GI 2 Flashcards
1
Q
Congenital Pyloric stenosis EPIDIOMIOLOGY + CAUSES
A
M > F
-Genetic predisposition for children from affected parents
-Acquired pyloric obstruction, as a result of
chronic duodenal ulcer with scarring
2
Q
Congenital Pyloric Stenosis PATHOPHYSIOLOGY + CLINICAL FINDINGS
A
Progressive hypertrophy of the circular muscular layer in the pyloric sphincter
Clinical findings:
Projectile vomiting; not bile stained fluid Palpable mass (“OLIVE”); epigastrium (70% cases)
Obvious hyperperistalsis
3
Q
GASTROPARESIS definitions
A
Decreased stomach motility, due to:
Autonomic neuropathy (e.g. Diabetes Mellitus)
Previous vagotomy
4
Q
GASTROPARESIS clinical findings + treatments
A
Clinical findings:
Early satiety and bloating
Vomiting of undigested food
Treatment:
Frequent, small meals
Metoclopramide
5
Q
Acute Gastritis CLINICAL FEATURES
A
Asymptomatic disease, or
Variable degrees of epigastric pain, nausea
and vomiting, or
More severe cases: Mucosal erosion,
ulceration, haemorrhage, haematemesis,
melena, or massive blood loss (rarely)
6
Q
Microscopic findings:
Mild Acute Gastritis:
Moderate oedema and slight vascular
congestion in the lamina propria Intact surface epithelium Scattered neutrophils, intraepithelial
More severe mucosal damage:
Erosion or loss of superficial epithelium
Formation of mucosal neutrophilic infiltrates
and purulent exudates Occurrence of haemorrhages
Acute Erosive Haemorrhagic Gastritis: Con-
current presence of erosion and haemorrhage
A
Acute Gastritis:
Microscopic findings:
7
Q
Acute Erosive Haemorrhagic Gastritis:
Causes + Clinical findings
A
Causes: NSAID, alcohol, H. Pylori, smoking,
severe burn (Curling ulcer), CNS injury
(Cushing ulcer)
Clinical findings:
Haematemesis Melena Iron deficiency
8
Q
Type A Chronic Atrophic Gastritis =
Autoimmune Gastritis:
Definition +localisation +complications
A
‘Abs to parietal cells (produce HCl and
intrinsic factor) and intrinsic factor (necessary for the absorption of Vit. B12 [Cobalamin])
Development of Pernicious anaemia
Localisation: Body and fundus
Association/Complications:
Achlorhydria with Hypergastrinaemia
Vit. B12 deficiency => Macrocytic anaemia
↑ Risk for gastric Adeno-Ca
9
Q
Type B Chronic Atrophic Gastritis =
H. Pylori (causes) associated Gastritis:
CLINICAL FINDINGS + COMPLICATIONS/ ASSOCIATIONS + localisation
A
-Localisation: Antrum and pylorus
Clinical findings: Increased gastric acid
secretion
Complications/Associations: Gastric and
duodenal peptic ulcers, gastric Adeno-
Carcinoma and Lymphoma (MALT-type)
10
Q
Type B Chronic Atrophic Gastritis =
H. Pylori associated Gastritis:
Pathophysiology:
A
Production of urease, protease
Conversion of amino groups in proteins to
ammonia, by Urease
Development of Chronic Gastritis and peptic
ulcer by the action of secretion products
Colonisation of mucous layer lining without
invasion of the wall
Attachment to blood group O receptors on
mucosal cells
11
Q
Microscopic findings:
Chronic inflammatory infiltrate in the
lamina propria
Intestinal metaplasia (similar to Barrett
Oesophagus) => Progression to Adeno-Ca
A
Type B Chronic Atrophic Gastritis =
H. Pylori associated Gastritis:
12
Q
ACUTE PEPTIC ULCER
Cause
A
Complication of therapy with NSAIDs or
due to severe physiologic stress
13
Q
ACUTE PEPTIC ULCER
Types of Ulcer (associated with stress factors):
A
. Stress Ulcers: Critically ill patients with shock,
sepsis or severe trauma
. Curling Ulcers: Proximal duodenum; Severe
burns or trauma
.Cushing Ulcers: Stomach, duodenum, or
oesophagus; Individuals with intracranial
disease; Increased rate of perforation
14
Q
Pathogenesis
. NSAID-induced ulcers:
Direct chemical irritation + Cyclooxygenase
inhi-bition =>Prevention of Prostaglandin
synthesis => Elimination of Prostaglandin‟s
protective effect
Prostaglandin’s protective effect: Enhanced
bicarbonate secretion and ↑ vascular perfusion
Ulcers associated with brain injury:
Direct stimulation of vagal nuclei =>Gastric
acid hypersecretion
Ulcers associated with critically ill patients:
Systemic acidosis =>Decrease in intracellular
pH of mucosal cells =>Mucosal injury
A
ACUTE PEPTIC ULCER
Pathogenesis:
15
Q
Macroscopic features:
Acute Ulcers:
Round; Size: <1cm Ulcer base: Brown to black
Acute Stress Ulcers:
Sharply demarcated Normal adjacent mucosa
Microscopic findings:
Layers of Ulcer:
-Necrotic debris
-Mainly, neutrophilic infiltration
A
’, ACUTE PEPTIC ULCER
16
Q
ACUTE PEPTIC ULCER
Clinical features + complications + treatment
A
Clinical features:
Nausea
omiting
Haematemesis
Complications:Perforation
