Upper And Lower gIT Diseases And Management Flashcards

Question

State the types of GERD

Answer 1

EROSIVE -PRESSENCE OF OESOPHAGEAL MUCOSAL BREAKS/ULCERS •NON EROSIVE -ABSENCE OF OESOPHAGEAL MUCOSAL BREAKS /ULCERS

Answer 2

True Superior third:striated muscle only Middle third:striated plus smooth Inferior third:smooth muscle only Areas of narrowing: At the area of the cricopharyngeus muscle Where the left mainstem bronchus and aortic arch cross At the hiatus of the diaphragm(at the level of T10) Upper oesophageal sphincter (formed by cricopharyngeus muscle):it prevents the passage of excess air into the stomach during breathing Lower oesophageal sphincter:(physiological sphincter):prevents the reflux of gastric contents into the oesophagus Histology:non-keratinized stratified squamous epithelium

Answer 3

Infertile vena cava:T8 Oesophagus:T10 Aorta:T12

Answer 4

When bolus enters the oesophagus,the upper sphincter relaxes when the larynx is lifted Peristalsis begins Circular fibers contract behind the bolus Longitudinal fibers shorten the distance Lower sphincter relaxes by receptive relaxation mechanism as food approaches Travel time for solids is 4-8secs and liquids is 1second True 30mmHg Achalasia Reflux of stomach content into the oesophagus causing reflux oesophagitis True

Answer 5

LES competence - LES PRESSURE VERSUS INTRGASTRIC PRESSURE - TRANSDIAPHRAGMATIC PRESSURE GRADIENT •CRURAL FIBERS OF THE DIAPHRAGM - contraction at LOS prevents reflux - acts like an external sphincter - large hiatus hernia can impair this mechanism •UNIQUE ANATOMY OF THE STOMACH -the angle of HIS -mucosal rossete - posterolaterial location of the fundus •OESOPHAGEAL CLEARANCE -by peristalsis - by saliva •Gastric emptying

Answer 6

Reflux is normally followed by oesophageal peristaltic waves which efficiently clear the gullet, alkaline saliva neutralises residual acid, and symptoms do not occur - gastroesophageal reflux is a normal physiologic phenomenon experienced intermittently by most people , particularly after a meal. -Several factors are known to be involved in the development of gastro-oesophageal reflux disease. -development is multifactorial Factors involved: •ABNORMALITIES OF THE OESOPHAGEL SPHINCTER •DISRUPTION OF ANATOMICAL BARRIER •DEFECTIVE OESOPHAGEL CLEARANCE •DELAYED GASTRIC EMPTYING •HYPERSECRETION OF ACID •INCREASED INTRA-ABDOMINAL PPRESSURE •DIETARY AND ENVIRONMENTAL FACTORS True

Answer 7

1. ABNORMALITIES OF THE OESOPHAGEL SPHINCTER - The lower oesophageal sphincter is tonically contracted under normal circumstances, relaxing only during swallowing. - GERD occurs when the LES pressure is lower than the intragastric pressure(hypotensive LES) - Some patients with gastro-oesophageal reflux disease have 1. an ATONIC(REDUCED) LES 2. transient increase in intra abdominal pressure 3. spontaneous(frequent episodes) inappropriate LES relaxation 2. DISRUPTION OF ANATOMICAL BARRIERS - associated with hiatal hernia - part of stomach pushes(bulges) into the chest cavity through an opening in the diaphragm where the oesophagus passes. - Hiatus hernia causes reflux because the pressure gradient between the abdominal and thoracic cavities, which normally pinches the hiatus, is lost. - the size of hiatal hernia is proportional to the frequency of LES relaxation 3. DEFECTIVE OESOPHAGEAL CLEARANCE - oesophageal defense mechanisms can be broken down into two 1. oesophageal clearance 2. mucosal resistance - oesopahgeal clearance functions to neutralize the acid reflux through the LES 1. Mechanical resistance is achieved by oesophageal peristalsis 2. chemical clearance is achieved with saliva - causes of defective esophageal clearance 1. infective peristalsis 2. reduced salivary secreation 3. reduced secretion from oesophageal submucosal glands - Poor oesophageal clearance leads to increased acid exposure time. PATHOPHYSIOLOGY OF GERD 4. DELAYED GASTRIC EMPTYING - Gastric emptying is delayed in patients with gastro-oesophageal reflux disease. - exact role remains to be clarified( reasons unknown) - results in an increase in the volume of gastric contents available for reflux into the oesophagus. PATHOPHYSIOLOGY OF GERD 5. INCREASED INTRA-ABDOMINAL PPRESSURE - conditions that increases intra-abdominal pressure can lead to GERD 1. OBESITY 2. PREQNANCY 3. BENDING 4. STRAINING 5. COUGHING 6. TIGHT CLOTHES ``` 6.DIETARY AND ENVIRONMENTAL FACTORS: agents that lowers LES 1. DIET -dietary fat - chocolate - alcohol - coffee coffee - cigarettes - Spicy foods - orange and tomato juices 2. MEDICATIONS - anticholinergics - beta adrenergic agonists - alpha adrenergic antagonists - calcium channel blockers - diazepam - theophylline - morphine - NSAIDS 3.POSITION / ACTIVITY - bending - straining - external pressure ( tight clothing, pregnancy) ```

Answer 8

Obesity Hiatal hernia Pregnancy Connective tissues disorders example scleroderma Delayed stomach emptying Smoking Eating large meals or eating late at night Consuming acid reflux triggers(fatty or fried food) Drinking certain drinsk(alcohol or coffee) Taking certain medications(eg aspirin) True

Answer 9

``` SIGNS & SYMPTOMS •Heartburn (pyrosis) •Sensation of discomfort or burning behind the sternum rising up to the neck •Occurs 1-2 hours after eating , often at night -provoked by 1.Vigorous exercise 2.Bending forward 3.Straining 4.Lying down ``` - Relived by 5. Antiacids 6. Sitting upright -Waterbrash •production of excessive amounts of saliva which is due to reflex salivary gland stimulation as acid enters the gullet •REGURGITATION •Effortless return of gastric contents into the pharynx •Bitter, acidic fluid in the mouth •NOCTURNAL? -wakes patients up with coughing and choking -provoked by lying down or bending over -less relived by antiacids -NON CARDIAC CHEST PAIN •RETROSTERNAL •EPIGASTRIC •CAN MIMIC ANGINA •MAY BE DUE TO REFLUX-INDUCED OESOPHAGEAL SPASMS Alarming signs: OTHER SIGNS & SYMPTOMS( ALARMING SIGNS ) ``` •DYSPEPSIA •DYSPHAGIA - food sticks or hangs up •ODYNOPHAGIA - retrosternal pain with swallowing •CHRONIC HOARNESS(DYSPHONIA) •EARLY SATIETY •COUGH •WHEEZING •VOMITING •GI BLEEDING •IRON DEFICIENCY ANEMIA •WEIGHT LOSS ``` PHYSICAL EXAMINATION FINDINGS •MAY BE NONE •EPIGASTRIC TENDERNESS •CHEST SIGNS( WHEEZING) ``` Differentials : GASTRITIS •PEPTIC ULCER •ESOPHAGITIS •ACHALASIA •CORONARY ARTERY DISEASE •ESOPHAGEAL MOTILITY DISORDERS •ESOPHAGEAL CANCER ```

Answer 10

Young patients who present with typical symptoms of gastro-oesophageal reflux, without worrying features such as dysphagia, weight loss or anaemia, can be treated empirically without investigation. -if the classic symptoms of heartburn and regurgitation exist in the absence of alarming symptoms ( other symptoms ), the diagnosis of GERD can be made clinically and treatment can be initiated Ivestigations •Upper gastro-intestinal tract endoscopy -This is performed to exclude other upper gastrointestinal diseases that can mimic gastro-oesophageal reflux and to identify complications. - allows direct visualization of the oesophageal mucosa and biopsy if need. -checks for presence and severity of erosive oesophagitis - detection of complications such as stricture or barret’s esophagus Ivestigations •AMBULATORY OESOPHAGEAL PH MONITIRING - mostly used in cases that are difficult to download •Twenty-four-hour pH monitoring is indicated if the diagnosis is unclear or surgical intervention is under consideration. •Accepted standard for establishing or excluding presence of GERD for those patients who do no have mucosal changes - This involves tethering a slim catheter with a terminal radiotelemetry pH- sensitive probe above the gastro-oesophageal junction. The intraluminal pH is recorded whilst the patient undergoes normal activities, and episodes of symptoms are noted and related to pH. A pH of less than 4 for more than 6–7% of the study time is diagnostic of reflux disease. •checks the amount and timing of reflux •Correlates the reflux and symptoms • most useful in • endoscopoy-negative patients •Patients with chest pains •Patients with pulmonary/upper respiratory symtoms INVESTIGATIONS •Chest X-ray - to rule out other causes or diseases • barium swallow with fluoroscopy •Useful in children •Patient swallows liquid barium while X-ray images are taken . The barium fills and coast the lining of the oesphagus so that it can diagnose anatomical abnormalities •Can detect stricture( location , length) •Mass( location , length) •Hiatal hernia( size, type) INVESTIGATIONS •Lower Oesophageal sphicter manometry -in cases that are difficult to diagnose Other useful tests - to rule out other diseases

Answer 11

Alleviate or eliminate the patient’s symptoms •Decrease the frequency or recurrence and duration of gastro esophageal reflux. •Promote healing of the injured mucosa •Prevent development of complications NON PHARMACOLOGICAL TREATMENT - LIFESTYLE MODIFICATIONS •Elevate head of bed by about 30degrees( 4-6 inches) or encourage patient to sleep on pillows •Patient must avoid lying down 3-4 hours after a meal •Patient must avoid over eating and large meals before bed time •Patient must avoid medications an foods that potentiate or aggravate symptoms or disease •CCB(Recent studies suggest that calcium channel blockers (CCBs), and particularly nifedipine, increase the risk of GERD by significantly reducing the tone of the LES, increasing esophageal exposure to gastric acid and reducing the amplitude and duration of esophageal peristalsis ), alpha agonists,NSAIDS,fats,alcohol, smoking , spicy foods ,fried food, carbonated beverages, onionsetc •Encourage weight reduction in patients especially in overweight and obese patients. •Avoid clothing that is tight around the waist. PHARMACOLOGICAL TREATMENT •ANTIACIDS •PROTON PUMP INHIBITORS •HISTAMINE H2 RECEPTOR ANTAGONISTS - REFER TO STANDARD TREATMENT GUIDELINES FOR FUTHER INFORMATIONON PHARMACOLOGICAL TREATMENTS SURGICAL TREATMENT( ANTI-REFLUX SURGERY) -Failed medical treatment •Patient preference •GERD COMPLICATIONS COMPLICATIONS •EROSIVE ESOPHAGITIS -A range of endoscopic findings, from mild redness to severe, bleeding ulceration with stricture formation, are recognized. •BARRETE’S ESOPHAGUS -Barrett’s oesophagus is a pre-malignant condition, in which the normal squamous lining of the lower oesophagus is replaced by columnar mucosa (columnar lined oesophagus; CLO) that may contain areas of intestinal metaplasia. •Benign oesophageal stricture -Fibrous strictures can develop as a consequence of longstanding oesophagitis, especially in the elderly and those with poor oesophageal peristaltic activity. The typical presentation is with dysphagia that is worse for solids than for liquids. Bolus obstruction following ingestion of meat causes absolute dysphagia •Anemia -Iron deficiency anaemia can occur as a consequence of occult blood loss from long-standing oesophagitis. Most patients have a large hiatus hernia and bleeding can stem from subtle erosions in the neck of the sac (‘Cameron lesions’). More complications -oesophageal stricture:result of healing of erosive oesophagitis May need dilation

Answer 12

1.GERD PUD(gastric ulcer) Hiatal hernia 2.upper GI endoscopy FBC Hb 3.GERD 4.patient should sleep with pillows and shouldn’t lie down straight but at an angle(I’ve forgotten the angle so check) Patient shouldn’t eat large meals at night Should stay away from spicy and acidy foods Should lie down three to four hours after eating Give PPI Check More on GERD management

Answer 13

True True True

Answer 14

ANATOMY AND PHYSIOLOGY OF THE STOMACH The stomach is divided into *4 major anatomic* regions : * The cardia* * The fundus* * The body* and * The pyloric antrum* The cardia is lined mainly by mucin secreting foveolar cell that form shallow glands that secrete mucus and bicarbonate The antral glands are similar but also contain endocrine cells such as G cells that release gastrin to stimulate luminal acid secretion by the parietal cells within the gastric fundus and the body. The well developed glands of the body and fundus contain chief cells that produce and secrete digestive enzymes such as pepsin.

Answer 15

Definition of gastritis Gastritis is the *inflammation* of the *gastric mucosa* caused by any several conditions including infection (H. pylori), Drugs (NSAIDs, alcohol), stress and autoimmune phenomena (atrophic gastritis). Diagnosis is by endoscopy. Treatment is directed at the cause but often includes acid suppression(a proton pump inhibitor or H2 blocker) and for H.pylori infection antibiotics. In severe gastritis bleeding is managed with IV fluids and blood transfusion as needed True

Answer 16

*Pathology* *of* *Gastritis* The gastric lumen is strongly acidic and with a pH close to 1. It's acidic environment contributes to digestion but also has the potential to damage the mucosa. Protective mechanisms of the stomach mucosa include: - mucin secreted by the foveolar cells forms a thin layer of mucus that prevents large particles from directly touching the epithelium. - layer of fluid covers the mucosa and has a neutral pH as a result of bicarbonate ion secretion by surface epithelial cells. Finally, the rich vascular supply to the gastric mucosa delivers oxygen, bicarbonate and nutrients while washing away acid that has back-diffused into the propria. Acute or chronic gastritis can occur after disruption of any of the protective mechanisms of the stomach mucosa. Reduced mucin synthesis in the elderly suggested to be one factor for increased susceptibility to gastritis. NSAIDs interferes with production of prostaglandins and bicarbonate secretion. Ingestion of harsh chemicals destroy the protective mechanisms of the stomach hence could cause gastritis. H.Pylori infections is also a major cause of gastritis

Answer 17

*Continuation* of pathology of gastritis H. pylori infection is also a major cause of gastritis. Below are the adaptive features of H. pylori to the gastric mucosa 1. Flagella, which allow the bacteria to be motile in viscous mucus. 2. Generates ammonia from endogenous urea, thereby elevating local gastric pH around the organism, protecting it from acidic pH of the stomach. 3. H. pylori has adhesions that enhance bacterial adherence to the surface of foveolar cells. 4. H. pylori produces toxin that may disrupt the stomach mucosa.

Answer 18

Classifications of gastritis Gastritis can be classified based on this *three* major ways: 1. Severity of mucosal injury as a. *Erosive* gastritis b. *Nonerosive* gastritis 2. Site of involvement a. *Cardia* gastritis b. *Fundus* gastritis c. *Body* gastritis d. *Antrum* gastritis 3. Histologically based on inflammatory cells a. *Acute* gastritis b. *Chronic* gastritis

Answer 19

1. Menetrier's diseases: Menetrier disease is a rare disorder characterized by massive overgrowth of mucous cells (foveola) in the mucous membrane lining the stomach, resulting in large gastric folds. 2. Eosinophilic gastritis Other classifications* include: 1. Gastritis caused by systemic disorder 2. Gastritis caused by physical agents 3. Infectious (septic) gastritis 4. Autoimmune Metaplastic Atrophic Gastritis 5. Post gastrectomy gastritis

Answer 20

EROSIVE GASTRITIS It is a gastric mucosal erosion caused by damage to mucosal defenses. It is typically acute, manifesting with bleeding, but may be subacute or chronic with few or no symptoms. Diagnosis is by endoscopy. Treatment is supportive, with removal of the inciting cause. NONEROSIVE GASTRITIS It refers to a variety of histologic abnormalities that are mainly the result of H.pylori infection. Most patients are asymptomatic. Diagnosis is by endoscopy. Treatment is eradication of H.pylori and sometimes acid suppression. Causes of erosive gastritis include NSAID, alcohol, stress, vascular injury and less commonly radiation, viral infection (eg. Cytomegalovirus), direct trauma(eg. nasogatric tubes) True

Answer 21

True ACUTE GASTRITIS It is a *transient(less than three days ) mucosal* *inflammatory* process that may be asymptomatic or cause variable degrees of epigastric pain, nausea and vomiting. In a more severe case may cause erosion, ulceration, hematemesis, melena or rarely, massive blood loss. CHRONIC GASTRITIS The symptoms and signs associated with chronic gastritis typically are *less* *severe* but more *persistent* than those of acute gastritis. Nausea and abdominal discomfort may occur sometimes vomiting but hematemesis is uncommon. Most common causes of chronic gastritis is infection with *Helicopter* *pylori* , *autoimmune* *phenomena* , *radiation* *injury* to the stomach mucosa and **chronic* *bile* *reflux*

Answer 22

MANITRIER'S DISEASE This is a rare idiopathic disorder that affects adults aged 30 to 60 and is more common among men. It manifests as a significant thinkening of the gastric folds of the gastric body but not the antrum. Gland atrophy and marked foveolar pit hyperplasia occur, often accompanied by mucus gland metaplasia and increased mucosal thickness with *little* *inflammation* . Hypoalbuminemia caused by GI protein loss may be present. As disease progresses the secretion of acid and pepsin decreases, causing hypochlorhydria. Symptoms include: epigastric pain, nausea, weight loss, edema and diarrhea Diagnosis is by endoscopy with deep mucosal biopsy or full thickness laparoscopic gastric biopsy Treatment: anticholinergics, antisecretory drugs and corticosteroids. Partial or complete gastric resection may be necessary in cases of severe hypoalbuminemia.

Answer 23

EOSINOPHILIC GASTRITIS It is usually *idiopathic* but may result from *nematode* *infestation* . It involves extensive infiltration of the mucosa, submucosa and muscle layers with eosinophils often occurs in the antrum. Symptoms: nausea, vomiting and early satiety Diagnosis: endoscopic biopsy of involved areas. Treatment: corticosteroids and surgery may be required for pyloric obstruction

Answer 24

GASTRITIS CAUSED SYSTEMATIC DISORDERS Such as sarcoidoses(The growth of tiny collections of inflammatory cells in different parts of the body.) ,TB, amyloidiosesioses,and other granulomatous diseases can cause gastritis. GASTRITIS CAUSED BY PHYSICAL AGENTS. Radiation and ingestion of corrosives (especially acidic compounds) can cause gastritis. Exposure to>16 Gy of radiation causes marked deep gastritis, usually involving the antrum more than corpus. Plyoric stenosis and perforation are possible complications of radiation-induced gastritis. INFECTIOUS (SEPTIC) GASTRITIS. Except for H. ployri infection, bacterial invasion of the stomach is *rare* and mainly occurs in *ischemia* , Debilitated or *immunocompromised* patients may devolop viral or *fungal* *gastritis* with cytomegalovirus,candida,histoplasmosis,or mucormycosis.

Answer 25

AUTOIMMUNE METAPLASTIC ATROPHIC GASTRITIS. Autoimmune metaplastic atrophic gastritis (AMAG) is an inherited autoimmune disease that attacks parietal cells, resulting in hypochlorhydria( low acid secretion) and decreased production of intrinsic factor. Consequently leading to atrophic gastritis ( atrophy or disfunction of the gastric glands),B12 malabsorption and frequently, pernicious anaemia. Risk of gastric adenocarcinoma increases 3-fold. Diagnosis is by endoscopy. Treatment is with parenteral vitamin B12. Post gastrectomy gastritis Is a gastric atrophy developing after a partial or subtotal gastrectomy

Answer 26

DIFFERENTIAL DIAGNOSIS ``` Peptic ulcer disease Gastric cancer GERD Gastroenteritis Crohn's disease Gastrinoma Gastric ulcers Peritonitis Enteric fever Food poisoning ``` ``` Complications: Anemia Gastric perforations Sepsis Gastroparesis Gastrointestinal bleeding Peritonitis ```

Answer 27

A.PUD Gastritis Gastroenteritis B.The stomach is located at the epigastric region . Organic pain is poorly localized. It radiates to the dermatome level, which receives visceral afferent from the organ concern. The stomach is supplied by pain afferent that reach the T7 and T8 spinal sensory ganglia by the same sensory ganglia and spinal segment as the epigastric region. Liver,spleen,duodenum,adrenal glands,pancreas Note not the full thing tho but some parts of these organs can be found in the region

Answer 28

*Definition* PUD is a break in the inner lining of the stomach or duodenum OR is a sore in the lining of the stomach or duodenum. There are common types of peptic ulcer: * *Gastric ulcer* which is occurs in the stomach lining and is characterized by upper abdominal pain(epigastric pain) which worsens with eating and so people with gastric ulcers mostly tend to starve to avoid the pain * Duodenal Ulcer* which occurs in the upper part of the small intestine, the duodenum and is also characterized by upper abdominal pain which occurs 3hrs after eating and it's also relieved with eating.

Answer 29

*Signs and Symptoms* The signs and symptoms normally depend on the type of peptic ulcer. As said earlier, with gastric ulcers patients normally complain about pain with eating whilst with duodenal ulcer, patients normally complain about abdominal pain when they're hungry and it's relieved with eating but the common signs and symptoms patients present with are * Upper abdominal pain mostly at the epigastric region of the abdomen * Bloating: This means your tummy swells because your stomach is full of gas or air. * Nausea and vomiting * Loss of appetite and weight loss mostly with patients with gastric ulcers

Answer 30

*Pathophysiology* Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. The epithelial cells of the stomach and duodenum secrete mucus in response to irritation of the epithelial lining and as a result of cholinergic stimulation. The superficial portion of the gastric and duodenal mucosa exists in the form of a gel layer, which is impermeable to acid and pepsin. Other gastric and duodenal cells secrete bicarbonate, which aids in buffering acid that lies near the mucosa. Prostaglandins of the E type (PGE) have an important protective role, because PGE increases the production of both bicarbonate and the mucous layer. In the event of acid and pepsin entering the epithelial cells, additional mechanisms are in place to reduce injury. Within the epithelial cells, ion pumps in the basolateral cell membrane help to regulate intracellular pH by removing excess hydrogen ions. Through the process of restitution, healthy cells migrate to the site of injury. Mucosal blood flow removes acid that diffuses through the injured mucosa and provides bicarbonate to the surface epithelial cells. Under normal conditions, a physiologic balance exists between gastric acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), H pylori infection, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing the back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, bicarbonate, mucosal blood flow, cellular restitution, and epithelial renewal.

Answer 31

*Causes* Some of the causes include * A prolonged use of NSAID's * A bacteria called H. Pylori * Tobacco Use * Stress * Dietary factors like eating a lot of spices * And it can also be genetic * Some medical conditions like Chron's disease can also be a cause

Answer 32

*Causes* Some of the causes include * A prolonged use of NSAID's * A bacteria called H. Pylori * Tobacco Use * Stress * Dietary factors like eating a lot of spices * And it can also be genetic * Some medical conditions like Chron's disease can also be a cause

Answer 33

* Complications* * Bleeding: Bleeding can occur as slow blood loss that leads to anemia or as severe blood loss that may require hospitalization or a blood transfusion. Severe blood loss may cause black or bloody vomit or black or bloody stools. * A hole (perforation) in your stomach wall: Peptic ulcers can eat a hole through (perforate) the wall of your stomach or small intestine, putting you at risk of serious infection of your abdominal cavity (peritonitis). * Obstruction: Peptic ulcers can block passage of food through the digestive tract, causing you to become full easily, to vomit and to lose weight either through swelling from inflammation or through scarring. * Gastric cancer: Studies have shown that people infected with H. pylori have an increased risk of gastric cancer.

Answer 34

*Management and Treatment* ``` *Patients with peptic ulcer disease should be warned about known or potentially injurious drugs and agents. Some examples are as follows: NSAID Alcohol Aspirin Caffeine Tobacco ``` * *Aims* - To reduce gastric acid secretion - To neutralize secreted gastric acid - To increase mucosal resistance to acid pepsin attacks - To eradicate H. Pylori * *Drugs* - Proton pump inhibitors like Omeprazole, lansoprazole and esomeprasole - Histamine Receptor antagonists like Cimetidine, Ranitidine and Famotidine - Antacids like Aluminum hydroxide and magnesium hydroxide - Mucosal strengtheners like misoprostol - Bismuth compound such as bismuth subsalicyclate - Alginates like Gaviscone * *H. Pylori eradication regimen* - Dual therapy: Omeprazole + single antibiotic such as amoxicillin - Triple therapy: Omeprazole + metronidazole + amoxicillin/clarithromycin for 1- 2 weeks - Quadruple therapy: Triple therapy + bismuth compound for 3 days

Answer 35

DEFINITION Gastroenteritis, also called stomach flu or bug is inflammation of the lining of the stomach and small and large intestines. The severity of gastroenteritis mainly depends on an individual’s immune system’s ability to fight the infection. This implies that, gastroenteritis is self limiting in non-immunocompromised individuals. EPIDEMIOLOGY It is responsible for significant morbidity and mortality worldwide with nearly 1.7 billion cases and at least 2million deaths per year many resulting from consumption of contaminated food and water. Also, it affects 3 to 5 billion children worldwide and is responsible for 12% of deaths in children less than 5 years. This condition is more common in developing countries where sanitation conditions are poor. However, Viruses are the most common cause of gastroenteritis in the US.

Answer 36

PATHOPHYSIOLOGY Adequate fluid balance in humans depends on the secretion and reabsorption of fluid and electrolytes in the intestinal tract; diarrhea occurs when intestinal fluid output overwhelms the absorptive capacity of the gastrointestinal tract. The 2 primary mechanisms responsible for acute gastroenteritis are (1) damage to the villous brush border of the intestine, causing malabsorption of intestinal contents and leading to an osmotic diarrhea, and (2) the release of toxins that bind to specific enterocyte receptors and cause the release of chloride ions into the intestinal lumen, leading to secretory diarrhea. ETIOLOGY This could be infectious or non-infectious.

Answer 37

People may experience : Pain areas: in the abdomen Gastrointestinal: diarrhoea, stomach cramps, belching, gagging, indigestion, nausea, vomiting, or flatulence Whole body: chills, dehydration, fatigue, fever, lethargy, light-headedness, or loss of appetite Also common: fast heart rate, headache, low urine output, weakness, or weight loss Diagnosis: A doctor will diagnose gastroenteritis by first taking a complete history of your symptoms. Often, lab test are not needed to diagnose this condition. • However, if you have persistent fever, blood in your stool or diarrhea , stool study tests for clostridium difficile, rotavirus and norovirus. • Serum electrolytes, blood urea nitrogen (BUN), and creatinine should be obtained to evaluate hydration and acid-base status in patients who appear seriously ill. • Complete blood count (CBC) is nonspecific, although eosinophilia may indicate parasitic infection. • Renal function tests and CBC should be done about a week after the start of symptoms in patients with E. coli O157:H7 to detect early-onset hemolytic-uremic syndrome. It is unclear whether this testing is necessary in patients with non–E. coli O157:H7 Shiga toxin infection. • Microscopy for confirming the presence of parasites, ova and cyst may be helpful. In summary: Investigations •Laboratory investigations are usually not necessary in patients with non-bloody diarrhea and no evidence of systemic toxicity i.e. gastroenteritis is usually diagnosed by symptoms that is produced , primarily diarrhea. •Selection of appropriate test is based on the history and physical examination findings -copious watery diarrhea -ingestion of potentially contaminated food -recent travel -known GI irritant -contact with similarly ill people -use of antibiotic and other drugs •In terms of sever or persistent cases , stool testing for culture and sensitivity and microscopic examination is ordered -if rectal examination shows occult blood -if watery diarrhea persists for > 48 hours •Other blood tests like FBC, BUN, serum electrolytes may be necessary -eosinophilia in FBC may indicate parasitic infections ``` Investigations •Viral -stool electron microscopy -PCR to determine viral genome -ELISA to detect viral antigens in stools -e.t.c •Bacterial -microscopy -stool culture -serological typing -e.t.c ```

Answer 38

Complications of gastroenteritis include the following: • Dehydration  • Malabsorption  • Transient lactose intolerance  • Chronic diarrhea  • Systemic infection (meningitis, arthritis, pneumonia) especially with Salmonella infections  • Sepsis (Salmonella, Yersinia, Campylobacter organisms)  • Hemolytic-uremic syndrome (much more common in children, especially with E coli O157:H7)  • Toxic megacolon  • Reactive arthritides (Salmonella, Shigella, Yersinia, Campylobacter, Giardia organisms)  • Persistent diarrhea  • Thrombotic thrombocytopenic purpura or TTP (E coli O157:H7)  • Guillain-Barré syndrome (Campylobacter -weight loss -Metabolic acidosis -systemic infections like aspiration pneumonia -electrolyte imabalance TREATMENT Gastroenteritis is usually an acute and self-limiting disease which does not require medication. Rest and rehydration are the mainstays of treatment. If your child has viral gastroenteritis, you should give your child an oral rehydration solution—such as Pedialyte, Naturalyte, Infalyte, and CeraLyte—as directed to replace lost fluids and electrolytes. Oral rehydration solutions are liquids that contain glucose and electrolytes. IV therapy can bring much-needed relief when you're suffering from the symptoms of a stomach virus. When you use IV fluids for the stomach flu, you are replenishing your body when it's dehydrated. The fluids contain high-quality vitamins, minerals, and electrolytes, which can help your body as you recover. However, If you are seeking relief from nausea or diarrhea, there are some prescription medications that can ease your symptoms. Antiemetic such as promethazine, prochlorperazine, metoclopramide, or ondansetron may be prescribed to stop the nausea and vomiting. You can also try an over-the-counter antidiarrheal medication, such as loperamide hydrochloride (Imodium) or bismuth subsalicylate (Pepto-Bismol). Antibiotics can be given only if the cause is bacterial and not viral or parasitic. NB: Do not use Pepto-Bismol in children ``` Pharmacological treatment •Treatment depends on the cause -antibioctics -antiemetics -antidiarrheal agents -antispasmodics -vaccines ``` Refer the pharmacology flashcards in the treatment of diarrhea in gastroenteritis PREVENTION * washing vegetables, fruits, and salads thoroughly before eating them. * avoiding close contact with people who have gastroenteritis. * drinking bottled water when traveling, especially in developing countries. * avoiding eating raw meat and fish. * Wash your hands with soap and running water * Swimmers should avoid swallowing water when they swim.

Answer 39

Regular Pepto-Bismol and Kaopectate, containing bismuth subsalicylate, are approved for kids 12 and older. Pepto-Bismol and Kaopectate contain aspirin-like ingredients and should not be used in children with chicken pox or flu-like symptoms because of the risk of Reye's syndrome, a rare but serious illness. Pepto-Bismol should only be used by adolescents and adults age 12 and older. A children's version of Pepto-Bismol is available for children age 2 and older, or you might try a natural method to address their symptoms. Regular Pepto-Bismol is a concern for children because its main ingredient is bismuth subsalicylate, a derivative of aspirin (acetylsalicylic acid or ASA). Medications containing ASA are associated with Reye's syndrome, a rapidly progressing brain disorder that isn't fully understood. The condition typically develops in people recovering from a viral infection. Most of the cases seen in children involved the use of aspirin to treat common illnesses such as influenza and chickenpox

Answer 40

INFECTIOUS GASTROENTERITIS • Viral gastroenteritis : They infect enterocytes in the villous epithelium of the small bowel. The result is transudation of fluid and electrolytes into the intestinal lumen; sometimes, malabsorption of carbohydrates worsens symptoms by causing osmotic diarrhea. Diarrhea is watery. Inflammatory diarrhea (dysentery), with fecal white blood cells (WBCs) and red blood cells (RBCs) or gross blood, is uncommon. Four categories of viruses cause most gastroenteritis: norovirus and rotavirus cause the majority of viral gastroenteritis, followed by astrovirus and enteric adenovirus. * Bacterial gastroenteritis: The bacteria most commonly implicated are Salmonella, Campylobacter, Shigella, Escherichia coli (especially serotype O157:H7), Clostridium difficile. Bacterial gastroenteritis is less common than viral. Bacteria cause gastroenteritis by several mechanisms like producing enterotoxins that adhere to intestinal mucosa without invading. These toxins impair intestinal absorption and cause secretion of electrolytes and water by stimulating adenylate cyclase, resulting in watery diarrhea. Also, Mucosal invasion occurs with other bacteria (eg, Shigella , Salmonella , Campylobacter , C. difficile , some Escherichia coli subtypes) that invade the mucosa of the small bowel or colon and cause microscopic ulceration, bleeding, exudation of protein-rich fluid, and secretion of electrolytes and water. The invasive process and its results can occur whether or not the organism produces an enterotoxin. The resulting diarrhea contains WBCs and RBCs and sometimes gross blood. * Parasitic gastroenteritis: The parasites most commonly implicated are Giardia lamblia and Cryptosporidium. Certain intestinal parasites, notably Giardia intestinalis (G. lamblia), adhere to or invade the intestinal mucosa, causing nausea, vomiting, diarrhea, and general malaise. It is usually acquired via person-to-person transmission (often in day care centers) or from contaminated water. Cryptosporidium parvum causes watery diarrhea sometimes accompanied by abdominal cramps, nausea, and vomiting. In healthy people, the illness is self-limited, lasting about 2 weeks. In immunocompromised patients, illness may be severe and prolonged, causing substantial electrolyte and fluid loss. Cryptosporidium is usually acquired through contaminated water. NB: infection transmission is fecal-oral. NON-INFECTIOUS GASTROENTERITIS This may occur from food sensitivity, inflammation of your gastrointestinal tract, medicines, stress, or other causes not related to infection. Your symptoms will usually last from 1 to 3 days, but can last longer. Antibiotics are not effective, but simple home treatment will be helpful.

Answer 41

Physical examination findings of Gastroenteritis -most useful findings will come from vital signs and assessing dehydration status * Vital signs= hypotension or tachycardia or fever may be present * Skin=reduced skin turgor, skin discoloration * Head = sunken fontanelles( in babies) * Eyes = sunken eye balls and darkened eye circles * Mucous membranes= dry * Abdomen= mild diffuse tenderness DIFFERENTIAL DIAGNOSIS People with the following disorders may present with similar symptoms as gastroenteritis ⁃ Irritable bowel syndrome ⁃ Ulcerative Colitis ⁃ Inflammatory bowel disease ⁃ Appendicitis ⁃ Intussusception: condition in which part of the intestine telescopes into itself. Intussusception is a medical emergency involving obstruction of the intestine. It can be fatal if not treated. It occurs most often in children. ⁃ Increased intracranial pressure (vomiting) ⁃ Cholecystitis

Answer 42

