies or at autopsy or when
complications such as perforation, bleeding or haemor-
rhage arise from the diverticulum.
The vitelline duct is supplied by two vitelline arter-
ies. Rarely, fibrous derivatives of these vitelline arteries
become connected from the tip of a Meckel’s divertic-
ulum to the mesenterium, resulting in the formation of
a mesodiverticular band. Mesodiverticular bands are
associated with an increased risk of mortality and can
cause sudden death. Small bowel loops are highly sus-
ceptible to incarceration and subsequent infarction if
they herniate below the mesodiverticular band.
Additionally, severe dehydration is very likely to
occur due to intestinal obstruction, and this may lead
to circulatory collapse.
Littre hernia is the protrusion of a Meckel’s diver-
ticulum through any hernial orifice. These hernias are
uncommon, with <50 cases reported in the 20th centu-
ry.10 Littre hernias are usually harmless and have min-
imal clinical manifestations, as there is no obstruction
to intestinal contents because of a patent ileal lumen.
Therefore, the only clinical findings may be a mass and
tenderness if the hernia is incarcerated. The usual sites
are inguinal (50%), femoral (20%), umbilical (20%)
and elsewhere (10%).10 Unexpected death occurs
rarely in cases of infarction and small bowel
obstruction.10
Mesenterium commune
Mesenterium commune is caused by the interruption of
intestinal rotation during foetal development.11 The
malpositioned intestines cannot develop a normal mes-
entery and are susceptible to volvulus. This is a serious
complication and, when diagnosed late, can lead to
sudden death as a result of haemorrhagic infarction
of the intestinal wall.
Duplications
Duplications are congenital cystic or tubular structures
lined by an inner mucosal membrane present in the
intestinal tract that have a common muscular wall
with the bowel segment.12 These can be located in
any part of the intestinal tract but are most frequently
found at the ileum and ileocaecal portion of the
caecum.12 Duplications can become symptomatic in
infants when they compress the surrounding intestinal
lumen causing obstruction, or they may act as a nidus
for an intussusception or a site for volvulus.
Duplications should always be considered in the list
7
of differentials for an infant presenting with gastroin-
testinal complaints. Patients may present with non-
specific signs and symptoms such as abdominal pain,
vomiting, palpable abdominal mass and bloody stool.12
An abdominal ultrasound can be helpful in diagnosing
this condition before complications arise. Sudden death
as a consequence of duplication cysts is very rare.
Deaths have been thought to occur as a result of
acute dehydration secondary to accumulation of fluid
in the intestine and numerous episodes of vomiting and
diarrhoea.12
Gastric heterotopia
Gastric heterotopia is a rare occurrence, with the
majority of lesions located in the duodenum. Gastric
heterotopia has been associated with duplication cysts
and may lead to ulceration, perforation and gastroin-
testinal bleeding, all of which can be life-threatening
situations and can lead to sudden death.12,13
Congenital and acquired causes
Abdominal hernias, volvulus and aneurysms may be
either congenital or acquired. A case of sudden unex-
pected death due to clinically undiagnosed neoplastic
disease in a 11-year-old child is described under the
section on "tumours".46 In this case, a gastric tumour
of adult-type was diagnosed at autopsy.46
Abdominal hernias
Inguinal hernia. An inguinal hernia is the protrusion of
an organ or part of an organ through the inguinal
canal. It can be either reducible or irreducible. In an
irreducible hernia, the contents of the hernia sac cannot
be replaced into the abdomen. An irreducible hernia is
associated with complications such as obstruction and
strangulation. In a strangulated hernia, the blood
supply to the contents of the sac is compromised,
which then become ischaemic or infarcted. The loop
of the gut may also become strangulated in the inguinal
hernial sac. Therefore, a strangulated inguinal hernia is
considered to be a surgical emergency. Mortality
increases in the absence of timely surgical intervention.
Incidences of sudden death can be decreased if proper
timely treatment is provided.