Treatment:
Proton pump inhibitors
Histamine H2 receptor antagonists
17
Q
Peptic. Ulcer. Disease
CAUSES + epidemiology
A
‘ Causes: H. pylori infection (most common);
NSAID use
Epidemiology: Lifetime risk for development of an ulcer: 10% for Males and 4% for Females
18
Q
Peptic ulcer disease location
A
-Gastric antrum and first portion of duodenum
-Oesophagus: Result of GOERD, ectopic gastric
mucosa
-Small intestine: Gastric heterotopia within a
Meckel diverticulum
19
Q
Peptic ulcer disease Pathogenesis
A
Imbalance btw mucosal defenses and
offensive agents Chronic Gastritis Peptic ulcer disease
H. pylori infection. (Gastric hyperacidity)
Parietal cell hyperplasia (GH)
Excessive secretory responses. (GH)
Impaired inhibition of stimulatory (GH)
mechanisms (e.g. Gastrin release)
Chronic renal failure and hyperparathyroidism =>↑ Gastrin production (GH)
Uncontrolled release of Gastrin (Zollinger-Ellison syndrome) => Multiple peptic ulcers
20
Q
Macroscopic features:
Lesions: <0.3 cm Shallow; 0.6 cm Deep
Round to oval
Sharply punched out defect
Base: Smooth and clean
Microscopic findings:
Base: Rich vascular granulation tissue
infiltrated with mononuclear leukocytes and a fibrous or collagenous scar
Possible involvement of the entire thickness
of the wall by scarring
A
PEPTIC ULCER DISEASE
21
Q
PEPTIC ULCER DISEASE Clinical features
A
Clinical features:
Epigastric burning or aching pain
Bloating and belching
Iron deficiency anaemia
Frank haemorrhage
Perforation
Occurrence of pain: 1-3 hours after meals
(during the day) and worse at night Relief of pain: Intake of alkali or food
22
Q
PEPTIC ULCER DISEASE
Treatment
A
-Antibiotics (H. pylori)
-Proton pump inhibitors => Neutralisation of
gastric acid
23
Q
MENETRIER DISEASE
-Hypertrophic or Hyperplastic
Gastropathy, Giant Hypertrophic Gastritis, and
Giant Hypertrophy of Gastric rugae
CRITERIA for DIAGNOSIS
A
Giant mucosal folds, involving the corpus and possibly antrum
Low acid production, even after stimulation
Mucosal protein loss
Histologic findings of corpus foveolar hyperplasia and glandular atrophy
24
Q
Macroscopic features:
Markedly hypertrophic rugae, resembling
cerebral convolutions
Abrupt transition between normal and diseased
mucosa
Typical form of the disease: Diffuse involvement
of the fundic portion, with sparing of the antrum
Localised form of the disease: Well-circum-
scribed cerebroid mass either in the fundus or
the antrum
A
‘MENETRIER DISEASE
25
: Microscopic findings:
On the surface of the folds: Gastric foveolae
enormously elongated, sometimes with a corkscrew (tortuous) appearance (foveolar hyperplasia)
Often, cystic dilation with mucous accumulation
Extension of cysts into the deeper mucosal
layers and even occasionally the submucosa
Reduction of the glandular component (corpus
gland atrophy)
Frequently, presence of non-specific
inflammation in the superficial mucosa
MENETRIER DISEASE
.
26
MENETRIER DISEASE
Clinical features:
Hypochlorhydria or achlorhydria and often
impressive hypoproteinaemia
27
MENETRIER DISEASE
Management
Adults: Fully developed disease is progressive
and requires subtotal gastrectomy
Paediatric cases of so-called Ménétrier Disease
are of the type that spontaneously resolve
(self-limited disease)
28
Gastric polyps is what ?
Neoplasm of stomach
29
Gastric polyps.
Pathogenesis: Develop as a result of:
-Epithelial or stromal cell hyperplasia
Inflammation
Ectopia
Neoplasia
30
Gastric polyps definition
Definition: Nodules or masses that project
above the level of the surrounding mucosa
31
Gastric polyps TYPES
Types of polyps:
Hyperplastic polyps Inflammatory polyps Fundic gland polyps Adenomas
32
-INFLAMMATORY & HYPERPLASTIC POLYPS
Pathogenesis
Chronic gastritis➡️ Injury and reactive hyperplasia
➡️Development of polyp
33
Macroscopy:
Ovoid lesions; Size: <1cm; Smooth surface Microscopy:
Irregular, cystically dilated and elongated foveolar
glands Oedematous lamina propria Acute and chronic inflammation Surface erosions (may be present)
INFLAMMATORY & HYPERPLASTIC POLYPS
34
FUNDIC GLAND POLYPS
Epidemiology
Epidemiology
Sporadic occurrence
Persons with Familial Adenomatous Polyposis
35
FUNDIC GLAND POLYPS
. Cause/Pathogenesis:
Cause/Pathogenesis:
Proton pump inhibitors Reduced acidity
Increased Gastrin secretion Glandular hyperplasia
36
FUNDIC GLAND POLYPS
Clinical features:
'Clinical features:
Nausea; Vomiting; Epigastric pain
37
Macroscopy: Well-circumscribed polyps in the
gastric body and fundus
Microscopy:
Cystically dilated, irregular glands Lining of the glands: Flattened parietal and
chief cells
.