``` Bacteria -vibrio cholerae -Escherichia coli -salmonella -shigella -campylobacter jejuni -etc •Virus -rotavirus -norovirus -astrovirus -enteric adenovirus -etc •Parasites -giardia lamblia -entamoeba hystolytica -cryptosporidium -etc •Chemicals -lead poisoning -etc •Drugs -antibiotics -etc ``` Mainly caused by microbes

Answer 43

True | True

Answer 44

Inflammatory bowel disease (IBD) is a relapsing and remitting condition characterized by chronic inflammation at various sites in the GI tract, which results in diarrhea and abdominal pain. There are two major types of IBD. They are: CROHN’S DISEASE (CD) Crohn's disease is a chronic transmural inflammatory disease that usually affects the distal ileum and colon but may occur in any part of the GI tract. Symptoms include diarrhea and abdominal pain. Abscesses, internal and external fistulas, and bowel obstruction may arise. ``` Ulcerative colitis (UC) is a chronic inflammatory and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea. UC is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. Long-term risk of colon cancer is high. ```

Answer 45

``` ENVIRONMENTAL •Diet •Smoking •Antibiotics •Latitude •Psychological stress ``` ``` GENETIC AND IMMUNOLOGAL •Early onset IBD •Turner’s syndrome •Glycogen storage disease •Immuno-dysregulation •Impaired epithelial barrier ``` ``` MICROBIOLOGICAL •Salmonella spp. •Shigella spp. •Campylobacter spp. •Clostridium difficile ```

Answer 46

The bowels are the intestines The large intestine comes before the smaller one Appendix is on the right side and from there you move up to the large intestine You can refer to the slide on IBD

Answer 47

Genetic factors mediate risk for IBD In an IBD patient the normal flora is likely perceived inappropriately as if it were a pathogen due to defective immune regulation Amplification of immune responses and release of inflammatory cytokines such as IL-1 and IL-2,TNF Mucous breakdown due to fibrinogenesis,collagen production,activation of tissue metalloproteinase and the production of other inflammatory mediators Inflammation In ulcerative colitis : there is inflammation of the colonic mucosa that usually involves the rectum and extends proximallynto involve all or part of the colon Mucosa becomes erythematous- edema occurs-hemorrhage-ulcers Pseudopolyps grow ,cryptitis(, Cryptitis is a term used in histopathology to describe inflammation of the intestinal crypts. The crypts are glands found in the lining of the intestines. They are sometimes called the crypts of Lieberkühn. Crypts of Lieberkuhn are pits between villi as pointed out by the green arrow in the figure below. The crypts of Lieberkuhn (often referred to simply as crypts) are similar to the gastric pits in the stomach. )toxic colitis or mégacôlon may occur- the bowel wall may become thin causing perforation Crohns: transmural spread of inflammation which leads to lymphedema Extensive inflammation may result in hypertrophy of the muscularis mucosae,fibrosis, and stricture formation (thickening bowel wall),which can lead to bowel obstruction Abscesses occur Fistulas often penetrate into the adjoining structures including other loops of bowel ,the bladder,psoas muscle,skin or anterior abdomen Cobblestones-lumen looks like a paved road

Answer 48

The major symptoms of UC are diarrhea, rectal bleeding, tenesmus (Tenesmus is the feeling that you need to pass stools, even though your bowels are already empty. ), passage of mucus, and crampy abdominal pain. •The severity of symptoms correlates with the extent of disease. •Some cases develop after an infection (e.g., amebiasis, bacillary dysentery) •For rectosigmoid (The rectosigmoid is that portion of the large intestine in which the narrow sigmoid colon undergoes a gradual enlargement before joining the rectum. )ulceration,the stool may be normal or hard and dry, but rectal discharges of mucus loaded with RBCs and WBCs. •If ulceration extends proximally, stools become looser and the patient may have > 10 bowel movements per day, often with severe cramps and distressing rectal tenesmus, without respite at night. The stools may be watery or contain mucus and frequently consist almost entirely of blood and pus. •Diarrhea is often nocturnal and/or postprandial.(occurring or done after a meal.) •Extraintestinal manifestations include peripheral arthritis, episcleritis(Episcleritis is an inflammatory condition affecting the episcleral tissue between the conjunctiva (the clear mucous membrane lining the inner eyelids and sclera) and the sclera (the white part of the eye) that occurs in the absence of an infection ),aphthous stomatitis, erythema nodosum, and pyoderma gangrenosum (a rare condition that causes large, painful sores (ulcers) to develop on your skin, most often on your legs. ) CD: •The most common initial manifestation is chronic diarrhea with abdominal pain, fever, anorexia, and weight loss. •The abdomen is tender, and a mass or fullness may be palpable. •Gross rectal bleeding is unusual except in isolated colonic disease. •Patients with severe abscess are likely to have marked tenderness, guarding, rebound, and a general toxic appearance. •Stenotic (narrowing or constriction of the diameter of a bodily passage or orifice )segments may cause bowel obstruction, with colicky pain(sharp, localized gastrointestinal or urinary pain that can arise abruptly, and tends to come and go in spasmlike waves ),distention, obstipation and vomiting. •Abscess formation (abdominal, pelvic or ischiorectal(These abscesses form when suppuration transverses the external anal sphincter into the ischiorectal space. The ischiorectal fossa is the space that exists between the internal surface of the perineal skin and the plane of the plate of the levator ani muscle. It is perceived as descending during inhalation and rising during exhalation.) •Fistulae (An abnormal connection between organs. )e.g. colovesical (bladder), colovaginal, perianal(the skin and the anus),enterocutaneous(an abnormal connection that develops between the intestinal tract or stomach and the skin. As a result, contents of the stomach or intestines leak through to the skin. Most ECFs occur after bowel surgery.),. An entero-vesical fistula may produce air bubbles in the urine (pneumaturia) •Perforation. •Beyond the gut: clubbing, skin, joint & eye problems

Answer 49

Diagnosis of IBD is based on clinical, laboratory, endoscopic and radiographic features. Laboratory tests include: ◂Full Blood Count (FBC) ◂Erythrocyte Sedimentation Rate (ESR) and C-reactive proteins - ↑(C-reactive protein is an annular pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. An ESR test measures how quickly red blood cells settle to the bottle of a test tube. Inflammation or infection can lead to extra proteins in the blood, which can make the red blood cells settle faster. When this happens, the ESR is higher.) ◂Serum ferritin - ↑ (indicates absorption problems) As ferritin is a positive acute phase reactant, a possible early inflammation in cases later developing IBD would result in increased ferritin concentrations. Despite this, low ferritin was associated with increased risk for IBD ◂Retro-screening ◂Hep B, C screening ◂Stool examination and cultures to rule out infectious cause of the diarrhea e.g., Clostridium difficile

Answer 50

``` Remember these ddx is for both of them: NSAIDS enteropathy IBS Intestinal tuberculosis Colon cancer ``` UC: ``` Amebic colitis Schistosomiasis CD Colon cancer Irritable bowel syndrome (IBS) Intestinal tuberculosis NSAIDS enteropathy Infectious colitis Colitis complicated by HIV Radiation colitis ``` CD: ``` Celiac disease Behcet’s disease UC Colon cancer Irritable bowel syndrome (IBS) Intestinal tuberculosis NSAIDS enteropathy Eosinophilic enteritis Microscopic colitis Diverticulitis ```

Answer 51

The aim of treatment is to: ◂Improve and maintain patient’s wellbeing ◂Eliminate symptoms and reduce intestinal inflammation ◂Prevent hospitalization, complications and surgery ◂Maintain good nutritional status These aims depend on the severity and location of the disease; side effects of medications; comorbidities among others. Amino salicylates – most effective in mild to moderate UC e.g. mesalazine, sulfasalazine etc. Aminosalicylates work by limiting the inflammation in the lining of the gastrointestinal tract. ◂Immune modifiers e.g. mercaptopurine, cyclosporine, methotrexate etc. ◂Antibiotics – most effective in CD e.g. metronidazole, ciprofloxacin ◂Corticosteroids e.g. prednisone, budesonide, hydrocortisone etc. ◂Biologics e.g. infliximab, adalimumab (anti-TNF agents) ◂Antidiarrheals e.g. loperamide etc. ◂Analgesics e.g. acetaminophen, codeine etc ◂Vitamin B12, vitamin D, calcium, multivitamin supplementation ◂Parenteral iron, for chronic iron deficiency anemia

Answer 52

Seen in UC and occasionally in CD Occasionally in UC and frequently in CD Seen in CD and rarely in UC Not seen in UC but frequent in CD and fistulas are seen in CD For More info on clinical interpretations from lab investigations check the slides given

Answer 53

1.Crohns disease Ulcerative Colitis (UC) Irritable Bowel Syndrome (IBS)(IBS is a disorder of the gastrointestinal (GI) tract. IBD is inflammation or destruction of the bowel wall, which can lead to sores and narrowing of the intestines. ) Celiac Disease. NSAIDS enteropathy Behçet’s disease Diverticulitis Colon Cancer. Vasculitis. Intestinal tuberculosis 2.Crohns disease 3. it is transmural, involving all layers of the bowel, not just the mucosa and the submucosa, which is characteristic of ulcerative colitis. Furthermore, Crohn disease is discontinuous, with skip areas interspersed between two or more involved areas. 4.colonoscopy or sigmoidoscopy FBC ESR and C reactive proteins(if increased confirms it) Serum ferritin if increased indicates absorption problems Stool c/s to rule out infectious cause of the diarrhea Retro screening 5. Corticosteroids e.g. prednisone, budesonide, hydrocortisone etc. ◂Biologics e.g. infliximab, adalimumab (anti-TNF agents) ◂Antidiarrheals e.g. loperamide etc. ◂Analgesics e.g. acetaminophen, codeine etc ◂Vitamin B12, vitamin D, calcium, multivitamin supplementation ◂Parenteral iron, for chronic iron deficiency anemia Antibiotics – most effective in CD e.g. metronidazole, ciprofloxacin

Answer 54

*DEFINITION OF PROCTITIS* Proctitis is inflammation of the lining of the rectum. The rectum is a muscular tube that is connect to the end of your colon. Stool passes through the rectum on its way out of the body. True

Answer 55

True It is continuous proximally with the sigmoid colon, and terminates into the anal canal. The rectum is approximately 15 cm (6 inches) long. The rectum is located within the pelvic cavity and is the most posterior of the pelvic viscera. True Male: anterior: rectovesical pouch,sigmoid colon,ileum,bladder,prostate,seminal vesicles Female:anterior:rectouterine pouch,sigmoid colon,ileum,vagina,cervix Both:posterior: Saccrum and coccyx,piriformis,coccygeus,levator ani,sacral plexus Function The rectum’s job is to receive stool from the colon, let you know that there is stool to be evacuated and to hold the stool until evacuation happens.

Answer 56

Proctitis may happen secondary to ulcerative colitis (UC), Chronic Radioation proctitis(Radiation proctitis is inflammation of the rectum that occurs as a result of damage to the rectum sustained from pelvic radiation given to treat a cancer such as prostate or cervical cancer. ) , Proctopathy (CRP)-Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. or Diversion Proctitis (DP)-Diversion colitis or diversion proctitis is a nonspecific inflammatory disorder that occurs in segments of the colon and rectum that are diverted from the fecal stream by surgery (eg, creation of a loop colostomy/ileostomy or an end colostomy/ileostomy with closure of the distal colon segment - Infectious causes include Clostridium difficile Enteric infections: (Campylobacter, Shigella, Escherichia coli, Salmonella and amebiasis) STI’s: (Gonorrhea, Chlamydia, Syphilis, Human Simplex Virus-"HSV", Lymphogranuloma venereum-"LGV", chancroid, Cytomegalovirus-"CMV", Human Papillomavirus-"HPV") ``` - Other causes include Ischemia Vasculitis Toxins as hydrogen peroxide enemas Medication side effect like antibiotics. ```

Answer 57

in women and homosexual men who practice anal-receptive intercourse,predominantly in young adults Moreover, patients with inflammatory bowel diseases are at higher risk of developing proctitis Incidence is more in males than females. Probably due to the rise of men sleeping with men. True

Answer 58

*PATHOLOGY BEHIND PROCTITIS* The main pathology behind proctitis is simply inflammation. All the causes of inflammation can be applied here. Inflammation is the response of vascularized living tissue to injury. It may be evoked by microbial infections, physical agents (notably radiation and trauma), chemicals, necrotic tissue, or immune reactions (for example in Inflammatory bowel diseases). Proctitis is associated with many conditions and for that reason, the underlying cause can used to derive the type of proctitis. For example, proctitis as a result of antibiotic may be said as antibiotic-induced proctitis, same for gonorrheal proctitis, herpetic proctitis, radiation proctitis, ulcerative proctitis, diversion proctitis and so on.

