13.4.2016 г.

Pathophysiology of the
digestive system

Blagoi Marinov, MD, PhD

Pathophysiology Department
Medical University of Plovdiv

Digestive system
overview

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Most frequent GI disorders

 Gastritis

 Peptic ulcer disease

 Pancreatitis

 Bowel obstruction

General etiology of GI disorders

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Acute Gastritis
definiton

Acute gastritis is a term covering a broad

spectrum of entities that induce inflammatory
changes in the gastric mucosa.

The different etiologies share the same general

clinical presentation. However, they differ in their
unique histologic characteristics.

Gastritis: classification

• Acute Gastritis:
 Irritants, drugs, chemicals, alcohol.

• Chronic Gastritis:
 Autoimmune: Pernicious anaemia.
• Anti-parietal cell & Anti-intrinsic factor AB.
 Chemical:
• NSAIDs, Bile reflus, Alcohol.
 Bacterial:
• Helicobacter pylori (most common)

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Gastritis:
Types

Gastritis
risk factors

 Environmental factors
 Radiation, smoking
 Diet
 Alcohol, spicy food
 Pathophysiologic conditions
 Burns, renal failure, sepsis
 Other factors
 Psychologic stress, NG tube

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Gastritis:
etiology

 Alcohol
 NSAIDs
 Helicobacter
 Stress/ICU associated
 Autoimmune

Acute gastritis:
pathogenesis
Exogenous factors Endogenous factors

• Irritants • Uremia
• Drugs • Diabetic coma
• Alcohol • Shock
• Aggressive
substances
 Bloodflow  HCO3-

Gastritis

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Acute Gastritis
Clinical Manifestations

 Anorexia
 Nausea
 Vomiting
 Epigastric tenderness
 Feeling of fullness
 Hemorrhage
• Common with alcohol abuse
• May be only symptom

Chronic Gastritis
definiton

Chronic gastritis is a histopathologic entity

characterized by chronic inflammation of the
stomach mucosa.

The epithelial changes may become dysplastic and

constitute a backround for the development of
carcinoma.

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Chronic H. Pylori gastritis

• Direct cytopathogenic
action (toxins, enzymes)
• Indirect effect pathogenic
effect on mucous
defense through bacterial
lipase and protease
• Urease activity
(urea  NH3)

Chronic autoimmune gastritis

(atrophic)

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Evolution of atrophic gastritis

• Pernicious anemia
 Gastrointestinal
syndrome
 Hematologic
 Neurologic
• Precancerosis
 Gastric carcinoma appears 3 to 20 times more
frequently in patients with atrophic gastritis.

Gastritis:
complication

 Dyspepsia (particularly alcohol, NSAIDs)

 Bleeding
 Loss of intrinsic factor (if body involved)
 Decreased gastric acid secretion
 Progression to ulcer
 Progression to cancer/lymphoma

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Peptic ulcer disease:

Definition

Defect of gastric or duodenal mucosa

which interfere over lamina muscularis
mucosae, submucosa or penetrates
across whole gastric or duodenal wall

Ulcer disease

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Localisation of ulcers

Location and Type of Ulcer:

• Type 1: Primary gastric ulcer. Associated with
diffuse antral gastritis.
• Type 2: Gastric ulcers with duodenal ulcers, most
likely secondary to duodenal ulcers.
• Type 3: Prepyloric or channel ulcer.
• Type 4: Proximal stomach or gastric cardia.

Acid hyper secretion common among type 2 and 3

ulcers. Type 1 an 4 pathophysiologycally the
same.

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Peptic ulcer disease:

Frequencies

• 10% of the world population (6-11% in different

sources)
• Men: Women– 7:1
• Duodenal : Gastric– 4:1
• Duodenal ulcer is prevalent in the age group 30-
50 (men > women)
• Gastric ulcer is predominant after the age of 40
(morbidity in men and women is equal)

Peptic ulcer disease

Classification:

Acute ulcer (ulcus acutum)

 smooth non-elevated borders and smooth base
 major bleeding into upper GIT

Chronic ulcer (ulcus chronicum)

 rushed and elevated boders, inflammation with
hypertrophic and fibrotic proliferation is
present
 the most frequent form of ulcer disease

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Etiology of PUD

Normal
Increased Attack
Hyperacidity, Zollinger
Ellison syndrome.

Weak defense
Stress, drugs, smoking
Helicobacter pylori*

Peptic ulcer disease:

Etiology
• Helicobacter pylori infection*
• Hyperacidity
• Drugs - anti-inflammatory
(NSAIDs) & Corticostroids.
• Cigarette smoking, Alcohol,
• Rapid gastric emptying
• Duodenal reflux.
• Personality and stress
• Genetic H.Pylori on the surface of
gastric epithelial cells
Hurry, Worry, Curry….!

