PMY 6110_2-2-Gastrointestinal Diseases.pdf

Clinical Biochemistry Gastrointestinal Disease
In the name of
God

By: Amir Nader Emami Razavi

June 26, 2012 Total slide. 126 3
Gastrointestinal disease
Peptic ulcer disease
Chronic duodenal ulcer
Chronic benign gastric ulcer
Zollinger-Ellison syndrome
Gastritis
Gastric cancer
Post gastrectomy syndrome
Acute pancreatitis
Chronic pancreatitis
Insulinoma
Glucagonoma
Somatostatinoma

Peptic Ulcer Disease (PUD)
What is it?
Group of chronic disorders characterized by ulcerating
mucosal lesions in upper GI tract
chronic inflammatory condition
common forms are duodenal and gastric ulceration
Where does it occur?
Stomach, duodenum
What causes PUD?
H. pylori or drug induced (most commonly by chronic NSAID
use)

Drugs that can cause PUD
methotrexate
cyclophosphamide
azathioprine
erythromycin
iron
corticosteriods
potassium chloride
NSAIDS

Signs and Symptoms of PUD
Can be symptomatic
anorexia, nausea, vomiting, belching, bloating, heartburn,
epigastric pain (pain in the upper abdomen)
awakened at night (usu. around 3am,)
duodenal ulcers
epigastric pain, tenderness, burning, aching between xiphoid
process and belly button
relieved with food intake or antacids
gastric ulcer
diffuse pain over midepigastrium (midstomach)
worsened by food

Characteristics and Comparisons
Between Gastric and Duodenal Ulcers
Gastric ulcer formation involves inflammatory
involvement of acid-producing cells but usually occurs
with low acid secretion.
Duodenal ulcers are associated with high acid and low
bicarbonate secretion.
Increased mortality and hemorrhage are associated with
gastric ulcers.

Pathology of Peptic Ulcer

Normal Stomach

Esophagus & Stomach Normal

Definition:
Ulceration (breach in mucosa) due to acid & pepsin
attack – peptic ulcer.
Deeper than just mucosa
Single, punched out, clean base

Etiology:
Helicobacter pylori infection.
Hyperacidity - eg. zollinger
ellison.
Drugs - anti-inflammatory
(NSAIDs) & Corticostroids.
Cigarette smoking, Alcohol,
Rapid gastric emptying
Personality and stress

H. Pylori organisms- silver st.

Pathogenesis:
Helicobacter pylori infection
Colonization of gastric mucous
Urease ammonia neutralization of acid  Rebound
acid production.
Protease – Mucous break down.
Weak mucosal resistance
Acid & Pepsin digestion of mucosa
Chronic Ulceration

Normal
Increased Attack
Hyperacidity
Weak defense
Helicobacter pylori
Stress, drugs, smoking
Etiology of PUD

Helicobacter pylori:
Most common infection in the world (20%)
10% of men, 4% women develop PUD
Positive in 70-100% of PUD patients.
H.pylori related disorders:
Chronic gastritis – 90%
Peptic ulcer disease – 95-100%
Gastric carcinoma – 70%
Gastric lymphoma
Reflux Oesophagitis.
Non ulcer dyspepsia

Peptic Ulcer Morphology:
90% ulcers in first portion of duodenum or
lesser curvature of stomach
80 to 90% cases single ulcer. Round Small
ulcers with sharply punched out edges
Small <2cm, clean base.
Microscopy: 4 zones.
Superficial necrotic layer.
Inflammatory cells zone.
Granulation tissue zone
Collagenous scar layer.

Gastric peptic ulcer

Gastric peptic ulcer:

Gastric Ulcer
Gastric ulcer:

Duodenal Peptic Ulcer

Peptic ulcer - Endoscopy

Gastric Ulcer

Gastric Ulcer
Punched out ulcer
Clean base
Small single
Radiating mucosal folds.
Benign ulcer.
No tumor.

Peptic Ulcer

Peptic Ulcer Microscopy:

PUD - Diagnosis
Endoscopy
Barium meal – contrast x-ray
Biopsy – bacteria & malignancy
H.Pylori:
Endoscopy cytology
Biopsy – Special stains
Culture
Urease Breath test.

CDU Camplications
Hemorrhage
Due to the ulcer’s eroding a blood vessel
Perforation
Through the anterior wall of the duodenal cap
Causing peritonitis
Penetration of the ulcer into the adjacent structures
Such as pancrease , biliary tract , liver, colon, abdominal wall, or
even long
Luminal abstruction
Caused by the gradual contraction of the ulser scar

Gastric Ulcer

Points to Remember:
A peptic ulcer is a sore in the lining of the
stomach or duodenum due to attack by acid &
Pepsin.
The major cause - H. pylori bacterium. Others
are NSAIDs. spicy food, stress are risk factors.
H. pylori can be transmitted from person to
person through close contact
A combination of antibiotics and H pump
inhibitors is the most effective treatment.

