GASTROENTEROLOGY AND EMERGENCY

GASTROENTEROLOGY

1.                Gastroesophageal reflux disease. Etiology and pathogenesis. Clinical forms.

is a chronic condition of mucosal damage caused bystomach acid coming up from the stomach into the esophagus

Gastro esophageal reflux disease

Etiology

Abnormalities of the lower oesophageal sphincter

Hiatus hernia: Herniation of the stomach through the diaphragm into the chest

Delayed oesophageal clearance

Gastric contents

Defective gastric emptying

Increased intra-abdominal pressure

Dietary and environmental factors

Patient factors: Visceral sensitivity

2.               
 The different types of GERD include:

• Gastroesophageal Reflux Disease (GERD)
  Gastroesophageal reflux disease (GERD), also known as acid reflux disease, occurs when the lower esophageal sphincter (LES) does not close properly and stomach contents leak back, or reflux, into the esophagus.
• Refractory Gastroesophageal Reflux Disease (Refractory GERD)
  The term refractory gastroesophageal reflux disease (refractory GERD) describes those patients who continue to have symptoms of gastroesophageal reflux despite standard treatment with proton pump inhibitors (PPIs).
• Nonerosive Reflux Disease (NERD)
  For some patients, GERD can cause erosive esophagitis, a condition that causes inflammation, swelling, or irritation of the esophagus. In recent studies, however, it has been found that less than half of GERD patient suffer from esophagitis. They have what is called nonerosive reflux disease, or NERD.
• Larygopharyngeal Reflux (LPR)
  When the lower esophageal sphincter (LES) is not functioning properly, there is a back flow of stomach acid into the esophagus. If this happens two or more times a week, it can be a sign of gastroesophageal reflux disease, or GERD. As with the lower esophageal sphincter, if the upper esophageal sphincter doesn't function properly, acid that has back flowed into the esophagus is allowed into the throat and voice box. When this happens, it's called Laryngopharyngeal Reflux, or LPR.

2. Symptoms of gastroesophageal reflux disease. Instrumental and laboratory methods of diagnostics. Principles of treatment.

The major symptoms are heartburn and egurgitation, often provoked by bending, straining or lying down. ‘Waterbrash’, which is salivation due to reflex salivary gland stimulation as acid enters the gullet, is often present. The patient is often overweight. Some patients are woken at night by choking as refluxed fluid irritates the larynx. Others develop odynophagia or dysphagia. A variety of other features have been described, such as atypical chest pain which may be severe and can mimic angina, and may be due to reflux-induced oesophageal spasm. Others include hoarseness (‘acid laryngitis’), recurrent chest infections, chronic cough and asthma. The true relationship of these features to gastro-oesophageal reflux disease remains unclear.

diagnosis

1. A presumptive diagnosis of GERD can be established in the setting of typical symptoms of heartburn and regurgitation. Empiric medical therapy with a proton pump inhibitor (PPI) is recommended in this setting. (Strong recommendation, moderate level of evidence)

2. Patients with non-cardiac chest pain suspected due to GERD should have diagnostic evaluation before institution of therapy. (Conditional recommendation, moderate level of evidence). A cardiac cause should be excluded in patients with chest pain before the commencement of a gastrointestinal evaluation (Strong recommendation, low level of evidence)

3. Barium radiographs should not be performed to diagnose GERD (Strong recommendation, high level of evidence)

4. Upper endoscopy is not required in the presence of typical GERD symptoms. Endoscopy is recommended in the presence of alarm symptoms and for screening of patients at high risk for complications. Repeat endoscopy is not indicated in patients without Barrett’s esophagus in the absence of new symptoms. (Strong recommendation, moderate level of evidence)

5. Routine biopsies from the distal esophagus are not recommended specifically to diagnose GERD. (Strong recommendation, moderate level of evidence)

6. Esophageal manometry is recommended for preoperative evaluation, but has no role in the diagnosis of GERD. (Strong recommendation, low level of evidence)

7. Ambulatory esophageal reflux monitoring is indicated before consideration of endoscopic or surgical therapy in patients with non-erosive disease, as part of the evaluation of patients refractory to PPI therapy, and in situations when the diagnosis of GERD is in question. (Strong recommendation, low level of evidence). Ambulatory reflux monitoring is the only test that can assess reflux symptom association (strong recommendation, low level of evidence).

8. Ambulatory reflux monitoring is not required in the presence of short or long-segment Barrett’s esophagus to establish a diagnosis of GERD. (Strong recommendation, moderate level of evidence)

9. Screening for Helicobacter pylori infection is not recommended in GERD patients. Treatment of H. pylori infection is not routinely required as part of antireflux therapy. (Strong recommendation, low level of evidence)

therapy

1. Weight loss is recommended for GERD patients who are overweight or have had recent weight gain. (Conditional recommendation, moderate level of evidence)

2. Head of bed elevation and avoidance of meals 2–3 h before bedtime should be recommended for patients with nocturnal GERD. (Conditional recommendation, low level of evidence)

3. Routine global elimination of food that can trigger reflux (including chocolate, caffeine, alcohol, acidic and/or spicy foods) is not recommended in the treatment of GERD. (Conditional recommendation, low level of evidence)

4. An 8-week course of PPIs is the therapy of choice for symptom relief and healing of erosive esophagitis. There are no major differences in efficacy between the different PPIs. (Strong recommendation, high level of evidence)

5. Traditional delayed release PPIs should be administered 30–60 min before meal for maximal pH control. (Strong recommendation, moderate level of evidence). Newer PPIs may offer dosing flexibility relative to meal timing. (Conditional recommendation, moderate level of evidence)

6. PPI therapy should be initiated at once a day dosing, before the first meal of the day. (Strong recommendation, moderate level of evidence). For patients with partial response to once daily therapy, tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and/or sleep disturbance. (Strong recommendation, low level of evidence).

7. Non-responders to PPI should be referred for evaluation. (Conditional recommendation, low level of evidence, see refractory GERD section).

8. In patients with partial response to PPI therapy, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief. (Conditional recommendation, low level evidence).

9. Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett’s esophagus. (Strong recommendation, moderate level of evidence). For patients who require long-term PPI therapy, it should be administered in the lowest effective dose, including on demand or intermittent therapy. (Conditional recommendation, low level of evidence)

10. H2-receptor antagonist (H2RA) therapy can be used as a maintenance option in patients without erosive disease if patients experience heartburn relief. (Conditional recommendation, moderate level of evidence). Bedtime H2RA therapy can be added to daytime PPI therapy in selected patients with objective evidence of night-time reflux if needed, but may be associated with the development of tachyphlaxis after several weeks of use. (Conditional recommendation, low level of evidence)

11. Therapy for GERD other than acid suppression, including prokinetic therapy and/or baclofen, should not be used in GERD patients without diagnostic evaluation. (Conditional recommendation, moderate level of evidence)

12. There is no role for sucralfate in the non-pregnant GERD patient. (Conditional recommendation, moderate level of evidence)

13. PPIs are safe in pregnant patients if clinically indicated. (Conditional recommendation, moderate level of evidence)

Surgical options for GERD

1. Surgical therapy is a treatment option for long-term therapy in GERD patients. (Strong recommendation, high level of evidence)

2. Surgical therapy is generally not recommended in patients who do not respond to PPI therapy. (Strong recommendation, high level of evidence)

3. Preoperative ambulatory pH monitoring is mandatory in patients without evidence of erosive esophagitis. All patients should undergo preoperative manometry to rule out achalasia or scleroderma-like esophagus. (Strong recommendation, moderate level of evidence)

4. Surgical therapy is as effective as medical therapy for carefully selected patients with chronic GERD when performed by an experienced surgeon. (Strong recommendation, high level of evidence)

5. Obese patients contemplating surgical therapy for GERD should be considered for bariatric surgery. Gastric bypass would be the preferred operation in these patients. (Conditional recommendation, moderate level of evidence)

6. The usage of current endoscopic therapy or transoral incisionless fundoplication cannot be recommended as an alternative to medical or traditional surgical therapy. (Strong recommendation, moderate level of evidence)

3.                Functional gastric dyspepsia. Etiology and pathogenesis. Classification.

Functional dyspepsia (FD) is a chronic disorder of sensation and movement (peristalsis) in the upper digestive tract.

Non-ulcer dyspepsia is sometimes called functional dyspepsia. It means that no known cause can be found for the symptoms.

Etiology

The cause of functional dyspepsia is unknown; however, several hypotheses could explain this condition even though none can be consistently associated with FD. Excessive acid secretion, inflammation of the stomach or duodenum, food allergies, lifestyle and diet influences, psychological factors, medication side effects (from drugs such as non-steroidal anti-inflammatory drugs and aspirin), and Helicobacter pylori infection have all had their proponents.

Classification

Postprandial Distress Syndrome

Epigastric Pain Syndrome

   

4.                Functional gastric dyspepsia. Principles of treatment.

Dietary and Lifestyle Modifications

Medications

    H2 Receptor Antagonists: cimetidine (Tagamet®), ranitidine (Zantac®), famotidine (Pepcid®), and nizatidine (Axid®).

    PPIs: omeprazole (Losec®), lansoprazole (Prevacid®), pantoprazole sodium (Pantoloc®), esomeprazole (Nexium®), rabeprazole (Pariet®), and pantoprazole magnesium (Tecta®).

5.                Chronic gastritis. Etiology and pathogenesis. Classification (Sydney).

Etiology

Causes: Chronic gastritis is polyetiologic disease. The main causes of chronic gastritis are:

1) Infection - Helicobacter pylori.

2) Immunologic factors, which lead to the production of the autoantibodies to the parietal cells.

3) Chemical factors, which lead to the injury of the gastric mucosa (alcohol, aspirin and other NSAIDs, reflux of bile and pancreatic secretions).

4) Radiation or thermal injury.

Factors, which promote to the development of the chronic gastritis, are exogenous and endogenous. Exogenous factors are:

1) abnormality of the order of nutrition, overeating, insufficient chewing of food, abuse of hot and spicy food;

2) smoking and alcohol;

3) professional harm (swallowing of metallic dust or other chemical substances);

4) prolonged intake of some medicines (aspirin and other

NSAIDs, corticosteroids).

Endogenous factors are:

1) chronic infections,

2) endocrine diseases,

3) metabolic disorders,

4) autointoxication (renal failure).

Pathogenesis

Atrophic gastritis is associated with serum antiparietal and anti-intrinsic factor antibodies. Cell-mediated immunity also contributes to the disease. T lymphocytes infiltrate the gastric mucosa and contribute to epithelial cell destruction and resulting gastric atrophy. Atrophic gastritis involves the fundus and the body of the stomach. With progressive degeneration of the mucosa, gastric secretion progressively fails. Hydrochloric acid secretion fails first, followed by pepsinogen secretion and finally by the secretion of intrinsic factor. As intrinsic factor secretion fails, the body becomes depleted of vitamin B12 and pernicious anemia develops.

Helicobacter pylori (H. pylory) are gram-negative rods that have

the ability to colonize and infect the stomach. The bacteria survive

within the mucous layer that covers the gastric surface epithelium and

the upper portions of the gastric foveolae. The infection usually is

acquired during childhood. Once the organism has been acquired, has

passed through the mucous layer, and has become established at the

luminal surface of the stomach, an intense inflammatory response of

the underlying tissue develops. Previously this type of gastritis was

known as type B gastritis.

Chemical gastritis is caused by injury of the gastric mucosa by

reflux of bile and pancreatic secretions into the stomach, but it can

also be caused by exogenous substances, including NSAIDs,

acetylsalicylic acid, chemotherapeutic agents, and alcohol. These

chemicals cause epithelial damage, erosions, and ulcers that are

followed by regenerative hyperplasia, histologically detectable as

foveolar hyperplasia and damage to capillaries, with mucosal edema,

hemorrhage, and proliferation of smooth muscle in the lamina propria.