FUNDIC GLAND POLYPS
38
-Epidemiology:
10% of all gastric polyps
Mostly, sessile and growth in tubulo-villous or
pure villous pattern; pure pedunculated tubular lesions are rare
Ages: 50-60 yrs.; M:F = 3:1
'GASTRIC ADENOMA
39
GASTRIC ADENOMA
Cause/Pathogenesis:
Cause/Pathogenesis:
Chronic gastritis➡️ Atrophy and intestinal
metaplasia
40
GASTRIC ADENOMA
Risk for malignant transformation:
Risk for malignant transformation:
Dependent on lesion‟s size (risk elevated with
lesions >2cm)
Presence of Adeno-CAs in up to 30% of gastric
adenomas
41
Microscopic features:
Histologically, two types:
Adenomas with intestinal differentiation
(Goblet cells and/or Paneth cells) Adenomas with gastric differentiation
(Columnar cells containing neutral mucin)
Epithelial dysplasia, classified as:
Low-grade: Enlargement, elongation and hyper-
chromasia of nuclei, epithelial crowding, pseudo- stratification
High-grade: More severe cytologic atypia and
irregular architecture (glandular budding, gland-within-gland, cribriform pattern)
Gastric adenoma
42
GASTRIC ADENOMA
Localisation:
Localisation: Antrum of the stomach
43
ZOLLINGER ELLISON SYNDROME
Cause
Caused by gastrin-secreting tumours, Gastrinomas
44
ZOLLINGER ELLISON SYNDROME
Localisation:
>80% of Gastrinomas arise within
the triangle defined as the confluence of the cystic
and common bile duct superiorly, the second and
third portions of the duodenum inferiorly, and the
neck and body of the pancreas medially
45
ZOLLINGER ELLISON SYNDROME
Epidemiology and Genetics:
Epidemiology and Genetics:
75% of patients = Sporadic, solitary tumours;
Surgical resection
25% of pts. = Association with Multiple
Endocrine Neoplasia type I (MEN type I);
Multiple tumours or metastatic disease;
Somatostatin analogues
46
ZOLLINGER ELLISON SYNDROME
Clinical manifestations
-Duodenal ulcers or
chronic diarrhoea
47
ZOLLINGER ELLISON SYNDROME
. Pathological findings within Stomach:
'Pathological findings within Stomach:
5x increase in number of parietal cells => Doubling of oxyntic mucosal thickness
Hyperplasia of mucous neck cells, mucin hyperproduction
Proliferation of endocrine cells => Small dysplastic nodules (sometimes), true
Carcinoid Tumours (rarely)
48
ZOLLINGER ELLISON SYNDROME
Diagnostic procedures:
.. Diagnostic procedures:
Somatostatin Receptor Scintigraphy
Endoscopic Ultrasonography
49
ZOLLINGER ELLISON SYNDROME
Treatment:
Treatment: Blockade of acid hypersecretion:
Proton pump inhibitors or
High-dose H2 histamine receptor antagonists
50
ZOLLINGER ELLISON SYNDROME
Progression:
Progression:
In general, slow growing tumours
60-90% of Gastrinomas are malignant
51
CARCINOMA OF THE STOMACH
Epidemiology:
Epidemiology:
Most common after 50 yrs.
Men > Women
Most frequent occurrence in blood group A persons
52
CARCINOMA OF THE STOMACH
Aetiologic factors
Aetiologic factors: '.
-H. pylori
- Nitrosamines from dietary amines and nitrites used in food preservatives. Smoked fish (Japan)
-Excessive salt intake and diet low in fresh fruits and vegetables
-Achlorhydria and Chronic Gastritis +/- Pernicious Anaemia
-Menetrier disease (Giant Hypertrophic Gastritis) Familial cases associated with mutations to E-Cadherin gene (CDH1):
. -Diffuse infiltrating signet-ring cell CAs
-Patients with these mutations =>. Development of lobular CA of the breast
-Patients with Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer) => Increased risk for
gastric CA
53
-CARCINOMA OF THE STOMACH
Pathogenesis:
Mutations:
. Mutations:
Germline mutations in CDHI (encodes E-Cad-
herin); Protein contributing to epithelial inter-
cellular adhesion; Loss of E-Cadherin function
=>Development of diffuse type gastric cancer
Germline mutations in Adenomatous Polyposis
Coli (APC) genes (patients with FAP) =>
Increased risk of intestinal type gastric cancer
Acquired mutations of β-Catenin = Sporadic
intestinal type gastric cancer
TP53 mutations = Majority of sporadic gastric
cancers of both histologic types
54
CARCINOMA OF THE STOMACH
Pathogenesis (cont.):
H. pylori:
Pathogenesis (cont.):
H. pylori:
H. pylori induced Chronic Gastritis =>
Increased production of pro-inflammatory
proteins (IL-1β and TNF)
Polymorphisms related to enhanced production
of these cytokines => Intestinal-type gastric CA
55
CARCINOMA OF THE STOMACH
Pathogenesis (cont.):
EBV:
EBV:
EBV-positive tumours characterised by:
1.Localisation: Proximal stomach
2.Diffuse morphology
3,Marked lymphocytic infiltrate
56
Characteristics:
Localisation: Minor curvature of the antrum
or pre-pyloric region => Spread to the adjacent organs, peritoneum, regional lymph nodes and liver
Distal sites:
Virchow node: Supra-clavicular lymph