Answer 59

*Ulcerative proctitis* Ulcerative proctitis is simply ulcerative colitis that is isolated at the rectum. I hope we are well informed about what ulcerative colitis is. If not, kindly revisit yesterday’s presentation on Inflammatory Bowel disease. *Radiation proctitis* Occurs secondary to ischemic and fibrotic changes due to radiation therapy. Radiation injury occurs with doses 8 Gy (Gray (Gy) is the unit used to measure the total amount of radiation that the patient is exposed to. )or higher causing damage to intestinal cell DNA with helical breaks and inability to replicated and undergo normal cellular repair. *Diversion proctitis*: Proximal fecal or Bowel diversion surgery allows stool to safely leave the body when—because of disease or injury—the large intestine is removed or needs time to heal. Proximal fecal diversion causes increased nitrate-reducing bacteria and decreased obligate anaerobes resulting in short-chain fatty acids deficiency. Diversion colitis may also be due to a reduction in nutrients delivered to the cells that live in the defunctioned colon after fecal matter has stopped passing through. Proctitis due to STI’s The aforementioned sexually transmitted microorganisms can cause proctitis. STI’s (Gonorrhea, Chlamydia, Syphilis, Herpes Simplex Virus - HSV, Lymphogranuloma venereum-LGV, chancroid, CMV-Cytomegalovirus, HPV-Human Papillomavirus)

Answer 60

*SIGNS AND SYMPTOMS OF PROCTITIS* Inflammation of the rectal lining results in these *general symptoms* seen in proctitis. - Feeling of rectal fullness - Anal and rectal pain - Diarrhea, usually frequent, small amounts - Frequent or continuous urge to have a bowel movement (tenesmus) - Pain in the lower left abdomen - Passing mucus through the rectum - Rectal bleeding True KEY TERM: Rectal Tenesmus – a clinical symptom, where there is a feeling of constaltly needing to pass stools, despite an empty colon. When the word “tenesmus” is used by itself, it usually means rectal tenesmus. That said, there is another type relating to the urinary bladder called "vesical tenesmus"

Answer 61

*Other likely symptoms* Proctitis usually runs a mild, intermittent course over many years. Occasionally there is neurological involvement with urinary bladder dysfunction, weakness and burning of the lower limbs (parasthesias) and pain in the thighs. Men may have difficulty maintaining penile erections This is because the rectal area is closely related to the above structures... as we can see from our structure highlight. *PHYSICAL EXAMINATION FINDINGS* When perform an examination such as proctosigmoidoscopy or proctoscopy it will reveal the following about the rectal lining: - Pallor or erythema - Loss of usual vascularity of mucosa - Prominent telangiectasis - Friability - Bleeding - Ulcerations - Edema - Scattered areas of scarring - Vesicles/pustules - Strictures Some of these examination findings are key to certain types of proctitis. For instance, individuals with ulcerative proctitis show ulcers in the rectum. Ulcerations are usually accompanied by rectal bleeding, straining of rectal muscles (tenesmus) and an anal discharge of bloody mucus.

Answer 62

*INVESTIGATIONS* Diagnosis of proctitis is made when proctosigmoidoscopy (internal examination of the lower large bowel or colon reveals inflammation of the mucus lining of the rectum with a clearly demarcated upper border above which the lining is normal. The remainder of the colon and small intestine is found to be normal. This finding is supported with some lab investigations. LABORATORY INVESTIGATIONS FBC: performed to evaluate leukocytosis, if an infections etiology or severity of anemia due to blood loss C-reactive protein level: It is elevated in patients with extensive pancolitis (Pancolitis is an inflammation of the entire colon. The most common cause is ulcerative colitis (UC). Pancolitis can also be caused by infections like C. difficile, or can be associated with inflammatory disorders like rheumatoid arthritis (RA) ) but is frequently normal in patients with only distal disease (I.e. proctitis) Cultures of rectal swab help diagnose gonorrhea or chlamydia Cultures of vesicular fluid (Vesicles are small fluid-filled sacs or blisters that can appear on your skin. The fluid inside these sacs may be clear, white, yellow, or mixed with blood. Vesicles are fluid-filled lesions less than 5 mm (1/2 cm). If the fluid-filled lesion is greater than 0.5 mm, it's called a bulla. ) or cytologic scrapings aid in the diagnosis of HSV Serum Veneral Disease Research Laboratory (VDRL) test and dark field examination of scraping from the base of the chancre reveals spirochetes and confirms the diagnosis of syphilis Stool specimen for C. difficile toxin

Answer 63

*Treatment/Management* Aim The goal of proctitis treatment are to reduce inflammation, control pain, and treat the underlying cause. Specific treatments depend on the cause of proctitis. Managing underlying conditions helps to relieve symptoms.

Answer 64

*NON-PHARMACOLOGICAL* Aim for providing comfort during the examination. Lifestyle adjustments to relieve proctitis: - Take in diet that may reduce proctitis pain. Avoid spicy, acidic, or fatty foods during bouts of diarrhea. - Rehydrate: Drink plenty of fluids, but avoid drinking caffeinated sodas, coffees, and teas. Caffeine, however, can irritate the digestive system. Drinking prevents dehydration from frequent loose stools and eases the passage of stool. *PHARMACOLOGICAL* Drug therapy consists of antibiotics, antivirals, corticosteroids and GI agents. *ANTIBIOTICS* These agents are active against most microbes that cause proctitis. Microbes such as anaerobic bacteria C. difficle, N.gonorrhoeae, mycoplasma, chlamydia, and rickettsia species. Examples include: Metronidazole, Vancomycin, Ciprofloxacin, Ceftriaxone, Doxycycline, Penicilin G, Tetracycline *RECTAL ANTI-INFLAMMATORY AGENTS* These agents decrease inflammation associated with proctitis. Examples include: sulfasalazine and mesalamine *ANTIVIRAL* These agents are used for the treatment of viral or Herpes-related proctitis. For example, acyclovir *CORTICOSTEROIDS* These agents have anti-inflammatory properties. Dexamethasone, prednisolone, prednisone

Answer 65

*COMPLICATIONS* Complications of proctitis may include the following Chronic ulcerative colitis Fistula formation Abscess Treatment failure Perforation Anemia Rectal prolapse

Answer 66

1. I’ll enquire about his sexual history, especially if he had experience of engaging homosexual practice. 2.rectal prolapse Anusitis POSSIBLE ANSWERS All differentials diagnosis relating to proctitis caused by sexually transmitted microbes. (Gonorrhea, Chlamydia, Syphilis, HSV, Lymphogranuloma venereum, chancroid, CMV, HPV). Therefore, we could have gonorrheal proctitic, syphilitic proctitis 3. POSSIBLE ANSWERS Just like mentioned earlier, we could investigate the following. FBC: performed to evaluate leukocytosis, if an infections etiology or severity of anemia due to blood loss Cultures of rectal swab help diagnose gonorrhea or chlamydia Cultures of vesicular fluid or cytologic scrapings aid in the diagnosis of HSV Serum Veneral Disease Research Laboratory (VDRL) test and dark field examination of scraping from the base of the chancre reveals spirochetes and confirms the diagnosis of syphilis Stool specimen (stool R/E) for C. difficile toxin Besides confirming the presence of an infection... he reported with blood rectal discharge so having a good look at his HB is important. 4. POSSIBLE ANSWERS Antibiotics, antiviral, anti-inflammatory agents to treat bacterial infections, viral infections and inflammations respectively. Based on laboratory investigations confirmation of the underlying infection. 5. It's better for the partner too should be screened for any STI and treated if any. They should use protection Seek counseling on homosexuality

Answer 67

*_Definition_* 📍 *_Pruritis Ani*_ is also called _*anal itch_ ,* is an irritating, itching sensation around the *anus* ( the opening through which stool passes out of the body). *What are the types of* *pruritus ani?* There are two main types of pruritus ani, namely: *_primary*_ and _*secondary._* 📍 *_Primary ( idiopathic (relating to or denoting any disease or condition which arises spontaneously or for which the cause is unknown.)_* *_pruritus ani_* :This condition has no identifiable underlying cause. This is the most common type of pruritus ani. 📍 *_Secondary pruritus*_ _*ani_* :This condition may be due to many different underlying causes. They may include infections, contact dermatitis or other dermatological conditions, systemic diseases, and other factors.

Answer 68

It is estimated that 1-5% of the population is affected. Pruritus ani is about 4 times more likely to occur in men than in women. Primary or idiopathic pruritus ani accounts for the majority (about 50-90%) of cases.Pruritis ani most commonly affects adults, affecting from 1% to 5% of people in the general population. The condition is most common in people age 40s to 60s. There are many causes of pruritis ani, and an accurate diagnosis is important in order to treat the specific cause.

Answer 69

*_Pathophysiology of*_ _*PRURITIS ANI_* 📍The pathophysiology of pruritus ani has not been elucidated yet. It has been hypothesized that when sensory nerves in the perianal area are stimulated, skin irritation and subsequent pruritis is induced; consequently, the skin is excessively scratched, which causes skin injury.

Answer 70

*_Etiology_* *_What causes pruritus ani (anal itching)?_* 📍 *_Pruritis ani_* is usually not caused by poor hygiene. Rather, the overuse of soaps and other topical products to clean the anal region or vigorous scrubbing with a washcloth or rough toilet paper can cause irritation. 📍 *_A hypersensitivity_* reaction may occur if perfumed powders, lotions, creams, ointments, or other products are applied in the anal region. 📍 *_Excess perspiration_* or moisture may become trapped in the anal area if constricting or tight-fitting underwear is worn. Some foods and beverages, such as carbonated drinks, caffeinated beverages (coffee, tea, colas) and spicy or acidic foods (tomatoes, citrus fruits) have been linked to the condition. Having frequent bowel movements (diarrhea) or infrequent ones (constipation) may also play a role. *_Other causes of pruritus ani include:_* 📍 *_Infections_* : Some types of bacteria, fungi (yeast), or parasites can cause itching. Staphylococcus aureus or Streptococcus pyogenes (types of bacteria), Candida albicans (a yeast), pinworms (mainly inchildren), and Sarcoptes scabiei (scabies mites) are some organisms that result in itching and irritation. 📍 *_Dermatological*_ _*conditions:_* Psoriasis, contact dermatitis (inflammation due to allergens or other irritants), or atopic dermatitis (a chronic condition found in patients with allergies) may cause a rash in the perianal region. 📍 *_Inflammatory bowel disease (Crohn’s disease)_* 📍 *_Psychological factors_* such as stress or anxiety. 📍 *_Systemic diseases:_* These include diabetes mellitus, leukemia, lymphoma, thyroid disease, renal disease, and liver disorders (obstructive jaundice). 📍 *_Colorectal and anal*_ _*disorders:_* Rectal prolapse, internal or external hemorrhoids, anal fissures (ulcers), or fistulas (abnormal tube-like passages) are associated with pruritus ani. Residual amounts of feces may be difficult to remove with large external hemorrhoids. Internal hemorrhoids may cause bleeding, fecal soiling, or drainage. 📍 *_Systemic or topical*_ _*medications:_* Use of drugs such as quinine, colchicine, and mineral oil has been linked to pruritus ani. 📍 *_Fecal or urinary*_ _*incontinence_* : Children and the elderly are more likely to experience incontinence of the bowel or bladder.

Answer 71

*_Other causes( Predisposing factors) of pruritus ani include;_* 📍Chronic anorectal disease, 📍HIV-related infections, 📍Diabetes-remember diabetes can cause skin infections and illnesses and these can cause itching 📍Cancer 📍Illnesses that produce *_hyperbilirubinemia._*-It is thought that bile salts that deposit into the skin are responsible for the pruritus (itching)

Answer 72

*_Symptoms_* Anal itching may be associated with; 📍Redness 📍Burning 📍Soreness. The itching and irritation may be temporary or more persistent, depending on the cause. *_Signs;_* Anal itching is severe or persistent if 📍You have anal bleeding or stool leakage

Answer 73

*_DIAGNOSIS AND TESTS_* *_How is pruritus ani (anal itching) diagnosed?_* 📍The doctor will obtain a full medical history and perform a physical examination to identify possible underlying causes, such as dermatological conditions and other illnesses. He or she will visually inspect the area to look for changes in *skin color* or *texture,* *rashes,* or *lesions* . 📍The doctor will ask about any medications that you take and the type and frequency of bowel movements. 📍The doctor may obtain skin specimens and perform tests to screen for bacterial or other infections. 📍Parents of children who may have pinworms can place a small piece of surgical tape, or scotch tape, near the child’s anus before bedtime. *The worms are* *more likely to* *emerge at night* . *In the morning, when the child* *awakens, the tape* *can be removed to* *see if the worms or* *their eggs are present.* *_This is called the scotch*_ _*tape test._*

Answer 74

*_Physical Examination findings_* 📍Physical examination focuses on the anal region, particularly looking for perianal skin changes, signs of fecal staining or soilage (suggesting inadequate hygiene), and hemorrhoids. 📍External inspection should also note the integrity of the perianal skin, whether it appears dull or thickened (suggesting chronicity), and the presence of any cutaneous lesions, fistulas, excoriations(the act of abrading or wearing off the skin chafing and excoriation of the skin. 2 : a raw irritated lesion (as of the skin or a mucosal surface) )or signs of local infection. Sphincter tone is assessed by having the patient contract the sphincter during digital rectal examination. The patient should then be asked to bear down as if for a bowel movement, which may show prolapsing internal hemorrhoids. *_Anoscopy_* may be necessary to further evaluate the anorectum for hemorrhoids.

Answer 75

The following screening laboratory tests are recommended: CBC count with differential: People with iron deficiency of any kind may develop pruritus, which is the medical term for itchy skin This test assists in uncovering polycythemia vera, in which the hemoglobin level, hematocrit value, WBC count (including absolute neutrophil count; see the Absolute Neutrophil Count calculator), and platelet count are elevated. Abnormalities are also seen in persons with hematologic malignancies. Patients with iron deficiency may have microcytosis and low hemoglobin levels. However, those with pruritus and iron deficiency may not be anemic; tests of and serum iron, ferritin, and total iron-binding capacity may be ordered to confirm or exclude the diagnosis. Serum creatinine and blood urea nitrogen values: Persons with chronic renal failure have elevated levels. When the kidneys fail, the build-up of waste in your blood can cause severe itching. Serum alkaline phosphatase and bilirubin, direct and indirect: Elevated levels may suggest cholestasis. If elevated, antimitochondrial antibody and serum anti–hepatitis C tests may be ordered to confirm primary biliary cirrhosis and hepatitis C, respectively, if these are suspected. Other tests may be needed to confirm other causes of cholestasis. A positive antimitochondrial antibody finding has 98% specificity for primary biliary cirrhosis. Bile Salts- Those with liver disease may have higher levels of bile salt building up under the skin, which may cause itching. Normally, bilirubin is made in the liver and removed from the body in digestive fluid called bile, but people with liver or gallbladder problems may end up with too much bilirubin that accumulates in their blood and skin. One side effect of jaundice is intense and uncontrollable itching. Cholestasis is Any condition in which the flow of bile from the liver stops or slows. Thyrotropin and thyroxine: The results assist in ruling out hypothyroidism and hyperthyroidism. Fasting glucose value, if prompted by signs or symptoms Stool for occult blood in patients aged 40 years or older: A positive result suggests possible malignancy in the GI tract. Although persistent rectal itching (pruritus ani) can be a sign of rectal cancer, it is not the most common cause. HIV antibody test, if risk factors are present Skin biopsy for routine pathology and immunofluorescence to exclude subacute occult autoimmune conditions such as pemphigoid and dermatitis herpetiformis

Answer 76

*_MANAGEMENT /TREATMENT._* *_How is pruritus ani (anal itching) treated?*_ _*(Pharmacological)_* 📍 *_Usually, treatment_* focuses on establishing and maintaining a routine for proper anal hygiene. If a secondary or underlying cause is found, the treatment will depend on the specific condition. 📍 *_Topical medications:_* Topical steroids, such as creams or ointments containing 1% hydrocortisone, may help to relieve itching and irritation. The cream or ointment may be applied two or three times to the affected area each day. 📍 *_Topical capsaicin_* has been studied as an alternative to steroids for patients with chronic pruritus ani. 📍 *_Oral medications:_* Antibiotic or antifungal medications may be prescribed if an infection is present. 📍 *_Methylene blue injection_* (anal tattooing): This technique may be used to treat more advanced cases that do not respond to topical medications. Methylene blue (a dye) is injected under the skin in the perianal region thought that the methylene blue relieves pain and itching by deadening the nerve ending dye is injected. Again..depending depending on the extent of itching one can add an anti-histamine agent to it...like Cetirizine to bring down the itching *_What are some tips for self-care?*_ _*(Non- pharmacological )_* 📍 *_Resist the urge to scratch._* The itching might seem worse at night, so people might unconsciously scratch the anal area with their fingernails during sleep. 📍 *_Wear clean, soft_* cotton gloves at bedtime to prevent irritation and infection. 📍 *_Keep the perianal area clean and dry._* Use clear water instead of soap or moistened toilet paper to clean the perianal region after a bowel movement. 📍 *_A shower head be_* used to gently clean the perianal area. Use a hair dryer on a low setting to dry the area. If using toilet paper or a towel, gently pat or blot the area until it is dry. 📍 *_Apply a small amount_* of cornstarch or piece of cotton to the area to keep it dry during the day. A small cotton gauze pad can be used instead. 📍 *_Do not use soap_* when cleansing the anal area or scrub vigorously with toilet paper or a washcloth. 📍 *_Avoid using perfumed_* creams, lotions, bubble baths, powders, or other products that may cause irritation to the area. 📍 *_Eat foods high in fiber._* A healthy diet can help prevent diarrhea or constipation and ensure regular bowel movements. 📍 *_Avoid any foods_* that might go promote itching, such spicy or acidic foods or caffeinated beverages. 📍 *_Avoid wearing tig_* constricting underwear. Cotton underwear can helpV to absorb moisture better than synthetic fabrics. 📍 *_Make sure underwear_* Can fits properly and change it frequently. Wash clothing with fragrance-free detergents. 📍 *_Use topical medications as directed._* Apply the cream or ointment sparingly and discontinue use if the itching does not subside or gets worse. Common topical agent used is Anusol gel You can also encourage sit baths...where you put warm (not hot) water in bucket and add salt to it..then patient sits on it twice daily for about a week. patient can do savlon baths as well...adding savlon to the water for bathing savlon alone to the water...patient adds soap to it for bathing

Answer 77

*_Complications_* 📍Rectal cancer (11 percent), 📍Anal cancer (6 percent), 📍Adenomatous polyps (4 percent), 📍Colon cancer (2 percent). 📍Hemorrhoids (20 percent) and anal fissures (12 percent) were the most common pruritus-related anorectal diseases.

Answer 78

*_Differential diagnosis_* 📍Dermatological conditions: 📍Psoriasis, : skin disease marked by red, itchy, scaly patches. 📍contact dermatitis (inflammation due to allergens or other irritants), or atopic dermatitis (a chronic condition found in patients with allergies) may cause a rash in the perianal region. 📍Inflammatory bowel disease (Crohn's disease) 📍Psychological factors such as stress or anxiety. *_Conclusion_* *_What can cause dryness and irritation in the anal area?_* The anal area may become dry and irritated due to the use of harsh soaps, sanitary wipes, or rough toilet paper to clean the area after a bowel movement. A hypersensitivity reaction may occur if perfumed powders, lotions, creams, ointments, or other products are applied in the anal region. Excess perspiration or small amounts of fecal matter can cause irritation and itching.

Answer 79

Diarrhoea is the passage of loose, liquid or watery stool. ➢In many regions Diarrhoea is defined as passage of three or more loose or watery stools in 24 hour period. ➢However it is the recent change in consistency and character of stool than the number of stools that is more important. ➢In most cases the mother knows what is abnormal stool for her child. ➢It is a killer disease in children. ➢One in four deaths in children under the age of 5yrs. is due to diarrhoea.

Answer 80

Infectious Disease Agents Causing Diarrhoea. BACTERIA 1.Escherichia coli It produces heat labile (LT) and heat stable (ST) entertoxins. E.COLI - COULD BE ➢Enteropathogenic- Causes infantile diarrhoea. ➢Entero toxigenic – Causes travellers diarrhoea. ➢Enteroinvasive- Dysentery type of diarrhoea. ➢Enteroadherent ➢Enterohaemorrhagic VIBRIO CHOLERAE- produces enterotoxins ➢Vibrio para haemolyticus- Invasive. ➢Non-Cholerae vibrios Infectious Disease Agents SHIGELLAE–Invasive, produce bloody diarrhoea or Dysentery. ➢CAMPYLOBACTER JEJUNI – invasive. ➢SALMONELLAE OTHER THAN S.TYPHI- invasive. ➢STAPHYLOCOCCUS AUREUS- entrotoxins ➢CLOSTRIDIUM PERFRINGENS- enterotoxins. 3. VIRUSES ➢Rotavirus – invasive. 4. PARASITES ➢E. histolytica- invasive. ➢Giardia Lamblia- non invasive.(Noninvasive diseases usually do not spread to or damage other organs and tissues. Noninvasive procedures do not involve tools that break the skin or physically enter the body.)

Answer 81

Most of the diarrheal agents are transmitted by the fecal-oral route •Some viruses (such as rotavirus) can be transmitted through air •Nosocommial transmission is possible •Shigella (the bacteria causing dysentery) is mainly transmitted person-to-person

Answer 82

Wet seasons Wet season Dry season

Answer 83

Cholera: 2 years and above, uncommon in very young infants •Shigellosis: more common in young children aged below 5 years •Rotavirus diarrhea: more common in young infants and children aged 1-2 years •E. coli diarrhea: can occur at any age •Amebiasis: more common among adults

Answer 84

ACUTE WATERY DIARRHOEA. ➢DYSENTRY (BLOOD IN STOOLS). ➢PERSISTENT DIARRHOEA.

Answer 85

1.ASSESSMENT OF DEHYDRATION DOES THE CHILD HAVE SIGNS OF DEHYDRATION? IS DEHYDRATION MILD OR SEVERE? Look at : t General condition-if it’s mild diarrhea the patient will be restless or irritable if it’s severe patient will be lethargic ,floppy or unconscious Eyes-if mild,they’ll be sunken.if severe, they’ll be deeply sunken and dry Tears on cry:absent in mild and severe dehydration Mouth and tongue:dry if mild and very dry if severe Thirst:thirsty and drinks eagerly if mild and thirsty but drinks poorly or is unable to drink if severe Assess also for skin pinch:If mild, Goes back slowly, takes 1 to 2 seconds If severe, Goes back very slowly, takes more than 2 seconds After assessing for these you decide if there’s some mild dehydration or there’s severe dehydration If mild : treat with Plan B With WHO recommended ORS solution to correct some dehydration. If severe: Plan C With IV infusion urgently to correct severe dehydration and to prevent death

Answer 86

LABORATORY INVESTIGATIONS ➢FEEDING DURING DIARRHOEA ➢RATIONAL USE OF DRUGS ➢FLUID THERAPY Stool microscopy •Dark field microscopy of stool for cholera •Stool cultures •ELISA for rotavirus •Immunoassays, bioassays or DNA probe tests to identify E. coli strains

Answer 87

APPROPRIATE FLUID THERAPY - ORS ➢OTHER FLUIDS -SSS (Sugar salt solution) The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid absorption in the small intestine via a cyclic AMP-independent process

Answer 88

Using this criteria THREE CATEGORIES OF CASES. ➢Cases with No Signs of dehydration- Plan-A. ➢Cases with some signs of dehydration- Plan-B ➢Cases with severe dehydration-Plan -C

Answer 89

Treat for Diarrhoea at Home Counsel the mother on the 4 Rules of Home Treatment: •Give Extra Fluid •Give Zinc Supplements (age 2 months up to 5 years) •Continue Feeding •When to Return(For a follow up visit at the hospital) 1. GIVE EXTRA FLUID (as much as the child will take) TELL THE MOTHER: •If the child is exclusively breastfed : Breastfeed frequently and for longer at each feed. If passing frequent watery stools: - For less than 6 months age give ORS and clean water in addition to breast milk - If 6 months or older give one or more of the home fluids in addition to breast milk. PLAN A ctd. •If the child is not exclusively breastfed: Give one or more of the following homefluids;ORSsolution, yoghurtdrink,milk,lemondrink,riceorpulses- based drink, vegetable soup, green coconut water or plain clean water. •It is especially important to give ORS at home when: - the child has been treated with Plan B or Plan C during this visit. - the child cannot return to a clinic if the diarrhoea gets worse. • TEACH THE MOTHER HOW TO MIX AND GIVE ORS. GIVE THE MOTHER 2 PACKETS OF ORS TO USE AT HOME. •SHOW THE MOTHER HOW MUCH FLUID TO GIVE IN ADDITION TO THE USUAL FLUID INTAKE: <2 months: 5 spoons after each loose stool. 2 months up to 2 years:1/4 cup to 1/2 cup after each loose stool. 2 years or more:1/2 cup to 1 cup after each loose stool. PLAN A ctd. Tell the mother to: -Give frequent small sips from a cup. -If the child he child vomits, wait 10 minutes. Then continue, but more slowly. -Continue giving extra fluid until the diarrhoea stops . 2. GIVE ZINC SUPPLEMENTS FOR 14 DAYS 3. CONTINUE FEEDING 4. WHEN TO RETURN : -Child becomes sicker -Not able to drink or breastfeed -Blood in stool  -Drinking poorly -Develops a fever

Answer 90

Six teaspoons of sugar plus half teaspoon of salt plus two 50cl of water 50centilitre is equal to 0.5litres

Answer 91

PLAN B:Treat For Some Dehydration with ORS • SHOW THE MOTHER HOW TO GIVE ORS SOLUTION. -Give frequent small sips from a cup. -If the child vomits, wait for 10 minutes. Then continue, but more slowly. -Continue breastfeeding whenever the child wants. •AFTER 4 HOURS: -Reassess the child and classify the child for dehydration. -Select the appropriate plan to continue treatment. -Begin feeding the child . •IF THE MOTHER MUST LEAVE BEFORE COMPLETING TREATMENT: -Show her how to prepare ORS solution at home. -Show her how much ORS to give to finish 4-hour treatment at home. 