Menezes et al.14 describe a case of potentially pre-
ventable sudden unexpected death due to a gastrointes-
tinal cause wherein a 60-year-old was found lying dead
near a place of worship. Following an autopsy, the
cause of death was opined as that consequent to
small intestinal strangulation caused by herniation of
a loop of the small intestine in a right-sided inguinal
hernial sac (Figures 1 to 3).14 In such a case, the mech-
anisms of death may be quite complex and include fluid
8 Medicine, Science and the Law 58(1)
Figure 1. Inguinal hernia evident as scrotal swelling with the
buried penis.
Source: Reproduced with permission from Menezes et al.14
Figure 2. Bowel loops dissected out from the inguinal hernial sac.
Source: Reproduced with permission from Menezes et al.14
Figure 3. A partly inflammatory and partly gangrenous segment
of the herniated intestinal loop.
Source: Reproduced with permission from Menezes et al.14
and electrolyte imbalance, intestinal haemorrhagic
infarction and marked translocation and systemic
exposure to aerobic and anaerobic bacteria with their
associated toxins.
Internal hernia. An internal hernia is the protrusion of an
internal organ through the peritoneum or mesentery.
Internal hernias are categorised according to the loca-
tion of the defect and fall into six distinct groups: trans-
mesenteric hernia, hernia through the foramen of
Winslow, paraduodenal hernia, pericaecal hernia, trans-
omental hernia and paravesical and pelvic hernia.15
Internal hernias may cause obstruction, strangulation
and gangrene of the intestine. If left untreated, the mor-
tality rate is >50%.8 These mostly arise as a complica-
tion of gastrointestinal surgery in the case of the elderly.
These elderly victims usually have an underlying disease
such as diabetes mellitus, chronic renal failure or gas-
trointestinal cancer.15 Transmesenteric hernia is the
most common type and is difficult to distinguish from
other benign conditions, especially in the presence of
minimal symptoms. Open or laparoscopic examination
is the only way to form a definitive diagnosis of trans-
mesenteric hernia. Hence, a delayed or wrong diagnosis
increases mortality in patients and may result in sudden
death. The mechanism of death may be either hypovo-
laemic shock due to severe vomiting or septic shock as a
postoperative complication.
Diaphragmatic hernia. Congenital diaphragmatic hernia
is a rare anomaly with high morbidity and mortality.
While congenital diaphragmatic hernias mostly present
in neonates, a small percent of patients may present
with the condition after the neonatal period during
early childhood. Chhanabhai et al.16 report a case of
sudden unexpected death due to congenital diaphrag-
matic hernia in a previously healthy 22-month-old
child. The cause of sudden death is related to the
sequelae of sudden cardiopulmonary compression
owing to a sudden herniation of the abdominal con-
tents into the left thoracic cavity.16 Sudden unexpected
death due to congenital diaphragmatic hernia has also
been reported in previously healthy 2-, 4- and 24-
month old children.17 The predisposing factor for the
sudden herniation of abdominal contents through the
diaphragmatic defect into the left thoracic cavity is the
increased intraabdominal pressure from coughing,
vomiting or straining during a bowel movement.
Vandy et al.18 describe an autopsy case of death due
to congenital diaphragmatic herniation of the abdom-
inal contents into the left thoracic cavity in a 30-month-
old child. In this case, the child had presented to the
hospital with acute abdominal pain and vomiting.18 In
addition to the diaphragmatic hernia, the autopsy
revealed an associated gastric volvulus with necrosis
Menezes et al.
and rupture.18 Navarro-Crummenauer et al.19 describe
a case of death due to previously undiagnosed congen-
ital diaphragmatic hernia in a 14-month-old child
wherein the autopsy revealed herniation of the terminal
ileum, caecum, colon and greater omentum into the left
thoracic cavity causing significant compression of the
left lung. In this case, although the child had presented
to the hospital with acute abdominal pain and vomit-
ing, the cause of death was opined as respiratory insuf-
ficiency based on the autopsy findings.19 Navarro-
Crummenauer et al.19 stressed upon the importance
of considering a late manifestation of congenital dia-
phragmatic hernia in children presenting with recurrent
gastrointestinal and/or respiratory symptoms.