Helecobacter pylori

Toludine Blue stain – H pylori

Urease production test

“You get ulcer, not from what
you eat, but from what’s eating
you..!”

Hmmmm……… H.pylori

Increased numbers of
Increased numbers of
parietal cells with no
parietal cells with no
change in surface and
change in surface and
foveolar mucous cells.
foveolar mucous cells.

Zollinger Ellison Syndrome
Tumour Location
Symptoms
Pancreas 50-60%
Duodenum 40-50%
20-25% Related to MEN-1
50-70% Malignant (lymphnode
metastases)
Gastrinoma Triangle 80%
Gastritis
Recurrent ulcers
Diarrhea (malabsorption)

 0.1 to 1 percent of patients with peptic ulcer disease .
 Underestimation!
symptoms similar to typical peptic ulcer .
symptoms may be controlled by standard doses of an
antisecretory drug
patients may not be tested for hypergastrinemia
Gastrinomas can be either sporadic (80 percent) or
associated with multiple endocrine neoplasia type 1

Signs of ZES
 Multiple ulcers
 Diarrhea
 ulcer in atypical site
 resistant ulcer
 enlarged folds
 severe esophagirtis

Diarrhea in ZES
The high rate of acid volume load that cannot be
absorbed by the intestine
The excess acid exceeds the neutralizing capacity of
pancreatic bicarbonate . The exceptionally low pH of the
intestinal contents inactivates pancreatic digestive
enzymes, interferes with the emulsification of fat by bile
acids, and damages intestinal epithelial cells and villi.
The extremely high serum gastrin concentrations may
inhibit absorption of sodium and water by the small
intestine,

ZES diagnosis
Exclude hyperacidity!
>100mM/L in 12 hour overnight
secretion of HCl
Check gastrin,
if >1000=ZES.
<1000 but abnormal secretin
test to be performed
+200 pg/ml is ZES
Secretin chalenge test

ZES treatment
any patient with a sporadic gastrinoma and
without evidence of metastatic spread of disease
should be offered exploratory laparotomy with
curative intent
laparotomy is not routinely recommended for
patients with ZES as part of MEN 1 since the
multifocal nature of the tumors in this disorder
almost uniformly precludes cure of gastrin
hypersecretion

Definition
The term gastritis is used to denote
inflammation associated with mucosal injury
Gastritis is mostly a histological term that needs
biopsy to be confirmed
Gastritis is usually due to infectious agents
(such as Helicobacter pylori) and autoimmune
and hypersensitivity reactions.

Definition
Epithelial cell damage and regeneration without
associated inflammation is properly referred to
as “gastropathy”.
Gastropathy may be referred without histological
evidence and just according to gross
appearance in endoscopy or radiology
Gastropathy is usually caused by irritants such
as drugs (eg, nonsteroidal antiinflammatory
agents and alcohol), bile reflux, hypovolemia,
and chronic congestion.

Acute Esophagitis & Gastritis

Gross–histologic correlation?

CLASSIFICATION
GASTRITIS
ACUTE COMMON CHRONIC
EMAG
AMAG
BILE HP
STRESS
NSAID

CLASSIFICATION
Acute vs. chronic
Acute refers to short term inflammation
Acute refering to neurophilic infiltrate
Chronic referring to long standing forms
Chronic referring to mononuclear cell infiltrate
especially lymphocyte and maccrophages

Mucosal congestion, edema, inflammation &
ulceration
ACUTE GASTRITIS
MORPHOLOGY

Acute hemorrhagic erosive
hemorrhagic and erosive lesions shortly after
exposure of the gastric mucosa to various
injurious substances or a substantial reduction in
mucosal blood flow

nonsteroidal antiinflammatory drugs [NSAIDs],
alcohol, or bile acids) or to mucosal hypoxia
(such as in trauma, burns [Curling's ulcers] or
sepsis) or to a combination of factors such as
with antineoplastic chemotherapy

Gastric and duodenal ulceroinflammatory ulcers
occurring during severe damage to the central
nervous system (Cushing's ulcers) are often
considered in this group

specific pathogenetic factor in NSAID-induced
acute hemorrhagic and erosive gastropathy is
the inhibition of prostaglandin production.
Prostaglandins, especially those of the E class,
protect against acute mucosal injury due to
NSAIDs and other injurious substances by
several mechanisms, including the stimulation of
mucus and bicarbonate secretion, and
maintenance of mucosal blood flow

Hemorrhagic or erosive gastropathy may be
associated with the development of gastric or
duodenal ulcers. Acute ulceration is most likely
to occur in relation to shock-induced
hemodynamic instability (ie, the stress ulcer
syndrome).