Classification (Sydney)

Modified Sydney’s system, which was accepted in 1994 in Houston

1) Atrophic gastritis;

2) Non-atrophic gastritis;

3) Special or distinctive forms of gastritis: chemical, radiative,

lymphocytic, eosinophilic, isolated granulomatous gastritis and

others.

6.                Chronic gastritis. Symptoms and methods of diagnostics. Treatment.

Diagnosis

CHRONIC ATROPHIC (AUTOIMMUNE) GASTRITIS

Gastroscopy. The diagnosis of chronic gastritis can only be ascertained histologically. Therefore, histological assessment of endoscopic biopsies is essential. Tissue sampling from both the gastric antrum and corpus is essential to establish the topography of gastritis and to identify atrophy and intestinal metaplasia.

Laboratory studies. Decreased serum pepsinogen I levels and the ratio of pepsinogen I to pepsinogen II in the serum can be used to assess gastric atrophy. The finding of low pepsinogen I levels (< 20 ng/mL) has a sensitivity of approximately 96.2% and a specificity of 97% for detection of fundus atrophy. Antiparietal and anti-intrinsic factor antibodies may be present in the serum. Low serum cobalamin (vitamin B-12) levels (<100 pg/mL).

Gastric juices analysis reveals achlorhydria, both basal and stimulated, and hypergastrinemia.

CHRONIC NON-ATROPHYC

(HELICOBACTER PYLORI-ASSOCIATED) GASTRITIS

Gastroscopy is helpful for analyzing the subepithelial
microvascular architecture, as well as the mucosal surface
microstructure and tissue biopsy.

Methods of determining H. pylori:
Rapid urease test from gastric biopsy tissue.
Bacterial culture of gastric biopsy is usually performed in the
research setting or to assess antibiotic susceptibility in patients for
whom first-line eradication therapy fails.
Urea breath test with nonradioactive carbon isotope (13C) or
with radioactive carbon isotope (14C). The carbon 13 urea breath test
is based on the detection of the products created when urea is split by
the organism. Patients are asked to drink urea (usually with a
beverage) labeled with a carbon isotope (carbon 13 or carbon 14).
After a certain duration, the concentration of the labeled carbon is
measured in the breath. The concentration is high only when urease is
present in the stomach. Because the human stomach does not produce
urease, such a reaction is possible only with H. pylori infection.
H. pylori fecal antigen test. This is a novel rapid test based on
monoclonal antibody immunochromatography of stool samples. It has
been reported to be very specific (98%) and sensitive (94%). The
results are positive in the initial stages of infection and can be used to
detect eradication after treatment.
H. pylori serology. The serology test has a high (>90%)
specificity and sensitivity. It is currently based on the quantitation of
immunoglobulin G antibodies against H. pylori by the means of an
enzyme-linked immunosorbent assay. It is useful for detecting a newly
infected patient, but it is not a good test for follow-up of treated
patients because the results do not indicate present infection with
H. pylori. The antibody titer may remain elevated for a long time after
H. pylori eradication. The number of false-positive results is agerelated

and increases with age.

Treatment.

           CHRONIC NON-ATROPHYC

(HELICOBACTER PYLORI-ASSOCIATED) GASTRITIS

 `` Twice-daily proton pump inhibitors or ranitidine

(lansoprazole 30 mg, omeprazole 20 mg, or ranitidine 400 mg

orally twice daily);

 Clarithromycin 500 mg orally twice daily;

 Amoxicillin 1000 mg or metronidazole 500 mg orally twice

daily.

Quadruple therapies (with indicated adult dosing):

 Proton pump inhibitors (lansoprazole 30 mg or omeprazole 20

mg) orally twice daily;

 Tetracycline HCl 500 mg orally 4 times daily;

 Bismuth subsalicylate 120 mg orally 4 times daily;

 Metronidazole 500 mg orally 3 times daily.

CHRONIC ATROPHIC (AUTOIMMUNE) GASTRITIS

Once atrophic gastritis is diagnosed, treatment can be directed to

correct complications of the disease, especially in patients with

autoimmune atrophic gastritis who develop pernicious anemia (in

whom vitamin B-12 replacement therapy is indicated).

CHEMICAL GASTRITIS

Proton pump inhibitors have demonstrated efficacy in controlled

trials for the treatment chemical gastritis. An empiric 2-4 week trial of

an oral proton pump inhibitor (omeprazole, rabeprazole, or

esomeprazole 20-40 mg/d; lansoprazole, 30 mg/d; pantoprazole,

40 mg/d) is recommended.

7.                Gastroduodenal ulcers. Etiology and pathogenesis.

Etiology

The 2 major aetiologic factors responsible for peptic ulceration are infection by the gram-negative gastric pathogen Helicobacter pylori and the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). There is some synergy between these 2 major causes.  Duodenal ulcers are almost always associated with H pylori infection, and gastric ulcers with NSAID use.

Rarer causes include gastric ischaemia (responsible for the 'stress ulcers' that occur commonly in patients with multiple organ failure in intensive care units), Zollinger-Ellison syndrome (a syndrome of gastric acid hypersecretion caused by a gastrin secreting neuro-endocrine tumour), certain medications (e.g., potassium chloride, bisphosphonates), infections (CMV in patients with HIV, and occasionally HSV), and Crohn's disease. A small but increasing proportion of peptic ulcers seem truly idiopathic.

Pathogenesis

The normal stomach and duodenum maintain a balance between the protective factors (mucus layer, bicarbonate secretion, protective prostaglandins, blood flow) and aggressive factors (gastric acid and proteolytic enzyme pepsin). Peptic ulcer disease develops when aggressive factors overcome the protective mechanism. Any process that increases gastric acidity (individuals with increased maximal and basal acid output), decreases prostaglandin production (nonsteroidal anti-inflammatory drugs, or interferes with the mucous layer (H. pylori infection) can cause such an imbalance and leads to peptic ulcer disease.

8.                Clinical manifestations of gastroduodenal ulcers (ulcers of stomach and duodenal ulcer). Diagnostics methods. Complications.

Clinical picture

Complaints. Patients may present with a wide variety of symptoms, or they may remain completely asymptomatic. Classic gastric ulcer pain is described as pain occurring shortly (15-20 min) after meals. The pain from gastric ulcer is typically located in the epigastrium; however, it can also be perceived in the right upper quadrant. Patients with gastric ulcer have vomiting, which relieve stomach pain. So, in some cases patients provoke vomiting by

their selves to relieve pain. Dyspepsia, including belching, bloating, distention, fatty food intolerance may be present in gastric ulcer. Anorexia may occur with gastric ulcers.

 The epigastric pain in duodenal ulcer can be sharp, dull, burning, or penetrating. It generally occurs 2-3 hours after meals and often awakens the patient at night. Pain is often relieved by food. Many patients experience a feeling of hunger. About 20-40% of patients describe bloating, belching, or symptoms

 suggestive of gastroesophageal reflux (heartburn esophageal chest pain, regurgitation of acidic fluid).

Diagnostics methods

Upper gastrointestinal radiography.

Endoscopy

Gastric juices analysis

Complications.

Complications of peptic ulcer disease include hemorrhage,

perforation, penetration and gastric outlet obstruction. Patients with

gastric ulcers are also at risk of developing gastric malignancy.

9.                Treatment of gastroduodenal ulcers.

Dietary factors

Diet may be of some importance. Some products, which

stimulate gastric acid secretion (coffee, alcohol), should be restricted

in acute cases. Ulcer patients who smoke should be urged to decrease

or stop smoking.

Acid Neutralizing / Inhibitory Drugs

Proton pump inhibitors (omeprazole, esomeprazole,

lansoprazole, rabeprazole, and pantoprazole) are the most potent acid

inhibitory agents available.

H2-receptor antagonists (ranitidine, famotidine, and nizatidine)

significantly inhibit basal and stimulated acid secretion to comparable

levels when used at therapeutic doses.

Antacids are now rarely, if ever, used as the primary therapeutic

agent but instead are often used by patients for symptomatic relief of

dyspepsia. The most commonly used agents are mixtures of aluminum

hydroxide and magnesium hydroxide (Maalox, Gaviscon).

Cytoprotective Agents

Sucralfate is insoluble in water and becomes a viscous paste

within the stomach and duodenum, coats the ulcer bed and promotes

healing.

Bismuth induces ulcer healing by ulcer coating; prevention of

further pepsin/HCl-induced damage; binding of pepsin; and

stimulation of prostaglandins, bicarbonate, and mucous secretion. but

does not decrease gastric acid production. It is commonly used as one

of the agents in an anti-H. pylori regimen.

Prostaglandin analogues (Misoprostol) enhance mucous

bicarbonate secretion, stimulate mucosal blood flow, and decrease

mucosal cell turnover.

Therapy of H. Pylori

H. pylori should be eradicated in patients with documented

peptic ulcer disease. H. pylori therapy is described previously (see

chronic non-atrophic gastritis).

Surgery

Surgical intervention in peptic ulcer disease can be viewed as

being either elective, for treatment of medically refractory disease, or

as urgent/emergent, for the treatment of an ulcer-related complication.

The development of pharmacologic and endoscopic approaches for the

treatment of peptic disease and its complications has led to a

substantial decrease in the number of operations needed for this

disorder. Refractory ulcers are an exceedingly rare occurrence.

Surgery is more often required for treatment of an ulcer-related

complication.

gestive of gastroesophageal reflux (heartburn esophageal chest pain, regurgitation of acidic fluid).

10.           Special forms of ulcer localization: pyloric channel ulcers, multiple ulcers, giant ulcers. Stress ulcers.

11.           Functional bowel disease. Definition. Irritable bowel syndrome. Classification. Diagnostic criteria.

Irritable bowel syndrome (IBS) is a functional gastrointestinal

disorder characterized by abdominal pain and altered bowel habits in the absence of specific and unique organic pathology.

Classification

IBS can be classified as either diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), or with alternating stool pattern (IBS-A) or pain-predominant.

Clinical picture

Complaints include abdominal pain, a feeling of incomplete

evacuation (tenesmus), altered bowel habits, abdominal distention,

mucorrhea.

Abdominal pain. Pain frequently is intermittent, crampy without

radiation. Acute episodes of sharp pain alternate on a more constant

dull ache. Common sites of pain include the lower abdomen,

specifically the left lower quadrant. The onset of pain typically is

associated with a change in stool frequency or form and commonly is

relieved by defecation.

Altered bowel habits. Constipation variably results in complaints

of hard stools of narrow caliber, painful or infrequent defecation, and

intractability to laxatives. Diarrhea usually is described as small

volumes of loose stool, with evacuation preceded by urgency or

frequent defecation. Postprandial urgency is common. Alternating

habits are common. Characteristically, one feature predominates in a

single patient, but significant variability exists among patients.

Abdominal distention. Patients frequently report increased

amounts of bloating and gas. People with irritable bowel syndrome

may manifest increasing abdominal circumference throughout the day.

Clear or white mucorrhea of a noninflammatory etiology is

commonly reported.

Diagnosis

clear diagnostic markers exist for irritable bowel syndrome,

thus the diagnosis of the disorder is based on clinical presentation. The

Rome III criteria for the diagnosis of irritable bowel syndrome require

that patients have had recurrent abdominal pain or discomfort at least

3 days per month during the previous 3 months that is associated with

2 or more of the following:

Abdominal pain or discomfort characterized by the following:

- Relieved by defecation

- Associated with a change in stool frequency

- Associated with a change in stool consistency.

Supporting symptoms include the following:

- Altered stool frequency

- Altered stool form

- Altered stool passage

- Mucorrhea

- Abdominal bloating or subjective distention.