Congenital diaphragmatic hernia presents rarely in
adulthood. Moreover, sudden death secondary to a
posterolateral Bochdalek hernia, a type of congenital
diaphragmatic hernia, is even more rarely reported in
adults.20–22 Chui and Tan report a case of sudden death
resulting from a perforated gastric ulcer in an incarcer-
ated Bochdalek hernia in an adult.20 Salacin et al.21
report another case of Bochdalek hernia leading to
sudden death in adulthood. In this case, Bochdalek
hernia was first diagnosed at autopsy.21 Another case
of sudden death due to a previously undiagnosed con-
genital diaphragmatic hernia in an adult is reported by
De-Alwis and Mitsunaga.22 They stress the importance
of early diagnosis of such anomalies followed by
prompt surgical treatment in order to avoid
fatalities.22Kato et al. report a case of sudden death
secondary to congenital diaphragmatic hernia in a 43-
year-old man wherein the lethal mechanism was attrib-
uted to compromised respiration from the collapsed
left lung secondary to herniation of the abdominal vis-
cera into the left thoracic cavity.59
Volvulus
Volvulus is the cause of 1–7% of large bowel obstruc-
tions in Western countries.23 It most commonly occurs
in the ileocaecal and sigmoid regions. It presents as a
surgical emergency when there is obstruction of the
intestine and compromise of blood supply due to twist-
ing of the intestine around a mesenteric attachment.
Ischaemic necrosis of the twisted part with gangrene
may occur, followed by death due to sepsis and elec-
trolytic imbalance. Patients may be predisposed to vol-
vulus due to several factors such as a malrotation of the
midgut, large redundant sigmoid colon on a long
narrow-based mesentery or chronic constipation with
laxative use or high-fibre diet.23 Congenital midgut vol-
vulus is also reported in the literature.57 This condition
can be life threatening to the newborn.
Sigmoid volvulus is primarily seen in elderly patients
with pre-existing dementia and other psychiatric
9
conditions. The mortality rate can reach up to 50%
in such patients.23 Unexpected death most commonly
occurs in elderly patients because of minimal symptom-
atology, presence of multiple unrelated conditions,
communicating disabilities and their general reluctance
to see the doctor.
Omond and Byard report an autopsy case of death
resulting from an acute gastric volvulus in a 55-year-
old woman.58 The lethal mechanisms in such cases of
acute gastric volvulus include peritonitis resulting from
gastric perforation due to gastric wall necrosis from a
compromised gastric blood supply and overwhelming
distension of the stomach from swallowed air and fluid,
hypovolaemic shock resulting from obstruction or
compromised respiration resulting from significant
left lung compression due to the gastric volvulus push-
ing the left diaphragm upwards.58
Aneurysm
An aneurysm is a permanent pathological localised
dilatation of an artery.24 Splanchnic aneurysms occur
at numerous sites and are rather common features
appearing in 0.1–2% of the population.25
Around 60% of these aneurysms are found in the
splenic arteries, which is by far the most common site,
followed by 5% in the gastric arteries.25The pathogenic
mechanisms behind the formation of splanchnic aneur-
ysms may include inflammation, arteriosclerosis, con-
genital malformation and medial degeneration.
Symptoms can range from asymptomatic to non-
specific gastrointestinal disorders and recurrent pain.
However, their rupture can result in intraperitoneal
or intragastric haemorrhages with high mortality
rates and sudden death.25,26 Moawad et al.63 report a
case of life-threatening gastrointestinal haemorrhage
due to the intragastric rupture of a splenic artery aneu-
rysm with erosion into the stomach.