Answer 92

PLAN C: Severe Dehydration •Severely dehydrated children and young infants need to have water and salts quickly replaced. Plan C requires rapid hydration using IV fluids or a nasogastric (NG) tube. It is important to note that rehydration therapy using IV fluids or using a nasogastric (NG) tube is recommended only for children who have SEVERE DEHYDRATION. NOTE: Plan C should only be provided in the health facility or the ORS/ORT centers and administered by medical officer to manage severely dehydrated children and young infants

Answer 93

``` Sanitation - Hand washing - Exclusive breast feeding - Clean food ➢Environmental sanitation ➢Elimination of Reservoirs ➢Breaking the channel of transmissions ``` ``` PREVENTION OF DIARRHOEA? ELIMINATION OF RESERVOIRS: ➢Prevention of dehydration ➢Correction of dehydration -Maintenance of hydration ➢Chemotherapy ➢Restoration of Nutritional Status. ➢Diarrhoea- Leads to malnutrition ➢Increase in Breast feeding frequency ➢Increase in diet. ``` ``` Other ways of preventing diarrhea Vitamin –A prophylaxis ➢Improved Nutrition ➢Immunization -Measles immunization ``` ROTA VIRUS VACCINE ➢Two live oral attenuated rotavirus vaccines were licensed in 2006. Now there are three. ➢Monovalent human rotavirus vaccine (Rotarix). ➢The pentavalent bovine- Human reassortant vaccine (Rota Teq) ➢They Provide 75-80% protection against rotavirus diarrhoea and 90-100% protection against rotavirus disease.

Answer 94

Low osmolarity ORS ➢Zinc (10mg Elemental Zinc for infants 2-6 month of age 20mg Zinc for children > 6 months for 14 days) ➢Feeding of energy dense foods in addition to Breast feeding ➢Hygiene ➢Antimicrobials for gross blood in stools or shigella + culture.

Answer 95

Helminths are worm-like parasites that survive by feeding on a living host to gain nourishment and protection, sometimes resulting in illness of the host. 1. Cestodes aka TAPEWORMS 2. Nematodes aka ROUNDWORMS 3. trematodes FLUKES Parasite is an organism that benefits from another organism by living in or on that organism. A host could be any organism that houses another organism (parasite)

Answer 96

True MIcroparasites and Macro parasites microparasites are the parasitic organisms that cannot be seen with the naked eyes because the are small macroparasite is the opposite why? because they can be seen with the naked eyes Helminths are macroparasites 1. Definitive host 2. intermediate host Definitive host is a host in whom a parasite reaches its adult form and or undergoes a sexual phase of development intermediate host is a host in whom a parasite passes from one or more phases of its sexual development

Answer 97

True | True

Answer 98

CESTODES( tape worms) ---- TAENIA SOLIUM(PORK TAPEWORM) , TAENIA SAGINATTA(CATTLE) ........these are flat worms with segmentted body. They have scolex and proglotids They have suckers present at the scolex 2. 2. Nematodes Most commonest is _Ascaris_ _Lumbricoides_ ``` Others include Necator species Trichuris trichura Strongyloides species Toxocara species ``` Most of the nematode species shades common lifecycle Most also diecious and hence produces without the male partners Each of their eggs are distinctive for laboratory investigation recognition purposes Pin worms are common in US 3. *Trematodes* also known as flukes We have Liver flukes Blood borne flukes Lung flukes The most commonest infection we have here in Africa especially *Zimbabwe* They are constantly infected by the *Schistosoma* species True Tissue nematodes Intestinal nematodes

Answer 99

Fecaoral route or ingestion Skin penetration Let me explain what u see The skin and the GI are the local defense The skin uses its epithelial cells as a boundary against infection but some parasitic worms by pass that and this will lead to failure So this means The skin serves as a defense but worms such as pin worms destroys this defense by penetrating it directly by ingesting it way through first by attachment And second is by burrowing Schistosoma larvae penetrate skin when one bathes in affected pool Filarial worms also breach the skin barrier not by themselves but through bites of mosquitoes (culex or anopheles?? So from this kind of entry there can be rashes on the skin as a result of the epidermal damage "Sorry I used the word epithelial cells it wrong skin is epidermal cells right" The second form of entry is the most commonest Which is the Ingestion? The GI becomes the defense but what specifically defence is used in the GIT It is the HCL of course but u see most of the eggs of these worms are encysted and this kind of egg shell if I may say, is resistant to acid After breaching what actually happens?? They are dissemenated to by this two ways Ypu must have notice that each organism has a preffered location in the body right Selection is based on 1) nutrient availability 2) least resistance for example But before all this Those that entered through the mouth always lodges in the intestine and they will 'excyst' meaning they shed off their protective cyst coating And metamorphosis into the larvae stage one. Note that larvae are named differently The larvae stage one is not that strong and hence look for ways to move out of the intestine and this is by burrowing through the intestine this will result in GI bleeding and inflammation that will cause excessive mucous and ions secretion if they are in the large intestine this normally leads to dysentry and diarrhoea and if in the small intestine will cause impaired nutrient absorption leading to malnutrition and co Those that are in the small intestine after penetrating the small intestine find their way to the blood stream and this leads to blood borne dissemination Flukes, taenia and Ascaris normally uses this blood circulation route And gradually they enter into portal circulation and some lodges in the liver, brain , muscles lungs and the spleen etc..... Some goes to the extent of lodging in the bladder example is schistosoma They cause further psychology after landing at any of the above mentioned organs and these leads to a some of the complications that may be witnessed. Tissue migrators such as Dracunculo medinesis that causes guinea worm infections, filarial worms such as W. Bancrofti and pin worm sometimes work their way to the nearest circulating vein or lymphatic vessel and they are carried in the extracelluar fluid of the blood to either the GIT or stays in the lymphatic vessels . Some migrate superficially example guinea worm and hence after the sore they create on the skin they can be seen.....but not always Why?? Filarial worm enters during its larvae stage Schistosoma also enters during their larvae stage and migrate to the urogenital system..... Hope it is well?? So far so good there are more details to this but will speak on the immune defenses against those that travels in the blood briefly When the larvae get access to blood note they mostly are bigger in size and are multicelluar This simple fact shouldnt be underestimated Because they are multicelluar they normally cannot be phagocytosed by macrophages hence cell mediated immune response is not possible to eliminate them ......they even feed on the blood and if the initial infective population is plenty they can collectively drink a cup of blood a day right 😁......its true and with this normally they will lead to granulomatous inflammation after acute inflammation fails (90% of the cases) Granulomatous inflammation occurs mosltybin tissues like those that finally settle in the lungs leading to eusinophilic pneumonia especially in ascariasis or liver leading to hepatitis or urogenital tract or bladder ( especially schistosoma is markedly concerned with this granulomatous inflammation which leads to dysuria and hematuria) The innate immunity u see there simply talks about the inflammation part of defense which I have spoken briefly about So what about the adaptive immunity This leads as to the topic of *antibody mediated immune responses* This Antibody mediated immube response is the one that actually deals with helminths And it is the one that provides certain clues u will use in diagnosis of most helminthiasis *Immunoglobin E* mediated response Let me explain this one briefly The first phase of this kind of defense is 1. Recignition of antigen or foreign body by dendritic cell Or FC receptors 2nd phase is after the body recognizes a foreign body Macrophages present to the T lymphocytes by secreting interleukin 4 , 5 , 4 to stimulate a specific type of T lymphocytes called the T helper cells subtype 2 Also known as TH2 cells Become activated and they in tend secretes interleukin 4 Interleukin 4 stimulates the production of IgE which then binds to mast cells and eusinophils that were recruited at the site where the antigen is present and they releases substances that breaks down this foreign substances.

Answer 100

``` Neurocysticercosis Cerebral edema Blindness Hepatitis Eusinophilic pneumonia Bladder carcinomas Cystitis Hepatitis Intestinal obstruction Ulcerative colitis Etc. ``` Signs and symptoms ``` Nausea Vomiting Low grade fever Diarrhoea Nonspecific abdominal pains ```

Answer 101

Treatments Pharmacologic part A 1.Anti-helminthes Heinrich Amankwah Bediako: Drugs used against helminths Benzimidazoles (albendazole, mebendazole) These agents act by inhibiting both helminth glucose uptake, causing depletion of glycogen stores, and fuma rate reductase. Albendazole is used for hookworm, ascariasis, threadworm, Strongyloides infection, trichinel losis, Taenia solium (cysticercosis) and hydatid disease. Mebendazole is used for hookworm, ascariasis, thread worm and whipworm. The drugs are administered orally. Absorption is relatively poor, but increased by a fatty meal. Significant adverse effects are uncommon. Bithionol Bithionol is used to treat fluke infections with Fasciola hepatica. It is well absorbed orally. Adverse effects are mild (e.g. nausea, vomiting, diarrhoea, rashes) but rela tively common (approximately 30% Diethylcarbamazine Diethylcarbamazine (DEC) is an oral agent used to treat filariasis and loiasis. Treatment of filariasis is often fol lowed by fever, headache, nausea, vomiting, arthralgia and prostration. This is caused by the host response to dying microfilariae, rather than the drug, and may be reduced by pre-treatment with corticosteroids. Ivermectin Ivermectin binds to helminth nerve and muscle cell ion channels, causing increased membrane permeabil ity. It is an oral agent, used in Strongyloides infection, filariasis and onchocerciasis. Significant side-effects are uncommon. Niclosamide Niclosamide inhibits oxidative phosphorylation, causing paralysis of helminths. It is an oral agent, used in Taenia saginata and intestinal T. solium infection. Systemic absorption is minimal and it has few significant side-effects Piperazine Piperazine inhibits neurotransmitter function, causing helminth muscle paralysis. It is an oral agent, used in ascariasis and threadworm (Enterobius vermicularis) infection. Significant adverse effects are uncommon, but include neuropsychological reactions such as vertigo, confusion and convulsions. Praziquantel Praziquantel increases membrane permeability to Ca++ , causing violent contraction of worm muscle. It is the drug of choice for schistosomiasis, and is also used in T. saginata, T. solium (cysticercosis) and fluke infections (Clonorchis, Paragonimus) and in echinococcosis. It is administered orally and is well absorbed. Adverse effects are usually mild and transient, and include nausea and abdominal pain Pyrantel pamoate This agent causes spastic paralysis of helminth muscle through a suxamethonium-like action. It is used orally in ascariasis and threadworm infection. Systemic absorp tion is poor and adverse effect is uncommon Thiabendazole Thiabendazole inhibits fumarate reductase, which is required for energy production in helminths. It is used orally in Strongyloides infection and topically to treat cutaneous larva migrans. Significant adverse effects are uncommon 2.anagelsics Use WHO ladder for pain treatment *Non pharmacologic part B* Oral Hydration in servere diarrhoea

Answer 102

Wash often Avoid soil contaminated with poop Don’t est raw or undercooked meat Treat pets with worms

Answer 103

✅Pancreatitis happens when the pancreas becomes inflamed. It's often painful. There are two forms of pancreatitis Thay are; Acute pancreatitis and Chronic pancreatitis The pancreas is important for digestion of food and managing the blood sugar for energy after digestion ✅Aetiology ⭕Alcohol abuse ⭕Gall stones ⭕Hypercalcemia ⭕Hypertriglyceridemia ⭕Drugs (such as Pentamide,HCTZ) ⭕Infections (such as Mumps, coxsackie virus etc) ⭕Pancreatic ductus division ⭕Trauma ⭕Inherited autosomal dormant disorders And many more Gallstones

Answer 104

✅Pathophysiology ✴The pathophysiology of acute pancreatitis is characterised by a loss if intracellular and extracellular compartmentation by an obstruction of pancreatic secretary transport (uct. If the duct is blocked or injured, these enzymes can leak out and cause pain and swelling and inflammation. It can be a gallstone or a pancreas stone blocking it) and by activation of pancreatic enzymes.(Pancreatitis occurs when digestive enzymes become activated while still in the pancreas, irritating the cells of your pancreas and causing inflammation. ) ✴Once the disease has been initiated, the appearance of interstitial oedema and inflammatory infiltration are the basic features of acute pancreatitis For the chronic pancreatitis, we may see more deteriorating features of the pancreas as compared to the acute Also, the pancreas may become less functional as compared to that of the chronic

Answer 105

✅Complications ⭕Kidney failure: Acute pancreatitis can cause kidney failure which can be treated with dialysis if the kidney failure is severe and persistent. ⭕Breathing problems ⭕Infections ⭕Pseudocyst(pathological collection of fluid in an organ or in the body. It looks like a cyst but differs from a cyst because it lacks a clearly defined epithelial layer, hence it name pseudo-cyst) ⭕Malnutrition ⭕Diabetes ⭕Pancreatic cancer

Answer 106

✅Signs and symptoms ⭕Epigastric pain with radiation to the back ⭕Low grade fever ⭕Nausea and vomiting ⭕Tachycardia-You know that pancreatitis can cause failure of the kidneys. This will cause abnormal functioning of the kidneys They will not be able to regulate water and electrolyte in our body, hence will cause tachycardia. since the kidney isn't able to perform...there's pressure on the heart . ⭕Orthostasis-Orthostasis is a form of low blood pressure that happens when standing up from lying down or sitting ⭕Discolouration around umbilicus (Cullen's sign) or Flanks (Grey Turner's sign) suggest hemoperitonemia or retroperitoneal hemorrhage

Answer 107

✅Laboratory Investigations ✴Acute pancreatitis is confirmed by medical history, physical examination and typically blood test ( amylase or lipase ). ✴NB: Blood amylase or lipase are typically elevated 3 times the normal level during acute pancreatitis. ✴In some cases,when the blood tests are not elevated and the diagnosis is still in question, abdominal imaging might be performed ✴The imaging performed may include; ⭕Computerised Tomography ⭕Magnetic Resonance ⭕Cholangiopancreatography ⭕Transabdominal Ultrasound

Answer 108

✅Treatment ⭕Early eating ⭕Pain medications ⭕Intravenous fluids ⭕Medication changes ⭕Procedure to remove duct obstruction ⭕Gall bladder surgery: untreated, gallstone pancreatitis can cause serious complications. Gallstone pancreatitis will usually need to be treated in the hospital. You may need surgery or an endoscopic procedure (ERCP) to remove the gallstone. You may need to have your gallbladder removed to reduce your risk of further problems. The most common cause of severe acute pancreatitis is gallstones blocking the pancreatic duct. ⭕Pancreas removal (pancreatectomy) ⭕Treatment for alcohol dependence ⭕Pain management ⭕Changes to diet ⭕Enzymes to improve digestion Yes, one can live without a pancreas Such an in individual has to be injected with enzymes always to help in digestion and the control of sugar levels

Answer 109

Pancreatitis could be due to the surgery(The most common cause of severe acute pancreatitis is gallstones blocking the pancreatic duct. This can sometimes occur even if the gallbladder has been previously removed) Or pancreatic cancer

Answer 110

True True Couinaud’s model of functional anatomy of the liver is the most popular. True

Answer 111

COUINAUD'S DESCRIPTION OF THE LIVER In Couinaud's description of the functional anatomy of the liver, the liver is divided into eight functionally independent segments, each having their independent vascular outflow, inflow and biliary drainage. In the centre of each segment, there is a branch of hepatic artery, portal vein and bile.

Answer 112

ANATOMY OF THE LIVER The liver is located in the upper right-hand portion of the abdominal cavity, beneath the diaphragm, and on top of the stomach, right kidney, and intestines. Shaped like a cone, the liver is a dark reddish-brown organ that weighs about 3 pounds. Oxygenated blood flows in from the aorta in the heart to the hepatic artery to the liver Nutrient-rich blood flows in from the GIT especially the small intestine which absorbs nutrients and water to the liver through the hepatic portal vein The hepatic artery carries blood from the aorta to the liver, whereas the portal vein carries blood containing the digested nutrients from the entire gastrointestinal tract, and also from the spleen and pancreas to the liver. (The arteries (red) carry oxygen and nutrients away from your heart, to your body's tissues. The veins (blue) take oxygen-poor blood back to the heart. )

Answer 113

ORGANS THE LIVER IS ATTACHED TO The gallbladder, a separate organ that works closely with the liver, is attached to the bile duct. True . The gallbladder stores bile and releases it back into the duct on cues from the stomach. FUNCTIONS OF BILE Bile is a fluid that is made and released by the liver and stored in the gallbladder. Bile helps with digestion. It breaks down fats into fatty acids, which can be taken into the body by the digestive tract. Bile contains: Mostly cholesterol. FUNCTIONAL PART OF THE LIVER Lobules are the functional units of the liver and consist of millions of cells called hepatocytes. HEPATOCYTES Hepatocytes perform most of the liver's functions — metabolism, storage, digestion, and bile production.

Answer 114

FUNCTIONS OF LIVER The liver is an essential organ of the body that performs over 500 vital functions. The Liver removes harmful substances, (such as ammonia and toxins) from the blood and then breaks them down or transforms them into less harmful compounds. Albumin is a major protein made by the liver that plays an important role in regulating blood volume and distribution of fluids in the body. The liver regulates most chemical levels in the blood and excretes a product called bile. This helps carry away waste products from the liver. All the blood leaving the stomach and intestines passes through the liver. The liver processes this blood and breaks down, balances, and creates the nutrients and also metabolizes drugs into forms that are easier to use for the rest of the body or that are nontoxic. Production of bile, which helps carry away waste and break down fats in the small intestine during digestion Production of certain proteins for blood plasma Production of cholesterol and special proteins to help carry fats through the body Conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy) and to balance and make glucose as needed Regulation of blood levels of amino acids, which form the building blocks of proteins Processing of hemoglobin for use of its iron content (the liver stores iron) Conversion of poisonous ammonia to urea (urea is an end product of protein metabolism and is excreted in the urine) Clearing the blood of drugs and other poisonous substances Regulating blood clotting Resisting infections by making immune factors and removing bacteria from the bloodstream Clearance of bilirubin, also from red blood cells. If there is an accumulation of bilirubin, the skin and eyes turn yellow. When the liver has broken down harmful substances, its by-products are excreted into the bile or blood. Bile by-products enter the intestine and leave the body in the form of feces. Blood by-products are filtered out by the kidneys, and leave the body in the form of urine. DIGESTION Liver. The liver has many functions, but its main job within the digestive system is to process the nutrients absorbed from the small intestine. Bile from the liver secreted into the small intestine also plays an important role in digesting fat and some vitamins It breaks down fats that are eaten, converting excess carbohydrates and protein into forms that are stored for later use, while synthesizing other fat, like cholesterol. The liver produces bile to help break down and absorb fats. Waste products and toxins are removed through bile.

Answer 115

If signs and symptoms of liver disease do occur, they may include: Skin and eyes that appear yellowish (jaundice) Abdominal pain and swelling. Swelling in the legs and ankles. Itchy skin. Dark urine color. Pale stool color.-(Bile salts are released into your stools by your liver, giving the stools a brown color. If your liver is not producing enough bile, or if the flow of the bile is blocked and not draining from your liver, your stools may become pale or clay-colored.) Chronic fatigue. Nausea or vomiting. ``` Common liver enzymes include: Alkaline phosphatase (ALP). Alanine transaminase (ALT). Aspartate transaminase (AST). Gamma-glutamyl transferase (GGT). ``` 1. Blood tests a. ALP b. AST c. ALT d. GGT ``` Alanine aminotransferase (ALT) (Alanine transaminase (ALT) is a transaminase enzyme (EC 2.6. 1.2). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) ) is found in hepatocytes but enters the bloodstream after injury or necrosis. It is used to detect hepatocellular injury, especially acute hepatitis..... (normal ranges: infant-60 years 15-35iu/L; 0-1 year 13-45iu/L). ```

Answer 116

Alkaline phosphatase (ALP) is found in hepatocytes. Elevated serum concentration results from interference with hepatic excretion, although isolated elevation can be present in bone disorders.... (normal range: <600iu/L).

Answer 117

Alpha1-fetoprotein (AFP) elevates due to hepatic regeneration in liver disorders. Also used as a marker of tumour activity and is the primary diagnostic test of hepatocellular carcinoma (normal range: <10mcg/L). True

Answer 118

Ammonia is elevated in hepatic cell failure as a result of a decrease in protein metabolism. It can be a first sign of rare inborn errors of metabolism affecting the urea cycle (normal ranges: neonate 64-107mcmol/L; child 21-50mcmol/L; adult 11-32mcmol/L).

Answer 119

excessive haemolysis of red blood cells or an enzyme deficiency, an obstruction in bile flow (cholestasis) (normal ranges: total 3-20mcmol/L; conjugated <3.4mcmol/L; unconjugated <19mcmol/L). *Bile salts* are synthesised and conjugated in the liver and secreted in bile. High serum bile salt concentration can indicate an abnormality in the hepatobiliary system (normal range: total <14mcmol/L).

Answer 120

Caeruloplasmin Known hepatic dysfunction canaliculi borders (Bile canaliculi also known as bile capillaries are thin tubes that receive bile secreted by hepatocytes. The bile canaliculi eventually merge and form bile ductules. The bile passes through canaliculi to the hepatic bile ducts and then into the common hepatic duct which drains directly into the duodenum)(normal range: 5-55iu/L). the presence and progression of hepatitis (A.B,C) Prothrombin time (PT) relates to the ability to initiate the clotting process. cholestatic-related vitamin K deficiency without marked hepatocellular impairment. But if it does not normalise, this denotes severe intrahepatic disease (normal range: 0-6 months 13-18 seconds; 6 months 10-13 seconds).

Answer 121

*Urine tests* Urine tests can measure several components of the liver. 24-hour copper excretion - The diagnosis of Wilson’s disease (inability to effectively metabolise copper) is aided by measuring urine copper concentrations before and after pencillamine. While it is an indicator of Wilson’s disease, copper excretion can also be elevated in cholestasis, sclerosing cholangitis, chronic active hepatitis and nephrotic syndrome (normal range <1.25mcmol/24 hours). Urinalysis - Dark yellow or orange urine can indicate bile. Two urinalysis tests are specific to liver disease: - Bilirubin: increased levels can occur in different forms of liver disease such as obstructive jaundice, hepatitis or cirrhosis; - Urobilinogen: raised levels occur with increased haemoglobin catabolism, increased enteric production of urobilinogen and increased production and reabsorption of urobilinogen and reduced uptake by the enterohepatic circulation.