Symptoms not consistent with irritable bowel syndrome should

alert the clinician to the possibility of an organic pathology.

Associated symptoms and signs which increase the likelihood of

organic disease include: recent onset (irritable bowel syndrome is

defined by chronicity), progressive symptoms, blood in stools,

nocturnal diarrhea, painless diarrhea, steatorrhea, weight loss, fever,

positive HIV status. The absence of the above supports the diagnosis

of irritable bowel syndrome.

Investigations

Blood test is normal.

Stool test will usually be negative for occult blood.

Colonoscopy and barium enema are normal.

12.           Treatment of irritable bowel syndrome.

Therapy

Diet. Fiber supplementation may improve symptoms of

constipation and diarrhea. Individualize the treatment because few

patients experience exacerbated bloating and distention with highfiber

diets.

Pharmacologic treatment. The selection of pharmacologic

treatment remains symptom directed.

Anticholinergics (Dicyclomine hydrochloride (Bentyl),

Hyoscyamine sulfate (Levsin)) - are antispasmodics that inhibit

intestinal smooth-muscle depolarization at the muscarinic receptor.

Decrease fecal urgency and pain. Useful with diarrhea-predominant

symptoms.

Antidiarrheals (Loperamide (Imodium), Diphenoxylate

hydrochloride 2.5 mg with atropine sulfate 0.025 mg (Lomotil)) - are

nonabsorbable synthetic opioids. They prolong gastrointestinal tract

transit time and decrease secretion via peripheral _-opioid receptors.

Improve stool frequency and consistency, reduce abdominal pain and

fecal urgency, and may exacerbate constipation.

Prokinetics (metoclopramide, domperidone, Cisapride

monohydrate (Propulsid), Tegaserod (Zelnorm)) - are promotility

agents, proposed for use with constipation-predominant symptoms.

Accelerate gastrointestinal tract transit, thus increasing stool

frequency and improving consistency.

Tricyclic antidepressants (imipramine (Tofranil), amitriptyline) -

provide antidepressive and analgesic properties.

Bulk-forming laxatives (Methylcellulose (Citrucel), Psyllium

(Metamucil, Fiberall, Reguloid, Konsyl) - may use these agents as

fiber supplementation to improve symptoms of constipation and

diarrhea. Use is controversial.

13.           Malabsorption syndrome. Etiology. Pathogenesis. Clinical picture. Diagnosis. Therapy. Tropical diarrhea.

Etiology and Pathogenesis

Malabsorption constitutes the pathological interference

with the normal physiological sequence of digestion (luminal phase), absorption (mucosal phase) and transport (postabsorptive phase) of nutrients.

Luminal phase. Impaired nutrient hydrolysis (1) pancreatic insufficiency), (2) inadequate mixing of nu trients due to rapid intestinal transit (gastrojejunostomy, total and partial gastrectomy, intestinal resection). Impaired fat solubilization (1) decreased bile salt synthesis from severe parenchymatous liver disease (cirrhosis);(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (primary biliary cirrhosis, primary sclerosing cholangitis); (3) impaired enterohepatic bile circulation, as seen in small bowel resection or regional enteritis; (4) bile salt deconjugation due to small bowel bacterial overgrowth. Decreased nutrient availability (1) cofactor deficiency (gastric surgery), (2) bacterial overgrowth can cause a decrease in the availability of substrates, including carbohydrates, proteins, and vitamins (vitamin B12, folate).

Mucosal phase. Impaired nutrient absorption (1) decreased

absorptive surface area, as seen in intestinal resection of intestinal bypass; (2) damaged absorbing surface, as seen in Celiac Sprue, Tropical Sprue, Crohn’s's disease, AIDS enteropathy, chemotherapy, or radiation therapy; (3) infiltrating disease of the intestinal wall, such as lymphoma and amyloidosis; and (4) infections, including bacterial overgrowth, giardiasis, Whipple's disease, cryptosporidiosis, and microsporidiosis. Malabsorption of specific substances (lactose intolerance).

Postabsorptive phase. Disturbances of mesenteric circulation.

Obstruction of the lymphatic system, both congenital (intestinal

lymphangiectasia, Milroy disease) and acquired (Whipple disease, neoplasm [including lymphoma], tuberculosis), impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy.

Clinical picture

Steatorrhoea

Undigested food in the stool

Weight loss and nutritional disturbances

Diarrhea

Flatulence and abdominal distention

Edema

Muscle wasting and atrophy

Anemia

Dermatologic manifestations.

Neurologic manifestations

Diagnosis

Blood test: may reveal a macrocytic or microcytic anemia.

Biochemical blood test:may reveal low serum levels of

cholesterol, protein and albumin, sodium, potassium, chloride and

calcium, iron, vitamin B12, increased prothrombin time.

Stool fat analysis

Testing for unabsorbed carbohydrate. Unabsorbed carbohydrate

produces stool with an acid pH of feces.

The urinary D-xylose test for carbohydrate absorption provides

an assessment of proximal small-intestinal mucosal function.

The bile acid breath test is used if one suspects bile acid

malabsorption

Barium contrast x-rays of the small intestine.

Endoscopic biopsy

Ultrasound, CT and MRI

Therapy

Dietary modification is important in some conditions: glutenfree

diet in celiac disease, lactose avoidance in lactose intolerance.

Replacement therapy (replacement of nutrients, electrolytes and

fluid) is used in patients with malabsorption syndromes.

Pancreatic enzymes are supplemented orally in insufficiencies.

Enteral supplements, bile salt binding agents, vitamins and minerals are also used in treatment.

Antibiotic therapy will treat Small Bowel Bacterial overgrowth.

Cholestyramine or other bile acid sequestrants will help reducing

diarrhea in bile acid malabsorption.

Jejunostomy is a surgical procedure done to allow placement of

feeding tube as one treatment option for a variety of causes of

malabsorption.

Notion of tropical diarrhea

Malabsorption due to small intestinal disease in a patient in or from the tropics. There has to be an absence of other intestinal disease or parasites. Its manifestations resemble those of celiac disease

Diarrhoea

Steatorrhoea or fatty stool (often foul-smelling and whitish in colour)

Indigestion

Cramps

Weight loss and malnutrition

Fatigue

Left untreated, nutrient and vitamin deficiencies may develop in patients with tropical sprue.[1] These deficiencies may have the following symptoms:

Vitamin A deficiency: hyperkeratosis or skin scales

Vitamin B12 and folic acid deficiencies: anaemia

Vitamin D and calcium deficiencies: spasm, bone pain, numbness and tingling sensation

Vitamin K deficiency: bruises

Diagnosis

Abnormal flattening of villi and inflammation of the lining of the small intestine, observed during an endoscopic procedure.

Presence of inflammatory cells (most often lymphocytes) in the biopsy of small intestine tissue.

Low levels of vitamins A, B12, E, D, and K, as well as serum albumin, calcium, and folate, revealed by a blood test.

Excess fat in the feces (steatorrhoea).

Thickened small bowel folds seen on imaging

The small bowel histological changes closely resemble Celiac disease, although partial villous atrophy rather than subtotal villous is the usual lesion.

Treatment

Dehydration and electrolyte deficiencies must be

corrected in severe diarrhea

 Tetracycline 1 g daily in divided doses for 28 days

(up to 6 months)

 Folic acid and Vitamin B12 supplementation are given

as this relieves folate deficiency and improves

absorption

 The small bowel mucosa soon returns to normal

14.           Celiac disease. Etiology. Pathogenesis. Clinical picture. Diagnosis. Principles of treatment.

Etiology

Autoimmune

Pathogenesis

Loss of immune tolerance to gliadin peptide antigens derived from wheat, rye, barley, and related grains is the central abnormality of coeliac disease. These peptides are resistant to human proteases, allowing them to persist intact in the small intestinal lumen. It is unknown how these peptides gain access to the lamina propria, but leading hypotheses include faulty tight junctions, endothelial cell transcytosis, sampling of the intestinal lumen by dendritic cells, and passage during resorption of apoptotic villous enterocytes.

In the intestinal submucosa these peptides trigger both innate and adaptive immune activation

Clinical picture

The symptoms range from significant malabsorption of multiple nutrients with diarrhea, steatorrhea, weight loss, and the consequences of nutrient depletion (i.e., anemia and metabolic bone disease) to the absence of any gastrointestinal symptoms but with evidence of the depletion of a single nutrient.

Diagnosis

blood antibody tests

The diagnosis of celiac sprue requires the presence of characteristic histopathologic changes on small-intestinal biopsy together with a prompt clinical and histopathologic response following the institution of a gluten-free diet.

Therapy

About 90% of patients who have the characteristic findings of celiac sprue will respond to complete dietary gluten restriction. n The remainder constitute a heterogeneous group (whose condition is often called refractory sprue) that includes some patients who (1) respond to restriction of other dietary protein, e.g., soy; (2) respond to glucocorticoids; (3) are “temporary,” i.e., the clinical and morphologic findings disappear after several months or years; or (4) fail to respond to all measures and have a fatal outcome

15.           Inflammatory bowel disease: ulcerative colitis. Pathogenesis. Clinical features.

Etiology

The exact etiology of ulcerative colitis is unknown, but

the disease appears to be multifactorial and polygenic. Proposed

causes include genetic factors, immune system reactions,

environmental factors, non-steroidal anti-inflammatory drug use, low levels of antioxidants, psychological stress factors.

Pathogenesis

1) Bacterial antigens are taken up by specialised M cells, pass between

leaky epithelial cells or enter the lamina propria through ulcerated mucosa.

(2) After processing, they are presented to type 1 T-helper cells by

antigen-presenting cells (APC) in the lamina propria.

(3) T-cell activation

and differentiation results in a Th1 T cell-mediated cytokine response

(4) with secretion of cytokines, including interferon-gamma (IFN-γ). Further

amplification of T cells perpetuates the inflammatory process with

activation of non-immune cells and release of other important cytokines,

including interleukin (IL)-12, IL-23, IL-1 IL-6 and tumour necrosis factor

(TNF). These pathways occur in all normal individuals exposed to an

inflammatory insult and this is self-limiting in healthy subjects. In

genetically predisposed persons, dysregulation of innate immunity may

trigger inflammatory bowel disease.

Clinical picture
depending on the severity stage

Complaints. The main complaints are diarrhea, rectal bleeding,

tenesmus, passage of mucus, and different degrees of abdominal pain,

from mild discomfort to painful bowel movements or painful

abdominal cramping with bowel movements. Patients are commonly

fatigued, which is often related to the inflammation and anemia that

accompany disease activity. Weight loss is also common.

Variability of symptoms reflects differences in the extent of

disease (the amount of the colon and rectum that are inflamed) and the

intensity of inflammation.

Ulcerative proctitis refers to inflammation that is limited to the

rectum. In many patients with ulcerative proctitis, mild intermittent

rectal bleeding may be the only symptom. Other patients with more

severe rectal inflammation may, in addition, experience rectal pain,

urgency (sudden feeling the need to defecate and a need to rush to the

bathroom for fear of incontinence), and tenesmus (ineffective, painful

urge to move one's bowels).

Proctosigmoiditis involves inflammation of the rectum and the

sigmoid colon (a short segment of the colon contiguous to the rectum).

Symptoms of proctosigmoiditis, like that of proctitis, include rectal

bleeding, urgency, and tenesmus. Some patients with

proctosigmoiditis also develop bloody diarrhea and cramps.

Left-sided colitis involves inflammation that starts at the rectum

and extends up the left colon (sigmoid colon and the descending

colon). Symptoms of left-sided colitis include bloody diarrhea,

abdominal cramps, weight loss, and left-sided abdominal pain.