Aging, arteriosclerosis as a result of pre-existing
hypertension, medial degeneration secondary to
Marfan’s syndrome, pregnancy, congenital cardiovas-
cular diseases and trauma are considered predisposing
factors for aneurysm formation.26 Complications of
aneurysms include thrombosis, embolisation and dis-
section which can also be a cause of sudden death.24
Acquired causes
Intussusception
Intussusception is a process in which a segment of the
intestine invaginates into another segment of the intes-
tine, causing bowel obstruction. It can also compro-
mise the blood supply to the affected part of the
intestine which can cause perforation, infection and
10
necrosis of the affected tissue. Intussusception is mostly
idiopathic but several pathologies have been associated
with it such as Meckel’s diverticulum, omphalomesen-
teric duct abnormalities, mesenteric defects, enlarged
mesenteric lymph nodes, polyps, neoplasms, mesenteric
cysts and mural haematomas. It is a major cause of
intestinal obstruction and the second most common
cause of acute abdominal surgical emergency in chil-
dren.27 Signs and symptoms are usually detectable and
are those of intestinal obstruction. However, they may
be completely absent or quite subtle. Around 13–20%
children experience ‘painless intussusception’ without
any discomfort or colic, and therefore if death occurs,
it will be sudden in nature and only determined at
autopsy.28 Death occurs because of a combination of
factors such as intestinal obstruction causing peritoni-
tis, electrolyte imbalance or compromised blood supply
followed by intestinal infarction and shock.
Superior mesenteric artery thrombosis
Acute intestinal ischaemia precipitated by superior
mesenteric artery thrombosis has a high mortality of
about 60–75%.29 It can present as a rare complication
of chronic cocaine use, and the diagnosis is extremely
difficult to make. The mechanisms behind
cocaine-induced tissue damage are very well under-
stood, and it is known that cocaine causes arterial vaso-
constriction, activation of intravascular thrombosis
cascades and accelerated atherosclerosis. Sudden
death in a young patient with a history of abdominal
complaints should raise suspicion for stimulant drug
abuse and abdominal visceral artery thrombosis.
Dissection
Dissection is defined as penetration of blood into the
vessel wall through an intimal tear, normally involving
the aorta, but can also involve visceral arteries.24 The
predisposing factors for a dissection are the same as
those for an aneurysm and include hypertension,
Marfan’s syndrome, trauma, pregnancy and congenital
cardiovascular diseases.
The difficulty in diagnosing and promptly treating a
ruptured artery dissection, due to its non-specific symp-
toms and rapid evolution into shock, is a big contrib-
uting factor to sudden death.24
Gastric dissecting aneurysms are very rare lesions
with the same risk factors as splenic artery dissections.
These can arise in intramural as well as extravisceral
gastric vessels.26 Intramural dissecting aneurysm rup-
ture results in haemorrhage into the gastric lumen lead-
ing to haematemesis, whereas extravisceral dissecting
aneurysm rupture results in haemoperitoneum.26 In
extravisceral gastric dissecting aneurysm rupture, the
Medicine, Science and the Law 58(1)
initial haemorrhage may occur in the lesser omentum
or subserosal space. This may eventually lead to a ‘free
rupture’ into the omental bursa or peritoneal cavity
after a tear of the serous membrane.26
In these dissecting ruptures, the shock symptoms
follow a biphasic pattern. The haemodynamic status
may be stable in the initial phase, and then quickly
worsens due to massive free bleeding several hours
afterwards. The term ‘double rupture phenomenon’
has been coined for this phenomenon and is thought
to be the mechanism of sudden death.26 It has been
observed in both splenic and gastric dissecting aneur-
ysms ruptures.
Aortoenteric fistula
Aortoenteric fistula (AEF) occurs due to spontaneous
erosion of an abdominal aortic aneurysm into the intes-
tine and may cause sudden unexpected death. It is a
rare aetiology of upper gastrointestinal bleeding and
most commonly occurs at the third and fourth portion
of the duodenum.30 Early and preoperative diagnosis is
extremely difficult, and the mortality rate is almost
100% if the surgery is delayed.30
Described as ‘uniformly fatal’, AEF, an uncommon
cause of upper gastrointestinal tract haemorrhage, with
a reported incidence of 0.07%, most often results in
sudden unexpected death.31 As described by Sir
Astley Cooper in 1829, AEF presents with a classic
triad of massive gastrointestinal haemorrhage, pulsatile
abdominal mass and abdominal pain.31 A few weeks
before presenting with the classic triad, patients with
AEF usually experience self-resolving, small volume
gastrointestinal haemorrhages also known as ‘herald
bleeds’.