Answer 122

Radiological investigation Radiological investigation can show the presence and extent of liver damage. Abdominal X-ray is useful for showing opaque stones and calculi in the biliary tract (see 2). Ultrasound is useful for detecting cysts, abscesses and strictures in the vessels as it detects structures as small as 1-2mm. Doppler facilities also enable blood flow and velocity to be calculated (see 3). Angiography uses an arterial injection of contrast medium to visualise the lumens of liver arteries. Radiographic images are taken with fluoroscopy and X-ray to highlight the abnormality. Endoscopic retrograde cholangiopancreatography (ERCP) - This involves the endoscopic cannulation of the papilla of Vater in the duodenum to gain access to the bile and pancreatic ducts. It is used to establish causes of biliary problems, remove obstructions in the biliary system and precisely delineate anatomy for surgery. Percutaneous transplenic cholangiogram (PTC) is used to clear obstruction or to determine the patency of the portal vein. Specialist nuclear scans include: positron emission tomography; hepatoiminodiacetic acid scan and magnetic resonance cholangiopancreatography (MRCP)

Answer 123

*LIVER BIOPSY* Histological examination of the liver tissue can aid diagnosis and provide information about the severity of liver disease *Other investigations* Various alternative tests can be useful 1.Eye tests: Kayser-Fleischer (KF) rings are pigmented corneal rings caused by an accumulation of copper. They also serve as a diagnostic feature of Wilson’s disease, but can also be present with prolonged cholestasis. KF rings are usually absent in children <10 years and difficult to see in green/brown eyes. 2.Faecal fat: the definitive test for steatorrhoea (normal range: breastfed infant <1g/24 hours; <6 years <2g/24 hours; 6 years <4g/24 hours).

Answer 124

What is Jaundice? The word Jaundice is from a French word “Jaunice” which means “yellowness”. Jaundice also known as Icterus is the yellowish discoloration of the skins, eyes and mucosal surfaces. This is as a result high levels of bilirubin in the blood. When RBCs are near the end of their life span (120 days) they are eaten by macrophages. This mostly happens in the the spleen and some lymph nodes. As the macrophages eat up the RBCs, it splits them. Globin is further broken down into amino acid and heme into iron and protoporphyrin The protoporphyrin is converted into Unconjugated bilirubin (UCB). This type of bilirubin is fat soluble Albumin in the blood then binds to the UCB and carries it to the liver where the hepatocytes convert the Unconjugated bilirubin into conjugated bilirubin by the help of the enzyme URIDINE GLUCURONYL TRANSFERASE. Conjugated bilirubin is water soluble unlike the Unconjugated bilirubin From the hepatocytes the conjugated bilirubin (CB) is secreted into the bile canaliculi and moves into through the bile duct to the gall bladder for storage. After eating the g bladder secretes bile into the duodenum. This bile contains the CB. The CB is converted into urobilinogen (UBG) by the intestinal microbes in the gut. Some of the UBG is reduced to stercobilin which is excreted and responsible for the brown color of faeces . Some UBG is recycled and absorbed into the blood where it is spontaneously oxidized into urobilin; most of which is sent to the liver and some to the kidneys for excretion. This is responsible for the yellow color of urine If a stage in the metabolism process is interrupted, let’s say the hepatocytes cannot conjugate the UCB or they die so early releasing the CB they were able to produce, this will cause increased level of bilirubin in the blood (i.e. either UCB or CB or Both). This results in the yellowish discoloration of the skin and eyes known as Jaundice Usually it takes about > 2.5mg/dl of serum concentration of bilirubin to give the skin the symptom of the jaundice. either UC Bilirubin or CJ in the blood may cause jaundice if levels is greater than 2.5mg/dl The earliest sign of jaundice is the yellowing of the sclera of the eye. This is because the sclera tissue has a higher affinity for bilirubin and hence binds so much to it which results in the yellowish discoloration of the eye before the skin Jaundice can be checked for by watching the sclera of the eyes, the skin or underneath the tongue Because it is highly vascularized and because external factors ( Eg: trauma) can cause the eyes to be red such that it won’t give you a clear sign of jaundice.

Answer 125

Let’s look at the causes… The principal cause of jaundice is as a result of increased level of bilirubin in the blood. This can happen in different ways of which I classified them into three 1. Pre-hepatic causes - Hemolytic anaemia - Blood transfusion - Hemolytic drugs 2. Hepatic causes - Hepatitis - Cirrhosis - Hepatic carcinoma - Syndromes. Eg: Gilbert’s, Crigler Najjar and Dubin-Johnson syndromes. 3. Post Hepatic/ Obstructive Jaundice: impaired flow into the intestines - Pancreatitis - Pancreatic cancer - Acaculous cholecystitis Use the pathophysiology to understand the classification and the diseases under than cause jaundice - Extravascular Hemolytic Anaemia In this condition, RBCs are broken down earlier than expected causing the macrophages to eat them up and the process continues - Ineffective Haematopoesis Where RBCs are not formed quite right causing macrophages to break them down. When the conditions happen, the hepatocytes are overwhelmed by the number of the unconjugated bilirubin to be conjugated. -In some instances the excess UCB stays in the blood -In other cases where hepatocytes are able to conjugate the UCB to CB, there’s increased level of CB in the bile which increases the risk of pigmented bilirubin gallstones. When this happens, there’s increased level of CB released into the duodenum which is converted into Urobilinogen (UBG) Part of the UBG is converted to Urobilin (UB) in the blood of which most is sent to the liver and some to the kidneys. Since we are dealing with high levels of CB this time around, the amount of urobilin (UB) sent to the kidneys will also be much causing the urine to look darker. - Obstructive Jaundice * Blockage of bile flow by gallstones, pancreatic carcinoma, cholangio carcinoma or parasites (eg: liver fluke) * This causes increased pressure in the duct hence leaking bile between the tight junctions of the hepatocytes into the blood together with bile salts, acids, and cholesterol. * When the above are deposited in the skin, they cause Pruritis (Itchy skin) * It can also cause cholesterolemia, xanthomas, and dark urine. * It also causes increased fat excretion (Stratorrhoea) and * Decreased fat soluble vitamin absorption NB: Unconjugated bilirubin (UCB) is not excreted because it is not water soluble. In the 2 conditions mentioned, too much Unconjugated bilirubin is created.

Answer 126

There are other conditions where the hepatocytes cannot keep up with the increased UCB load. Eg: Physiologic Jaundice of the Newborn _PHYSIOLOGIC JAUNDICE OF THE NEWBORN _ Newborn hepatocytes have a lower amount of the enzyme UGT (Uridine 5'-diphospho-glucuronosyltransferase ) which is responsible for conjugating UCB. After birth, UCB can be very high due to the action of macrophages destroying the fetal RBCs. This is typically normal but complications may arise when UCB levels rise a lot. Since UCB is fat soluble it can collect at the Basal Ganglia of the brain which is known as *KERNICTERUS* (Kernicterus is a type of brain damage that can result from high levels of bilirubin in a baby's blood. It can cause athetoid cerebral palsy and hearing loss. )and cause damage to the brain or death. Treatment of this condition is phototherapy (Phototherapy is treatment with a special type of light (not sunlight). Photo-oxidation adds oxygen to the bilirubin so it dissolves easily in water. Your baby may be placed under a special lamp that emits light in the blue-green spectrum. ) where the UCB changes shape making it more soluble and hence can be urinated. This method is a super-effective and non-invasive way of getting excess bilirubin out of the blood.

Answer 127

GENETIC DISORDERS THAT PRESENT WITH JAUNDICE Those that are caused by increased levels of Unconjugated bilirubin - Gilbert’s Syndrome * Low uridine glycuronyl transferase (UGT) reducing the conjugation in the hepatocytes. * When there is increased haemolysis which may be due to stress, infection or starvation, it will cause increased level of Unconjugated bilirubin in the blood leading to jaundice - Crigler Najjar Syndrome * No UGT at all * Over concentration of UCB in blood leading to kernicterus * It usually fatal Those that are caused by increased levels of Conjugated bilirubin - Dubin-Johnson Syndrome * An autosomal recessive disorder caused by deficiency in protein (MRP2) which carries conjugated bilirubin into the bile duct * When MRP2 is defective, MRP3 is upregulated just that it sends the CB into the blood instead of the bile duct which cause increased CB in the blood and darker urine.

Answer 128

VIRAL HEPATITIS When hepatocytes get infected and start to die, they loose the ability to conjugate UCB causing increased levels of Unconjugated bilirubin in the blood. Also hepatocytes cause bile to leak into the blood when they die because they are not able to line the bile duct anymore; this causes increased level of conjugated bilirubin in the blood which results in a more darker urine.

Answer 129

DIAGNOSIS OF JAUNDICE Diagnosis is based on the history: - Risk factors of hepatitis. Eg: sex between men, living with an infected person. -Risk factors of cancer. Eg: Smoking, family history, and age. LAB INVESTIGATIONS - FBC - Liver function test - Bilirubin fractionation - Urinalysis to measure the amount of certain substances in your urine - Imaging tests, such as an MRI or ultrasound, to examine your liver, gallbladder, and bile ducts to rule out other forms of jaundice An endoscopy could also be done to take a look at the liver and take sample (biopsy) if necessary for analysis for cancer

Answer 130

TREATMENT - Depends on the underlying cause For Hemolytic conditions, treatment options include 1. Blood transfusion 2. Cessation of hemolytic drugs In the case of acute cholecystitis, consider surgery (cholecystectomy) In carcinoma of the head of the pancreas, treatment involves oncological work up

Answer 131

Refers to abnormal enlargement of the liver True predominantly located in the right hypochondrium and epigastric areas, and extends into the left hypochondrium. 5th ICS in the Rt MCL down to the costal margin a fibrous layer, known as Glisson’s capsule. It is comprised of a large right lobe and smaller left lobe

Answer 132

PHYSIOLOGY OF THE LIVER –Synthesis of bile and prothrombin –Excretion of drugs, toxics, poisons, bile pigment and heavy metals –Metabolism of carbohydrates, fats and proteins –Protective by conjugation, destruction, phagocytosis, antibody formation and excretion –Storage of glycogen, iron, fat, vitamin A & D

Answer 133

Hypertrophy or hyperplasia of the cells intrinsic to the liver storage. E.g fat, malnutrition, obesity, diabetes mellitus –Inflammation. E.g hepatitis –Infiltration of cells. E.g cystic masses secondary or metastatic processes –Increased size of vascular space. E.g intrahepatic obstruction to hepatic vein outflow, hepatic vein thrombosis, CCF –Increased size of biliary space. E.g congenital hepatic fibrosis –Idiopathic

Answer 134

``` Infection –Congestive –Degenerative and infiltrative –Storage disorders –Neoplasia –toxins ``` Infections: Along the biliary tress – cholangitis B.Along portal vein – amoebiasis, schistosomiasis, bacterial infections C.Along hepatic artery ➢ bacterial – typhoid, brucellosis, tuberculosis, syphilis, weil’s disease. ➢Viral – infective hepatitis, infectious mononucleosis ➢Protozoan – malaria, kala-azar ➢Fungal – actinomycosis, histoplasmosis ➢Parasitic – echinococcosis (hydatid cyst)

Answer 135

Congestive: ``` CONGESTIVE –Congestive cardiac failure –Cardiomyopathy –Congestive pericarditis –Budd-chiari syndrome: Budd-Chiari syndrome is a condition in which the hepatic veins (veins that drain the liver) are blocked or narrowed by a clot (mass of blood cells). This blockage causes blood to back up into the liver, and as a result, the liver grows larger. ``` NEOPLASIA –Hepatocellular carcinoma –chlangiocarcinoma or bile duct cancer: cancer in the slender tubes that carry bile, the digestive fluid, through the liver. STORAGE DISORDERS –Neimann-pick disease: Niemann-Pick is a rare, inherited disease that affects the body's ability to metabolize fat (cholesterol and lipids) within cells. These cells malfunction and, over time, die. –Gaucher’s disease: Gaucher disease is a rare genetic disorder passed down from parents to children (inherited). When you have Gaucher disease, you are missing an enzyme that breaks down fatty substances called lipids. Lipids start to build up in certain organs such as your spleen and liver. –amyloidosis: The build-up of amyloid proteins in the heart, kidneys, liver or other organs. Amyloid is an abnormal protein that is usually produced in the bone marrow and can be deposited in any tissue or organ. ``` TOXINS –Alcohol –Arsenic –Phosphorous: –chlorpromazine: Chlorpromazine can cause mild and transient serum enzyme elevations and is also a well known cause of clinically apparent acute and chronic cholestatic liver injury. ```

Answer 136

DEGENERATIVE & INFILTRATIVE –Alcoholic fatty liver(An increased build-up of fat in the liver. ) –Lymphomas(example hodgkins lymphoma causes hepatomegaly and splenomegaly) –Leukemias(Leukemia cells may build up in the liver and spleen, making them larger. This might be noticed as a fullness or swelling of the belly, or feeling full after eating only a small amount. ) –Multiple myeloma or Kahlers disease(cancer of plasma cells.) CAUSES OF PAINFUL HEPATOMEGALY –Congestive cardiac failure –Viral hepatitis –Hepatic amoebiasis(Single or multiple areas of PUS due to infection by any ameboid protozoa (AMEBIASIS). A common form is caused by the ingestion of ENTAMOEBA HISTOLYTICA) –Pyemic abscess(Pyaemia (or pyemia) is a type of sepsis that leads to widespread abscesses of a metastatic nature. It is usually caused by the staphylococcus bacteria by pus-forming organisms in the blood.) –Hepatoma –Actinomycosis(Abdominal actinomycosis is a rare infectious disease, caused by gram positive anaerobic bacteria, that may appear as an abdominal mass and/or abscess .the infection likely enters the liver thereby causing the growth) –Budd-chiari syndrome(Budd-Chiari syndrome is a condition in which the hepatic veins (veins that drain the liver) are blocked or narrowed by a clot (mass of blood cells). This blockage causes blood to back up into the liver, and as a result, the liver grows larger.) RISK FACTORS FOR HEPATOMEGALY –Chronic liver disease –Liver cancer –Autoimmune disorders, especially ones that affect the liver –Obesity (according to WHO, a BMI of 30 and above is obese)-can cause Inflammation or fatty liver. –Sickle cell disease(hepatic sequestration crisis is rarer. This happens when red blood cells get trapped in the liver and cause it to enlarge. It can lead to anemia because there are not enough red blood cells circulating in the blood) –Inflammatory bowel disease(hepatomegaly can occur as a complication of IBd. In some people with inflammatory bowel disease (IBD), the liver can become inflamed or damaged. )

Answer 137

``` SYMPTOMS –Right hypochondrium pain –Jaundice –Abdominal distension –Abdominal discomfort –Nausea and vomiting (haematemesis) –Melena stool –Anorexia –Anaemia –Fever –Malaise –breathlessness ``` ``` SIGNS ➢Neck – engorged veins, raised JVP ➢Chest – spider naevi, gynecomastia ➢Skin – scratch marks ➢CNS – tremors & dystonia Abdomen 1.Engorged veins 2.abdominal walls moves with respiration 3.There might be obvious visible swelling or asymmetry on chest expansion 4.Liver palpable on inspiration ```

Answer 138

FINDINGS TO BE NOTED IN PALPATING HEPATOMEGALY –Local rise of temperature –Tenderness –Extent of enlargement below costal margin –Margin – sharp or round/ regular or irregular –Surface – smooth, irregular or nodular –Consistency – soft, firm or stony hard –Pulsatility – pulsatile or not pulsatile

Answer 139

``` AVERAGE LIVER SIZE –The average liver size varies by age and can be approximately be 1.6.4 cm for 1 to 3 months 2.7.6 cm for 4 to 9 months 3.8.5 cm for 1 to 5 years 4.10.5 cm for 5 to 11 years 5.11.5 to 12.1 cm for 12 to 16 years 6.13.5 cm +/- 1.7 cm for adult women 7.14.5 cm +/- 1.6 cm for adult men ```

Answer 140

``` DIFFERENTIAL DIAGNOSIS –Hepatitis –Biliary tract obstruction –Autoimmune disease –Cystic fibrosis ```

Answer 141

Full blood test: raised white cell count in infection –Liver enzymes to evaluate liver function –Liver function test: albumin, evidence of hepatic dysfunction clotting-functional hepatic impairment –Abdominal X-ray, a noninvasive X-ray study to evaluate abdominal organs –Abdominal ultrasonography to measure the size of the liver INVESTIGATION –Abdominal computerized tomography ( CT ) can help to obtain accurate anatomical information about the patient’s liver. –Biopsy to rule out cancer

Answer 142

NON-PHARMACOLOGICAL TREATMENT 1. Reduce weight 2. Eat healthy food 3. Reduce or stop alcohol consumption 4. Regular exercise PHARMACOLOGICAL TREATMENT Treatment options depend upon the underlying disorders that caused the hepatomegaly.

Answer 143

describes the condition of pathologic fluid collection within the abdominal cavity thus , abnormal accumulation of serous fluids (edema ) within the peritoneal cavity mostly associated with some disorders. •They may be as a result of complication of cirrhosis , congestive heart failure, malignancy or peritonitis •The fluid collects in spaces within the abdomen . It is very painful and can set the stage for an infection within the abdomen. True Pancreatic Ascites This develops when a cyst that has a thick fibrous wall or pseudocyst , bursts and permit pancreatic juices to enter the abdominal cavity. Chylous Ascites: Chylous ascites is when chyle collects in the belly. Chyle is a milky fluid made in the bowels (intestines) during digestion. It has a milky appearance caused by a lymph that has leaked into the abdominal cavity . Although it is sometimes caused by trauma, abdominal surgeries , tuberculosis or another peritoneal infection, it is normally a symptom of lymphoma or some other cancer. Endocrine Ascites It is a rare disorder to ascites. It happens when sometimes a symptom of the endocrine system affects women who are taking fertility drugs. Renal Ascites It is also a rare disorder which happens when blood levels of albumin dip below normal .

Answer 144

CAUSES The two most important factors in the production of ascites due to chronic liver disease are ; 1. Low levels of albumin in the blood that causes a change in the pressure necessary to prevent fluid exchange . This change in pressure allows fluid to seep out of the blood vessels. 2. An increase in the pressure within the branches of the portal vein that run through the liver. Portal hypertension is caused by the scarring that occurs in cirrhosis . Blood that cannot flow through the liver because of the increased pressure leaks into the abdomen and causes ascites Other conditions that contributes to ascites development include ; 1. Hepatitis 2. Heart or kidney failure 3. Inflammation & fibrous hardening of the sac that contains the heart.

Answer 145

SIGNS AND SYMPTOMS OF ASCITES ``` Small amount of fluid in the abdomen do not usually produce symptoms , however massive accumulations may cause the following ; •Rapid weight gain •Abdominal discomfort and distention •Shortness of breath •Swollen ankles •Vomitting •Bloating •Indigestion: The build-up of fluid may put pressure on the bowel making the person want to eat less, become constipated or experience a burning pain in the centre of the chest (indigestion). Nausea (feeling sick) and vomiting (being sick) can also occur. There may be an increase in pressure on the lungs or sometimes build-up of fluid in the lungs, causing shortness of breath, especially when lying flat. •Sense of fullness ```

Answer 146

Ascitic fluid can accumulate as a transudate or an exudate. Amounts of up to 35 liters are possible. •Roughly, transudates are a result of increased pressure in the hepatic portal vein (>8 mmHg, usually around 20 mmHg (e.g., due to cirrhosis), while exudates are actively secreted fluid due to inflammation or malignancy. As a result, exudates are high in protein and lactate dehydrogenase and have a low pH(<7.30), a low glucose level, and more white blood cellss. Transudates have low protein (<30 g/L), low LDH, high pH, normal glucose, and fewer than 1 white cell per 1000 mm3. Clinically, the most useful measure is the difference between ascitic and serum albumin concentrations. A difference of less than 1 g/dl (10 g/L) implies an exudate. •Portal hypertension plays an important role in the production of ascites by raising capillary hydrostatic pressure within the splanchnic bed.(The splanchnic circulation consists of the blood supply to the gastrointestinal tract, liver, spleen, and pancreas. It consists of two large capillary beds (splanchnic beds)partially in series) •Regardless of the cause, sequestration of fluid within the abdomen leads to additional fluid retention by the kidneys due to stimulatory effect on blood pressure hormones, notably aldosterone. (So it’s like the water is more in the abdomen so it’s not getting to the kidney much anymore so the kidneys are trynna retain the little that they have left) The sympathetic nervous system is also activated, and renin production is increased due to decreased perfusion of the kidney. Extreme disruption of the renal blood flow can lead to hepatorenal syndrome. Other complications of ascites include spontaneous bacterial peritonitis (SBP), due to decreased antibacterial factors in the ascitic fluid such as complement

Answer 147

CLASSIFICATION OF ASCITES •Ascites exists in three grades: •Grade 1: mild, only visible on ultrasound and CT •Grade 2: detectable with flank bulging and shifting dullness •Grade 3: directly visible, confirmed with the fluid wave/thrill test

Answer 148

Vitals:fever,tachycardia,tachypnea General :jaundice,encephalopathy,resp distress Jvp:distension due to right heart failure Resp:pleural effusion Abdomen:inspection-everted umbilicus,flank fullness,striae Percussion-flank dullness(if absent this means that there is less than ten percent chance of having ascites ),there is at least 1.5litres of ascites if dullness is present ),shifting dullness,fluid thrill Lower limbs-edema

Answer 149

``` High gradient (greater than or equal to 1.1g/dL(11g/L)-A high gradient (SAAG >1.1 g/dL) indicates portal hypertension and suggests a nonperitoneal cause of ascites. Such conditions may include the following: Cirrhosis. Fulminant hepatic failure : Cirrhosis Liver metastases Cardiac ascites Portal vein thrombosis Budd-Chiari syndrome Hypothyroid ``` ``` Low gradient(less than 1.1g/dL(11g/L): Peritoneal carcinomatosis Tuberculosis peritonitis Pancreatic ascites Biliary ascites Nephrotic syndrome Serositis: Serositis: Inflammation of the serous tissues of the body (the tissues that line the lungs, heart, abdomen, and inner abdominal organs). ```

Answer 150

Depending on the clinical situation, fluid may be sent for the following laboratory tests: •Gram stain - In a retrospective review of 796 peritoneal fluid samples, the evaluation of Gram stain results rarely provided clinically useful information for the detection of spontaneous bacterial peritonitis [16] •Cell count (elevated counts may suggest infection) •Bacterial culture •Total protein level •Triglyceride levels (elevated in chylous ascites) •Bilirubin level (may be elevated in bowel perforation) •Glucose level •Albumin level, used in conjunction with serum albumin levels obtained the same day (used to calculate SAAG; see the Ascites Albumin Gradient calculator) •Amylase level (elevation suggests pancreatic source) •Lactate dehydrogenase (LDH) level •Cytology Patients suspected of having ascites based on history and physical exam should undergo radiographic imaging Ultrasound is the most cost effective modality I’m cirrhotic patients,US,CT and MRImay reveal evidence of a modular liver

Answer 151

Treatment for ascites •Treatment for ascites will depend on what’s causing the condition. •If you have a bacterial or viral infection, the doctor will treat the underlying cause and will prescribe other therapy to relieve symptoms. •Diuretics •Diuretics are commonly used to treat ascites and are effective for most people with the condition. These drugs increase the amount of salt and water leaving your body, which reduces pressure within the veins around the liver. •While you’re on diuretics, your doctor may want to monitor your blood chemistry. You’ll probably need to reduce your alcohol use (if you drink alcohol) and your salt intake. Paracentesis •In this procedure, a doctor uses a long, thin needle to remove the excess fluid from your abdomen. They insert the needle through the skin and into the abdominal cavity. •You may need this if you have severe or recurrent ascites, or if symptoms don’t improve with diuretics. Surgery •In some cases, a surgeon may plant a permanent tube, called a shunt, in the body. It reroutes blood flow around the liver and reduces the need for regular drainage. A shunt may be suitable if diuretics don’t help. •Your doctor may recommend a liver transplant if ascites doesn’t respond to treatment and you have severe liver disease •If ascites results from heart failure, you may also need surgery. Non pharmacological: Immediate cessation of alcohol consumption Counseling on sodium diet and fluid restriction Medication used should be monitored for hepatotoxicity Hepatically metabolized drugs have the potential to accumulate in patients w liver disease I/O charting,daily with measurement Pharmacological- Diuretics:spironolactone plus or minus furosemide,albumin replacement Procedural:paracentesis-diagnostic and therapeutic

Answer 152

``` Infection Tense ascites Abdominal wall hernias Hepatic hydrothorax Hepatorenal syndrome Dilutional hyponatremia ```

Answer 153

DEFINITION Hepatic encephalopathy is a nervous system disorder brought on by severe liver disease. When the liver doesn’t work properly, toxins build up in the blood. These toxins can travel to the brain and affect brain function. People with hepatic encephalopathy may seem confused. Treatments can rid the body of toxins and reverse this temporary condition. TYPES Hepatic encephalopathy is sometimes broken down into three subtypes: Type A, which is associated with acute liver failure; Type B, which is associated a portosystemic shunt (a shunt that bypasses the liver, A portosystemic shunt is simply an abnormal passage way that allows blood from the GI tract to bypass the liver) with no existing liver disease present; and Type C, which is associated with scarring and poor function of the liver (cirrhosis), which often occurs with chronic liver disease.