Pancolitis or universal colitis refers to inflammation affecting

the entire colon (right colon, left colon, transverse colon and the

rectum). Symptoms of pancolitis include bloody diarrhea, abdominal

pain and cramps, weight loss, fatigue, fever, and night sweats. Some

patients with pancolitis have low-grade inflammation and mild

symptoms that respond readily to medications. Generally, however,

patients with pancolitis suffer more severe disease and are more

difficult to treat than those with more limited forms of ulcerative

colitis.

Fulminant colitis is a rare but severe form of pancolitis. Patients

with fulminant colitis are extremely ill with dehydration, severe

abdominal pain, protracted diarrhea with bleeding, and even shock.

They are at risk of developing toxic megacolon (marked dilatation of

the colon due to severe inflammation) and colon rupture (perforation).

Patients with fulminant colitis and toxic megacolon are treated in the

hospital with potent intravenous medications. Unless they respond to

treatment promptly, surgical removal of the diseased colon is

necessary to prevent colon rupture.

16.           Inflammatory bowel disease: ulcerative colitis. Diagnosis and principles of treatment.

Diagnosis

Blood test reveals anemia, thrombocytosis, and elevated ESR,

which correlate with disease activity.

Biochemical blood test reveals hypoalbuminemia, hypokalemia,

hypomagnesemia, elevated alkaline phosphatase and elevated Creactive

protein.

Serologic test. Perinuclear antineutrophil cytoplasmic antibody

(p-ANCA), a myeloperoxidase antigen, is more commonly found in

ulcerative colitis.

Stool test is used to exclude infection and parasites, since these

conditions can cause colitis that mimics ulcerative colitis.

Colonoscopy reveals edema, hyperemia of the mucosa.

Ulcerations and mucopurulent exudates may be present. Islands of

normal tissue may have the appearance of pseudopolyps. Numerous

biopsy samples should be obtained.

Barium contrast studies. The earliest radiologic change of

ulcerative colitis is a fine mucosal granularity. With increasing

severity, the mucosa becomes thickened, and ulcers are seen. Haustral

folds may be normal in mild disease, but as activity progresses they

become edematous and thickened. In addition, the colon becomes

shortened and narrowed. There may be postinflammatory polyps or

pseudopolyps.

Therapy

The goals of treatment with medication are to 1) induce

remissions, 2) maintain remissions, 3) minimize side effects of

treatment, 4) improve the quality of life, and 5) minimize risk of

cancer.

Medications used in reducing inflammation in Ulcerative colitis

include anti-inflammatory drugs, corticosteroids, immunosuppressant

agents, antimicrobials and antidiarrheal medicines.

Anti-inflammatory drugs. These agents have anti-inflammatory

effects. They are used to maintain remission. Sulfasalazine is useful

in treating mild-to-moderate ulcerative colitis and maintaining

remission. It acts locally in the colon to reduce the inflammatory

response and systemically inhibits prostaglandin synthesis.

Mesalamine is the drug of choice for maintaining remission. It is

useful for the treatment of mild-to-moderate ulcerative colitis. It is

better tolerated and has less adverse effects than sulfasalazine. Enema

and suppository forms are typically used in patients with distal colitis.

Tumor Necrosis Factor Inhibitor. These agents prevent the

endogenous cytokine from binding to cell surface receptor and

exerting biological activity. These agents adversely affect normal

immune responses. Infliximab is a chimeric mouse-human

monoclonal antibody to tumor necrosis factor alpha. Infliximab is

indicated for the treatment of moderate-to-severe active ulcerative

colitis in patients who have experienced inadequate response to

conventional therapy. Adalimumab is a recombinant human antitumor

necrosis factor alpha IgG1 monoclonal antibody that blocks

inflammatory activity of TNF-alpha. This agent is indicated for

ulcerative colitis unresponsive to immunosuppressant medicines

(corticosteroids, azathioprine, 6-mercaptopurine).

Immunosuppressant Agent. These agents regulate key factors of

the immune system. Azathioprine (Imuran) is effective as a steroidsparing

or steroid-reducing agent and for use in maintenance therapy.

Administration is oral. Onset of action can be delayed up to 3-6

months. Cyclosporine is effective as a means of avoiding surgery in

patients with severe ulcerative colitis refractory to intravenous

corticosteroids. It is given as an intravenous infusion. 6-

Mercaptopurine is effective as a steroid-reducing or steroid-sparing

agent and for use in maintaining remission. Administration is oral.

Onset of action can be delayed up to 3-6 months.

Antimicrobials. In several controlled, trials, antibiotics have not

been shown to provide consistent benefits for the treatment of active

ulcerative colitis. Thus, they are usually administered on an empiric

basis in patients with severe colitis in whom they may help with

averting a life-threatening infection. Ciprofloxacin, Metronidazole

can be used.

Corticosteroids. Corticosteroids decrease inflammation by

suppressing migration of polymorphonuclear leukocytes and reversing

increased capillary permeability. They are used for induction of

remission in moderate-to-severe active ulcerative colitis. They have

no benefit in maintaining remission; long-term use can cause adverse

effects. Methylprednisolone, Prednisone, Hydrocortisone can be

used in treatment of Ulcerative Colitis.

Antidiarrheal. These agents are nonabsorbable synthetic

opioids that provide symptomatic relief in the treatment of ulcerative

colitis. They prolong gastrointestinal transit time and decrease

secretion. Loperamide (Imodium) improves stool frequency and

consistency, reduces abdominal pain and fecal urgency.

17.           Definition of chronic colitis (non-ulcer). Etiology. Pathogenesis. Clinical features. Factors associated with the development of chronic colitis.

18.           Chronic colitis (non-ulcer). Diagnosis and differential diagnosis. Treatment.

19.           Inflammatory bowel disease: Crohn's disease. Pathogenesis. Clinical features. Diagnosis and principles of treatment.

Etiology

The exact cause of Crohn’s disease remains unknown. Current

theories implicate the role of genetic, microbial, immunologic, environmental, dietary, vascular, and even psychosocial

factors as potential causative agents. It has been suggested that patients have an inherited susceptibility for an aberrant

immunologic response to one or more of these provoking factors.

Pathogenesis

1) Bacterial antigens are taken up by specialised M cells, pass between

leaky epithelial cells or enter the lamina propria through ulcerated mucosa.

(2) After processing, they are presented to type 1 T-helper cells by

antigen-presenting cells (APC) in the lamina propria.

(3) T-cell activation

and differentiation results in a Th1 T cell-mediated cytokine response

(4) with secretion of cytokines, including interferon-gamma (IFN-γ). Further

amplification of T cells perpetuates the inflammatory process with

activation of non-immune cells and release of other important cytokines,

including interleukin (IL)-12, IL-23, IL-1 IL-6 and tumour necrosis factor

(TNF). These pathways occur in all normal individuals exposed to an

inflammatory insult and this is self-limiting in healthy subjects. In

genetically predisposed persons, dysregulation of innate immunity may

trigger inflammatory bowel disease.

Clinical picture depending on the severity stage

Clinical features are characterized by periodic exacerbations and

remissions.

Complaints. The main complaints are abdominal pain, diarrhea,

meteorism (flatus) and bloating, low-grade fever, weight loss and

generalized fatigue.

Pain is often crampy or steady in the right lower quadrant or

periumbilical area. It may be colicky, especially in the lower

abdomen.

Diarrhea is nonbloody and often intermittent. If the colon is

involved, patients may report diffuse abdominal pain accompanied by

mucous, blood and pus in the stool.

Patients may also present with complaints suggestive of

intestinal obstruction: postprandial bloating, cramping pain increased

after meals and relieved by defecation, and loud borborygmi. Once the

bowel lumen becomes chronically narrowed, patients complain of

constipation and obstipation.

Therapy

The goals of treatment of Crohn's disease are to reduce the

underlying inflammation, which then relieves symptoms, prevents

complications, and maintains good nutrition.

Medications used in reducing inflammation in Crohn's disease

include anti-inflammatory drugs, corticosteroids, other

immunosuppressants and antibiotics.

Anti-inflammatory drugs. Mesalamine reduces the

inflammation, tends to work best in Crohn's disease affecting mainly the colon and to some extent the small intestine. Oral and rectal suppository forms are available. Long-term use may delay relapse of the disease. Sulfasalazine tends to work best in Crohn's disease affecting mainly the colon. It does not work well in the small intestine.Long-term use generally does not delay relapse.

Corticosteroids: Prednisone and Budesonide reduce

inflammation and suppress the immune system. They can be used in the short term only. Corticosteroids are indicated in persons with severe systemic symptoms (for example, fever, nausea, weight loss) and in those who do not respond to anti-inflammatory agents.

Immunosuppressants: Azathioprine, methotrexate, infliximab,

adalimumab, certolizumab and natalizumab may be used in treatment of Crohn's disease. Infliximab (Remicade) is a monoclonal antibody that acts against tumor necrosis factor alpha, a natural product of the immune system that promotes inflammation. Infliximab is used to treat moderately severe-to-severe Crohn's disease that does not get better with other medications. When given as an intravenous infusion, its effects last for approximately 12 weeks. Repeated doses may be required.

Antibiotics reduce inflammation indirectly by reducing infection.

Metronidazole, besides acting as an antibiotic, has

immunosuppressive and anti-inflammatory properties. Ciprofloxacin, Cephalosporin, Ampicillin, Tetracycline, Sulfonamide, and others can be used.

20.           Inflammatory bowel disease: ulcerative colitis and Crohn's disease. Differential diagnosis and complications (intestinal and extraintestinal).

21.           Chronic cholecystitis. Etiology. Pathogenesis.

Etiology and pathogenesis-

Chronic inflammation of the gallbladder wall is almost always associated with the presence of gallstones and is thought to result from repeated bouts of subacute or acute cholecystitis or from persistent mechanical irritation of the gallbladder wall by gallstones.

Role of infection in cholecystitis-

The presence of bacteria in the bile occurs in >25% of patients with chronic cholecystitis.

The presence of infected bile in a patient with chronic cholecystitis undergoing elective cholecystectomy probably adds little to the operative risk. Chronic cholecystitis may be asymptomatic for years, may progress to symptomatic gallbladder diseasesor to acute cholecystitis, or may present with complications.

Cholelithiasis-

Choledocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones). This condition causes mechanical jaundice and liver cell damage, and requires treatment by cholecystectomy.

 Patients with cholelithiasis typically present with pain in the right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty meal.

Patients may have jaundice, dark urine and pale feces. 

Physical examination. Jaundice of the skin or eyes is an important physical finding in biliary obstruction.

Murphy's sign is often negative on physical examination in choledocholithiasis, helping to distinguish it from cholecystitis.

 In this case Biochemical blood test may reveal elevation in alkaline phosphatase, increase in conjugated bilirubin and increase cholesterol level.

  The diagnosis is confirmed with either a magnetic resonance cholangiopancreatography, an endoscopic retrograde cholangiopancreatography (ERCP) or an intraoperative cholangiogram.

 Treatment involves removing the stone using ERCP. Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.

22.           Chronic cholecystitis. The major symptoms and diagnosis of chronic cholecystitis. Complications. Principles of treatment.

Clinical picture-

Chronic cholecystitis is asymptomatic.it may progress with symptomatic gall bladder disease or acute cholecystitits or may present with it’s complications .

Diagnosis in strumental and laoratory  diagnosis-

Blood test. -

Leucocytes count results are normal in uncomplicated biliary colic; an abnormality suggests complicated biliary disease such as cholecystitis.

Biochemical blood test-

AST, ALT, alkaline phosphatase, bilirubin, and amylase assay results are normal in uncomplicated biliary colic; an abnormality suggests a complication such as cholecystitis, cholangitis, or pancreatitis.