Causes of AEF include aortic infections (tuberculo-
sis, syphilis, fungal and septic aortitis), peptic ulcer dis-
ease, abscess, gastrointestinal malignancies, lymphoma,
penetrating/eroding foreign bodies, radiotherapy or
previous aortic surgery.31
Sudden unexpected death in the elderly as a result of
aortoduodenal fistula–related haemorrhage associated
with penetrating atherosclerotic ulcer or atherosclerotic
aneurysm of the abdominal aorta is reported in the
literature.31,32
Abdominal apoplexy
Abdominal apoplexy or idiopathic spontaneous intra-
peritoneal haemorrhage is a rare but important cause
of sudden death. Conditions predisposing to spontane-
ous haemoperitoneum include liver disorders, splenic
disorders, gynaecological disorders, haematological
disorders, vascular disorders, inflammatory disorders
and coagulation disorders. Bleeding can be
Menezes et al.
retroperitoneal or intraperitoneal and is associated
with hypertension in 33–50% cases and atherosclerosis
in 80–87% cases.33 Haemorrhage is usually preceded
by a vessel rupture, most commonly at the site of an
aneurysm. The vessels most commonly involved are the
middle colic artery, pancreaticoduodenal arteries and
the gastroduodenal artery.33,61 Abdominal apoplexy
due to rupture of the short gastric artery is also
reported in the literature.62 In fatal cases, the source
of intraperitoneal haemorrhage may remain unidenti-
fied, despite a detailed post-mortem examination of the
visceral organs, peritoneal folds and major abdomino-
pelvic vessels.33 A thorough knowledge of the vascular
anatomy and a meticulous dissection of the vasculature
are certainly required to identify the definite source of
bleeding at autopsy.
Cocaine-induced haemorrhage
The use of cocaine has been associated with fatal and
sudden intraluminal gastrointestinal haemorrhage.34
Cocaine use can cause intestinal infarction, ischaemia,
perforation and haemorrhage. It exerts direct vasocon-
strictive effects by enhancing calcium influx across
endothelial membranes. Vasoconstriction is further
enhanced because of direct sympathomimetic effects
of cocaine. The vasoconstriction leads to hypoperfu-
sion and ischaemic infarction of the intestine.
Perforation secondary to ulcers
Peptic ulcer disease and its complications are a signif-
icant cause of sudden, unexpected mortality worldwide,
particularly in the elderly and chronically ill, with atyp-
ical presentations causing a delay in diagnosis.35 In
childhood, fatal gastric rupture secondary to peptic
ulcer disease is rarely reported.36
This fatal and potentially treatable ‘abdominal
catastrophe’ is clearly underreported, as only a small
number of patients who die undergo autopsy.37,38
Notably in the literature, the presentation of peptic
ulcer disease is silent and painless, which further
makes timely diagnosis difficult in elderly patients.35
Co-existing medical conditions such as cardiovascu-
lar disease, pulmonary disease, chronic liver disease
and diabetes mellitus are strong predictors of morbidity
and mortality. Perforations of longer than 48 hours
and advancing age are two other important risk fac-
tors. Additionally, gastric ulcer perforation has a three
times higher risk of mortality in comparison to duode-
nal ulcer perforation.38
Recent epidemiologic data suggest a rise in perfora-
tions and bleeding from these ulcers.38 Approximately
15% of peptic ulcer disease patients will have
11
gastrointestinal haemorrhage at some point in their
lives, and around 6% will develop a perforated ulcer.38
Peritonitis and shock secondary to perforation are
well-recognised sudden causes of death. A case series as
well as other well-documented articles support the
importance of this claim.38 Another study places the
total mortality of in-hospital perforations at 88%.39
Vagal reflex inhibitory influences causing rapid exhaus-
tion of the neuro-circulatory dynamics in response to
the intense and sustained pain at the site of perforation
of the gastric ulcer is suggested as a mechanism of
sudden death when death occurs before any signs of
peritonitis develop.40
Another ulcerative cause of perforation leading to
sudden death is stercoral ulcers, which are rare ulcers,
primarily occurring in the sigmoid colon and rectum.41
These occur because of pressure necrosis of the mucosa
by a large, hard faecolith matter. The most important
factor predisposing to stercoral ulcer is chronic consti-
pation. Stercoral perforation is associated with a very
high risk of mortality and is usually not diagnosed
before an autopsy.
