Gastroenterology Flashcards
Gastroesophageal reflux disease
Inappropriate transient relaxation of lower esophageal sphincter (most common) or low basal LES tone (scleroderma). Contributing factors such as delayed esophageal clearence, delayed gastric emptying, increased intra-abdominal pressure, hiatus hernia (worsens reflux). Acid hypersecretion by Zollinger-Ellison syndrome is a rare cause.
Features
- Typical: heartburn, acid regurgitation
- Atypical: chest pain, dysphagia, odynophagia
- Respiratory: chronic cough, wheezing, aspiration pneumonia
- Others: sore throat, hoarsness, dental erosions
Investigations
- Clinical diagnosis with symptom history and relief following trial of PPI (80% sensitive for reflux)
- Gastroscopy: rule out other differentials, distinguishes between esophagitis and non-esophagitis reflux, diagnoses Barrett’s esophagus
- Esophageal manometry: diagnose abnormal peristalsis/decreased LES tone
Management
- PPI most effective
- PRN: antacids
- weight loss, elevating head of bed for nocturnal symptoms
Complications
- esophageal stricture
- ulcer
- bleeding
- Barrett’s esophagus and esophageal adenocarcinoma
Barrett’s esophagus
Metaplasia of normal squamous epithelium to abnormal columnar epithelium, results in displacement of squamocolumnar junction at gastroesophageal junction.
More common in males, >50, Caucasians, smokers, overweight, long history of reflux symptoms.
Diagnosis
- endoscopy + biopsy: low-high grade dysplasia
- rate of malignant transformation is approx 0.4% per year for all BE patients prior to dysplasia
Managment
- high grade dysplasia: sureillence with intensive biopsy, endoscopic ablation/resection
- low grade dysplasia: surveillence gastroscopy with esophageal mucosal biopsy, one year after initial diagnosis then every 3 yrs
- PPI high dose in all patients
Dysphagia
Oropharyngeal (difficulty initiating swallow)
- Neurological: cortical, bulbar, peripheral
- Muscular: muscular dystrophy, polymyositis, myasthenis gravis, cricopharyngeal
- Structural: Zenker’s diverticulum, thyromegaly, cervical spur
Esophageal (inability to move food down esophagus)
Solid foods = Mechanical obstruction
- Progressive: carcinoma (age >50 + wt loss), peptic stricture (heartburn)
- Intermittent: Lower esophageal ring
Solid foods + liquids = Neuromuscular disorder
- Progressive: achalasia, scleroderma (relux symptoms)
- Intermittent: diffuse esophageal spasm
Achalasia
Failure of smooth muscle relaxation at LES, progressive loss of peristaltic function. Usually idiopathic but can be secondary to malignancy.
Pathophysiology
- inflammatory degeneration of Auerbach’s plexus, increase in LES pressure, incomplete relaxation of LES with swallowing.
Diagnosis
- CXR: no air in stomach, dilated esophageus
- Barium swallow: “bird’s beak” at LES
- Manometry: definitive diagnosis
Treatment
- dilation of LES with balloon + GERD prophylaxis, 50% good response
- botulinum injection into LES
- myomectomy
Scleroderma
Systemic disease characterised by vasculopathy and tissue fibrosis. Dysphagia caused by reflux and/or dysmotility, resulting in stricture.
Pathophysiology:
- Blood vessel damage, intramural neuronal dysfunction, distal esophageal muscle weakening, aperistalsis and loss of LES tone, reflus and stricture
Diagnosis:
- Clinical features of scleroderma
- manometry: decreased pressure in LES, decreased peristalsis in body of esophagus
Treatment
- medical: aggressive PPI therapy
- surgery: anti-reflux surgery
Diffuse esophageal spasm
Normal peristalsis interspersed with frequent, repetitive, spontaneous, high pressure, non-peristaltic waves. Idiopathic.
Diagnosis
- Barium swallow: “corkscrew”
- Manometry: >30% but <100%
Treatment
- reassurance
- medical: nitrates, CCB
- surgical: long esophageal myotomy if unresponsive to medical, balloon dilatation
Esophageal diverticula
Outpouching of one or more layers of GI tract.