nodes with metastasis of gastric CA
Krukenberg tumours: Bilateral involvement
of the ovaries by tumour metastasis;
Tumour consisted of signet ring-cells
CARCINOMA OF THE STOMACH
Characteristics:
57
Macro-/Microscopic features:
A. Intestinal type:
Association with H. pylori
Polypoid carcinoma; solid mass projecting
into the lumen
Possible, ulceration
DD: Peptic Ulcer (smooth base, non-elevated
punched out margins) vs. CA (Ulcer with
irregular necrotic base and firm raised
margins)
:. CARCINOMA OF THE STOMACH
A. Intestinal type:
58
. Macro-/Microscopic features (cont.):
Synonym: Linitis plastica, leather-bottle
stomach
NO association with H. pylori
Macroscopy: Thickened, rigid stomach wall Microscopy: Diffuse signet-ring cells
infiltrates with accompanying extensive
fibrosis
CARCINOMA OF THE STOMACH
Infiltrating or Diffuse CA:
59
LYMPHOMA OF THE STOMACH
Cytogenetic abnormalities:
Cytogenetic abnormalities: (11;18) trans-location;
Involvement of MALT1 and IAP2 genes; High predictive value, since its presence associated with unresponsiveness to: i. Antibiotic treatment and ii. Therapy with oral alkylating agents
60
Microscopic features:
Dense infiltrate of small lymphoid cells, often
accompanied by scattered reactive lymphoid follicles Lymphoid cells: Variable admixture of small lympho-
cytes, centrocyte-like cells, and monocytoid cells Common finding, focal or extensive plasmacytoid
differentiation Possible presence of „Dutcher bodies‟ (true intra-
nuclear eosinophilic inclusions made up of immu-
noglobulin) Great diagnostic significance Important diagnostic sign: Infiltration of the
glandular epithelium by neoplastic lymphocytes,
resulting in so-called „lympho-epithelial lesions‟
EXTRANODAL MARGINAL ZONE LYMPHOMA (MALT)
Microscopic features:
61
LARGE B-CELL LYMPHOMA
-High-grade, aggressive lymphoma
-Usually, in individuals over the age of 50 years
62
LARGE B-CELL LYMPHOMA
Clinical manifestation:
Clinical manifestation:
Large palpable mass (and still excellent physical
condition of the patients)
63
Macroscopic findings:
with a tendency to spare the pylorus
Large lobulated (sometimes polypoid) mass
Commonly, superficial or deep ulceration
LARGE B-CELL LYMPHOMA
64
LARGE B-CELL LYMPHOMA
Preferred (predilection) localisation
Site of predilection: Distal half of the stomach,
with a tendency to spare the pylorus
65
Microscopic features:
Most cases composed of cells resembling
large non-cleaved cells (centroblasts) but with a slightly more abundant cytoplasm, sometimes resulting in a plasmablastic or immunoblastic appearance
Multinucleated cell forms resembling Reed-
Sternberg cells may be present The phenotypic features are those of B cells
LARGE B-CELL LYMPHOMA
66
Differential diagnosis w/ Undifferentiated CARCINOMA
. Microscopic features favouring Lymphoma:
Lack of continuity between epithelium and
tumour cells
Lack of suggestion of an acinar pattern
Preservation of muscularis mucosae fibers
Immuno-cytochemical evaluation of lymphoid
and epithelial markers in difficult cases
LARGE B-CELL LYMPHOMA
67
LARGE B-CELL LYMPHOMA
Prognosis and Progression
Prognosis and Progression
Prognosis for gastric Large B-Cell Lymphoma,
substantially better than for gastric Carcinoma
The overall 5-year disease-free survival rate:
Approximately 60%
Favourable prognostic features:
Small tumour size Superficial mural invasion Absence of regional lymph node involvement
.
68
CARCINOID TUMOURS
Definition
Originate from endocrine organs (e.g. endocrine pan-
creas) and neuroendocrine-differentiated GI epithelia
(e.g. G-cells) as well as tracheo-bronhial tree and lungs
69
CARCINOID TUMOURS
. Gastric Carcinoids are associated with:

Gastric Carcinoids are associated with:
Endocrine cell hyperplasia
Chronic atrophic gastritis
Zollinger-Ellison syndrome
70
CARCINOID TUMOURS
. Grading based mainly on:
Grading based mainly on:
Mitotic index
Ki-67 immuno-positive cells (%)
71
Macroscopic features:
Intramural or submucosal masses => Small
polypoid lesions
Yellow or tan in appearance
Intense Desmoplasia => Kinking of the bowel
and obstruction
Microscopic findings:
Arrangement of the cells in: i. Islands, ii.
Glands, iii. Trabeculae, iv. Strands, or v. Sheets
Cells:
Scant, pink granular cytoplasm
Round to oval stippled nucleus
CARCINOID TUMOURS
72
CARCINOID TUMOURS
Immunohistochemistry
Immunohistochemistry: Neuron-Specific Enolase
(NSE), Chromogranin, Synaptophysin
73
CARCINOID TUMOURS
Clinical features:
Clinical features:
Symptoms depend on hormones produced by the Tm
Carcinoid Syndrome:
Cause: Secretion of vasoactive substances (e.g.
kinins, VIP, angiotensin II, (nor)epinephrine, etc.)