Ultrasonography-

Ultrasonography is the most sensitive and specific test for the detection of gallstones.

It provides information about the size of the common bile duct and hepatic duct and the status of liver parenchyma and the pancreas.

Thickening of the gallbladder wall and the presence of pericholecystic fluid are radiographic signs of acute cholecystitis.

Complication -

 Passage of gallstones from the gallbladder into the common bile duct can result in a complete or partial obstruction of the common bile duct.

Frequently, this manifests as mechanical/obstructive jaundice.

Pancreatitis, another complication of gallstone disease, presents with more diffuse abdominal pain, including pain in the epigastrium and left upper quadrant of the abdomen.

Charcot triad (right upper quadrant pain, fever, and jaundice) is associated with common bile duct obstruction and cholangitis. 

GanGrene anD perforation Gangrene of the gallbladder results from ischemia of the wall and patchy or complete tissue necrosis.

fistula formation and Gallstone ileus Fistula formation into an adjacent organ adherent to the gallbladder wall may result from inflammation and adhesion formation. Fistulas into the duodenum are most common, followed in frequency by those involving the hepatic flexure of the colon, stomach or jejunum, abdominal wall, and renal pelvis.

limey (milk of calcium) bile and porcelain Gallbladder - Calcium salts in the lumen of the gallbladder in sufficient concentration may produce calcium precipitation and diffuse, hazy opacification of bile or a layering effect on plain abdominal roentgenography.

Therapy-

-Medical

Cholesterol gallstones can sometimes be dissolved by oral ursodeoxycholic acid, but it may be necessary for the patient to take this medication for up to two years. Gallstones may recur, however, once the drug is stopped.

Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy following endoscopic retrograde cholangiopancreatography.

Gallstones can be broken up using a procedure called extracorporeal shock wave lithotripsy (often simply called "lithotripsy"), which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces.

They are then passed safely in the feces. However, this form of treatment is suitable only when there is small number of gallstones.

-Surgical. Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Surgery is only indicated in symptomatic patients.

The lack of a gallbladder may have no negative consequences in many people.

However, there is a portion of the population - between 10 and 15% - who develop a condition called postcholecystectomy syndrome which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% risk of developing chronic diarrhea.

Diet-

 Avoid fried foods ,fatty foods and particular fats like hydrogenated fats,saturated fats.

Avoid alcohol intake, reduce the ammount od carbohydrates.

Take more green vegetables and fruits.

Indication for surgery-

Common bile duct obstruction

Asymptomatic gall stones

One or more episodes of biliary pain

Previous diagnose of acute cholecystitis.

23.           Chronic pancreatitis. Definition. Pathogenesis. Classification.

Definition-

Chronic pancreatitis is characterised by chronic inflammation, calcification and atrophy of the pancreas. It is caused by alcohol in >75% of cases.

The early disease is dominated by chronic abdominal pain, with time pain diminishes and exocrine and endocrine insufficiency dominate.

Etiologic risk factors-

Alcohol and smoking

Biliary tract disease

Iatrogenic

Metabolic disorders ,hyper glyceridaemia,hypercalcaemia.

Trauma of pancreas

Congenital disorders eg-cystic fibrosis

Auto immune pancreastitis

Drug eg-sulfonamides,loop diuretics.

Idiopathic-thought to be early and late onset subgroups.

Abdominal radiotherapy-causes of obstruction CP include pancreatic adenocarcinoma,neuroendocrine tumors and intra papillary mucinous tumors.

Haemochromatosis- genetic disease caused by too much iron in the body.

Pancreas divisum-patient born with duct which do not function properly.

Pathogenesis-

Pathogenic theories have been developed including

1-oxidative stress

2-toxic metabolic

3-stone with duct obstruction

4-necrosis -fibrosis

Oxidative stress-

Products of hepatic mixed function oxidase activity -> chronic reflux of bile into pancreatic duct -> damage of pancreas

Toxic metaboilc-

Alcohol changing the intracellular metabolism->direct toxic to aciner cells ->produce pancreatic lipid accumilation,fattty degeneration,cellular necrosis -> widespread fibrosis

Stone with duct obstruction-

Alcohol intake increase lithogenicity of pancreatic juice -> stone formation ->chronic contact of stones with epithelial cells ->ulceration and scarformation ->atrophy and fibrosis ->obstruction of the acne.

Necrosis fibrosis theory-

Scarring and extrinsic compression of the pancreatic ductules ->obstruction -> stasis,atrophy,stone formation.

Classification-

1)by etiological sign-

   A-primary (initial) pancreatitis-  inflammatory process in the pancreas only

   B- secondary pancreatits- disease spread in other organs of GIT, this is long term period.

2)bu morphological sign-

Edematous form

Sclerotic form

Fibrous

Pseudocytic

With calcification of the pancreas

3)by special features of the clinical pictures-

   A-chronic recurrency(relapsing) pancreatits-

During the period between the attack the patient feels satisfactory.

   B-chronic painful pancreatitis-

   C-chronic unpainful pancreatitis-

   D-chronic pseudocytic-cyst which compresses the common bile duct,duodenum ,pylorus.

   E-chronic cholecysto pncreatitis-with symptoms of chronic cholecystitis and chronic pancreatitis.

   F-chronic calculous cholecystitis-calicum deposit in ducts and parenchyma of pancreas.

4)by the cause of the disease-

   A- mild degree of severity

   B-a moderate degree of severity

   C- a severe forrm

24.           Chronic pancreatitis. Symptoms and methods of diagnostics. Treatment.

Instrumental and laboratory methods
of examination (ultrasound, X-ray, CT).

Clinical picture-

Abdominal Pain -pain may begin gradually and persist for days or weeks.

Pain is located in the epigastrium, right or left subcostal areas or around the umbilicus, characteristically it may radiate to the back and relief may be obtained by crouching forward or leaning forward over a chair.

The patient may also complain about pain related to their food intake, especially those meals containing a high percentage of fats and protein.

Pain with nausea vomiting.

Decrease appetite

exocrine insufficiency due to this  malabsorption ,diarrhea,weight loss steatorrhea with foul smell  and greasy stool.

Diabetes is a common complication due to the chronic pancreatic damage and may require treatment with insulin.

During physical examination a tender fullness or mass may be palpated in the epigastrium, suggesting the presence of a pseudocyst or an inflammatory mass in the abdomen. 

A few patients with severe, intractable pain exhibit a characteristic mottled erythema or hyperpigmentation over their abdomens or back; on further questioning, these patients will reveal that they sustained burns to the skin while applying hot water bottles, heating pads, or electric pads over the area in an attempt to relieve pain.

Instrumental and laboratory methods of diagnosis-

Laboratory-

-Biochemical blood test. Elevations of serum amylase and lipase are found only during acute attacks of pancreatitis, usually early in the course of the disease.

In the later stages of chronic pancreatitis, atrophy of the pancreatic parenchyma can result in serum enzyme levels within the reference range, even during acute attacks of pain.

-Serum bilirubin and alkaline phosphatase can be elevated, indicating stricture of the common bile duct due to edema, fibrosis or cancer. 

-Feces analysis. The common symptom of chronic pancreatitis, steatorrhea, can be diagnosed by two different studies: Sudan chemical staining of feces or fecal fat excretion of 7 grams or more over a 24hr period on a 100g fat diet. 

To check for pancreatic exocrine dysfunction, the most sensitive and specific test is the measurement of fecal elastase, which can be done with a single stool sample, and a value of less than 200 ug/g indicates pancreatic insufficiency.

Instrumental-

-Abdominal x-ray. Pancreatic calcifications, often considered pathognomonic of chronic pancreatitis, are observed in approximately 30% of cases.  Computed tomography scan.

This study is indicated to look for complications of the disease and is useful in planning surgical or endoscopic intervention.

-Endoscopic retrograde cholangiopancreatography (ERCP) provides the most accurate visualization of the pancreatic ductal system and has been regarded as the criterion standard for diagnosing chronic pancreatitis. 

-Magnetic resonance cholangiopancreatography (MRCP) imaging provides information on the pancreatic parenchyma and adjacent abdominal viscera, and MRCP uses heavily T2-weighted images to visualize the biliary and pancreatic ductal system.

-Endoscopic ultrasonography. Recent studies suggest that endoscopic ultrasonography may be the best test for imaging the pancreas.

 By placing the transducer immediately adjacent to the pancreas, the endoscopic approach eliminates interference by bowel gas and enables the use of high-frequency transducers to provide more detailed imaging.

Eleven sonographic criteria have been developed that identify characteristic findings of chronic pancreatitis.

Plain x-ray of abdomen

Angiography and venography.

Barium swallow

Biopsy of pancreas.

Therapy-

The goals of treatment are as follows: 

Modify lifestyle that may exacerbate the natural history of the disease  Enable the pancreas to heal itself  Determine the cause of abdominal pain and alleviate it 

Detect pancreatic exocrine insufficiency and restore digestion and absorption to normal  Diagnose and treat endocrine insufficiency.

In early stage alcohol-induced chronic pancreatitis, lasting pain relief can occur after abstinence from alcohol, but in advanced stages, abstinence does not always lead to symptomatic improvement.

Patients continuing to abuse alcohol develop either marked physical impairment or have a death rate 3 times higher than do patients who abstain.  Analgesics.

The abdominal pain can be very severe and require high doses of analgesics, sometimes including opiates. Initial therapy consists of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs).

For severe, refractory pain, narcotic analgesics often are required, starting with the least potent agents and progressing to more potent formulations as necessary.  

Pancreatic Enzyme Supplementation. These are used as dietary supplementation to aid digestion in patients with pancreatic enzyme deficiency.

Several preparations are available: Pancrelipase (Creon, Pancreaze, Ultresa, Viokace, Zenpep).

The aim is to provide at least 30,000 units of lipase. Surgery. Traditional surgery for chronic pancreatitis tends to be divided into two areas - resection and drainage procedures.

New and proven transplantation options prevent the patient from becoming diabetic following the surgical removal (resection) of their pancreas.

This is achieved by transplanting back in the patient's own insulinproducing beta cells.

 

Diet-

Diet and life-style changes. Cessation of alcohol consumption and tobacco smoking are important.

Eating low fat diet is very important.

Include adequate fat soluble vitamins and calcium in diet.

Medicamental-

Antidepressants.in addition to alleviating coexistent depression, tricyclic antidepressants may ameliorate pain and potentiate the effects of opiates.

Indications for surgery-

1-If the pain become sever and cannot treated by pain killers.

2-Pancreatic cancer

3-there are surgical complications of chronic pancreatitis.

25.           Chronic hepatitis. Etiology. Classification (Los-Angeles). The major symptoms (describe the clinical syndromes).

Etiology

Causes of chronic hepatitis are: viruses, autoimmune

disorders, alcohol, toxic influence, drugs induced, metabolic disorders

(amyloidosis, fatty liver, disturbances in protein metabolism, copper

and vitamins metabolism).

Viral Hepatitis. Viral Hepatitis B and C are the most common

causes of chronic hepatitis. Hepatitis B (HBV) is a DNA virus which

is transmitted parenterally. Individuals at high risk include intravenous

drug abusers, homosexual men and those exposed to blood and blood

products. The incubation period ranges from 1 to 6 months. Chronic

HBV develops in 10% of patients.

Hepatitis C (HCV) is an RNA virus that formerly accounted for

90% of post-transfusion hepatitis. The modes of transmission

(parenteral, sexual and perinatal) are similar to those of HBV. The

incubation period is 2 weeks to 6 months. Chronic hepatitis develops

in up to 85% of patients. Cirrhosis may develop in 20% of patients,

with an increased risk of hepatocellular carcinoma.