Features:
- motility disorders
- dysphagia, regurgitation, retrosternal pain, intermittent vomiting
Classification
Pharyngoesophageal (Zenker’s) diverticulum
- most common
- posterior pharyngeal outpouching, left-sided above cricopharyngeal muscle
- dysphagia, regurgitation, halitosis
Mid-esophageal diverticulum
- secondary to mediastinal inflammation, motor disorders,
- usually asymptomatic, no treatment required
Proximal to LES
- usually associated with motor disorders
- no treatment required
Webs vs Rings
Web = partial occlusion (upper esophageal) Ring = circumferential narrowing (lower esophagus)
Features
- asymptomatic with lumen >12mm
- Plummer-Vinson syndrome: upper esophageal web with dysphagia, iron deficiency.
- Schatzki’s ring: mucosal ring at squamo-columnar junction above a hiatus hernia, causes intermittent dysphagia with solids.
Infectious esophagitis
Mucosal inflammation and ulceration secondary to viral or fungal infection.
Risk factors:
- diabetes
- malignancy
- immunocompromised states
Features
- odynophagia, dysphagia
Treatment
- Candida: nystatin swish and swallow, fluconazole
- Herpes: self-limiting, aciclovir
- CMV: IV gancyclovir
Gastric secretion
Parietal cells
- gastric acid, intrinsic factor
- stimulated by histamine, ACh, gastrin
Chief cells
- pepsinogen
- stimulated by vagal input and local acid
G-cells
- gastrin
- stimulates H+ production from parietal cells
Superficial epithelial cells
- mucus, HCO3-
- protect gastric mucosa
Neuroendocrine cells
- somatostatin
- involved in neural, hormonal and paracrine pathways
Gastritis
Inflammation of the stomach mucosa.
Acute gastritis
- Hemorrhagic/erosive: alcohol, NSAID/aspirin, shock, physiological stress
- Helicobacter gastritis: H. pylori
Chronic gastritis
- Non-atrophic: H. pylori
- Atrophic: H. pylori, dietary, environmental, autoimmune
- Chemical: NSAID, bile
- Radiation: radiation injury
- Lymphocytic: celiac, drug
- Eosinophilic: food allergies
- Non-infectious granulomatous: Crohn’s, sarcoidosis
Features
- bleeding if erosive, non-erosive are asymptomatic
Management:
- H. pylori eradication
- NSAID avoidance
- Restrict food irritants: alcohol, spices
Peptic ulcer disease
Penetrates the muscularis mucosa and can result in scarring. Associated with cirrhosis, COPD, CRF.
Etiology
- H. pylori: 90% of duodenal, 60% of gastric
- NSAIDs: 35% of gastric, 7% of duodenal
- Physiologic stress-induced: <5% of gastric, <3% of duodenal
- Zollinger-Ellison: rare
- Idiopathic: 15% of duodenal, 10% of gastric
- Others: CMV, ischemic
Features:
- Gastric: atypical symptoms
- Duodenal: epigastric pain, burning, develops 1-3h after eating, relieved by eating or antacids, interrupts sleep, periodicity
- Complication: bleeding, perforation, gastric outlet obstruction, penetration into pancreas
Investigations
- endoscopy
- H. pylori tests
- fasting serum gastrin for Zollinger-Ellison syndrome
Management
- Stop NSAIDs
- Start PPI
- H.pylori eradication
- Smoking cessation
- Avoid alcohol, caffine and spices
Management of bleeding peptic ulcers
- NG tube + aspiration to confirm upper GI bleed
- IV pantoprazole 80mg starting dose + 8mg/h continuous infusion
- Erythromycin 250mg 30 prior to endoscopy
- Endoscopy to explore upper GI tract
- Establish risk of rebleeding/continuous bleed: increased age, bleeding diathesis, previous hx of PUD, comorbid disease, hemodynamically unstable
- Consider ICU admission if high risk
H. pylori-induced ulceration
Gram-negative glagellated rod, resides on gastric mucosa within the mucus layer. Can cause gastritis and decrease protection by mucus.