Clinical picture:
Cutaneous flushing Sweating Bronchospasm Colicky abdominal pain Diarrhoea
74
CARCINOID TUMOURS
Prognosis:
Prognosis: Depends primarily on tumour‟s location:
Foregut Carcinoid Tumours:
Oesophagus, Stomach, Duodenum
Rarely, metastases
Gastric carcinoids develop as a result of prolonged Gastrin hypersecretion in Zollinger
Ellison syndrome
Midgut Carcinoid Tumours:
Jejunum, Ileum
Multiple and aggressive
Poor outcome: i. Depth of local invasion,
ii. Increased size, iii. Necrosis, and iv. Mitosis
Hindgut Carcinoids:
Appendix vermiformis (benign), Colorectum Incidentalomas
Rectal Carcinoids:
Abdominal pain and weight loss
Occasionally, metastases
75
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
Mesenchymal tumours, derived from pacemaker
(myenteric interstitial) cells of Cajal
Most common mesenchymal tumour of the abdomen
76
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
Localisation
Localisation: Submucosa of stomach, small and
large intestine and extra-gastrointestinal sites
77
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
Pathogenesis
Pathogenesis:
75-80% of GISTs: Oncogenic, gain-of-function
mutations of the gene encoding the tyrosine kinase
c-KIT
8% of GISTs: Activating mutations of PDGFRA
78
Macroscopic features:
Primary lesions: Solitary, well circumscribed,
fleshy submucosal masses
Metastases: Multiple small serosal nodules or
fewer nodules in the liver
Microscopic features:
Thin, elongated spindle cells or
Plumper epithelioid cells
c-KIT (CD117) immuno-positivity in 95% of
GISTs
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
79
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
Clinical features:
Clinical features:
Symptoms are related to:
Mass effect
Mucosal ulceration
80
GASTRO-INTESTINAL STROMAL TUMOUR (GIST)
Prognosis
Prognosis, correlates with:
Tumour size
Mitotic Index (MI)
Location
Gastric GISTs less aggressive than small-
intestine GISTs
Gastric GISTs:
Recurrence or metastasis: <5cm tumours
Rare; >10cm and high MI <=> Common
81
HERNIATION
Definition
Definition: Any weakness or defect in the wall
of the peritoneal cavity may permit protrusion
of a serosa-lined pouch of peritoneum called
hernia sac
82
HERNIATION.
Localisation
Lo'calisation: Occurrence of acquired hernias
most commonly anteriorly (inguinal and
femoral canals or umbilicus, or at sites of
surgical scars)
83
HERNIATION
Complications:
Complications:
Visceral protrusion (external herniation)
Inguinal hernias (mostly with narrow orifices and large sacs): Entrapment of small bowel loops or portions of omentum => Pressure at the neck of the pouch => Impairment of venous drainage of the entrapped viscous => Stasis and oedema=> Increase in the bulk of the herniated loop => Permanent entrapment or incarceration => Over time, arterial and venous compromise (strangulation) => Infarction
84
ADHESIONS
Causes
. Causes:
Congenital
Acquired: Surgical procedures, infection or
other causes of peritoneal inflammation, such
as endometriosis
'
85
ADHESIONS
Complications
Complications: Development of closed loops
through which other viscera may slide =>
Entrapment => Internal herniation =>
Obstruction and strangulation
86
'VOLVULUS
Definition + clinical presentation
Complete twisting of a loop of bowel about its
mesenteric base of attachment, which produces
both luminal and vascular compromise
Clinical presentation: Features of obstruction
and infarction
87
VOLVULUS
Localisation
-Localisation: Large redundant loops of sigmoid
colon (most often), caecum, small bowel, stomach,
or transverse colon (rarely)
88
INTUSSUSCEPTION
Condition by which a segment of the intestine,
constricted by a wave of peristalsis, telescopes
into the immediately distal segment
89
INTUSSUSCEPTION
,. Progression:
'Progression: Once trapped, the invaginated
segment is propelled by peristalsis and pulls the
mesentery along
90
INTUSSUSCEPTION
Causes
Causes:
Infants and children: In some cases,
association with Rotavirus infection
Older children and adults: Intraluminal mass
or tumour (serves as the point of traction)
91
INTUSSUSCEPTION
Complications:
Complications: Untreated intussusception may
progress to intestinal obstruction, compression of
mesenteric vessels and infarction
92
INTUSSUSCEPTION
, Management
Management:
Infants and young children: Barium enema
(effectively reduces the intussusception)
Older patients: Surgical interventio
93
ISCHAEMIC BOWEL DISEASE
Classification of ischaemic damage to bowel:
Classification of ischaemic damage to bowel:
Mucosal infarction: Up to muscularis mucosae
Mural infarction of mucosa and submucosa
Trans-mural infarction: All three layers of the
wall
94
ISCHAEMIC BOWEL DISEASE
. Causes
Causes:
Acute or chronic hypo-perfusion => Mucosal or
mural infarctions
Acute vascular obstruction => Trans-mural
infarction
95
ISCHAEMIC BOWEL DISEASE
Causes of acute arterial obstruction:
Causes of acute arterial obstruction:
Severe atherosclerosis
Aortic aneurysm
Hypercoagulable states
Oral contraceptives
Embolisation of cardiac vegetations or aortic
atheromas
96
ISCHAEMIC BOWEL DISEASE
Causes of intestinal hypoperfusion:
Causes of intestinal hypoperfusion:
Cardiac failure Shock Vasculitides (PAN, Henoch-Schönlein purpura,
Wegener granulomatosis, etc.)
97
ISCHAEMIC BOWEL DISEASE
Pathogenesis:
Pathogenesis:
Phases of intestinal responses to ischaemia:
First phase: Occurrence of initial hypoxic
injury at the onset of vascular compromise
.