Answer 154

STAGES Stage 1: mild symptoms, such as loss of sleep and shortened attention span. Stage 2: moderate symptoms, such as memory loss and slurred speech. Stage 3: severe symptoms, including personality changes, confusion, and extreme lethargy. Stage 4: a loss of consciousness and coma.

Answer 155

True Cirrhosis True

Answer 156

Pathophysiology Ammonium detoxification is regulated by 2 enzymes in hepatic encephalopathy: glutaminase or glutamine synthetase. The first generates ammonia and the second detoxifies ammonia, so the treatments are aimed at the inhibition of glutaminase or the activation of glutamine synthetase. We now know that both enzymes are found not only in the liver, but also in the muscle, intestine, kidney, and brain, so current treatments can target each enzyme at separate sites. Pathophysiology cont'd The nitrogen containing compounds generated by the gut bacteria are either excreted or transported into the liver by the portal vein where they are metabolized through the urea cycle in healthy patients In patients with cirrhosis however, the hepatocytes are not functioning properly and are less capable of metabolizing the waste products. Shunts may also form due to the increase in portal pressure which allows blood to move from the portal system into the inferior vena cava. This blood still contains the nitrogenous compounds ( ammonia) which is able to cross the blood brain barrier and is metabolized by astrocytes to form glutamine from glutamate . More glutamine production increases oncotic pressure in the astrocytes causing it to swell.

Answer 157

CAUSES 1. Alcohol use. 2. Certain drugs that affect the nervous system, such as sleeping pills and antidepressants. 3. Constipation (being unable to pass stool, or poop, normally)-His encephalopathy was likely due to increased absorption of ammonia into the mesenteric blood supply due to very slow transit constipation. Such absorption of ammonia most likely overwhelmed hepatic excretion. 4. Dehydration or electrolyte imbalance.(Hypokalemia and metabolic alkalosis are considered precipitating factors for hepatic encephalopathy, as hypokalemia stimulates ammoniagenesis in the proximal tubule-electrolyte imbalance) 5. Digestive tract bleeding.-Upper gastrointestinal bleeding causes increased urea concentrations in patients with normal liver function and high ammonia concentrations in patients with impaired liver function. This ammoniagenesis may precipitate encephalopathy. 6. Infection.-can cause increased ammonia levels 7. Kidney disease. 8. Liver shunt.-liver shunt occurs when an abnormal connection persists or forms between the portal vein or one of its branches, and another vein, allowing blood to bypass, or shunt, around the liver. ... In some cases, multiple small shunts form because of severe liver disease such as cirrhosis.

Answer 158

Clinical presentation 1. Skin and eyes that appear yellowish (jaundice) 2. Abdominal pain and swelling. 3. welling in the legs and ankles. 4. Itchy skin. 5. Dark urine color. 6. Pale stool color. 7. Chronic fatigue. 8. Nausea or vomiting.

Answer 159

Physical examination In addition to changed level of consciousness, the hallmark of hepatic encephalopathy on the physical examination is the presence of asterixis. This is detected by having the patient hold out his outstretched arms and cocking his wrists back. In the presence of asterixis, there is a non-synchronized, intermittent flapping motion at the wrists. Asterixis (It results from the acute loss of muscle tone or contraction associated with passive or active hand/wrist extension, most likely induced by pathologic coupling of the thalamus and motor cortex. Asterixis, also known as hepatic flap or uraemic flap, is an important sign of metabolic encephalopathy that occurs due to dysregulation of the diencephalic motor centers in the brain that regulate innervation of muscles responsible for maintaining position. )is not specific to hepatic encephalopathy. It may also be seen in states such as renal failure (kidney wont be able to remove toxins in blood thereby causing loss of brain function thereby causing asterixis) and carbon dioxide retention.(there isn’t enough oxygen if there’s bunch carbon dioxide so there won’t be bunch oxygen in the brain causing asterixis) ``` Bilateral: Hepatic encephalopathy Uraemia (renal failure) Hypercarbia Unilateral: CNS lesions - thalamus, midbrain, basal ganglia, frontal lobe Subdural haematoma ``` Physical Examination Physical examination of patients with hepatic encephalopathy is usually remarkable for signs of personality changes, signs of altered level of consciousness, jerking movement of the limbs (asterixis), slurred speech, writing disturbances, monotonous voice and impaired memory. Appearance of the patient Patients with hepatic encephalopathy usually appear confused, drowsy and sometimes irritable Vital signs In patients with hepatic encephalopathy vital signs include: Blood pressure may be normal, low or high. Hypothermia or hyperthermia may be present Tachycardia with regular pulse may be present Skin Signs of liver disease may be seen, such as: Yellow skin Protracted and disabling pruritus Spider angiomas Palmar erythema HEENT(head,ears,eyes,nose,throat) Icteric sclera Dilated pupils, sluggishly responsive to light Ophthalmoscopic exam may be abnormal with findings of papilledema. (Papilledema, also known as papilloedema, is optic disc swelling that is secondary to elevated intracranial pressure) Neck Physical examination of neck is usually normal. Lungs Physical examination of lungs is usually normal Heart Physical examination of heart is usually normal Abdomen Signs of liver disease may be seen such as: Fluid collection in the abdomen (ascites) Abdominal tenderness A palpable liver in the epigastrium (hepatomegaly- feel with inspiration, relocate during expiration Back Physical examination of back is usually normal Genitourinary Physical examination of genitourinary system is usually normal Neuromuscular Jerking movement of the limbs (asterixis) is highly suggestive of hepatic encephalopathy Attention deficit and slow information processing[13] Abnormal paper and pencil tests Altered mental status may be seen Scoring on Glasgow coma scale may be low Clonus may be present[8](muscular spasm involving repeated, often rhythmic, contractions.) Hyporeflexia Positive (abnormal) Babinski reflex Bilaterally muscle weakness may be seen Examination cranial nerves is usually normal Extremities Athetosis (writhing, sinuous movements of the digits and extremities) may be present Jaundice can be seen in the eyes and on the skin

Answer 160

Laboratory investigations 1. Critical flicker frequency test(CFF): Critical flicker frequency (CFF) threshold is defined as the frequency at which a flickering light is indistinguishable from a steady, non-flickering light. CFF is useful for assessing the temporal characteristics of the visual system. 2. Ammonia blood test 3. FBC 4. Electroencephalogram (EEG) 5. Computed Tomography (CT) scan 6. MRI