Hepatitis D (Delta hepatitis, HDV) is caused by a small,

defective RNA virus that is infectious only in presence of HBV

infection. It can complicate acute HBV infection, but is seen more

commonly as a superinfection in patient with chronic HBV. The

combination of hepatitis B and D is worse than hepatitis B alone and

is more likely to cause serious chronic hepatitis and cirrhosis.

Autoimmune Hepatitis. Autoimmune hepatitis is now accepted

as a chronic disease of unknown cause, characterized by continuous

hepatocellular inflammation and necrosis, which tends to progress to

cirrhosis. The trigger for autoimmune chronic hepatitis is unknown,

but the damage to the liver is caused by the individual's lymphocytes

and by antibodies produced in the individual's own tissue. Most of the

patients are young women but postmenopausal women and males may

get the disease. Autoimmune chronic hepatitis is usually a progressive

disease ending in cirrhosis.

Alcoholic Hepatitis. Alcoholic hepatitis is a syndrome of

progressive inflammatory liver injury associated with long-term heavy

intake of ethanol. The pathogenesis is not completely understood.

Alcoholic hepatitis usually persists and progresses to cirrhosis if

heavy alcohol use continues.

Drug-Induced Hepatitis. Few medications still in use and

several that have been withdrawn from the market can also cause

chronic hepatitis. These include: isoniazid - used for tuberculosis;

methyldopa - used for hypertension; nitrofurantoin - used for urinary

tract infections; phenytoin - used for seizure disorders and some other

medications. These medications must be taken for long periods of

time. However, the number of cases of chronic hepatitis produced by

these medications is small. Chronic hepatitis caused by drugs is

usually recognized early. Stopping the medicine before cirrhosis has

developed usually reverses the disease.

Inherited Disorders. Some inherited disorders of metabolism

also can appear as chronic hepatitis. The most frequent of these

conditions is Wilson's disease - a familial disorder of copper

metabolism. Alpha-1-antitrypsin deficiency and tyrosinemia may

appear as chronic hepatitis although other features help in

distinguishing these rare conditions from those caused by viruses.

Classification of chronic hepatitis (Los Angeles, 1994)

1. Autoimmune hepatitis.

2. Chronic hepatitis B.

3. Chronic hepatitis B and D

4. Chronic hepatitis C.

5. Chronic hepatitis (which is not characterized otherwise).

6. Chronic hepatitis (not classified as viral or autoimmune).

7. Chronic hepatitis drug.

Chronic hepatitis E have been made to the classification, since the virus was discovered in 1995 after the approval of the classification.

26.           Features of the pathogenesis of viral hepatitis, autoimmune hepatitis.

viral hepatitis,

Under ordinary circumstances, none of the hepatitis viruses is known to be directly cytopathic to hepatocytes.

Evidence suggests that the clinical manifestations and outcomes after acute liver injury associated with viral hepatitis are determined by the immunologic responses of the host. Among the viral hepatitides, the immunopathogenesis of hepatitis B and C has been studied most extensively.

Hepatitis B (HBV)-

is a DNA virus which is transmitted parenterally. Individuals at high risk include intravenous drug abusers, homosexual men and those exposed to blood and blood products. The incubation period ranges from 1 to 6 months. Chronic HBV develops in 10% of patients.

Hepatitis C - 

The modes of transmission (parenteral, sexual and perinatal) are similar to those of HBV. The incubation period is 2 weeks to 6 months.

HCV can cause direct liver injury or indirect liver injury through immune‐mediated pathways. Pathways related to necrosis, apoptosis, angiogenesis are all up‐regulated leading to progressive fibrosis.

Hepatitis D (Delta hepatitis, HDV) -

is caused by a small, defective RNA virus that is infectious only in presence of HBV infection. It can complicate acute HBV infection, but is seen more commonly as a superinfection in patient with chronic HBV.

autoimmune hepatitis

IMMUNOPATHOGENESIS-

The weight of evidence suggests that the progressive liver injury in patients with autoimmune hepatitis is the result of a cell-mediated immunologic attack directed against liver cells.

In all likelihood, predisposition to autoimmunity is inherited, whereas the liver specificity of this injury is triggered by environmental (e.g., chemical, drug [e.g., minocycline], or viral) factors.

Cellular immune mechanisms appear to be important in the pathogenesis of autoimmune hepatitis. In vitro studies have suggested that in patients with this disorder, CD4+ T lymphocytes are capable of becoming sensitized to hepatocyte membrane proteins and of destroying liver cells.

Molecular mimicry by cross-reacting antigens that contain epitopes similar to liver antigens is postulated to activate these T cells, which infiltrate, and result in injury to, the liver.

Humoral immune mechanisms have been shown to play a role in the extrahepatic manifestations of autoimmune and idiopathic hepatitis. Arthralgias, arthritis, cutaneous vasculitis, and glomerulonephritis occurring in patients with autoimmune hepatitis appear to be mediated by the deposition of circulating immune complexes in affected tissue vessels, followed by complement activation, inflammation, and tissue injury. 

27.           Clinic of chronic hepatitis. Diagnostics. Degrees of activity of chronic hepatitis.

28.           Treatment of chronic viral hepatitis. Treatment of autoimmune hepatitis.

Chronic viral hepatitis therapy-

The goal of treatment of the chronic hepatitis B virus and chronic hepatitis C virus are to reduce the fibrosis and inflammation and to prevent progression to cirrhosis and it’s complications.

Medications For hepatitis B virus includes interferon (IFN) alpha-2a and the oral nucleoside or nucleotide analogues example lamivudine and adefovirdipivoxil.

Medication for hepatitis C virus includes IFN alfa-2b,IFN alfa-2a,consensus IFN( IFN alfacon-1,ribavirin in combination with IFN.

29.           Liver cirrhosis. Etiology. Classification.

Etiology-

Cirrhosis is a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules, resulting in the loss of liver function.

The progression of liver injury to cirrhosis may occur over weeks to years.  Causes: 

Alcoholic liver disease  

Chronic viral hepatitis B, C and D  

chronic autoimmune hepatitis 

Inherited metabolic diseases (hemochromatosis,

Wilson disease, α1 Antitrypsin deficiency)  

Biliary cirrhosis (primary biliary cirrhosis,

primary sclerosing cholangitis,

 autoimmune cholangiopathy,

secondary biliary cirrhosis - associated with chronic extrahepatic bile duct obstruction) 

 Chronic congestive heart failure (Cardiac cirrhosis)  Parasitic infections (schistosomiasis)  

Non-alcoholic steatohepatitis  

 Long term exposure to toxins or drugs  Cryptogenic cirrhosis (unknown cause).

Classification-

Classification of cirrhosis is based on

(1) its cause;

(2) size of the nodules;

(3) severity. 

Depending on the size of the nodules there are three macroscopic types of cirrhosis:

micronodular, macronodular and mixed.

In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm.

In macronodular cirrhosis (postnecrotic cirrhosis), the nodules are larger than 3 mm.

The mixed cirrhosis consists in a variety of nodules with different sizes.

The severity of cirrhosis is commonly classified with the ChildPugh score.

This score uses bilirubin, albumin, INR, presence and severity of ascites and encephalopathy to classify patients in class A, B or C.

 Class A has a favourable prognosis, while class C is at high risk of death. It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh.

30.           Pathogenesis of liver cirrhosis.

Liver cirrhosis cause by alcohol,hepatitis c virus infection ,non alcoholic diseases , non alcoholic liver cirrhosis alpha anti trypsin deficiency,hemachromatosis , wilson disease,primary cirrhosis,sclerosing cholangitis.

Due to these diseases liver develop severe inflammation,for an extended period of the time.

Over a long time fibrosis develop.

Development of scar tissue that replace  normal parenchyma, blocking the portal flow of blood through the organs.

When at least 70-80% of the liver function has been lost,the synthetic capacity of the liver is diminished.

31.           Primary biliary cirrhosis. Etiology and pathogenesis. Clinical picture.

Etiology-

PBC is seen in about 100–200 individuals per million, with a strong female preponderance and a median age of around 50 years at the time of diagnosis.

The cause of PBC is unknown; it is characterized by portal inflammation and necrosis of cholangiocytes in small- and medium-sized bile ducts.

Cholestatic features prevail, and biliary cirrhosis is characterized by an elevated bilirubin level and progressive liver failure.

Pathogenesis-

Bilirubin levels do not elevate untill the disease is extremely far advanced,which is usually after 5 - 10 years.

PBC has a strong association with other auto immune disease,such as sjogren syndrom (dry eyes and dry mouth )

Rheumatoid arthritis and scleroderma.

Clinical features-

most patients are actually asymptomatic. When symptoms are present, they most prominently include a significant degree of fatigue out of proportion to what would be expected for either the severity of the liver disease or the age of the patient.

Pruritus is seen in approximately 50% of patients at the time of diagnosis, and it can be debilitating. It might be intermittent and usually is most bothersome in the evening.

Pruritus that presents prior to the development of jaundice indicates severe disease and a poor prognosis.

Physical examination can show jaundice and other complications of chronic liver disease, including hepatomegaly, splenomegaly, ascites, and edema.

Other features that are unique to PBC include hyperpigmentation, xanthelasma, and xanthomata, which are related to the altered cholesterol metabolism seen in this disease.

Hyperpigmentation is evident on the trunk and the arms and is seen in areas of exfoliation and lichenification associated with progressive scratching related to the pruritus.

Bone pain resulting from osteopenia or osteoporosis is occasionally seen at the time of diagnosis.

32.           Pathogenesis of basic syndromes in liver cirrhosis (portal hypertension, ascites, hepatic encephalopathy.

Pathogenesis of basic syndromes in liver cirrhosis-

-Liver cells regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue.

In these nodules, regenerating hepatocytes are disorderly disposed. Biliary tract, central vein and the radial pattern of hepatocytes are absent.

Grossly abnormal liver architecture eventually ensues that can lead to decreased blood flow to and through the liver.

Decreased blood flow to the liver and blood back up in the portal vein and portal circulation leads to some of the serious complications of cirrhosis.

those are portal hypertension, hepatic encephalopathy and ascites.

Portal hypertension-

svenous compression and/or obstruction leading to an increase in vascular resistance.

in cirrhosis, it occurs at the level of the sinusoid and affects the hepatic microcirculation. In a cirrhotic liver, on‐going fibrogenesis results in the release of a number of endogenous factors such as endothelin‐1, α‐adrenergic stimulus and angiotensin II.

These factors cause vasoconstriction and increased vascular resistance. In addition, production of nitric oxide, a vasodilator, is reduced. 

-Ascites due to portal hypertension. In case of portal hypertension the abnormality in metaboilc processes occur. This leads to the decreasing of the albumin level in blood and cause ascite and edema.

Development of ascites in cirrhosis:

-encephalopathy

Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain. In cirrhosis, some blood leaving (eg-ammonia )the gut bypasses the liver as blood flow through the liver is decreased.

Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates. Both of these derangements can lead to hepatic encephalopathy as toxic metabolites ammonia , normally removed from the blood by the liver, increased ammonia level in blood and this can reach the brain.In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.

   

33.           The major symptoms (describe the clinical syndromes) of liver cirrhosis. Instrumental and laboratory methods of diagnostics.

Clinical picture-

 -Cutaneous manifestations of cirrhosis include: jaundice, spider naevi, petechial skin rash, palmar erythema, leuconychia (“white nails”) and finger clubbing.

Males may develop gynecomastia and impotence.

Females may have breast atrophy, irregular menses and amenorrhoea. Loss of axillary and pubic hair is noted in both men and women.

Patient may have edemas of lower extremities (soft and warm). Evidence of hepatic encephalopathy becomes increasingly common with advancing disease.

The person's breath may have a musty sweet odor (fetor hepaticus).Tongue is bright red color (crimson), with atrophy of the papillae.