Risk factors
Prior history of an adverse GI event (ulcer,
hemorrhage) increases risk four to fivefold
Age >60 increases risk five to sixfold
High (more than twice normal) dosage of a
NSAID increases risk 10-fold
Concurrent use of glucocorticoids increases risk
four to fivefold
Concurrent use of anticoagulants increases risk
10- to 15-fold

HP and NSAID
Patients with a history of uncomplicated or
complicated peptic ulcers (gastric, duodenal)
should be tested for H. pylori prior to beginning a
NSAID or low dose aspirin. If present, H. pylori
should be treated with appropriate therapy, even
if it is believed that the prior ulcer was due to
NSAIDs

Helicobacter pylori
Helicobacter pylori is a
spiral shaped, gram
negative bacterium
measuring
approximately 3.5
microns in length and
0.5 microns in width

Helicobacter pylori
Urease appears to be
vital for its survival
and colonization; it is
produced in
abundance, making
up more than 5
percent of the
organism's total
protein weight.

Helicobacter pylori
urease forms
ammonia and
bicarbonate that
neutralize gastric acid
and form a protective
cloud around the
organism

Helicobacter pylori
spiral shape, flagella
facilitate its passage
through the mucus
layer

Helicobacter pylori
H. pylori then
attaches to gastric
epithelial cells by
means of specific
receptor-mediated
adhesion

Chemical gastritis (acute ・ chronic)
Alcoholic gastritis
Drug induced gastritis (e.g., NSAID)
Reflux ( due to duodenal juice or bile) gastritis
Other chemical gastritis
Radiation gastritis
Allergic gastritis
Autoimmune gastritis
Special forms of gastritis
Non HP gastritis

Stress ulcer pathophysiology
Hypersecretion of acid –head trauma.
Defects in gastric glycoprotein mucus –In
critically ill patients, increased concentrations of
refluxed bile salts or the presence of uremic
toxins can denude the glycoprotein mucous
barrier
Ischemia – Shock, sepsis, and trauma can lead
to impaired perfusion of the gut.

Stress ulcer risk factors
Shock
Sepsis
Hepatic failure
Renal failure
Multiple trauma
Burns over 35 percent of total body surface area
Organ transplant recipients
Head or spinal trauma
Prior history of peptic ulcer disease or upper GI
bleeding

Gastric Neoplasia
Benign
Gastric polyps
Ectopic pancreas
Malignant
Gastric Adenocarcinoma
Gastric Lymphoma
Gastric Sarcoma

WHO Classification
5 main categories
Adenocarcinoma, Adenosquamous cell carcinoma,
squamous cell carcinoma, undifferentiated carcinoma
and unclassified carcinoma
Adenocarcinoma – subdivided
Papillary, tubular, mucinous, signet ring
Further subdivided based on differentiation

Cancer of Stomach
1. Incidence
a. Worldwide common cancer, but less common in US
b. Incidence highest among Hispanics, African Americans,
Asian Americans, males twice as often as females
c. Older adults of lower socioeconomic groups higher risk
2. Pathophysiology
a. Adenocarcinoma most common form involving mucus-
producing cells of stomach in distal portion
b. Begins as localized lesion (in situ) progresses to
mucosa; spreads to lymph nodes and metastasizes early in
disease to liver, lungs, ovaries, peritoneum

Cancer of Stomach
3. Risk Factors
a. H. pylori infection
b. Genetic predisposition
c. Chronic gastritis, pernicious anemia, gastric polyps
d. Achlorhydria (lack of hydrochloric acid)
e. Diet high in smoked foods and nitrates
4. Manifestations
a. Disease often advanced with metastasis when diagnosed
b. Early symptoms are vague: early satiety, anorexia,
indigestion, vomiting, pain after meals not responding to
antacids
c. Later symptoms weight loss, cachexia (wasted away
appearance), abdominal mass, stool positive for occult blood

Cancer of Stomach
5. Collaborative Care
a. Support client through testing
b. Assist client to maintain adequate nutrition
6. Diagnostic Tests
a.CBC indicates anemia
b.Upper GI series, ultrasound identifies a mass
c.Upper endoscopy: visualization and tissue
biopsy of lesion