Answer 161

``` CFF Critical flicker frequency (CFF) can detect a range of neuropsychological abnormalities from visual signal processing to cognitive functions making it a valuable tool in various fields including hepatology, neurology, psychiatry, and ophthalmology15,50,51. Patients are shown light pulses at an initial frequency of 60 Hz gradually reduced by 0.1 Hz decrements per second. Patients are asked to identify the time at which the apparently steady fused light begins to flicker. A critical flicker frequency of below 39 Hz diagnoses CHE with high sensitivity and specificity and test results correlate positively with those of paper-and-pencil neuropsychometric test52. Most published studies agree that the sensitivity and specificity of CFF diagnosing CHE is 80% and 65% respectively53. The CFF has the advantage of not being dependent on language, verbal fluency, numeracy or numerics, and therefore studies into its use have been performed in the United States, Europe and Asia37. It is a simple, easy-to-use, and reliable tool that is independent of education, gender, age, and literacy. In recent studies by Sharma et al, the CFF has been evaluated as an objective measure for grading CHE as well as assessing recovery of patients with cirrhosis from sedation after endoscopy53,54. Other studies assessed the use of CFF as a marker for objective HE evaluation in patients undergoing transjugular intrahepatic portosystemic shunt52,55. Romero-Gomez et al in their study found that CFF together with Child-Pugh class can predict the development of HE grade II and I in follow-up15. However, further validation and standardization studies are needed to determine its use and applicability in differentiating between HE grades 0 and I. It is not useful in grade III or IV HE either because patients’ attention and cooperation are required. Thus CFF has not been established as a diagnostic tool in OHE. A meta-analysis by Torlot et al37 has shown that CFF is a diagnostically accurate test, which could be used as an adjunct to conventional psychometric test batteries, such as PHES, but could only become a replacement screening test if further studies show an improvement in sensitivity. ``` 2. EEG Similar to clinical grading, the electroencephalogram (EEG) classifies HE in five grades of severity from normal to coma. In published studies, the diagnostic sensitivity for HE ranges between 43% and 100%34. In mild HE, the increase in confusion is associated with the initial EEG tracings that reveal posterior dominant alpha rhythm slowing, which is typically followed by a gradual appearance of theta and high-amplitude irregular delta waves as the HE progresses into coma. This neurophysiological method is associated with both inter- and intra-observer variability leading some to suggest a lack of objectivity56. An alternative objective approach is spectral analysis of the EEG, which is a computerized analysis of the frequency distribution in the EEG. Spectral analysis of the EEG is a simple technique, is more reliable than visual EEG reading, and has prognostic value for the development of HE and mortality in cirrhotic patients57,58. Digital analysis of the EEG analyses EEG in various regions of the brain making more sensitive than conventional or spectral EEG in detecting early HE. 85% of patients with no clinical symptoms of HE show abnormalities on digital analysis proving its high sensitivity for functional cerebral alterations59.

Answer 162

Differential diagnoses of encephalopathy are as follows : Intracranial lesions, such as subdural hematoma,intracranial bleeding, stroke, tumor, and abscess. Infections, such as meningitis, encephalitis, and intracranial abscess.

Answer 163

Treated or managed Once any precipitating factors have been addressed, treatment is aimed at lowering the level of ammonia and other toxins in your blood. Since these toxins originally arise in your gastrointestinal or GI system, therapies are aimed at your gut to eliminate or reduce the production of toxins. The two types of medications used to do this are lactulose, a man-made sugar, and antibiotics. Liver transplantation is the definitive treatment for patients with acute liver failure and hepatic encephalopathy. In patients with chronic hepatic encephalopathy, lactulose and rifaxamin (Rifaximin is in a class of medications called antibiotics. Rifaximin treats traveler's diarrhea and irritable bowel syndrome by stopping the growth of the bacteria that cause diarrhea. Rifaximin treats hepatic encephalopathy by stopping the growth of bacteria that produce toxins and that may worsen liver disease ) remain a mainstay of therapy. Antibiotics: Bacteria in your body make natural toxins from digested foods. Antibiotics, such as rifaximin (Xifaxan®️), stop bacterial growth. As a result, the body produces fewer toxins. Laxatives: Lactulose oral solution, a laxative made from lactose sugar, draws toxins into the colon. The laxative stimulates frequent bowel movements that help remove toxins from the body

Answer 164

1. brain herniation. 2. brain swelling. 3. organ failure.

Answer 165

1️⃣ *Definition* Cirrhosis is a *late-stage* result of liver disease or liver damage characterized by *irreversible progressive diffuse fibrosis* and *regeneration of nodules* **Fibrosis* is the thickening and scarring of connective tissue or the formation of fibrous tissue. **Nodules* result from localized proliferation of hepatocytes in response to injury. This means that cirrhosis occurs when there is prolonged persistent hepatocyte death such that the liver becomes thickened with mass and mass of protein and forms scar tissue and nodules to a point where it is no longer reversible...that is why we say it is an end/late-stage result of liver damage

Answer 166

a hexagonal-shaped *lobule* ...which is the structural unit of the liver ▫️Blood from the periphery flows through a low-pressure vascular channel *(sinusoid)* into a central vein in the center of the lobule. ▫️Inside the sinusoids are cells called *Kupffer cells* ....These are macrophages that remove toxins and protect the liver against infections. ▫️Between the layer of hepatocytes and the sinusoid is the *space of disse* where *stellate cells* are located. Stellate cells in a normal liver tissue stores vitamin A and are dormant ( *quiescent* *fibroblast* ) but become active after injury. Kupffer cells and stellate cells

Answer 167

*Histologically* cirrhosis is classified into 1. *Micronodular cirrhosis* Characterized by small nodules usually in alcoholic cirrhosis 2. *Macronodular* *Cirrhosis* Characterized by larger nodules True

Answer 168

3️⃣ *Causes of Liver cirrhosis* Liver cirrhosis occurs when there is persistent or recurrent hepatocyte death Thus any form of insults that result in persistent liver cell death is a cause ...such as in conditions like *chronic viral hepatitis*, *prolonged biliary damage*, *prolonged excessive alcohol intake*.. Most common causes of cirrhosis is chronic hepatitis and prolonged excessive alcohol intake. *General causes of cirrhosis are:* ▫️ *Chronic viral hepatitis* ▫️ *Prolonged alcohol* *consumption* ▫️ *Hemochromatosis*- Excess iron stored in the liver ▫️ *Autoimmune* *Hepatitis* - Your body's own immune system attacks heathy liver tissue causing damage ▫️ *Medications* misuse of Medications like drug over dose ▫️ *Celiac disease* : An immune reaction to eating gluten, a protein found in wheat, barley and rye. Over time, the immune reaction to eating gluten creates inflammation that damages the small intestine's lining, leading to medical complications. It also prevents absorption of some nutrients (malabsorption). ▫️ *Wilson's disease* - excess liver stored in the liver ▫️ Non-alcoholic liver disease ▫️blockage of the bile duct

Answer 169

True 5️⃣ *Pathophysiology* The cardinal feature of cirrhosis is - an increase in fibrous tissue - progressive and widespread death of liver cells - inflammation leading to loss of normal liver architecture Inflammation triggers cell repair and finally tissue scarring ▫️ Following liver injury, stellate cells are activated When activated, the stellate cells lose vitamin A ,proliferate and start to release mainly-transforming growth factor Beta 1...TGF-B 1 ▫️TGF-B1 causes the stellate cells themselves to secrete collagen (which is the main ingredient in extracellular matrix, fibrosis and scar tissue ▫️ As the fibrotic tissue build up, it starts to compress the portal veins and sinusoids ▫️ In a normal liver these stellate cells play key roles in the natural wound healing process but when the liver cells are *constantly injured* the stellate cells are *constantly* *activated* and *constantly* *produce* *collagen* and factors that lead to fibrosis Normal state〰️wound healing Constant injury〰️constant fibrosis ▫️ As the central veins in sinuses become compressed and push on the fluid inside pressure builds up leading portal hypertension ▫️ Higher portal vein pressure means that fluid in the blood vessel is likely to get pushed into tissues and across tissues into large open spaces like the peritoneal cavity ( *This is why ascites is a complication of cirrhosis* ) ▫️ The spleen becomes enlarged because blood cannot get to the liver and back flows into the spleen instead... this is known as👉 congestive *splenomegaly* ▫️ The circulatory system starts diverting blood away from the liver because of the high liver pressure...this is known as 👉 *Portosystemic shunt*

Answer 170

6️⃣ *Complications* *The most common serious complication is portal hypertension*(increase pressure in the portal veins due to compression by fibrous tissue...thus..there is backflow of blood to other tissues) It is from this portal hypertension that other complications of cirrhosis arise....namely: ▫️ *Esophageal Varices* The backflow of blood in the portal veins causes veins in the esophagus to be enlarged. As pressure builds, the veins can even burst causing severe internal bleeding ▫️ *Ascites* Build-up of fluid in the abdomen ▫️ *Splenomegaly* ▫️ *Hepatopulmonary* *syndrome* - blood vessels in and around the lungs widen (dilate), which affects the amount of oxygen that moves from the lungs into the bloodstream. ▫️ *Kidney failure* -the Portosystemic shunt (by means unknown), triggers renal vasoconstriction...this increases resistance in the kidney...blow flow to the kidney decreases, decreasing filtration and thus👉hepatorenal failure ▫️ *Hepatic encephalopathy* -This occurs when toxins from the intestines are not removed by the damaged liver and circulate in the bloodstream and build-up in the brain causing brain disorders 📌 *Other Complications* 📌 ``` Physiologically the liver performs functions such as -detoxification -estrogen metabolism -Bilirubin conjugation -Albumin production -clotting factor production Etc. ``` Since the liver has now become fibrotic and is unable to perform these functions...they reduce...as in : ▫️ *Detoxification decreases* - toxins get the brain and cause mental deficits...a condition called *hepatic* *encephalopathy* - Ammonia is no longer metabolized in the liver, these get to the brain and the patient might develop asterixis ( tremoring or jerky hands when outstretched) ▫️ *Decrease in estrogen* *metabolism* Liver metabolizes estrogen into inactive metabolites that can be excreted. Patients experience complications due to estrogen build-up like - gynecomastia - spider angioma -palmar erythema ▫️ *Decrease in bilirubin* *conjugation* Thus unconjugated bilirubin levels increase causing *Jaundice* ▫️ *Decrease in albumin* *production* - hypoalbuminemia ▫️ *Decrease in clotting factor* *production* - result in coagulation issues or problems with clotting ▫️ *Infections* ▫️ *Malnutrition*

Answer 171

7️⃣ *Stages of Cirrhosis* ⭕ *Compensated Cirrhosis* - This is the early stage of Cirrhosis - liver can still do most of it's functions - Patient is assymptomatic but may show non-specific symptoms such as weight loss, weakness, fatigue - lab work and imaging findings may not be abnormal - A liver biopsy may be the only way to confirm a diagnosis. ⭕ *Decompensated Cirrhosis* - This is the later stage of Cirrhosis - liver cannot function normally - Cirrhosis has worsened with noticeable symptoms - the condition is recognized based on history, physical exam and lab findings - one has at least one complication

Answer 172

8️⃣ *Signs and symptoms /*Clinical Features* ▫️ *Neurological* - Asterixis ( Hepatic flap): When the liver isn't functioning properly and isn't able to filter toxins, the toxins can build up in the blood and travel to the brain. This toxicity affects brain function. Liver diseases, such as cirrhosis or hepatitis, increase your risk of asterixis ▫️ *Head and neck* - Parotid gland swelling: increase in adipose tissue at the expense of acinar tissue in the salivary glands of patients with alcoholic cirrhosis ▫️ *Skin* - spider naevi ( angiomata) - Jaundice (bilirubin >2mg/dl) ▫️ *chest* - gynecomastia: liver disease there is an increased production of androstenedione by the adrenal glands, increased aromatisation of androstenedione to oestrogen, loss of clearance of adrenal androgens by the liver and a rise in SHBG, resulting in gynaecomastia. ▫️ *Abdominal* - hepatomegaly (liver is often hard, irregular and non-tender on palpation) - Splenomegaly - Ascites - caput Medusa: Caput medusae is the name for a cluster of swollen veins in your abdomen. The swelling usually appears around the belly button, and the veins branch out from a central point. They are typically painless, but they are a symptom of circulatory problems that are often related to liver disease ▫️ *Urogenital* - testicular atrophy. :The first step of the pathogenesis of testicular atrophy occurring in advanced cirrhosis seems to be the decreased expression of transferrin, showing a dysfunction of Sertoli cells and consequently the disruption in blood-testis barrier integrity. ▫️ *Extremities* - palmar erythema - clubbing-Clubbing may result from chronic low blood-oxygen levels. - Dupuytren's contracture - hypertrophic osteoarthropathy ▫️ *other signs* - easy bruising and bleeding - brownish or orange colour to urine (due to hepatourinary failure) - light colored stools - blood in stool - confusion * Hepatomegaly is common when the cirrhosis is due to alcoholic liver disease* *and Hemochromatosis* * A reduction of the liver size is especially common if the cause of cirrhosis is viral hepatitis or autoimmune liver* *disease*

Answer 173

9️⃣ *Diagnosis* Diagnosis is based on : ▫️ *Physical examination of* *signs and symptoms* ▫️ *Blood tests* Signs to elicit in results: *-* lower than normal levels of albumin and blood clotting factors since the liver is unable to make these proteins and clotting factors - Raised levels of liver enzymes suggest inflammation * AST:ALT ratio of >1 indicates the* *development of cirrhosis* - higher level of iron may indicate hemochromatosis ( a cause of cirrhosis) - presence of autoantibodies (may indicate autoimmune hepatitis or primary biliary cirrhosis) - high white blood cell count (indicates an infection) - high creatinine level (a sign of kigney disease that suggests late-stage cirrhosis) - elevated serum ammonia - high level of unconjugated bilirubin ``` ▫️ *Imaging tests* These show the size, shape and texture of the liver and can also determine the amount of scarring and fat in the liver and fluid in the abdomen - CT scan -abdominal ultrasound -MRI ``` ▫️ *Biopsy* To determine other causes or extent of liver damage, diagnosis of liver cancer and to confirm liver cirrhosis diagnosis ⏸️ *Investigations* ▫️Liver biopsy ▫️Liver function test - to evaluate liver enzymes, proteins and prothrombin time ▫️Liver ultrasound ▫️ Hepatic venous Pressure Gradient:to measure portal hypertension. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. ▫️ Transient Elastography - to measure liver stiffness ▫️ Metabolic Breath test: The 13C-methacetin breath test (MBT) has been shown to accurately assess the degree of liver damage. The MBT can reliably distinguish between early cirrhotic and non-cirrhotic patients with 95% sensitivity and 97% specificity.

Answer 174

🔟 *Differential diagnosis* ``` ▫️ chronic viral hepatitis ▫️ Autoimmune Hepatitis ▫️ Alcoholic liver disease ▫️ Non-alcoholic liver disease ▫️ Hepatocellular carcinoma ▫️Primary biliary cirrhosis ```

Answer 175

1️⃣2️⃣ *Management / Treatment* *Management* ▫️ slow further damage to the liver ▫️Prevent and treat symptoms ▫️ prevent and treat complications *Treatment* Treatment depends on what is causing the cirrhosis and how much damage exists ▫️ *Treat the cause of the disease* Some causes of cirrhosis can be treated as in: - In alcohol-induced cirrhosis, patient can try to stop drinking - antiviral medicines for hep B(eg *Entecavir* ) and C( eg *Glecaprevir* ) - Non-alcoholic liver disease~losing weight, exercise, following a healthy disease - blockage of the liver~ giving medications such as *ursodial* , or undergoing surgery to open the duct Ursodiol is a bile acid that decreases the amount of cholesterol produced by the liver and absorbed by the intestines. Ursodiol helps break down cholesterol that has formed into stones in the gallbladder. Ursodiol also increases bile flow in patients with primary biliary cirrhosis. Ursodiol is used to dissolve gallstones in patients who do not need to have their gallbladders removed or in those in whom surgery should be avoided because of other medical problems. - fatty liver due to cirrhosis can be treated with medications such as *Metadoxine* -Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood. Drinking a large amount of alcohol, even for just a few days, can lead to a build-up of fats in the liver. This is called alcoholic fatty liver disease, - wilson disease- medications such as *Trientine* : Trientine is used to treat Wilson's disease, a disease in which there is too much copper in the body. This medicine combines with excess copper in the body and may prevent your body from absorbing the copper in the foods you eat. ▫️ *Treat complications* - Beta blockers can be prescribed to reduce pressure in the veins - Variceal band ligation~ a surgical procedure to cut off bloodflow through the varices to stop or reduce further bleeding in *esophageal varices* - Lactulose can prescribed to absorb toxins in the blood that result from *hepatic encephalopathy* - Undergoing paracentesis to drain excess fluid in *ascites* - Diuretics to decrease extra fluid (edema) -Kidney failure~ medication, dialysis, kidney transplant (depending on the extent) ▫️ *Treat and prevent* *infections* -using antibiotics ▫️ *Liver Transplantation* ▫️ *Avoid nonsteroidal* *anti-inflammatory drugs* (Ibuprofen,celecoxib and aspirin) *and high doses of acetaminophen* NSAIDs may be tolerated in patients with mild chronic liver disease, but they should be avoided in all patients with cirrhosis because of the increased risk of hepatorenal syndrome and the dire consequences relating to this complication.they reduce kidney function and GFR

Answer 176

- Definition of terms Alcoholic Liver Disease is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis. Fatty liver: Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Continuing with the terms …. Alcoholic hepatitis: Alcoholic hepatitis is hepatitis (inflammation of the liver) due to excessive intake of alcohol Fibrosis: Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue. Cirrhosis: Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Moving on Hepatic stellate cell activation: In addition to their role in responding to hepatic injury, stellate cells in the healthy liver are the major storage site in the body for vitamin A. Stellate cells provide the liver with an ability to respond to injury and heal certain types of damage. Oxidative stress: defined as a disturbance in the balance between the production of reactive oxygen species (free radicals) Lipid peroxidation: is the chain of reactions of oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage Ethanal (Acetaldehyde) : It is a toxic compound produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase. •Lipogenesis: The conversion of fatty acids and glycerol into fats.

Answer 177

Let’s talk about risk factors Risk Factors: * Quantity of alcohol taken: Consumption of 60–80g per day for 20 years or more in men, or 20g/day for women significantly increases the risk of hepatitis and fibrosis by 6% to 41% * Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease • Sex: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in fat absorption due to the menstrual cycle may explain this phenomenon. Still with risk factors, we have * Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury. * Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease. Ending the risk factors we have … Iron overload (hemochromatosis): Iron deposition in the liver leads to enlargement and elevation in liver enzymes.This may cause right upper quadrant pain and predispose patients to fibrosis, cirrhosis and cancer. • Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.

Answer 178

Chronic consumption of alcohol results in the secretion of pro-inflammatory cytokines (TNF-alpha, Interleukin 6 [IL6] and Interleukin 8 [IL8]), oxidative stress, lipid peroxidation, and acetaldehyde toxicity. These factors cause inflammation, apoptosis and eventually fibrosis of liver cells. Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal. With the above image we see NADH is produced from the oxidation of alcohol by alcohol dehydrogenase. Excess NADH production breaks the redox balance between NADH and NAD+ and eventually leads to oxidative stress. Improper metabolism of ROS results in expression of hypoxia-inducible factor -1 alpha, which increases TNF-secretion, leading to immune response that intensifies the hepatocyte injury. We can see at the left hand side of the image that •excess NADH production leads to a decreased fatty acid oxidation and leads to a reduction in energy utilization and increased lipogenesis, resulting in steatosis(fatty liver) At the bottom of the image we see Ethanol ingestion leads to increase endotoxins released by bacteria living in the intestine. This activates immune cells in the liver (kupffer cells). When activated, Kupffer cells produce signaling molecules thus cytokines that promote inflammatory reactions as well as molecules called reactive oxygen species (ROS) which damage liver cells. Also following liver injury, stellate cells in the space of Disse are activated by cytokines produced by kupffer cells and hepatocytes. When activated the stellate cells lose vitamin A, proliferate and start to release many more cytokines but mainly- Transforming Growth Factor Beta1 (TGF-ß1). TGF -ß1 trigger the stellate cells themselves to secrete collagen (which is the main ingredient in extracellular matrix, fibrosis and scar tissue. Increased collagen synthesis then leads to fibrosis of the liver

Answer 179

The first stage is *Fatty change* Fatty change, or steatosis, is the accumulation of fatty acids in liver cells. These can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macro-vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into carbon dioxide (CO2) and water (H2O).This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver. So the second stage is *Alcoholic hepatitis* Alcoholic hepatitis is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic hepatitis (NIAAA, 1993). While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steato-necrosis and the inflammation appears to predispose to liver fibrosis. Inflammatory cytokines (TNF-alpha, IL6 and IL8) are thought to be essential in the initiation and perpetuation of liver injury and cytotoxic hepatomegaly by inducing apoptosis and severe hepatotoxicity. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF-α then triggers apoptotic pathways through the activation of caspases, resulting in cell death Okay with the last stage of Alcoholic liver disease, we have Cirrhosis or Liver Cirrhosis Cirrhosis is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis (cell death). Between 10% to 20% of heavy drinkers will develop cirrhosis of the liver. Without total abstinence from alcohol use, cirrhosis will eventually lead to liver failure. Late complications of cirrhosis or liver failure include portal hypertension (high blood pressure in the portal vein due to the increased flow resistance through the damaged liver), coagulation disorders (due to impaired production of coagulation factors), ascites (heavy abdominal swelling due to buildup of fluids in the tissues) and other complications, including hepatic encephalopathy and the hepatorenal syndrome. True

Answer 180

I believe we all have seen such a case before at our hospitals ``` patients will present with 1. Right upper quadrant discomfort 2. Nausea 3. Jaundice 4. Fever 5. Spider nevi 6. Portal hypertension 7. Ascites 8. Variceal bleeding-Abnormal veins in the lower part of the tube running from the throat to the stomach. Oesophageal varices usually develop when blood flow to the liver is blocked. They often occur in people with advanced liver disease. Esophageal varices sometimes form when blood flow to your liver is blocked, most often by scar tissue in the liver caused by liver disease. The blood flow begins to back up, increasing pressure within the large vein (portal vein) that carries blood to your liver. As the blood pressure in the portal vein system continues to increase, the walls of these expanded veins become thinner, causing the veins to rupture and bleed. This is called variceal bleeding. 9. Gynecomastia 10. Confusion 11. Weight loss ``` Moving to Complications we have * Portal hypertension * Spontaneous bacterial peritonitis-Peritonitis that develops without an abdominal rupture (spontaneous bacterial peritonitis) is usually a complication of liver disease, such as cirrhosis. Advanced cirrhosis causes a large amount of fluid buildup in your abdominal cavity. That fluid buildup is susceptible to bacterial infection. * Ascitis * Hepatic encephalopathy * Liver cancer

Answer 181

Diagnosis of ALD In the early stages, patients with ALD exhibit subtle and often no abnormal physical findings. It is usually not until development of advanced liver disease that stigmata of chronic liver disease become apparent. Early ALD is usually discovered during routine health examinations when liver enzyme levels are found to be elevated. These usually reflect alcoholic hepatic steatosis. Microvesicular and macrovesicular steatosis with inflammation are seen in liver biopsy specimens. (Microvesicular steatosis is characterized by the presence of numerous small vesicles of fat that do not displace the nucleus (Figures 1, 2). Macrovesicular steatosis is characterized by engorgement of the hepatocyte by a large fat globule that displaces the nucleus ),These histologic features of ALD are indistinguishable from those of nonalcoholic fatty liver disease. Continuing…….. Steatosis usually resolves after discontinuation of alcohol use. Continuation of alcohol use will result in a higher risk of progression of liver disease and cirrhosis. In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice, hepatomegaly, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation. Tender hepatomegaly may be present, but abdominal pain is unusual. Occasionally, the patient may be asymptomatic. True

Answer 182

Okay next thing is Differential diagnosis With the various signs , symptoms and other examination findings we may encounter at the hospital Other conditions present themselves as that of ALD so let’s note Differential diagnosis • Hemochromatosis: Iron overload • Wilson's disease; An inherited disorder that causes too much copper to accumulate in the organs.In Wilson's disease, copper isn't eliminated properly and instead accumulates, possibly to a life-threatening level. Symptoms typically begin between the ages of 12 and 23. It also presents with ascitis and jaundice. Viral hepatitis ; causes inflammation and damage to the liver and can also present with symptoms similar to that of ALD * Drug induced hepatitis; Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane, birth control pills), may injure the organ. * Autoimmune hepatitis; inflammation of the liver as a result of the immune system attacking the liver. Cholestatic jaundice; Any condition in which the flow of bile from the liver stops or slows.Cholestasis can be caused by a liver infection, gallstones and cancer and it has similar symptoms as that of Alcohol liver disease • Non alcoholic fatty liver disease (NAFLD); The accumulation of liver fat in people who drink little or no alcohol. The cause of NAFLD is unknown. Risk factors include obesity, gastric bypass surgery, high cholesterol and type 2 diabetes.

Answer 183

Investigations ``` 🔘 Liver biopsy 🔘Liver ultrasonography 🔘Liver function test: evaluate liver enzymes, proteins and prothrombin time 🔘Gamma-glutamyl transpeptidase test: This test measures the level of gamma-glutamyl transpeptidase (an enzyme that is produced in the liver, pancreas, and biliary tract). This test is often performed to assess liver function, to provide information about liver diseases, and to detect alcohol ingestion 🔘Hepatic venous Pressure Gradient 🔘Serum bilirubin test ```

Answer 184

Management of ALD •Abstinence Drinking cessation is considered the most effective therapy in patients with ALD. Abstinence from alcohol not only resolves alcoholic steatosis but also improves survival in cirrhotic patients. The effectiveness of abstinence is enhanced when it is combined with lifestyle modifications (e.g., behavioral interventions and dietary alterations) that are supervised by a nurse, primary care physician, or gastroenterologist/hematologist •Natural and Artificial Steroids Corticosteroid treatment, including the use of prednisolone, has been the most extensively used form of therapy, especially for moderate to severe alcoholic hepatitis, based on their ability to suppress the immune response and proinflammatory cytokine response •Nutritional Supplements Nearly all patients with severe alcoholic hepatitis and cirrhosis are malnourished and their degree of malnutrition correlates with disease severity and complications, such as variceal bleeding, ascites, infections, encephalopathy, and hepatorenal syndrome. Deficiencies in micronutrients (e.g., folate, vitamin B6, vitamin A, and thiamine) and minerals (e.g., selenium, zinc, copper, and magnesium) often occur in ALD and, in some instances, are thought to be involved in its pathogenesis •Liver Transplantations Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver.

Answer 185

*Treatment of complications* * Portal hypertension resulting from ALD can be maned it bea blockers suc as propranolol to lower portal pressure and potentially improve the liver function. * Diuretics such as furosemide can used to treat fluid build-up as a result of liver scarring. Cases where hepatic encephalopathy is present, Lactulose is frequently used to decrease ammonia levels. Certain antibiotics (such as rifaximin) and probiotics are other potential options. * For spontaneous bacterial peritonitis (SBP), a 10- to 14-day course of antibiotics is recommended. Recommended therapy for SBP consists of intravenous cefotaxime 2 grams every 8 hours (or a similar third-generation cephalosporin) for a duration of 5 days. * The only definitive treatment for Hepatorenal Syndrom is liver transplantation. The most suitable bridge treatment or treatment for patients who are not eligible for transplantation is a combination of terlipressin and albumin. * Liver cancer treatments vary but may include removal of part of the liver, transplant, chemotherapy and in some cases, radiation.

Answer 186

- Prognosis of ALD The long-term prognosis of individuals with alcoholic hepatitis depends heavily on whether patients have established cirrhosis and whether they continue to drink. With abstinence, patients with this disease exhibit progressive improvement in liver function over months to years, and the histologic features of active alcoholic hepatitis resolve. If alcohol abuse continues, alcoholic hepatitis invariably persists and progresses to cirrhosis over months to years. In one study, the estimated 5-year survival after hospitalization for severe alcoholic hepatitis was 31.8%. Abstinence was the only independent predictor of long-term survival. *•Prognosis Scoring System* The single most reliable indicator of severity of alcoholic hepatitis is the presence of hepatic encephalopathy. The American Association for the Study of Liver Diseases (AASLD) guideline recommends using prognostic scoring systems such as the Maddrey discriminant function (MDF)(Suggests which patients with alcoholic hepatitis may have a poor prognosis and benefit from steroid administration. Maddrey's Discriminant Function is useful in predicting short-term prognosis but is less useful for long-term prognosis. The equation used to calculate the Maddrey Score is: Bilirubin (mg/dL) + 4.6 times (prothrombin time in seconds minus control))to stratify illness severity and the risk of poor outcome, both initially and over the course of the illness and Model for end-stage liver disease (MELD) score which is also calculated using bilirubin, creatinine and international normalized ratio (INR) levels.

Answer 187

*LIVER ABSCESS* Liver abscess is defined as a pus-filled mass in the liver. Pus is a fluid composed of white blood cells and dead cells that typically forms when the body fights off infection. The majority of the liver abscesses are categorized as pyogenic or amoebic, although a minority are caused by parasites and fungi. An abscess is usually accompanied by swelling and inflammation in the surrounding area which can cause pain and swelling in the abdomen.

Answer 188

True umbilical vein catheterization and sepsis. underlying immune deficiency, severe malnutrition, or trauma frequently exists. True

Answer 189

*ANATOMY OF THE LIVER* The liver is located in the upper right quadrant of the abdominal cavity, beneath the diaphragm, and on top of the stomach, right kidney, and intestines. Shaped like a cone, the liver is a dark reddish-brown organ that weighs about 3 pounds. There are 2 distinct sources that supply blood to the liver; Oxygenated blood flows in from the hepatic artery Nutrient-rich blood flows in from the hepatic portal vein True

Answer 190

*PHYSIOLOGY OF THE LIVER* The liver regulates most chemical levels in the blood and excretes a product called bile. This helps carry away waste products from the liver. All the blood leaving the stomach and intestines passes through the liver. The liver processes this blood and breaks down, balances, and creates the nutrients and also metabolizes drugs into forms that are easier to use for the rest of the body or that are nontoxic. Some of the functions of the liver include the following: Production of bile, which helps carry away waste and break down fats in the small intestine during digestion. Production of certain proteins for blood plasma. Production of cholesterol and special proteins to help carry fats through the body. Conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy) and to balance and make glucose as needed. Regulation of blood levels of amino acids, which form the building blocks of proteins. Processing of hemoglobin for use of its iron content (the liver stores iron). Conversion of poisonous ammonia to urea (urea is an end product of protein metabolism and is excreted in the urine). Clearing the blood of drugs and other poisonous substances. Regulating blood clotting by synthesizing blood clotting factors. Resisting infections by making immune factors and removing bacteria from the bloodstream. Clearance of bilirubin, also from red blood cells. When the liver has broken down harmful substances, its by-products are excreted into the bile or blood. Bile by-products enter the intestine and leave the body in the form of feces. Blood by-products are filtered out by the kidneys, and leave the body in the form of urine.

Answer 191

Liver abscess is classified by etiology into three major types; -Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases. - Amoebic abscess due to Entamoeba histolytica accounts for 10% of cases. - Fungal abscess, most often due to Candida species, accounts for fewer than 10% of cases. ``` Risk factors for development of hepatic abscess include: ♦️Diabetes mellitus ♦️Liver cirrhosis ♦️Immunocompromised state ♦️Male sex ♦️Advanced age ♦️Proton-pump inhibitor use ♦️Billiary tract diseases ♦️Underlying malignancy ```

Answer 192

*PATHOPHYSIOLOGY OF LIVER ABSCESS* Liver abscess can be amebic, fungal or bacterial in origin. _Entamoeba_ _histolytica_ is the causative agent in amebic abscesses. It is contracted by ingestion of food or water contaminated by the cyst stage of the parasite. Amebiasis generally only involves the intestine but can invade the mesenteric venules resulting in liver abscesses. Its only host is the human. Pyogenic abscesses can be a result of instrumentation but are most often caused by _bacteria_ and ascending cholangitis (Cholangitis is an inflammation of the bile duct system. The bile duct system carries bile from your liver and gallbladder into the first part of your small intestine (the duodenum). ) in the setting of biliary obstruction. Microorganisms isolated are most often bowel flora. Other routes of contamination include the portal vein and hepatic artery. Fungal abscesses primarily are due to _Candida albicans_ and occur in individuals with prolonged exposure to antimicrobials, hematologic malignancies, solid-organ transplants, and congenital and acquired immunodeficiency. Patients with intra-abdominal infections may present with liver abscesses with extension of bacteria through the portal venous system.

Answer 193

ETIOLOGY OF LIVER ABSCESS Liver abscess can be caused by infections in the blood, gastrointestinal system, or abdomen. It can also be caused by injury from a surgical procedure or other trauma to the liver. Liver abscess may result from the following infectious causes: ♦️Bacterial infection in the bile-draining tubes ♦️Bacterial infections bowel the abdomen associated with appendicitis, diverticulitis, or perforated bowel ♦️Bloodstream infections ♦️Entamoeba histolytica infection (organism that also causes amebic dysentery; may be spread through water or through person-to-person contact) Liver abscess may result from diagnostic procedures in the liver, as well as accidental trauma including endoscopy of the bile-draining tubes. ``` *SYMPTOMS OF LIVER ABSCESS* ⭕Chest pain (lower right) ⭕Pain in the right upper abdomen (more common) or throughout the abdomen (less common) ⭕Clay-colored stools. ⭕Dark urine. ⭕Fever, chills, night sweats. ⭕Loss of appetite. ⭕Nausea, vomiting. ⭕Unintentional weight loss. ⭕Malaise ⭕Right shoulder pain due to phrenic nerve irritation. ⭕Cough ⭕Dysonea ⭕Anorexia ⭕Abdominal pain ⭕Hiccups from diaphragmatic irritation. ```

Answer 194

*SIGNS AND PHYSICAL EXAMINATION FINDINGS OF LIVER ABSCESS* Common physical examination findings associated with liver abscess may include: Appearance of Patient Patients with liver abscess appear ill and sweating . Appears thin due to weight loss and confused in later stages of disease. *Vital signs* High grade fever (>38°C) chills Tachycardia *Skin* Yellowish discoloration of skin (jaundice) *HEENT* Icteric sclera *Lungs* Reduced breath sounds or crepitations at right lung base may be heard. *Heart* Chest tenderness on palpation Audible pericardial friction rub (sign associated with high mortality) S1 and S2 are normal *Abdomen* Content is available under Hepatomegaly with point tenderness over the liver, in the intercostal spaces, or below the ribs. Epigastric mass if left lobe is involved Abdominal guarding or rebound tenderness Due to dullness on percussion. The movement on right side of the chest and abdomen is restricted (ascites) Abdominal distension in advanced cases Absent bowel sounds *Extremities* Bilateral pedal edema in advanced liver disease.

Answer 195

*DIFFERENTIAL DIAGNOSIS OF LIVER ABSCESS*. *_Infectious_* ♦️Bacterial •pyogenic liver abscess •Tuberculosis •Bartonella ♦️Fungal •Fungal liver abscess •Hepatosplenic Candidiasis •Endemic fungi ♦️Parasite/protozoa •Amoebic liver abscess •Hepatic Hydatid Cyst (Echinoccocus) •Fasciola (liver fluke) *_Non-infectious_* ♦️Malignancy •Hepatocellular Carcinoma •Metastasis ♦️Simple Cyst ♦️Hemangioma ♦️Biloma ``` Other differntials include; ♦️Acute Gastritis ♦️Cholecystitis ♦️Parapneumonic Pleural Effusion ♦️Empyema Thoracis ```

Answer 196

*LABORATORY INVESTIGATIONS* Some laboratory investigations that can be done to diagnose liver abscess includes; ⭕An abdominal ultrasound to locate an abscess. ⭕A CT scan with intravenous contrast, or injected dye, to find and measure the abscess. ⭕Blood tests to look for signs of infectious inflammation, such as an increased serum white blood count and neutrophil level. ⭕Blood cultures for bacterial growth to determine which antibiotic (s) is/are needed. ⭕An MRI of the abdomen. ⭕Serum antibody and antigen test to detect Entamoeba Histolytica. ⭕Stool cultures ⭕Chest X-ray can also be done *COMPLICATIONS OF LIVER ABSCESS* ♦️Sepsis ♦️Empyema resulting from contiguous spread or intrapleural rupture of abscess. ♦️Rupture of abscess with resulting peritonitis. ♦️Endophthalmitis when an abscess is associated with K pneumoniae bacteremia. ♦️Brain abscess which can cause permanent neurological damage.

Answer 197

*TREATMENTS* In general, both antibiotic therapy and adequate drainage are required for the treatment of liver abscess in combination. For fungal abscess, the antibiotics used are; •Fluconazole •Amphotericin B For amoebic abscess, the antibiotics used are; •Metronidazole * Tinidazole * Paramomycin or diloxanide For pyogenic abscess, the antibiotics used are; •Penicillinase resistant penicillin or first generation cefalosporin in case of Staphylococcal or Streptococcal infections. * Ampicillin combined with an aminoglycoside (ie. Gentamicin) for the treatment of the abscess secondary to a biliary disease. * Aminoglycoside with either metronidazole or clindamycin. * Quinolone antibiotics such as levofloxacin and metronidazole. True

Answer 198

*PREVENTION* | Immediate treatment for intraabdominal infections is the best preventive measure of liver abscesses.

Answer 199

Please it was made mention that diabetes mellitus is a risk factor of liver abscess and most people diagnosed with especially type 2 diabetes mellitus are males and so it makes them a risk factor of pyogenic liver abscess So please for the common modalities in diagnosing in UCC hospital, blood tests, blood and stool cultures, chest X-ray and serological tests can be done fbc, blood & stool culture and abdominal ultrasound

Answer 200

DEFINITION •Portal Hypertension is an increase in pressure within the portal vein, which carries blood from the digestive organs to the liver as a result oblockage in the blood flow through the liver. •veins coming from the stomach, intestines, spleen and pancrease merge into the portal vein, which then branches into smaller vessels and travels through the liver. High pressure in the portal system develops when blood cannot flow through the liver properly as a result of blocked blood vessels in the liver due to liver damage. •The increased pressure may lead to the development of varices (swollen veins) within the esophagus, stomach, rectum or umbilical area, which can rupture and bleed leading to life threatening complications.

Answer 201

•Prehepatic causes(before the liver) 1. portal vein thrombosis 2. Splenic vein thrombosis 3. Arteriovenous fistula( increased portal blood flow) 4. Splenomegaly •Hepatic causes 1. Cirrhosis of any cause( this is the most common cause of portal hypertension a. alcohol use disorder b) chronic viral hepatitis c) biliary atresia d) primary biliary cirrhosis 2. Primary sclerosing cholangitis 3) Chronic Pancreatitis 4) Hereditary hemorrhagic telangiectasia 5) Schistosomiasis 6) Nodular regenerative hyperplasia 7) Viral hepatitis 8) Fibrosis of space Disse 9) Fatty liver disease 9) Veno-occlusion disease •Post hepatic causes(behind the liver ) 1. Inferior vena cava obstruction 2. Right sided heart failure 3. Budd-Chiari Syndrome(hepatic vein thrombosis

Answer 202

True Liver cirrhosis True

Answer 203

The pathophysiology of portal hypertension is characterised by various pathologic processes and factors 1. Hepatic vasodilators 2. Splanchnic Vasodilators 3. Hyperdynamic Circulations 4. Portosystemic Collateral Circulation 5. Vasoconstrictors and Hepatic Vascular Bed 6. Endothelial Dysfunction

Answer 204

``` Hepatic Vasodilators;(they don’t work properly or they’re decreased and due to this there is increased intrahepatic vascular resistance or resistance in the liver vascular beds to the flow from the portal vein to the liver.) : the two hepatic vasodilators involved in portal hypertension are Nitric Oxide ( NO) and Carbon Monoxide ( CO). Nitric Oxide is a powerful endogenous vasodilator and it modulates the intrahepatic vascular tone. However, in cirrhotic liver, the synthesis of NO is insufficient to compensate for the activation of vasoconstrictor systems frequently associated with cirrhosis. This occurs despite a normal expression f of eNOS(endothelial nitric oxide synthase )mRNA (enos mrna produces nitric oxide). and normal levels of eNOS protein and decreased activity of hepatic eNOS in cirrhosis is due in part to increased expression of caveolin(Caveolin-1 (CAV1), the structural protein of caveolae in the plasma membrane, has emerged as a regulator of liver function. ). Therefore, the insufficient hepatic NO production may account for increase intrahepatic vascular resistance in cirrhosis. (The intrahepatic resistance refers to the resistance in the liver vascular bed to the flow that reaches the liver via the portal vein and can experimentally be assessed, based on Ohm's law, by measuring portal pressure changes when an increasing portal venous flow is applied. The primary cause of portal hypertension in cirrhosis is an increase in intrahepatic vascular resistance.) Carbon Monoxide (CO) is considered as an important modulator of intrahepatic vascular resistance. CO activates guanylate cyclase and thereby promotes smooth muscle relaxation. The inhibition of CO production increases portal resistance in normal liver and HO(hydrocarboxyl)/CO system is activated in patients with liver cirrhosis. ``` • Splanchnic Vasodilation: Increased levels of vasodilators are observed because of impaired hepatic function or development of portosystemic collaterals as most of them underwent hepatic metabolism. NO is involved in the regulation of splanchnic and systemic hemodynamics in portal hypertension. Cirrhotic patients show increased levels of serum and urinary concentrations of nitrate and nitrite which are products of NO oxidation. Glucagon is a vasodilator which is associated with splanchnic hyperemia and because of impaired hepatic function or development of portosystemic collaterals as most of them underwent hepatic metabolism. NO is involved in the regulation of splanchnic and systemic hemodynamics in portal hypertension. Cirrhotic patients show increased levels of serum and urinary concentrations of nitrate and nitrite which are products of NO oxidation. Glucagon is a vasodilator which is associated with splanchnic hyperemia and portal hypertension. Two mehanisms are considered for vasodilation by glucagon;relaxing the vascular smooth muscle and decreasing its sensitivity by endogenous vasoconstrictors such as norepinephrine, vasopressin and angiotensin II. . Hyperdynamic circulation: The portal hyprtension is directly related to portal inflow and/outflow resistance , as determined by Ohm’s law portal presure=portal venous inflow*outflow resistance Portal venous inflow is affected by hyperdynamic circulation, which is characterised by systemic and splanchnic vasodilation, low systemic resistance, plasma volume expansion and high cardiac index. Splanchnic vasodilation contributes to increasing substantial blood volume which returns to the portal venous system. Peripheral vasodilation activates endogenous neurohumoral systems that cause the retention of sodium which leads to expansion of plasma volume