Gastric dilatation
Gastric dilatation is another cause of sudden death in
all age groups, with mortality rates without rupture or
necrosis of the gastric wall, with necrosis, and with
rupture at 5.4%, 37.5% and 55.6%, respectively.42,43
Anorexia nervosa, polyphagia, volvulus, superior mes-
enteric artery syndrome and bulimia nervosa have all
been associated with cases of gastric dilatation and
rupture.42
Ishikawa et al.44 describe a case of sudden death due
to gastric rupture suspected to have been induced by
excessive eating. Regarding the rarity of this condition,
they reported only 47 cases over 50 years in the
Japanese literature.44 They further reported female
dominance, with a male:female ratio of 1:4, and mor-
tality, even with surgical intervention, at 65%.44
Gastric rupture and/or shock secondary to compres-
sion of inferior vena cava and disturbance of portal
blood flow resulting from gastric dilatation have been
implied as reasons for mortality.43 Hypovolaemic
shock may occur in anorexic patients because of an
imbalance in circulatory minerals and fluids as a
result of retention of gastric juices. Additionally, paral-
ysis of the bowel may significantly diminish the absorp-
tive function of the gut, and this may further
exacerbate shock.43 Another cause of sudden death
may be cardiac failure caused by vaso-vagal reflex as
a result of over-extension of the stomach. However,
this cannot be proven in forensic autopsies.
12
Tumours
One noteworthy entity related to gastric adenocarcino-
ma is pulmonary tumour thrombotic microangiopathy
(PTTM), which is a well-described complication result-
ing in rapidly progressive pulmonary hypertension, sec-
ondary to metastatic tumour cells occupying a large
proportion of small pulmonary arterioles.
Patients typically present with acute pulmonary
hypertension, progressing to right-sided heart failure
and sudden death, often before the actual gastric ade-
nocarcinoma is discovered.45 PTTM is reported to be
present in 25% of patients dying of such carcinomas.
However, the actual mortality associated with tumour
emboli remains at 8%.45
Sudden unexpected death due to clinically undiag-
nosed neoplasia in infancy and childhood (SUDNIC) is
another rare tumour-associated phenomenon in indi-
viduals with apparently normal activities until the
onset of acute signs and symptoms.46 The primary
tumours normally involve critical structures within
the heart or central nervous system. Non-central ner-
vous system and non-cardiac causes of SUDNIC are
rarer, and a 20-year (1984–2003) retrospective review of
autopsy records from the Hospital for Sick Children
(Toronto, Canada) include a single case of sudden
death due to previously undiagnosed widely dissemi-
nated gastric adenocarcinoma in an 11-year-old girl
with only symptoms of back pain. In the aforemen-
tioned patient’s case, death was attributed to pulmo-
nary tumour microemboli with pulmonary
hypertension and haemorrhage.46 Another retrospec-
tive study of paediatric autopsies at Great Ormond
Street Hospital (London, UK) over a 20-year period
(1996–2015) did not reveal any clinically undiagnosed
gastrointestinal neoplasms as the cause of SUDNIC.47
Due to its rarity, SUDNIC is usually not considered in
the differential diagnosis of sudden death in infancy
and childhood. Nevertheless, it can be an important
cause.46
Hayashi et al.48 describe a case of sudden unexpect-
ed death due to spontaneous perforation of an unclas-
sified small bowel tumour with intra-tumoural
haemorrhagic necrosis wherein a 62-year-old woman
was found lying dead in her single prison cell.