Palpation of the abdomen. Ascites and Caput Medusa develop in portal hypertension. Hepatomegaly is common in cirrhosis. The liver is often hard, irregular, and painless. Later liver may decreased in a size.

Splenomegaly and hypersplenism occurs in more advanced disease.  In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration.

Diagnosis-

Blood test- Blood test may reveal anemia, leukopenia, thrombocytopenia, markedly increased ESR level.

Biochemical blood test- Aminotransferases - AST and ALT are moderately elevated. However, normal aminotransferases do not exclude cirrhosis.

Alkaline phosphatase ,usually slightly elevated. Gamma-glutamyltranspeptidase ,correlates with alkaline phosphatase levels. It is typically much higher in alcoholic chronic liver disease.

Bilirubin , may elevate as cirrhosis progresses. Albumin - levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver.

Globulins ,increased due to shunting of bacterial antigens away from the liver to lymphoid tissue.

Serum sodium , hyponatremia due to inability to excrete free water results from high levels of ADH and aldosterone. Prothrombin time - increases since the liver synthesizes clotting factors.

Blood tests that check for conditions -that may cause cirrhosis include.

Antinuclear antibodies (ANA) - testing

anti-smooth-muscle antibody (ASMA) testing

(may help detect the presence of autoimmune chronic hepatitis. )

Anti mitochondrial antibody test (AMA) (which may help detect primary biliary cirrhosis.)

 Ferritin and iron tests(which may help diagnose iron overload, or hemochromatosis) 

Virus antibody testing for hepatitis B, C or tests for hepatitis virus genetic material (RNA or DNA) (which may help diagnose infection with certain hepatitis viruses. )

Blood alcohol level testing( These tests may detect alcohol use, which can cause alcoholic cirrhosis.)

Serum ceruloplasmin testing (which may help diagnose Wilsosns disease.)

Alpha1-antitrypsin level. (This may diagnose a condition in which people lack this protein (alpha1-antitrypsin deficiency). )

Ultrasound -is routinely used in the evaluation of cirrhosis (where it may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas.)

cirrhosis in imaging are an enlarged caudate lobe, widening of the liver fissures and enlargement of the spleen.

An enlarged spleen (splenomegaly), which normally measures less than 11-12Ԝcm in adults.

is very suggestive of cirrhosis with portal hypertension in the right clinical setting.

Ultrasound may also screen for hepatocellular carcinoma, portal hypertension.

FibroScan -(transient elastography), uses elastic waves to determine liver stiffness which theoretically can be converted into a liver score based on the METAVIR scale.

(The FibroScan produces an ultrasound image of the liver (from 20–80Ԝmm) along with a pressure reading (in kPa). The test is much faster than a biopsy (usually last 2.5-5 minutes) and is completely painless. It shows reasonable correlation with the severity of cirrhosis.)

Gastroscopy -(endoscopic examination of the esophagus, stomach and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. 

Liver biopsy- in which a sample of liver tissue is removed and analyzed, also may be done. It is the only test that can confirm a diagnosis of cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook.

34.           Medical management of liver cirrhosis.

cannot be reversed, but treatment could stop or delay further progression and reduce complications. A healthy diet is encouraged.

Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease risk of constipation; their role in preventing encephalopathy is limited.

Patients with decompensated cirrhosis generally require admission to hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment - often with diuretics, antibiotics, laxatives and/or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline.

Administration of saline is generally avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis. Liver transplantation.

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary.

35.           Treatment of: portal hypertension, ascites, encephalopathy, hepatorenal syndrome.

Hypertension-

Managed with propanolol to prevent bleeding.

Vitamin k- because of elevated prothrombin time

.

Ascites-

Edema and fluid overload in 3^rd space such as ascites are managed with diuretics.

Mostly spironolactone ,which results high aldesterone state.

Encephalopathy -

Is managed with neomycin or lactulose a nonabsorbed disaccharide that bacteria metabolize in the colon.making it more acidic it convert to NH3(not absorbed very well)----> NH4 ion.  This is excretion of NH3 from the body.

Hepatorenal syndrome- treatment of hepatorenal syndrome is connected with underlying liver disease.

Midodrine and alpha-agonist

And octreotide may be beneficial in hepatorenal syndrome.

Best treatment is liver transplantation.

36.           Describe the complications of liver cirrhosis.

Check Number 32

37.           Liver failure (hepatic insufficiency). Classification. Therapy.

liver failure  is characterised by the sudden loss of hepatic function due to hepatocyte necrosis resulting in hepatic encephalopathy (HE), jaundice and coagulopathy.

LF is rare, with an incidence of 1–6 cases/million/year in the Western world, and is associated with a high mortality.

 In the developing world, viral causes are more common than in the Western world where drug‐induced liver injury predominates.

Causes-

drugs

Paracetamol (acetominophen) is commonly implicated in overdoses along with non‐ steroidal anti‐inflammatory drugs (NSAIDs).

Poisons

Amanita species

Metabolic

Acute willson’s

Viral

Hepatitis A,B and E

Adeno virus, HSV/EBV

Others

Pregnancy associated liver disease

Infiltrative eg: lymphoma

classification-

	Hyper acute	Acute	Subacute
Time from jaundice to HE	0-7 days	1-4 weeks	4-12 weeks
Typical cause	Paracetamol	Hepatitis A,B and E	Drugs(non paracetamol)
Jaundice	mild	moderate	severe
Coagulopathy	Severe	moderate	mild

Therapy-

Few specific therapies are available. N‐acetylcysteine (NAC) is effective for paracetamol‐induced hepatoxicity. For patients with non‐paracetamol‐induced ALF, NAC is also recommended. In cases of acute HBV or reactivation or flare of HBV, treatment with antivirals is recommended.

Patients with liver failure should be managed in a HDU or ITU setting with early discussion with the local transplant centre.

-Cardiovascular: Assessment of volume status. Intravascular volume depletion is common. LF has similar characteristics to septic shock (i.e. low BP, peripheral vasodilatation, hyperdynamic circulation; ↑ heart rate, ↓ systemic vascular resistance, ↑ cardiac output). Central venous and arterial catheters may be required. The use of inotropic agents (e.g. norepinehrine) is common.

-Respiratory: Is the patient able to protect their airway? Elective intubation is recommended in those with GCS <8 or severe agitation/confusion (i.e. grade 3 encepholopathy). Assessment of arterial blood gases. Respiratory complications include pneumonia, aspiration and acute lung injury.

-Neurological: What is the GCS? Neurological dysfunction is common but can be subtle with rapid onset. Once the GCS is <8 the patient will have established brain oedema and will deteriorate rapidly.

Once the patient has become agitated or develops grade 1 or 2 HE or GCS drops to 12, they should be immediately transferred to liver transplant centre. They should be intubated pre‐transfer. Patients with high grade HE (>grade 3), young patients (<35 years) and those with a high serum ammonia level (>150 μmol/L) are at increased risk of developing cerebral oedema.

Seizures are a poor prognostic sign. Intracranial monitoring may be required.

-Renal and electrolytes: Renal dysfunction is common (>50%). Nephrotoxic drugs should not be given. Adequate volume resuscitation is required. The use of renal replacement therapy, if required, should be commenced early and is usually continuous veno‐venous haemodialysis.

Hypoglycaemia is common. ↑ Lactate reflects tissue hypoxaemia. Metabolic acidosis is common. Tight glucose control (6–10 mmol/L) is recommended. Avoid solutions that contain lactate (e.g. Hartmann’s). Patients are often intravascular depleted.

-Gastrointestinal: ALF is a hypercatabolic state and nutritional support is important.

-

Haematology: ↑ INR, ↓ platelets, ↓ fibrinogen. Correction of coagulopathy (fresh frozen plasma, platelets, cryoprecipitate) required only if there are signs of bleeding.

-Infection: A comprehensive septic screen is recommended in all ALF patients due to the increased susceptibility to bacterial and fungal infections. Prophylactic antibiotics and antifungals are recommended. Universal precautions are integral to avoid nosocomial infections.

38.           Metabolic liver disease: etiology and pathogenesis of alcohol liver disease. Features of treatment.

Alcohol is metabolised mainly in the liver through 2 main pathways: alcohol dehydrogenase and cytochrome P-450 2E1. In the liver, alcohol is metabolised to acetaldehyde by alcohol dehydrogenase, which then is metabolised to acetate by the mitochondrial enzyme acetaldehyde dehydrogenase. Alcohol dehydrogenase and acetaldehyde dehydrogenase reduce nicotinamide adenine dinucleotide (NAD) to NADH (reduced form of NAD). Excessive NADH in relation to NAD inhibits gluconeogenesis and increases fatty acid oxidation, which in turn promotes fatty infiltration in the liver.

The cytochrome P-450 2E1 pathway also metabolises alcohol, and generates free radicals through the oxidation of NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) to NADP. Chronic alcohol use upregulates cytochrome P-450 2E1 and produces more free radicals.

Chronic alcohol exposure also activates a third site of metabolism: hepatic macrophages, which produce TNF-alpha and induce the production of reactive oxygen species in the mitochondria.

Alcoholic people are usually deficient in antioxidants, such as glutathione and vitamin E. Therefore, oxidative stress promotes hepatocyte necrosis and apoptosis in these patients. Free radicals can also induce lipid peroxidation, which can cause inflammation and fibrosis. The alcohol metabolite acetaldehyde, when bound to cellular protein, produces antigenic adducts and induces inflammation. Alcohol also affects the barrier function of intestinal mucosa, producing endotoxaemia, which leads to hepatic inflammation.

Biomedical and cellular pathogenesis of liver injury  secondary to chronic ethanol ingestion.

39.           Metabolic liver disease: classification, etiology and pathogenesis of non-alcoholic fatty liver disease (hepatosis). Principles of treatment.

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non serious condition called fatty liver.

etiology and pathogenesis 

NAFLD is part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure. Not all patients have all the manifestations of the metabolic syndrome. Less is known about what causes NASH to develop. Researchers are focusing on several factors that may contribute to the development of NASH. These include:

• Oxidative stress (imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage)
• Production and release of toxic inflammatory proteins (cytokines) by the patient’s own inflammatory cells, liver cells, or fat cells
• Liver cell necrosis or death, called apoptosis
• Adipose tissue (fat tissue) inflammation and infiltration by white blood cells
• Gut microbiota (intestinal bacteria) which may play a role in liver inflammation

treatment.

• Weight reduction (diet + exercise, medications, surgery)
• Lipid lowering medications
• Insulin sensitizers (medications)
• Decrease the amount of liver inflammation by administering anti-oxidant medications, anti-apoptotic medications and anti-cytokine medications

40.           Disorders of bilirubin metabolism leading to hyperbilirubinemia (Gilbert’s, Crigler-Najjar’s, Rotor’s, Dubin-Johnson’s syndromes).

41.           Hemochromatosis. Etiology. Pathogenesis. Symptoms and methods of diagnostics. Principles of treatment.

Etiology-

HH is genetic disorder of unregulated iron absorption, leading to a state of iron overload.

Excess iron is deposited in organs, such as the liver, pancreas, pituitary, skin and joints, which over many years leads to organ damage and dysfunction.

The highest incidence of HH worldwide is seen in Ireland. It is infrequently encountered in southern Europe, Africa and Asia.

Pathogenesis-

In this disease there is an overabsorption of iron in the duodenum, leading to iron buildup in a number of tissues throughout the body.

This leads to chronic hepatic inflammation and fibrosis.

Clinical presentation-

Cardiomyopathy develops in 15% of the patient.

Arthralgias ,skin hyperpigmentation, diabetes,hypogonadism are also common.

Vibrio vulnificus and yersinia infections occur with increased frequency because of their avidity for iron.