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Pathogenesis of ulcer
disease

Gastric Ulcer Duodenal

• Less common - 1 • More common - 3

• Increase with age • Increase upto 35y
• High in high class • Equal
• A group common • O group common.
• Lower acid levels. • Higher acid levels
• H.pylori – 70% • H.pylori – 95-100%

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Gastric ulcer
• Ulcer of the corpus of the
stomach
• Prepyloric ulcer
Hypersecretion
• Gastric, preceded by
duodenal ulcer
The main pathogenetic unit is decreased mucosal
resistance of the stomach,
and the main pathogenetic factor – hypersecretion
of gastric juice.

Symptoms of gastric ulcer disease:

 epigastric pain after meal or during meal

 upper dyspeptic syndrome – loss of appetite,

nauzea, vomiting, flatulence

 vomiting brings relief

 reduced nutrition

 loss of weight

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Duodenal ulcer

• Elevated peptic activity of gastric juice

 Stress
 Humoral-hormonal stimuli
 Increasing the number and sensitivity of
gastric parietal cells
• Altered secretory and evacuational
capacity of the stomach
• Decreased resistance of duodenal
mucosa

Symptoms of duodenal ulcer

disease:
epigastric pain 2 hours after meal or on a
empty stomach or during night

pyrosis

good nutrition

obstipation

seasonal dependence (spring, autumn)

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A – penetration B – perforation
C – bleeding D - stenosis

Penetrating and perforating

ulcers

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Lifestyle Changes

• Discontinue NSAIDs.
• Acid suppression—Antacids
• Smoking cessation
• No dietary restrictions unless certain foods are associated with
problems.
• Alcohol in moderation
 Men under 65: 2 drinks/day
 Men over 65 and all women: 1 drink/day

• Stress reduction

Surgery

People who do not respond to medication, or who develop

complications:

 Vagotomy - cutting the vagus nerve to interrupt messages sent from

the brain to the stomach to reducing acid secretion.

 Antrectomy - remove the lower part of the stomach (antrum), which

produces a hormone that stimulates the stomach to secrete digestive
juices. A vagotomy is usually done in conjunction with an antrectomy.

 Pyloroplasty - the opening into the duodenum and small intestine

(pylorus) are enlarged, enabling contents to pass more freely from the
stomach. May be performed along with a vagotomy.

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10 min. break 

Pancreatitis
definition

Pancreatitis is an inflammatory process in

which pancreatic enzymes autodigest the
gland.

Acute pancreatitis occurs suddenly and

lasts for a short period of time and usually
resolves.

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Acute Pancreatitis: Etiology

• Alcohol abuse
• Gallstones
• Hyperlipidemia, Hypercalcemia
• Genetic/Idiopathic
• Hyperparathyroidism
• Shock, hypothermia.
• Infections - mumps
• Abdominal / surgical trauma
• Drugs: steroids & thiazide
• Peptic ulcer, Carcinoma,
• Snake/insect bite, poisoning.
• Tropical calcific Pancreatitis

Etiology
Biliary pancreatitis: About 40~60% of cases of
pancreatitis are associated with gallstone
disease, which, if untreated, usually gives rise
to additional acute attacks.
• Bile refluxpancreatic ductactivate
enzymes.
• Obstruction  increased duct pressure 
damage pancreatic acinus  distroy gland.

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Etiology
Alcoholic Pancreatitis:
Alcohol stimulates gastric acid secretion
which increases CCK-PZ (cholecystokin
and pancreozymin) excretion in duodenum
and then increases pancreatic secretion.
• Make the sphincter spasm and edema
• Increase duct pressure.
• Direct toxic to pancreas

Etiology
• Hypercalcemia:
hyperparahtyroidism and other disorders
accompanied by hypercalcemia are occasionally
complicated by acute pancreatitis, it is thought
that the increased calcium concentrations in
pancreatic juice that result from hypercalcemia
may prematurely activate proteases, they may
also facilitate precipitation of calculi in the duct.

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Etiology
Hyperlipidemia:
• pancreatitis seems to be a direct
consequence of the metabolic
abnormality. during an acute attack
usually associated with mormal serum
amylase levels, because the lipid
interferes with the chemical
determination for amylase; urinary
output of amylase may still be high.

Etiology

Drug-induced pancreatitis:
corticosteroids, estrogen-containing
contraceptives, azathioprine, thiazide
diuretics, and tetracyclines. Pancreatitis
associated with use of estrogens is
usually the result of drug-induced
hypertriglyceridemia.