Following an autopsy, the cause of death was opined
as peritonitis secondary to a jejunal malignant tumour
perforation. In a 10-year retrospective study of undiag-
nosed fatal malignancy in adult autopsies, Parajuli et
al. report a 69-year-old woman with clinically undiag-
nosed adenocarcinoma of the colon who died as a
result of perforation of the colon and subsequent
acute peritonitis.49
Other more unusual gastrointestinal-related causes
of sudden death include a case report of a 39-year-
Medicine, Science and the Law 58(1)
old woman with Gardner syndrome, a rare familial
disorder characterised by colonic as well as gastric
and small bowel polyps. The patient died from
marked hyponatremia (serum Na <130 mEq/L) and
hypokalaemia (serum K <3.5 mEq/L).50 However,
attributing it solely to Gardner syndrome remains
questionable.
Varices
Varices can rupture and bleed, leading to sudden unex-
pected death. Most varices pertaining to the gastroin-
testinal tract are caused by portal hypertension due to
cirrhosis of the liver. Various other aetiologies are
implicated in the rest of the small proportion of cases
of varices. For example, gastric varices can be caused
by splenic vein thrombosis related to pancreatitis or
malignancies of the pancreas and stomach in the
region of the splenic vein. Idiopathic small bowel and
colonic varices are also reported in the literature.
Gastric varices may be isolated or an extension of
the oesophageal varices downward along the curva-
tures of the stomach. Gastric variceal bleeding follow-
ing rupture tends to be more severe, with a higher
mortality rate compared to oesophageal varices.
Ectopic varices appear in locations other than the gas-
troesophageal region, and those pertaining to the gas-
trointestinal tract may be present in the duodenum,
jejunum, ileum, colon and anorectum.
Machida et al.51 report an autopsy case of death due
to ruptured duodenal varices after endoscopic ligation
of oesophageal varices in a 79-year-old woman.
Another two autopsy cases of bleeding from ruptured
duodenal varices in a 48-year-old man and 35-year-old
man are described by Hashiguchi et al.52 and Amin et
al.,53 respectively. Waxman et al.54 report two autopsy
cases of death due to massive rectal bleeding from rup-
tured rectal varices. Batoon and Zoneraich55 report a
case of misdiagnosed anorectal varices that resulted in
a fatal outcome in a 69-year-old woman. Olusola et
al.56 report a fatal case of intraperitoneal haemorrhage
resulting from ruptured ectopic varices located in the
rectovesical pouch in a 52-year-old man. Hayashi et
al.60 report an autopsy case of intra-abdominal bleed-
ing from ruptured ectopic varices of the mesentery of
the ascending colon in a 43-year-old man with a clinical
history of alcoholic liver cirrhosis.
Miscellaneous
Gastroenteritis may cause sudden death from severe
dehydration and electrolyte imbalance, especially in
infants. Several rare and unusual conditions that may
cause life-threatening gastrointestinal bleeding are not
described here. Miscellaneous causes also include those
Menezes et al.
that are iatrogenic, but these are not described here.
This review mainly deals with sudden unexpected
death from natural disease.
Conclusion
This review draws attention to the gastrointestinal
causes of sudden unexpected death and the associated
pathology of each cause, which may not have been
covered as extensively in previous medical literature.
In addition, related fatal cases encountered occasional-
ly in forensic autopsy practice are also discussed. We
aim to highlight the need for physicians to prevent
death in such conditions by ensuring that subclinical
cases are diagnosed correctly before it is too late and by
providing timely and efficacious treatment to the
patient concerned. In addition, this review would cer-
tainly benefit the forensic pathologist while dealing
with cases of sudden unexpected death due to gastro-
intestinal causes.
Acknowledgements
We would like to thank the editor (Diana Brahams) and pub-
lisher (SAGE Publishing) of Medico-Legal Journal for per-
mitting us to reuse the images (Figures 1 to 3) that were
originally published in Menezes et al.14
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship and/or publication of this
article.
Funding
The authors received no financial support for the research,
authorship and/or publication of this article.
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