Second phase: Reperfusion injury;Due to
increased permeability of capillaries and
arterioles => Increase of diffusion and fluid
filtration across the tissues, free radical
production, neutrophil infiltration and
release of inflammatory mediators
Severity of ischaemic bowel disease depends on:
-Time frame for its development
-Severity of vascular compromise
-Affected vessels
Intestinal vascular anatomy contributes
to distribution of ischaemic damage:
1. Watershed zones: Intestinal segments
particularly susceptible to ischaemia;
These are: Splenic flexure, Sigmoid
colon and Rectum
2. Morphologic configuration of intestinal
capillaries allows good blood supply
of crypts but leaves epithelial cells
vulnerable to ischaemia
98
Macroscopic features:
Distribution of lesions: Segmental and
irregular
Haemorrhagic and ulcerated mucosa
Oedema induced thickening of the wall
Severe disease (e.g. Acute arterial
thrombosis => Transmural infarction):
Extensive mucosal and submucosal
haemorrhage and necrosis; Coagulative
necrosis of muscularis propria (1-4 days)
=> Purulent serositis => Perforation
ISCHAEMIC BOWEL DISEASE
99
Microscopic findings:
Atrophy or sloughing of surface epithelium
Hyper-proliferative crypts
Recruitment of neutrophils within hours of
reperfusion
Acute phases of ischaemia: Bacterial super-
infection and enterotoxin release => Pseudo-
membrane formation
Chronic ischaemia: Fibrous scarring of the
lamina propria, and less common stricture
ISCHAEMIC BOWEL DISEASE
100
ISCHAEMIC BOWEL DISEASE
Clinical Features
Clinical Features:
Sudden, severe abdominal pain
Tenderness
Nausea and Vomiting
Bloody diarrhoea or melaena (“tarry” feces) =>
Vascular collapse and shock (due to blood loss)
Decline or disappearance of peristaltic sounds
Muscular spasm =>Board-like rigidity of the
abdominal wall
101
ISCHAEMIC BOWEL DISEASE
DD
DD: Acute appendicitis, perforated ulcer, acute
cholecystitis
102
ISCHAEMIC BOWEL DISEASE
. Complications
Complications: Break down of mucosal barrier
=> Bacteria enter the circulation => Sepsis
103
ANGIODYSPLASIA
Characterised by malformed submucosal and
mucosal blood vessels
104
ANGIODYSPLASIA
Localisation
Localisation: Caecum or right Colon
105
ANGIODYSPLASIA
Pathogenesis
Pathogenesis:
Normal bowel distention and contraction
=> Occlusion of the submucosal veins (penetrate through the muscularis propria) => Focal dilation and tortuosity of overlying submucosal and mucosal vessels
Caecum: Largest diameter of any colonic
segment => Greatest wall tension => Development of angiodysplasias (preferable locus)
Age related degenerative vascular changes
Angiodysplasia has also been linked to
aortic stenosis and Meckel diverticulum (congenital anomaly?)
106
Microscopic findings:
Ectatic nests of tortuous veins, venules,
and capillaries Separation of the vascular channels from
the intestinal lumen, by only the vascular
wall and a layer of attenuated epithelial
cells; As a result of this: Limited injury of
the vessel => Significant haemorrhage
ANGIODYSPLASIA
107
Malabsorption
Malabsorption: Characterised by defective
absorption of fats, fat- and water-soluble
vitamins, proteins, carbohydrates,
electrolytes and minerals, and water
108
! MALABSORPTION
Pathogenesis:
Pathogenesis:
Malabsorption results from disturbance in at
least one of the four phases of nutrient
absorption:
1. Intraluminal digestion, in which proteins,
carbohydrates, and fats are broken down into
forms suitable for absorption
2. Terminal digestion, which involves the
hydrolysis of carbohydrates and peptides by
disaccharidases and peptidases, respectively,
in the brush-border of the small intestinal
mucosa
3. Transepithelial transport, in which
nutrients, fluid and electrolytes are transported across and processed within the small intestinal epithelium
4. Lymphatic transport of absorbed lipids
109
MALABSORPTION
Clinical features:
Clinical features:
Chronic malabsorption: Chronic diarrhoea,
weight loss, anorexia, abdominal distention, borborygmi*, and muscle wasting
Hallmark of malabsorption <=> Steatorrhoea
(excessive faecal fat and bulky, frothy, greasy, yellow or clay-coloured stools)
* Borborygmus: A rumbling or gurgling noise made by the movement of fluid and gas in the intestines
110
MALABSORPTION SYNDROMES
Similarities among the various Malabsorption
Syndromes
General symptoms:
Diarrhoea Flatus Abdominal pain Weight loss
- Inadequate absorption of Vitamins and
Minerals:
Pyridoxine, folate, or Vitamin B12 deficiency
=> Anaemia and Mucositis
Vitamin K deficiency => Bleeding
Calcium, Magnesium, or Vitamin D
deficiencies => Osteopenia and Tetany
Vitamin A or B12 deficiencies => Peripheral
Neuropathy
111
DIARRHOEA
Definition:
'Definition: Increase in stool mass, frequency, or
fluidity, typically greater than 200gr per day
112
DIARRHOEA
Dysentery
'Dysentery: Painful, bloody, small-volume
diarrhoea
113
Classification of diarrhoea
'. 1. Secretory diarrhoea:
Characterised by isotonic (with plasma) stool
Persists during fasting
2. Osmotic diarrhoea:
Typical in lactase deficiency
Due to the excessive osmotic forces exerted
by unabsorbed luminal solutes
>50 mOsm more concentrated than plasma
Abates with fasting
3. Malabsorptive diarrhoea:
Result of generalised failures of nutrient
absorption