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Acute Pancreatitis - Pathogenesis

SUMMARY:
Lipase  Fat necrosis – Inflammation.
Protease  Blood Vessel injury – Bleeding.
Trypsin  Kallikrein  Thrombosis - Necrosis

Acute pancreatitis
clinical manifestations

• Abdominal distention
• Abdominal guarding
• Abdominal tympany
• Hypoactive bowel sounds
• Severe disease: peritoneal signs,
ascites, jaundice, palpable
abdominal mass, Grey Turner’s
sign, Cullen’s sign, and signs of
hypovolemic shock

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Grey Turner Sign - Cullen’s Sign

Severe

Mild

Acute Pancreatitis:
Common Complications

 Pulmonary  Metabolic
 Atelactasis  Metabolic acidosis
 Hypocalcemia
 Pleural effusions  Altered glucose
 ARDS metabolism
 Cardiovascular  Hematologic
 Cardiogenic  DIC
shock  GI bleeding
 Renal
 Neurologic
 Prerenal failure
 Pancreatic
encephalopathy

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Chronic Pancreatitis:
 Painful, relapsing, inflammation, fibrosis & exocrine
atrophy.
 Malabsorption, hypoalbuminemia, weight loss,
 Type I DM (if sufficient loss of islets).
 Recurrent Jaundice - gall stone.
 Types:
 Toxic metabolic- 70%: Alcohol, Hyperlipidaemia,
toxins, drugs, hypercalcaemia.
 Idiopathic-20%: Early/Late.
 Others: Genetic, autoimmune, Post necrotic.
 Destruction of exocrine pancreas, Fibrosis, cystic ducts
remain. (both true & pseudocyst).
 Calcification, lithiasis & Malignant transformation.

Bowel obstruction (Ileus)

 Definitions:
 Ileus : Mechanical or functional intest.
Obstruction (Adynamic or paralytic).
 Mechanical obstruction :complete or
partial blockage of the intestinal lumen.
 Simple obstruction: one obstructing
point.

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COMMON CAUSES OF INTESTINAL

OBSTRUCTION ACCORDING TO AGE

Intussusception

80% of intussusception occur in children

under 2 years

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Etiology?
• Outside the wall
• Inside the wall
• Inside the lumen

Lesions Extrinsic to Intestinal Wall

• Adhesions (usually postoperative)

• Hernia
 External (e.g., inguinal, femoral, umbilical, or ventral hernias)
 Internal (e.g., congenital defects such as paraduodenal,
foramen of Winslow, and diaphragmatic hernias or
postoperative secondary to mesenteric defects)
• Neoplastic
 Carcinomatosis, extraintestinal neoplasm
• Intra-abdominal abscess/ diverticulitis
• Volvulus (sigmoid, cecal)

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Lesions Intrinsic to Intestinal Wall

• Congenital • Neoplastic
 Malrotation  Primary neoplasms
 Duplications/cysts  Metastatic neoplasms
• Traumatic • Inflammatory
 Hematoma  Crohn's disease
 Ischemic stricture • Miscellaneous
• Infections  Intussusception
 Tuberculosis  Endometriosis
 Actinomycosis  Radiation
 Diverticulitis enteropathy/stricture

Intraluminal/ Obturator Lesions

• Gallstone
• Enterolith
• Bezoar
• Foreign body

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Where?
 May occur at any point in length of small bowel

CLASSIFICATION

1. Mechanical obstruction obturation

obstructoin intestine compression lesions in
the intestinal wall

2. Nonmechanical obstruction
dynamic ileus----->including paralytic ileus

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Dynamic vs Mechanical
Ileus Obstruction
 Gas diffusely through  Large small intestinal
intestine, incl. colon loops, less in colon
 May have large diffuse  Definite laddered A/F
A/F levels levels
 Quiet abdomen  “Tinkling”, quiet= late
 No obvious transition  Obvious transition
point on contrast study point on contrast study
 Peritoneal exudate if  No peritoneal exudate
peritonitis

Pathophysiology

 Hypercontractility – hypocontractility
 Massive third space losses
 oliguria, hypotension, hemoconcentration

 Electrolyte depletion
 Bowel distension--increased intraluminal
pressure--impedement in venous return--
arterial insufficiency

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Local Effects of Obstruction

1. Hyperperistalsis->abnormal peristalsis
2. Secretion increase and absorption
decrease
3. Accumulation of fluids and electrolytes
4. Distension of intestinal lumen
5. Edema of the bowel wall ->anoxemia-
>necrosis

Systemic Effects of Obstruction

1. Water and electrolyte losses

2. Toxic materials and toxemia

3. Cardiopulmonary dysfunction

4. Shock

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Clinical features

 1. Abdominal pain
 2. Vomiting
 3. Obstipation
 4. Distention

Partial vs Complete
 Flatus  Complete obstipation
 Residual colonic gas  No residual colonic
above peritoneal gas on AXR
reflection /p 6-12h
 Adhesions  Early complete from
 60-80% resolve with high-grade partial
non-operative Mx  Almost all should be
 Must show objective operated on within
improvement, if 24h
none by 48h
consider OR

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Thank You

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