Cancer of Stomach
7. Treatment
a. Surgery, if diagnosis made prior to metastasis
1.Partial gastrectomy with anastomosis to
duodenum: Bilroth I or gastroduodenostomy
2.Partial gastrectomy with anastomosis to
jejunum: Bilroth II or gastrojejunostomy
3.Total gastrectomy (if cancer diffuse but limited
to stomach) with esophagojejunostomy

Fungating Carconoma

Gastric Surgical Procedures

b. Complications associated with gastric surgery
1. Dumping Syndrome
a.Occurs with partial gastrectomy; hypertonic, undigested
chyme bolus rapidly enters small intestine and pulls fluid into
intestine causing decrease in circulating blood volume and
increased intestinal peristalsis and motility
b.Manifestations 5 – 30 minutes after meal: nausea with
possible vomiting, epigastric pain and cramping, and diarrhea;
client becomes tachycardic, hypotensive, dizzy, flushed,
diaphoretic
c.Manifestations 2 – 3 hours after meal: symptoms of
hypoglycemia in response to excessive release of insulin that
occurred from rise in blood glucose when chyme entered
intestine

Treatment: dietary pattern to delay gastric emptying
and allow smaller amounts of chyme to enter
intestine
Liquids and solids taken separately
Increased amounts of fat and protein
Carbohydrates, especially simple sugars, reduced
Client to rest recumbent or semi-recumbent 30 – 60
minutes after eating
Anticholinergics, sedatives, antispasmodic
medications may be added
Limit amount of food taken at one time

Common post-op complications
Pneumonia
Anastomotic leak
Hemorrhage
Relux aspiration
Sepsis
Reflux gastritis
Paralytic ileus
Bowel obstruction
Wound infection
Dumping syndrome

Nutritional problems related to rapid entry of food into the
bowel and the shortage of intrinsic factor
Anemia: iron deficiency and/or pernicious
Folic acid deficiency
Poor absorption of calcium, vitamin D
Radiation and/or chemotherapy to control metastasic spread
Palliative treatment including surgery, chemotherapy; client
may have gastrostomy or jejunostomy tube inserted

Pancreas

Function
Exocrine
precursor digestive enzymes
lipases
Endocrine
metabolic hormones
Insulin from β cells
Glucagon from α cells

Exocrine Pancreas
The final product of the exocrine pancreas is a
clear isotonic solution with a pH in the range of
8. The 2 distinct components of exocrine
secretion are enzyme secretion and
water+electrolyte secretion.
Cholecystokinin is the most potent endogenous
hormone known to stimulate enzyme secretion.
Secretin is the most potent endogenous
stimulant of pancreatic electrolyte secretion.

Endocrine Pancreas
The release of insulin into the portal blood is controlled
by the concentration of blood glucose, vagal
interactions, and local concentrations of somatostatin.
The major stimulus for glucagon release is a fall in
serum glucose.
Pancreatic polypeptide appears to function for
regulation of pancreatic exocrine secretion and biliary
tract motility.
Somatostatin has a broad inhibitory spectrum of
gastrointestinal activity

Factors Leading to Pancreatitis
Alcohol intake – usually 5
to 10 years
Prior biliary disease
Abdominal surgery or
diagnostics
Trauma
Recent viral infections
Medications
Mostly middle aged men

Pathophysiology
Inflammation from an insult or injury
Causes activation of pancreatic enzymes
Enzymes autodigest and cause fibrosis
Leads to thrombi and necrosis of tissue
Fat necrosis occurs
Fats bind to calcium
Results in hypocalcemia

More Patho
Necrosis of blood vessels
Fibers in blood vessels and ducts are dissolved
Vasodilation starts due to vessel damage
Results in bleeding and hemorrhage
May be acute or chronic
May be mild to necrotizing

Acute Pancreatitis
Nonbacterial inflammatory disease caused by
activation, interstitial liberation, and
autodigestion of the pancreas by its own
enzymes.

Acute Pancreatitis Aetiology
Gallstones and Alcohol account for 90%
Hyperlipidemia
Hypercalcemia
Familial
Pancreatic duct obstruction
Tumour
Pancreas divisum
Viral infection
Scorpion venom
Drugs
Idiopathic

Acute Pancreatitis
Symptoms and signs
Midepigastric abdominal pain, radiating to
the back
Nausea and vomiting
Fever and tachycardia
Epigastric tenderness
Abdominal distention
Bluish discoloration in the flank (Grey
Turner’s sign)

Acute Pancreatitis
Diagnosis
It is supported by appropriate laboratory
determinations and radiographic findings
Serum amylase is the most widely used lab
test
Hyperamylasemia is commonly observed
within 24 hrs. of the onset and gradually
returns to normal