Answer 205

Portosystemic Collateral Circulation: Formation of collaterals is a complex process involving the opening, dilation and hypertrophy of preexisting vascular channels. Collaterals develop in response to the increased portal pressure.A minimum HVPG threshold of 10mmHg should be reached for the devlopment of portal systemic collaterals. Increased production or exagerated response of the hepatic bed to vasoconstrictors: Different vasoconstrictive factors have been involved in the regulation of hepatic vascular tone leading to portal hypertension. These include adrenergic agonist such as norepinephrine causes an increase in intrahepatic vascular resistance. Also, hyperresponse of the hepatic bed is as a result of overproduction of thromboxane A2 by COX-1 isoenzyme. Angiotensin II is another powerful vasoconstrictorwhich contributes to increasing hepatic resistance. Endothelins(ET-1and ET-3), specifically ET-1 increases portal perfusion pressure by increasing intrahepatic resistance in normal and cirrhotic livers •Endothelial dysfunction: In normal conditions, the endothelium is able to generate vasodilator stimuli in response to increases in blood volume, blood pressure or vasoconstrictor agents in an attempt to prevent or attenuate the concomitant increase in pressure. Endothelial dysfunction in cirrhosis has been attributed to reduced NO bioavailability In summary, the factors above contribute to the pathophysiology of portal hypertension by increasing portal blood flow or increase in vascular resistance or both. Increase in portal venous inflow maintains or aggravates portal hypertension

Answer 206

The complications of portal hypertension are the complication of liver failure 1. Gastrointestinal bleeding from varices 2. Ascites: Ascites is lymphatic fluid that leaks across hepatic sinusoidal endothelium due to high hepatic sinusoidal pressure portal hypertension develops, the formation of collateral vessels and arterial vasodilation progress, which results in increased blood flow to the portal circulation. Eventually the hyperdynamic circulatory syndrome develops, leading to esophageal varices or ascites. 3.Hepatic encephalopathy Signs and symptoms Hematemesis or Melena: may indicate gastroesophageal variceal bleeding or bleeding from portal gastrophy. The term portal hypertensive gastropathy (PHG) defines a wide spectrum of diffuse macroscopic lesions that appear in the gastric mucosa of patients with portal hypertension * Mental status change: indicating portosystemic encephalopathy * Increasing abdominal girth: may indicate ascites formation * Abdominal pain and fever: may indicate spontaneous bcterial peritonitis * Hematochezia: may indicate bleeding from portal colopathy (disease of the colon) : Hematochezia is the passage of fresh blood per anus, usually in or with stools. Portal hypertensive colopathy (PHC) is a condition in which changes occur in the mucosal membrane of colon in patients affected with portal hypertension and liver cirrhosis

Answer 207

Laboratory studies are directed towards investigating the causes of cirrhosis, which is the most common cause of portal hypertension 1.Full blood count: The presence of anemia(Up to 70% of cirrhotic patients have reduced hemoglobin levels. The pathogenesis of anemia in cirrhosis is complex and multifactorial, and includes portal hypertension- induced sequestration, alterations in erythropoietin, bone marrow suppression and increased blood loss ) , leukopenia (low level of white blood cells in the blood, which can interfere with the ability to fight infection. )and thrombocytopenia(low number of platelets in the blood. Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease.) may be present in patients with cirrhosis. Anemia may be secondary to bleeding, nutritional deficiencies or bone marrow suppression secondary to alcoholism 2.Liver disease-associated tests: Abnormal liver function can be approached astransaminitis [an elevation of the plasma activity of aspartate aminotransferase (AST) and alanine aminotransferase(ALT)] or cholestasis (Cholestasis is defined as a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts. Therefore, the clinical definition of cholestasis is any condition in which substances normally excreted into bile are retained. The serum concentrations of conjugated bilirubin and bile salts are the most commonly measured) [ an elevation of bilirubin, especially conjugated bilirubin with or without increased alkaline phosphatase(ALP) activity, with both occuring in cirrhosis 3. Coagulation test: Synthetic function of the liver is impaired in cirrhotic patient, therefore, coagulopathy with prolonged PT, plasma thromboplastic time (PTT)is expected. Prolonged International Normalized ratio is suggestive of impaired hepatic synthetic function 4. Blood urea nitrogen(BUN),creatinine and electrolytes: BUN and creatinine levels may be elevated in patients with esophageal varices as a complication of portal hypertension. 5. Duplex Doppler Ultrasound :Nodular liver surface , splenomegaly, and collateral circulation is suggestive of cirrhosis and portal hypertension 6. CT scanning and MRI: CT scan findings suggestive of portal hypertension include collaterals arising from the portal system and dilatation of the inferior vena cava. MRI detects presence of portosystemic collaterals and obstruction portal vasculature 7. Upper GI endoscopy:Presence of esophageal varices is suggestive of portal hypertension. However,it absence does not rule it out .

Answer 208

Treatment is directed towards the cause of portal hypertension. Gastroesophageal variceal hemorrhage is the most lethal complication of portal hypertension, therefore most of the treatment focuses on it. •Pharmacological treatment includes the administration non selective beta-blockers(, By slowing the heart rate and widening the blood vessels, beta-blocker medicines such as propranolol and nadolol appear to lower the blood pressure in varices that bypass the liver. In people who have esophageal varices, beta-blockers have been shown to reduce the risk of having a first episode of bleeding.) most commonly propranolol and nadolol. •Endoscopy procedures such as scleropathy.(Sclerotherapy is a medical procedure used to treat varicose veins and "spider veins." A solution is injected directly into a vein, causing the lining of the blood vessel to swell and stick together. Over time, the vessel turns into scar tissue that fades from view. Abnormal veins in the lower part of the tube running from the throat to the stomach.Oesophageal varices usually develop when blood flow to the liver is blocked. ) and variceal ligation (endoscopic variceal banding (or ligation):During variceal banding, a doctor uses an endoscope to place an elastic ring that looks like a rubber band around an enlarged vein. Banding the vein in this manner will cut off blood flow through the vein. )can be used to prevent th recurrence of variceal hemorrhage •Surgical care includes the use of decompressive shunts, devascularization pocedures and liver transplant Treatment of patients without variceal hemorrhage includes low sodium diet and diuretics PREVENTION •Maintaining good nutritional hanits and keeping a healthy lifestyle will help the liver function properly. Some of them include 1.Donot use alcohol or street drugs or abuse drugs 2.Do not take any over-the-counter or prescription drugs without first consulting a physician 3.Reduce sodium(salt) intake

Answer 209

Liver failure is an uncommon condition in which rapid deterioration of liver function results in coagulopathy and alteration in the mental status ( (encephalopathy) Liver failure indicates that liver has sustained injury Fulminant hepatic failure(Fulminant hepatic failure (FHF) is usually defined as the severe impairment of hepatic functions or severe necrosis of hepatocytes in the absence of preexisting liver disease.): •Encephalopathy starts within 8 weeks Non fulminant hepatic failure •Encephalopathy starts between 8 to 26 weeks Acute liver failure (ALF) is a rare condition characterized by abrupt onset of severe liver injury •Acute liver failure is loss of liver function that occurs rapidly in days or weeks usually in a person who has no pre-existing liver disease. •It is a medical emergency that requires hospitalization.

Answer 210

True ``` Viral hepatitis •Drug induced hepatotoxicity •Toxin related hepatotoxicity •Vascular causes •Metabolic causes ```

Answer 211

VIRAL HEPATITIS •Viral hepatitis is an infection that causes liver inflammation and damage. •Researchers have discovered several different viruses that causes hepatitis including hepatitis A, B, C,D and E. DRUG INDUCED HEPATOTOXICITY •Drug induced hepatotoxicity is an acute or chronic liver injury secondary to drugs or herbal compounds. TOXIN RELATED HEPATOTOXICITY •This is an inflammation of the liver caused by exposure to chemicals or drugs, or from drinking excessive amount of alcohol. VASCULAR CAUSES •The following are vascular causes of hepatic failure: ischemic hepatitis ( consider especially in the setting of severe hypotension or recent hepatic tumor chemoembolization), Hepatic vein thrombosis or hepatic veno-occlusive disease. METABOLIC CAUSES •Reye syndrome ( fatty liver + encephalopathy), Reye syndrome is characterized by acute noninflammatory encephalopathy and fatty degenerative liver failure.,-(rare but serious condition that causes confusion, swelling in the brain and liver damage.) •Alpha1-antitrypsin. (shape and blockage) -(Alpha-1 antitrypsin protein usually travels from your liver through your blood to protect your lungs and other organs. But if the proteins aren't the right shape, they can get stuck in your liver. This can cause cirrhosis, severe liver damage and scarring, and liver cancer.) •Wilson disease. (copper accumulation, As the copper builds up in the liver, it begins to damage the organ. After enough damage, the liver releases the copper directly into the bloodstream, which carries the copper throughout the body. ) •Galactosemia (Decreased liver enzyme to break down)-This disease is caused by elevated levels of galactose (a sugar in milk) in the blood resulting from a deficiency of the liver enzyme required for its metabolism (breakdown). Too much galactose builds up in the blood. This accumulation of galactose can cause serious complications such as an enlarged liver •Fructose intolerance. (Def. of aldolase B which results in inability to convert fructose 1 phosphate into dihydroxyacetone and glyceraldehyde.) MALIGNANCIES •Primary liver tumour (hepatocellular carcinoma). •Secondary tumour includes hepatic metastasis or breast, lung cancer.

Answer 212

``` Signs and symptoms OF ALF •Hepatic encephalopathy •Sudden jaundice •Pain and tenderness in the upper right side of the stomach •Ascites •Nausea •Vomiting •Melena ``` DIAGNOSTIC EVALUATION •History collection •Physical examination •Prothrombin time-longer-than-normal PT can mean a lack of or low level of one or more blood clotting factors (factors I, II, V, VII, or X). It can also mean a lack of vitamin K; liver disease, such as cirrhosis; or that a liver injury has occurred. Liver disease that results in decreased bile salt synthesis leads to impaired vitamin K absorption and deficiency. •Blood cultures. For patients with suspected infection-Infection. Parasites and viruses can infect the liver, causing inflammation that reduces liver function. •electroencephalography

Answer 213

MANAGEMENT OF ALF •Treatment of acute liver failure consists of drugs and liver transplantation •Pharmacological management includes certain antidotes to reverse the effects of ALF and various medications to reduce ICP •Antidotes neutralize toxic agents or counteract any form of poisoning ``` PHARMACOLOGICAL INTERVENTION •Penicillin G. •Activated charcoal •N-Acetylcysteine (improves liver function. N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, has been used to loosen thick mucus in the lungs and treat acetaminophen overdose for decades. However, NAC can also boost the immune system, suppress viral replication, and reduce inflammation.) •Osmotic diuretics •Barbiturate •Benzodiazepine •Anaesthetic agents ``` LIVER TRANSPLANTATION •When acute liver failure cannot be reversed only treatment maybe a liver transplant •Liver transplantation is indicated for many patients with ALF

Answer 214

``` COMPLICATIONS •Kidney failure •Cerebral edema •Bleeding disorders •Infections ``` PREVENTIVE MEASURES •Limit the amount of alcohol •Avoid eating wild mushrooms •Get vaccinated for hepatitis

Answer 215

Hepatitis is simply the inflammation of the hepatocytes or the liver cells. •It can be acute , when the symptoms last for less than 6 months or chronic when the symptoms persist for more than 6 months. Viruses (Hepatitis A, B, C, D and E, Yellow Fever etc.) •Drugs (allopathic, alternative and herbal preparations) e.g. methyldopa, isoniazid, ketoconazole •Alcohol •Autoimmune Response •Hereditary eg Wilson’s disease •Inflammatory bowel disease – ulcerative colitis,

Answer 216

* The etiological agents such as the viruses(Hepatitis A, B, C, D and E, Yellow Fever) enters the bloodstream and infect the hepatocytes and multiply. The body begins to produce immune response to remove the infectious agents, by sending cytotoxic T cells and natural killer cells to the virus and thereby release inflammatory cytokines. The inflammatory response is normal, but in the process of eradicating the infection, host tissues of the liver is injured and this damages the liver. * In Alcoholic hepatitis, in the process of breaking down excess alcohol by the liver, the liver causes inflammation when it recognizes the excess by-products of the alcohol as foreign in the liver and progressively cause liver cell injury.

Answer 217

Symptoms * Right hypochondrial pain * Fever (occurring 1 to 4 weeks before the jaundice appears) * Malaise * Anorexia * Nausea * Vomiting * Yellow or dark coloured urine * Pale stools * Itching * Fatigue * Confusion Signs •Right hypochondrial tenderness •Hepatomegaly •Asterixis •Jaundice •mild splenomegaly (uncommon except in Epstein–Barr virus (EBV)infection. •Mild hepatomegaly (but rapid shrinkage occurs in severe hepatitis) •cervical lymphadenopathy (uncommon) •Skin manifestations include spider naevi scratch marks in the pruritic phase, and rarely urticarial rash

Answer 218

``` Causes(Common) 1.Hepatitis A 2.Hepatitis B 3.Hepatitis C 4.Hepatitis D 5.Hepatitis E Less common 6.Cytomegalovirus 7.Epstein–Barr virus-The Epstein–Barr virus, formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. 8.Herpes Virus 9.Yellow Fever •They differ in their tendency to cause acute and chronic infections. ``` * Hepatitis A, B, C, and E can all initiate an acute self-limited hepatitis * Only hepatitis B and C can cause chronic viral hepatitis. * Hepatitis D co-infects patients infected with hepatitis B.

Answer 219

``` Hep A- common name-infectious Hep B-Serum C-post transfusion non-A and non-B D-Delta E-Enteric non-A and non-B ``` ``` Hep A-viral structure-naked RNA like picornavirus Hep B-Envelope,DNA like hepadnavirus HepC-Envelope RNA like flavivirus HepD-Envelope RNa HepE-naked RNA (calici like) ``` ``` HepA-fecal oral B-parenteral,sexual C-same D-same E-fecal oral ``` ``` HepA-short B-long C-Same D-intermediate E-Short ``` ``` HepA-abrupt B-insidious C-same D-abrupt E-same(abrupt) ``` ``` HepA-severity-mild or asymptomatic B-occasionally severe C-usually subclinical D-occasionally to often severe E-mild but severe in pregnant women ``` ``` A-very low B-low C-low D-high to very high E-low but high in pregnant women ``` ``` A-No B-Yea C-Yes(common) D-Yes E-No ``` ``` A-none B-HCC,cirrhosis C-same D-cirrhosis,fulminant hepatitis E-none ```

Answer 220

Picornavirus Fecal oral •Common in children but often asymptomatic. •Common in overcrowding and poor sanitation areas •Vehicles of transmission : water and shellfish . True

Answer 221

Serilogical Test : Infected people make an antibody to this HAV antigen (anti-HAV). * Anti-HAV of the IgM type indicates a primary immune response in the blood at the onset of the clinical illness and is diagnostic of an acute HAV infection. * Anti-HAV of the IgG type is of no diagnostic value but it can be used as a marker of previous HAV infection. Its presence indicates immunity to HAV. Improving sanitation conditions, especially overcrowding and poor sanitation. * Active immunisation with an inactivated virus vaccine gives substancial protection. * Immediate protection can be provided by immune serum globulin given post-exposure to the virus. * There is no role for antiviral drugs in the therapy of HAV infection

Answer 222

The HBV consists of a core containing DNA and a DNA polymerase enzyme needed for virus replication. Surface protein Dane virus and it’s surface protein known as Hep B surface antigen circulate in the blood True Hep B True Vertical transmission from mother to child in the perinatal period is the most common cause of infection. True

Answer 223

``` Horizontal transmission (10%) • Injection drug use • Infected unscreened blood products • Tattoos/acupuncture needles • Sexual (homosexual and heterosexual) ``` * Vertical transmission (90%) * HBsAg-positive mother general, transmission of viruses can occur through two pathways: horizontal and vertical transmission. In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring. ``` Parenteral drug users •Men who have sex with men •Close contacts of infected individuals •Newborn of infected mothers •Regular sexual partners •Patients with chronic liver disease •Medical, nursing and laboratory personnel ```

Answer 224

●Serological tests HBV contains several antigens to which infected persons make immune responses. These antigens and their antibodies are important in identifying HBV infection. NB: IgM shows recent infection IgG shows chronic infection. Hepatitis B surface antigen (HBsAg) •HBsAg is an indicator of active infection, and a negative test for HBsAg makes HBV infection very unlikely. •HBsAg appears in the blood and usually lasts for 3–4 weeks but can persist to 5 months. Investigation of HBV HBsAg longer than 6 months is chronic infection •Antibody to HBsAg (anti-HBs) usually appears after about 3–6 months and persists for many years or perhaps permanently. •Anti-HBs implies either previous infection (anti-HBc present) or previous vaccination(anti-HBc is absent). Hepatitis B core antigen (HBcAg). HBcAg is not found in the blood, but antibody to it (anti-HBc) appears early in blood. •Anti-HBc is initially of IgM type and IgG antibody appearing later. •Anti-HBc (IgM) can sometimes reveal an acute HBV Infection between when the HBsAg has disappeared and develeping of anti-HBs. Hepatitis B e antigen (HBeAg). •HBeAg is an indicator of viral replication. Its appearance is followed by the production of antibody (anti-HBe). The HBeAg reflects active replication of the virus in the liver. Some intepretations : •Chronic HBV infection = presence of HBsAg and anti-HBc (IgG) in the blood. * Continued active replication of the virus in the liver and infectious = presence of HBeAg. * The low viral replication and less infectious = absence of HBeAg or anti-HBeAg(Antibody of HBeAg) Viral load and genotype •HBV-DNA can be measured by PCR in the blood. •Measurement of viral load is important in monitoring antiviral therapy . •Specific HBV genotypes (A–H) can also be identified using PCR.

Answer 225

Acute •Treatment is supportive with monitoring. •There is no definitive evidence that antiviral therapy reduces the severity or duration of acute hepatitis B. •Full recovery occurs in 90–95% of adults. The remaining 5–10% develop a chronic hepatitis B infection that usually continues for life. Chronic HBV •Infection passing from mother to child at birth leads to chronic infection in the child in 90% of cases. •Chronic infection is also common such as those with Down’s syndrome or human immunodeficiency virus (HIV) infection. •No drug is consistently able to eradicate hepatitis B infection completely. •The indication for treatment is a high viral load in the presence of active hepatitis, as demonstrated by elevated serum transaminases. Two different types of drug are used to treat hepatitisB: 1. direct-acting nucleoside/nucleotide analogues eg Lamivudine, Entecavir and tenofovir. These act by inhibiting the reverse transcription of pre-genomic RNA to HBV-DNA by the enzymeHBV-DNA polymerase. 2.Pegylated interferon-alfa. This is most effective in patients with a low viral load and serum transaminases(ALT and AST) greater than twice the upper limit of normal, in whom it acts by potentiating the native immune response.

Answer 226

``` This is caused by an RNA flavivirus. • •Hepatitis C is the cause of what used to be known as‘non-A, non-B hepatitis’. • True True ```

Answer 227

Serology and virology •The HCV protein contains several antigens that give riseto antibodies in an infected person and these are used in diagnosis. •It may take 6–12 weeks for antibodies to appear in the blood following acute infection such as a needlestick injury. •Active infection is confirmed by the presence of serum hepatitis C RNA in anyone who is antibody-positive. •Anti-HCV antibodies persist in serum even after viral clearance, whether spontaneous or post-treatment . Intravenous drug misuse 2. Unscreened blood products for transfusion 3. Vertical transmission (3% risk) 4. Parenteral transmission (i.e. Contaminated needles or Needlestick injury) 5. Sharing toothbrushes/razors

Answer 228

The treatment of choice was dual therapy (pegylated interferon-alfa given as a weekly subcutaneous injection + oral ribavirin, a synthetic nucleotide analogue) •The availability of triple therapy with protease inhibitors such as telaprevir and the above dual therapy.

Answer 229

True HDV contains a single antigen to which infected individuals make an antibody (anti-HDV). •Delta antigen appears in the blood only transiently, and in practice diagnosis depends on detecting anti-HDV. Effective management of hepatitis B prevents hepatitis D.

Answer 230

An RNA virus that is endemic True Disease is spread via the faecal–oral route; in most cases, it presents as a self-limiting acute hepatitis and does not usually cause chronic liver disease Management is the same as HAV

Answer 231

FBC : The white cell count is usually normal with a relative lymphocytosis. * Liver function tests : AST, aspartate aminotransferase and ALT alanine aminotransferase are raised at the time of the onset of symptoms whilst the serum alkaline phosphatase(ALP) level is only slightly increased. * Serological tests confirm the aetiology of the infection(HBsAg, HCV Antibody, Hepatitis A IgM, Hepatitis E IgM) * Prothrombin Time (PT) or Erythrocyte Sedimentay Rate : Prolonged PT indicates the severity of the hepatitis. * Urinary R/E : shows excess urobilinogen in early and late phases. * Abdominal Ultrasound: To check splenomegaly, hepatomegaly etc * Liver biopsy

Answer 232

Non-pharmacological treatment •Rest •High calorie fluids (especially glucose drinks, fruit juice, light porridge, koko, rice-water, mashed kenkey) •Intravenous fluids if volume deplete . •Any food that the patient can tolerate. •Avoid alcohol •Drugs such as sedatives and narcotics, which are metabolised in the liver, should be avoided eg Paracetamol Pharmacological treatment •Supportive care (analgesia, fluid replacement, etc. as required) General Management of Hepatitis •Most individuals do not need hospital care. •. No specific dietary modifications •are needed. Alcohol should be avoided during the •acute illness. Elective surgery should be avoided in cases •of acute viral hepatitis, as there is a risk of post-operative •liver failure. •Liver transplantation is very rarely indicated for •acute viral hepatitis complicated by liver failure, but •is commonly performed for complications of cirrhosis •resulting from chronic hepatitis B and C infection. GENERAL MANAGEMENT commonly performed for complications of cirrhosis •resulting from chronic hepatitis B and C infection.

Answer 233

``` Drug-induced jaundice •Alcoholic hepatitis •Acute Wilson's disease •Acute fatty liver Disease •Ischaemia, generally after profound hypotension over many hours •Progressive malignant infiltration ``` ``` Acute liver failure •Cholestatic hepatitis(hepatitis A infection mostly leads to) •Aplastic anaemia •Chronic liver disease •Cirrhosis (hepatitis B and C) •Relapsing hepatitis ``` Chronic: Chronic liver Disease •cirrhosis •hepatocellular carcinoma

Upper And Lower gIT Diseases And Management Flashcards

(261 cards)