gastrointestinal disease lecture(ppt)

Clinical Biochemistry Gastrointestinal Disease

In the name of God


By: Amir Nader Emami Razavi

April 11, 2023 Total slide. 126 3


Gastrointestinal disease

Peptic ulcer diseaseChronic duodenal ulcerChronic benign gastric ulcerZollinger-Ellison syndromeGastritisGastric cancerPost gastrectomy syndromeAcute pancreatitisChronic pancreatitisInsulinomaGlucagonomaSomatostatinoma



Peptic Ulcer Disease (PUD)

What is it?Group of chronic disorders characterized by ulcerating mucosal lesions in upper GI tractchronic inflammatory conditioncommon 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 symptomaticanorexia, nausea, vomiting, belching, bloating, heartburn, epigastric pain (pain in the upper abdomen)awakened at night (usu. around 3am,)

duodenal ulcersepigastric pain, tenderness, burning, aching between xiphoid process and belly buttonrelieved with food intake or antacids

gastric ulcerdiffuse 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 stomach80 to 90% cases single ulcer. Round Small ulcers with sharply punched out edgesSmall <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 UlcerGastric 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

HemorrhageDue to the ulcer’s eroding a blood vessel

PerforationThrough the anterior wall of the duodenal cap

Causing peritonitis

Penetration of the ulcer into the adjacent structuresSuch as pancrease , biliary tract , liver, colon, abdominal wall, or even long

Luminal abstructionCaused 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



Zollinger-Ellison syndrome

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



Zollinger-Ellison syndrome

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 radiologyGastropathy 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 HPSTRESS

NSAID



CLASSIFICATION

Acute vs. chronicAcute 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

BenignGastric polyps

Ectopic pancreas

MalignantGastric Adenocarcinoma

Gastric Lymphoma

Gastric Sarcoma



WHO Classification

5 main categories Adenocarcinoma, Adenosquamous cell carcinoma, squamous cell carcinoma, undifferentiated carcinoma and unclassified carcinoma

Adenocarcinoma – subdividedPapillary, tubular, mucinous, signet ring

Further subdivided based on differentiation



Cancer of Stomach

1. Incidencea. Worldwide common cancer, but less common in US b. Incidence highest among Hispanics, African Americans, Asian Americans, males twice as often as femalesc. Older adults of lower socioeconomic groups higher risk

2. Pathophysiologya. Adenocarcinoma most common form involving mucus-producing cells of stomach in distal portionb. 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 Factorsa. H. pylori infectionb. Genetic predispositionc. Chronic gastritis, pernicious anemia, gastric polypsd. Achlorhydria (lack of hydrochloric acid)e. Diet high in smoked foods and nitrates

4. Manifestationsa. Disease often advanced with metastasis when diagnosedb. Early symptoms are vague: early satiety, anorexia, indigestion, vomiting, pain after meals not responding to antacidsc. 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



Post gastrectomy syndrome

b. Complications associated with gastric surgery1. 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 intestineLiquids and solids taken separatelyIncreased amounts of fat and proteinCarbohydrates, especially simple sugars, reducedClient to rest recumbent or semi-recumbent 30 – 60 minutes after eatingAnticholinergics, sedatives, antispasmodic medications may be addedLimit amount of food taken at one time




Common post-op complicationsPneumoniaAnastomotic leakHemorrhageRelux aspirationSepsisReflux gastritisParalytic ileusBowel obstructionWound infectionDumping 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 spreadPalliative treatment including surgery, chemotherapy; client may have gastrostomy or jejunostomy tube inserted



Pancreas



Function

Exocrineprecursor digestive enzymes

lipases

Endocrinemetabolic 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%HyperlipidemiaHypercalcemiaFamilial Pancreatic duct obstruction

TumourPancreas divisum

Viral infectionScorpion venomDrugsIdiopathic



Acute PancreatitisSymptoms 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 PancreatitisDiagnosis

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 PancreatitisDiagnosis

Elevated amylase levels may occur in other acute abdominal conditions, though levels rarely exceed 500 IU/dLUrinary 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 HaematocritHypocalcaemia (Calcium being complexed with fatty acids)



Acute PancreatitisGlasgow prognostic system



Acute PancreatitisTreatment

Goals of medical treatmentReduction 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 Chronic Pancreatitis

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



Chronic PancreatitisMedical 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 glucoseMale<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 insulinomasurgeon’s choice



Glucagonoma Syndrome

Tumour Location

Symptoms

Pancreas>90% malignant

Necrolytic migratory erythemaWeight lossAnemiaTrombosisImpaired glucose toleranceDiarrhoea

Glocagenoma Syndrome



Histopathology

Tumour Markers

Radiology

Agyrophil staining, CgA, glucagon:500pg/ml glicentin

p-CgA, p-glucagon

Octreoscan, Endoscopic ultrasound,CT-angiography, MRI

GlocagenomaSyndrome/Diagnosis



Somatostatinoma Syndrome

Tumour Location

Symptoms

DuodenumPancreasColon/Rectum>80% mixed tumours

GallstonesSteatorrheaImpaired glucose toleranceOften “non-functioning” tumours!

Somatostatinoma Syndrome



Somatostatinoma Syndrome/Diagnosis

Histopathology

Tumour Markers

Radiology

Argyrophil staining, CgASomatostatin

p-CgA, p-Somatostatin(s-Gastrin, p-Glucagonom, mixed tumour)

Endoscopic ultrasonographyCT-angiography, MRIColonoscopyUS (liver metastases)

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