Associated with steatorrhoea
Relieved by fasting
4. Exudative diarrhoea:
Due to inflammatory disease
Characterised by purulent, bloody stools
Continues during fasting
114
COELIAC DISEASE
. Synonyms
Synonyms: Coeliac Sprue or Gluten-sensitive
Enteropathy
115
COELIAC DISEASE
. Causes
Causes: Immune-mediated enteropathy,
triggered by the ingestion of Gluten-containing
cereals (e.g. wheat, rye, barley) in genetically
predisposed individuals
116
COELIAC DISEASE
Predisposing factors:
Predisposing factors:
Class II HLA-DQ2 or HLA-DQ8 alleles
Association with: Type I Diabetes Mellitus,
Thyroiditis, Sjögren syndrome, IgA nephro-
pathy, Down syndrome and Turner syndrome
117
COELIAC DISEASE
Pathogenesis:
Pathogenesis:
Digestion of Gluten into amino acids and
peptides (Gliadin peptide; resistant to degradation by gastric, pancreatic and small intestinal proteases)
Deamidation of Gliadin by tissue trans-
glutaminase
Interaction of deamidated Gliadin with APCs
Presentation of the former to the CD4+ T cells
-Production of cytokines (IFNγ) by the latter
(CD4+ T) => Tissue damage
B cell response: Production of the following
Antibodies:
Anti tissue trans-glutaminase (anti-tTG)
Anti-deamidated Gliadin
- Anti-endomysial
-Deamidated Gliadin peptides induce
epithelial cell to produce IL15
IL15 triggers activation and proliferation of
CD8+ T cells
CD8+ T cells express NKG2D (MIC-A
receptor) and become cytotoxic, thus kill
enterocytes that express MIC-A
Tissue damage favours the movement of
Gliadin across the epithelium =>
Perpetuation of the disease‟s cycle
118
COELIAC DISEASE
Localisation
Localisation: Second portion of duodenum or
proximal jejunum
119
'Microscopic findings:
Increased numbers of intraepithelial CD8+ T
cells
Intraepithelial lymphocytosis
Crypt hyperplasia (Increased crypt mitotic
activity => Limitation in differentiation
ability of absorptive enterocytes => Defects in
terminal digestion and trans-epithelial
transport)
Villous atrophy (Loss of mucosal and brush-
border surface area => Malabsorption)
Fully developed disease: Increased numbers
of plasma cells, mast cells and eosinophils,
within upper part of the lamina propria
COELIAC DISEASE
120
COELIAC DISEASE
Clinical Features:
Silent coeliac disease + Latent coeliac disease
-Silent coeliac disease:
Positive serology
Villous atrophy
Absence of symptoms
- Latent coeliac disease:
Positive serology
Absent villous atrophy
121
COELIAC DISEASE
Clinical Features (cont.):
Symptomatic adult coeliac disease:
Symptomatic adult coeliac disease:
Anaemia (Iron, Vitamin B12 and folate
deficiency)
Diarrhoea
Bloating
Fatigue
122
COELIAC DISEASE
Clinical features
Pediatric coeliac disease:
Classic symptoms;
Classic symptoms; 6-24 months
Irritability
Abdominal distention
Anorexia
Diarrhoea
Failure to thrive
Weight loss or muscle wasting
123
. Clinical Features (cont.):
Pediatric coeliac disease:
Non-Classic symptoms (older children)
Abdominal pain
Nausea
Vomiting
Bloating or constipation
Pruritic blistering skin lesion (Dermatitis
herpetiformis or Duhring's disease)
124
COELIAC DISEASE
Laboratory Findings:
Laboratory Findings:
IgA Abs to tissue trans-glutaminase
IgA or IgG Abs to deamidated Gliadin
Absence of HLA-DQ2 or HLA-DQ8 (high
negative predictive value)
125
Coeliac-disease associated malignancies:
.
Coeliac-disease associated malignancies:
Enteropathy-associated T Cell Lymphoma
Small intestinal Adenocarcinoma
126
TROPICAL SPRUE
+ epidemiology
Malabsorption syndrome
Epidemiology:
Occurrence, almost exclusively in people living
in or visiting the tropics
Generally endemic; although epidemics have
been reported
127
-TROPICAL SPRUE
Causes
Causes:
No definite causal organism
Overgrowth of aerobic enteric bacteria has been documented
Proposed aetiologic factors: Various infections,
including Cyclospora or enterotoxigenic bacteria
128
. TROPICAL SPRUE
Histologic findings
Histologic findings:
Similar to Coeliac disease, but:
Total villous atrophy <=> Uncommon in tropical
sprue
Tropical Sprue involves the distal small bowel
Enlarged (megaloblastic) nuclei within epithelial
cells (reminiscent of those seen in pernicious
anaemia)
129
TROPICAL SPRUE
Clinical features
Clinical features:
Malabasorption usually manifested within days
or a few weeks of an acute diarrhoeal enteric infection
High frequency of folate or Vit. B12 deficiencies
130
AUTOIMMUNE ENTEROPATHY
X-linked disorder characterised by severe
persistent diarrhoea and autoimmune disease
MOSTLY IN YOUNG CHILDREN
131
AUTOIMMUNE ENTEROPATHY
IPEX: Severe familial form
-Acronym for:
Immune dysregulation
Polyendocrinopathy '
Enteropathy
X-linkage
132
AUTOIMMUNE ENTEROPATHY
Causes
Causes: Germline mutation in the FOXP3 gene
(located on the X chromosome)
133
AUTOIMMUNE ENTEROPATHY
Pathogenesis:
Pathogenesis:
FOXP3: Transcription factor expressed in
CD4+ regulatory T cells
Individuals with IPEX and FOXP3 mutations
=> Defective T-regulatory function
Link between less severe forms of autoimmune
enteropathy and other defects in regulatory T
cell function
134
Microscopic findings:
Increased numbers of intraepithelial
lymphocytes within the small intestine
Often, presence of neutrophils
Autoantibodies to enterocytes and goblet cells
(common), antibodies to parietal or islet cells
(in some cases)