Acute Pancreatitis
Diagnosis
Elevated amylase levels may occur in other acute
abdominal conditions, though levels rarely exceed
500 IU/dL
Urinary amylase excretion is increased and this
may be very helpful in cases where the serum
amylase level has returned to normal.
Other lab. Findings
Moderate leukocytosis
Mild bilirubin elevation (<2mg/dL)
Raised Haematocrit
Hypocalcaemia (Calcium being complexed with fatty
acids)

Acute Pancreatitis
Glasgow prognostic system

Acute Pancreatitis
Treatment
Goals of medical treatment
Reduction of pancreatic secretory stimuli
Correction of fluid and electrolyte derangements

Chronic Pancreatitis
Is an entity encompassing recurrent or persistent
abdominal pain of pancreatic origin combined
with evidence of exocrine and endocrine
insufficiency and marked pathologically by
irreversible parenchymal destruction.
It is associated with alcohol abuse,
Hyperparathyroidism, congenital anomalies of
the pancreatic duct and pancreatic trauma. It
may also be idiopathic.

Patients typically present in the fourth or fifth
decade with a history of alcohol abuse and with
epigastric or back pain.
Anorexia and weight loss may be present.
1/3 of pts. Have insulin-dependent diabetes
1/4 of pts have steatorrhea.
Narcotic abuse is common

pancreatic calcifications in ~50%
pancreatic parenchymal nodularity,
calcifications and pancreatic ductal dilatation.

Signs and Symptoms of
Abdominal pain: intense, burning,
Abdominal tenderness
Ascites
Steatorrhea
Jaundice

More S & S of Chronic
Dark urine
Signs and symptoms of diabetes
Dyspnea
Orthopnea
Weight loss

Diagnostics
Elevated amylase, lipase, and urine amylase
Elevated glucose, bilirubin, alkaline phosphatase
Elevated WBCs
Hypocalcemia
Hypomagnesia

Medical Treatment
Control of abdominal pain
Treatment of endocrine and exocrine
insufficiency

Insulinoma
•Characteristic clinical manifestation is fasting
hypoglycemia with symptoms
• insulinomas arise from cells of ductular/acinar
system of the pancreas

Insulinoma
Incidence
0.4/100,000 person-yrs (4 cases/million/year)
So rare that few institutions have accrued
enough experience to provide data

Insulinoma
Symptoms
Confusion, visual changes, unusual behavior
Sympathoadrenal symptoms include
palpitations, diaphoresis, and tremulousness
Amnesia as well

Insulinoma
Information based on a collection of 224 patients
out of Olmsted County, Minnesota
Of those 224, 8% had MEN neoplasia
Tumor distribution:
87% had single benign lesions
7% benign tumors-multiple
6% had malignant insulinomas

Insulinoma
Established by demonstrating inappropriately
high serum [insulin] during a spontaneous or
induced episode of hypoglycemia
Virtually all insulinomas are islet cell tumors
After diagnosis, imaging used to localize tumor

Insulinoma/diagnosis
Serum glucose
Male<55mg/dl
Female<35mg/dl
Plasma insulin level
>15 mu/l
Plasma proinsulin level
>40 pmol/l

Insulinoma/treatment
Surgical removal
partial pancreatectomy
enucleation of insulinoma
surgeon’s choice

Glucagonoma Syndrome
Tumour Location
Symptoms
Pancreas
>90% malignant
Necrolytic migratory erythema
Weight loss
Anemia
Trombosis
Impaired glucose tolerance
Diarrhoea
Glocagenoma Syndrome

Histopathology
Tumour Markers
Radiology
Agyrophil staining, CgA,
glucagon:500pg/ml
glicentin
p-CgA, p-glucagon
Octreoscan, Endoscopic ultrasound,
CT-angiography, MRI
Glocagenoma
Syndrome/Diagnosis

Somatostatinoma Syndrome
Tumour Location
Symptoms
Duodenum
Pancreas
Colon/Rectum
>80% mixed tumours
Gallstones
Steatorrhea
Impaired glucose tolerance
Often “non-functioning” tumours!
Somatostatinoma Syndrome

Somatostatinoma
Syndrome/Diagnosis
Histopathology
Tumour Markers
Radiology
Argyrophil staining, CgA
Somatostatin
p-CgA, p-Somatostatin
(s-Gastrin, p-Glucagonom, mixed
tumour)
Endoscopic ultrasonography
CT-angiography, MRI
Colonoscopy
US (liver metastases)

PMY 6110_2-2-Gastrointestinal Diseases.pdf

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