Diagnosis-

In serum test-

Elevated iron level and diminished iron binding capacity (>300 micro gram /l in men and after menopausal women , in young women >200 micro gram /l)

Ferritin also elevated.

Liver biopsy is the most accurate test and abnormal C282Y gene.

MRI can eliminate the need for biopsy if both are present.

Treatment-

Phlebotomy is used to remove large ammount of iron from body.

Deferoxamine and deferasirox are used only in those who cannot undergo phlebotomy.

42.           Wilson's disease. Etiology. Pathogenesis. Symptoms and methods of diagnostics. Principles of treatment.

Etiology-

An autosomal recessive disorder that leads to impaired cellular transport of copper and accumulation in the liver, brain and cornea. Affects 1 in 30 000 live births. Occurs due to mutations of the ATP7B gene on chromosome 13. Variable clinical penetrance with presentation in childhood or adulthood. Majority of patients present between the ages of 5 and 35 years.

Pathogenesis-

This is an autosomal recessive disorder,leading to the diminished ability to excrete copper from the body and also increased absorption of the copper from the small intestine.

Clinical picture-

Copper build up in brain,liver and cornea.

Basal ganglia dysfunction contribute to the movement disorder that develops.

10% of the patient have the psychiatric disturbance.

Kayser-fleischer rings (blue -grey color lines) are found in the eye on slit lamp.

Tremor and parkinson’s occur in 1/3 of patients.

Fanconi syndrome (glucosuria,amino aciduria ,hypouricaemia and proximal renal tubular acidosis) and type 2 proximal renal tubular acidosis develop in the kidney.

Jaundice , steatosis ,acute liver failure.

Diagnosis-

Wilson’s disease should be considered in any patient with unexplained liver, neurologic or psychiatric symptoms.

• Slit‐lamp examination: examine for KF rings.

• Serum ceruloplasmin: decreased by 50% but can be normal.

• Serum copper: low. Can be high in patients with cholestasis.

• 24‐hour urinary copper: >1.6 μmol/24 hours. Can be high in patients with an acute hepatitis or with cholestasis. Raised by penicillamine in affected patients more than carriers.

• Liver biopsy: parenchymal copper >4 μmol/g dry weight. Changes include steatosis to macronodular cirrhosis.

• Mutation analysis: whole gene sequencing is possible. Recommended for screening first‐degree relatives of patients with Wilson’s disease.

Treatment-

1)D‐penicillamine: Promotes urinary excretion of copper and induces metallothionein (endogenous chelator of metals). Usually taken 1–2 hours before meals to inhibit dietary absorption of copper.

Adequacy of treatment can be monitored by performing 24‐hour urinary copper excretion.

Goal of therapy is to increase urinary copper excretion from baseline levels and a normal serum copper.

2)Trientine: Chelates copper and then promotes urinary copper excretion. Associated with iron deficiency. Fewer side effects than D‐penicillamine.

3)Zinc: Reduces uptake of copper from the gastrointestinal tract and induces metallothionein in enterocytes. Bound copper is then excreted faecally.

4)Liver transplantation: Medical therapy is rarely effective in patients with acute liver failure.

 43.           Functional biliary disorders (gallbladder and Oddi's sphincter dysfunction). Diagnostic criteria. Therapy depending on a form of the dysfunction.

Functional gallbladder disorder is defined as biliary pain resulting from a primary gallbladder motility disturbance in the absence of gallstones, sludge, microlithiasis, or microcrystal disease. The diagnosis is considered in patients with typical biliary-type pain who have had other causes for the pain excluded.

Following removal of the gallbladder, biliary pain has been attributed to sphincter of Oddi

dysfunction (SOD). SOD represents intermittent obstruction to the flow of biliopancreat‐

ic secretions through the sphincter of Oddi in the absence of biliary stones or a ductal

stricture

Clinical criteria — Consensus guidelines (the Rome IV criteria) have been developed to help diagnose functional gallbladder disorder. Patients who fulfill these criteria should undergo an evaluation for functional gallbladder disorder, whereas patients who do not fulfill all of the criteria should be evaluated for alternative causes of their abdominal pain. 

Rome IV criteria for functional gallbladder disorder require:

●Biliary pain

●Absence of gallstones or other structural pathology

In addition, the criteria that are supportive of functional gallbladder disorder, but are not required, include: 

●Low ejection fraction on scintigraphy

●Normal liver enzymes, conjugated bilirubin, and amylase/lipase

To fulfill the Rome IV criteria for biliary-type pain, patients need to have pain that:

●Is located in the epigastrium and/or right upper quadrant

●Occurs at variable intervals (not daily)

●Lasts at least 30 minutes

●Builds up to a steady level

●Is severe enough to interrupt daily activities or lead to an emergency department visit

●Is not significantly (<20 percent) relieved by bowel movements, postural changes, or acid suppression

Criteria that are supportive of biliary pain, but are not required, include: (a) pain that is associated with nausea and vomiting, (b) pain that radiates to the back and/or right subscapular region, and (c) pain that awakens the patient from sleep in the middle of the night.

 MANAGEMENT — Cholecystectomy is the treatment for functional gallbladder disorder. Patients are candidates for cholecystectomy if they fulfill the clinical criteria for functional gallbladder disorder, if alternative explanations for their symptoms have been excluded, and if their gallbladder ejection fraction (GBEF) is reduced (<40 percent).

Alternative therapies, such as bile acid composition modifiers, promotility agents, and anti-inflammatory drugs, have not been adequately studied

1.                Emergency care in pulmonary hemorrhage.

Immediate treatment of P-Hem should include tracheal

suction, oxygen and positive pressure ventilation. To assist in decreasing P-Hem, mean

airway pressure should be increased, either by a relatively high PEEP Positive End Expiratory Pressure cmH2O) or by high frequency ventilation. Correct underlying abnormalities, especially

disorders of coagulation. When blood loss is large, prompt blood transfusion may be

needed to maintain an adequate circulating blood volume. The outcome is dependent on

the cause of P-Hem. Mortality is 30 to 40%.

2.                Emergency treatment in patients with attack of bronchial asthma.

Oxygen: Administration of oxygen through nasal cannulae or a mask is recommended to maintain SaO2 at greater than 90% (> 95% in pregnant women and patients with concomitant heart disease).

Inhaled short-acting β2-agonists:  10 mg of salbutamol

Corticosteroids: Continue prednisolone 40-50 mg daily for at least five days or until recovery

Ipratropium bromide: Add nebulised ipratropium bromide (0.5 mg 4- to 6-hourly) 

• Consider giving an infusion of IV magnesium sulfate (only after consultation with senior medical staff) for patients with life-threatening or near-fatal asthma, or with acute severe asthma who have not had a good initial response to inhaled bronchodilator therapy.

Antibiotics are not routinely indicated.

3.                Emergency treatment in uncomplicated hypertensive crisis.

Captopril (sublingual)

Nifedipine

Nitroglycerin

Monoxidine

Beta blockers

4.                Emergency treatment in complicated hypertensive crisis.

  IV infusions only

Nitroglycerin

labetalol

Enalaprilat

Clonidine

Hydralazine

Esmolol

5.                Emergency care of patients with unstable angina.

Aspirin 525mg chewing

clopidlogel 300 - 600 mg chewing

beta blockes

Morphine IV start from 1mg and increase. nitric oxide can be used in place of morphine

6.                Analgesia in myocardial infarction patients.

Morphine IV start from 1mg and increase

7.                Emergency therapy of cardiogenic shock.

1. Initial stabilization. If there is a high flow of O2, endotracheal intubation, intravenous access, cardiac rhythm, and pulse oximetry monitoring should be considered.
2. Rhythm disturbances, hypoxemia, hypovolemia, and electrolyte abnormalities should be identified and treated.
3. Aspirin 160 to 325 mg. The patient should chew and swallow unless there is an allergy or contraindication.
4. Intravenous nitroglycerin or morphine sulfate, titrated to response, should be administered as needed for chest pain, as well as hemodynamic parameters monitored.
5. For mild to moderate hypotension, in absence of hypovolemia, dobutamine 2.5 to 20.0 µg/kg per min should be administered. For severe hypotension dopamine 2.5 to 20.0 µg/kg per min should be used, titrated to desired effect and utilized at the lowest dose possible.
6. Intravenous nitroglycerin 5 to 100 µg/min and sodium nitroprusside 0.5 to 10.0 µg/kg per min should be used to improve cardiac output through reduction of preload and afterload.
7. Intra-aortic balloon pump. To decrease afterload the measure should be temporized and diastolic pressure and coronary perfusion augmented.
8. Thrombolytic therapy, percutaneous transluminal angioplasty (PCTA), emergent CABG should be used as indicated or available.
9. Cardiology and cardiac surgery should be consulted early. Transfer should be arranged if indicated.

8.                Emergency care for patients with attack of heart asthma.

9.                Emergency care in pulmonary edema.

10.           Emergency care in the paroxysm of atrial fibrillation.

• The management of AF involves control of the arrhythmia (by rhythm or rate control) and thromboprophylaxis to prevent strokes.
• Treat any underlying cause - eg, acute infection, hyperthyroidism. AF may revert on treatment or resolution of an associated problem - eg, acute infection or alcohol intoxication.
• Treat associated heart failure.

11.           The urgent aid in patients with a paroxysm of supraventricular tachycardia.

12.           Emergency therapy in patients with a paroxysm of ventricular tachycardia.

Direct current cardioversion is recommended for patients presenting with sustained VT and haemodynamic instability.
In patients presenting with sustained haemodynamically tolerated VT in the absence of structural heart disease (e.g. idiopathic RVOT), i.v. flecainide or a conventional beta-blocker, verapamil or amiodarone may be considered.

13.           The urgent aid in patients with ventricular asystole.

14.           The urgent aid in patients with ventricular fibrillation and flutter.

15.           Emergency aid for patients with onset of Morgagni-Adams-Stokes.
Stokes-Adams syndrome was the chief impetus for development of a device that monitors and regulates the heartbeat (artificial pacemaker) and these have been in use for over 30 years. Surgical implantation of a pacemaker into the heart is still the treatment of choice. In emergency situations, anticholinergics or sympathomimetics may be prescribed temporarily while a temporary pacemaker is inserted until a permanent pacemaker can be implanted.

16.           Emergency aid for patients with gastrointestinal bleeding.

• Correct fluid losses (place two wide-bore cannulae and also send bloods at the same time). Either colloid or crystalloid solutions may be used to achieve volume restoration prior to administering blood products; red cell transfusion should be considered after loss of 30% of the circulating volume.[3]
• Transfuse patients with massive bleeding with blood, platelets and clotting factors in line with local protocols for managing massive bleeding. Major haemorrhage protocols should be in place.[3]
• Decisions on blood transfusion should be based on the full clinical picture; over-transfusion may be as damaging as under-transfusion.[6][7] 
• Platelet transfusions should not be offered to patients who are not actively bleeding and are haemodynamically stable.
• Platelet transfusions should be offered to patients who are actively bleeding and have a platelet count of less than 50 x 109/L.
• Fresh frozen plasma should be used for patients who have either a fibrinogen level of less than 1 g/L, or a prothrombin time (INR) or activated partial thromboplastin time greater than 1.5 times normal.
• Prothrombin complex concentrate should be used for patients who are taking warfarin and actively bleeding.
• Recombinant factor Vlla should not be used except when all other methods have failed.

Recommendations emphasise early risk stratification, using validated prognostic scales, and early endoscopy (within 24 hours). The following formal risk assessment scores are recommended by the National Institute for Health and Care Excellence (NICE) for all patients with acute UGIB:

17.           Emergency aid for patients with gastrointestinal bleeding from varices of esophagus.

18.           Emergency care in patients with anaphylactic shock.