. AUTOIMMUNE ENTEROPATHY
135
AUTOIMMUNE ENTEROPATHY
Treatment
-Treatment:
Immunosuppressive medications (e.g. cyclo-
sporine)
Bone marrow transplantation (in rare cases)
136
LACTASE (DISSACHARIDASE) DEFICIENCY
Dissacharidases
. Dissacharidases: Located in the apical
brush-border membrane of the villus
absorptive epithelial cells
.Biochemical defect Unremarkable biopsy
histology
137
Two types of lactase deficiency:
1. Congenital lactase deficiency:
Cause + clinical + management
1. Congenital lactase deficiency:
Epidemiology & Genetics: Rare, autosomal
recessive disorder
Cause: Mutation in the gene encoding lactase
Clinic: Explosive diarrhoea with watery, frothy
stools and abdominal distention upon milk
ingestion
Management: Termination of milk/milk
products consumption, thus remove of the
osmotically active, but unabsorbable lactose
from the lumen
138
Acquired lactase deficiency:
Cause + clinical
2. Acquired lactase deficiency:
Cause: Down-regulation of lactase gene
expression
Disease presents after childhood
Onset of disease, sometimes associated with
enteric viral or bacterial infections
Clinic: Abdominal fullness, diarrhoea, and
flatulence, due to fermentation of the
unabsorbed sugars by colonic bacteria;
triggered by ingestion of lactose-containing
dairy products
139
ABETALIPOPROTEINAEMIA
Rare autosomal recessive disease,
characterised by an inability to secrete
triglyceride-rich lipoproteins
140
'ABETALIPOPROTEINAEMIA
Causes
Causes: Mutation in the Microsomal
Triglyceride Transfer Protein (MTP) that
catalyses transport of triglycerides,
cholesterol esters, and phospholipids
141
-ABETALIPOPROTEINAEMIA
Pathogenesis
Pathogenesis: MTP-deficient enterocytes
unable to export lipoproteins and free fatty
acids => Mono-glycerides cannot be assembled
into chylomicrons => Buildup of triglycerides
within the epithelial cells
142
ABETALIPOPROTEINAEMIA
Microscopic findings + Histochemistry
Microscopic findings: Lipid accumulation
in small intestinal epithelial cells
Histochemistry: Oil red-O (demonstration
of lipids)
143
ABETALIPOPROTEINAEMIA
Clinical features:
Clinical features:
Presentation in infancy:
Failure to thrive
Diarrhoea
Steatorrhoea
144
ABETALIPOPROTEINAEMIA
Laboratory findings:
Laboratory findings:
Complete absence of all plasma lipoproteins
containing apolipoprotein B
Failure to absorb essential fatty acids =>
Deficiencies of fat-soluble vitamins
Presence of acanthocytic red cells (burr cells) in
peripheral blood smears, due to lipid membrane
defects
145
'PSEUDOMEMBRANOUS COLITIS
Synonym: Antibiotic-associated diarrhoea
Cause
Cause: Clostridium difficile; 20% present in
hospitalised adults
146
-PSEUDOMEMBRANOUS COLITIS
Pathogenesis
Pathogenesis:
Prolonged intake of antibiotics => Disruption of the normal colonic microbiota => Overgrowth of C.
difficile => Release of toxins => Ribosylation of
small GTP-ases (Rho) =>
=> Disruption of the epithelial cytoskeleton
=> Loss of tight junction barrier
=> Release of cytokines
=> Apoptosis
147
Macro-/Microscopic features:
Pseudo-membranes, consisting of an adherent
layer of inflammatory cells and debris
Stripped surface epithelium
Lamina propria, with:
Dense infiltrate of neutrophils
Occasional fibrin thrombi within capillaries
Distention of damaged crypts by a mucopurulent exudate => “Eruption” to the surface, in a fashion reminiscent of a volcano
PSEUDOMEMBRANOUS COLITIS
148
PSEUDOMEMBRANOUS COLITIS
Clinical Features:
. Clinical Features:
Fever
Leukocytosis
Abdominal pain
Cramps
Hypo-albuminaemia
Watery diarrhoea
Dehydration
Faecal leukocytes
Occult blood
149
'PSEUDOMEMBRANOUS COLITIS
Diagnosis + Treatment
Diagnosis: Detection of C. difficile toxin
Treatment: Metronidazole or Vancomycin
150
WHIPPLE DISEASE + cause
Rare, multi-visceral chronic disease
Causative agent: Tropheryma whippelii
(Gram [+] actinomycete)
151
WHIPPLE DISEASE
Localisation
Localisation: Mesenteric lymph nodes,
synovial membranes of affected joints, cardiac
valves, brain, and other sites <=> Accumulation
of bacteria-laden macrophages
152
Macroscopic features:
Shaggy gross appearance to the mucosal
surface, due to villous expansion caused by the dense macrophage infiltrate
White to yellow mucosal plaques, due to
lymphatic dilatation and mucosal lipid deposition
WHIPPLE DISEASE
153
Microscopic findings: Dense accumulation
of distended, foamy macrophages in the small
intestinal lamina propria
WHIPPLE DISEASE
154
Histochemistry: Periodic Acid-Schiff (PAS)-
positive, diastase-resistant granules (represent
lysosomes stuffed with partially digested bacteria),
within macrophages
WHIPPLE DISEASE
155
WHIPPLE DISEASE
Differential Diagnosis
Differential Diagnosis:
Intestinal Tbc (PAS [+] and acid-fast stain [+])
Whipple disease (PAS [+] but acid-fast stain [-]
156
WHIPPLE DISEASE
Clinical symptoms:
Clinical symptoms: Accumulation of organism-
laden macrophages within the small intestinal
lamina propria and mesenteric lymph nodes =>
Lymphatic obstruction (impaired lymphatic
transport) => Malabsorptive diarrhoea
157
WHIPPLE DISEASE
Clinical presentation: Triad of:
Diarrhoea
Weight loss
Malabsorption
158
WHIPPLE DISEASE
Extra-intestinal symptoms:
Extra-intestinal symptoms:
Arthritis and arthralgia
Fever
Lymphadenopathy
Neurologic, cardiac, or pulmonary
disease