Clinical outcomes
- Non-erosive gastritis: 100% of patients but asymptomatic
- Peptic ulcer: 15%
- Gastric malignancy
Investigations
- Urea breath test (affected by PPI)
- Serology (can remain positive after treatment)
- Stool antigen
- Histology (gold standard, affected by PPI)
- Rapid urease test on biopsy
Treatment
- Triple therapy for 7-14d: omeprazole BID + amoxicillin 1g BID + clarithromycin 500mg BID
- Quadruple therapy
- Sequential therapy
NSAID-induced ulceration
Cause gastric mucosal petechiae in all users, erosions in most users and ulcers in some users. Also inhibits mucosal COX, decreased prostaglandin synthesis, decrease mucus protection.
Risk factors:
- previous peptic ulcer/UGIB
- age
- high dose of NSAIDs
- concomitant steroid use
- concomitant cardiovascular disease
Management
- prophylactic PPI recommended with above risk factors
- lower NSAIDs, or switch to paracetamol
Stress-induced ulceration
Ulceration or erosion in upper GI tract of ill patients, usually in ICU, most common in fundus.
Risk factors
- mechanical ventilation
- anticoagulation
- multiorgan failure
- septicemia
- severe surgery/trauma
- CNS injury
- burns >35% body surface
Management
- PPI/H2-blockers decreases risk of upper GI bleed but may increase risk of pneumonia
Acute diarrhea
Inflammatory - disruption of intestinal mucosa - bloody, small volume, high frequency, often lower abdominal cramping with urgency +/- tenesmus - fecal WBC and RBC positive Causes - Bacterial: Shigella, Salmonella, Campylobacter, Yersinia, E. coli (0157:H7), C. difficile - Protozoal: E. histolytica - Others: NSAIDs, IBD, ischemic
Non-inflammatory
- intestinal mucosa intact
- watery, large volume, upper/periumbilical pain
- fecal WBC negative
Causes
- Bacterial: s. aureus, C. perfringens, E. coli, Salmonella enteritidis, Vibrio cholera
- Protozoal: Giardia lamblia
- Viral: rotavirus, norwalk, CMV
- Drugs: antibiotics, colchicine, laxatives, antacids/magnesium
Chronic diarrhea
> 14d of loose bowel motions.
Inflammatory
- IBD
- Infectious: C. difficile, TB, CMV, HSV
- Ischemic bowel
- Radiation colitis
- Neoplasia
Secretory
- Stimulant laxatives
- Post-ileal resection/cholecystectomy (bile salts)
- Bacterial toxins
- Vasculitis
- Neoplasia: colon ca, carcinoid, VIPoma
- Addison’s disease
- Congenital syndromes
Steatorrhea
- Giardia lamblia
- Celiac sprue
- Chronic pancreatitis
- Diabetes mellitus
Osmotic
- Osmotic laxatives
- Lactose intolerance
- Chewing gum (sorbitol, mannitol)
Functional
- IBS
- Constipation with overflow
- Anal sphincter dysfunction
Maldigestion and malabsorption
Maldigestion: inability to break down large molecules
- post-gastrectomy
- pancreatic insufficiency
- bile salt deficiency
Malabsorption
- inadequate absorption area: Whipple’s disease, giardiasis, celiac, radiation
- drug induced: cholestyramine, ethanol, antibiotics
- diabetes
Sites of absorption:
- Duodenum: iron, calcium, carbohydrates
- Jejunum: iron, calcium, folic acid, carbohydrates, protein
- Ileum: IF-B12 complex
Celiac disease
Autoimmune reaction of gliadin. HLA-DQ2 found in 80-90% of patients. 15% of first degree relatives, peak presentation at infancy.
Features
- diarrhea, weight loss, anemia, symptoms of vitamin/mineral deficiency, failure to thrive, bloating, gas iron deficiency
- disease is usually most severe in proximal bowel, iron, calcium, folic acid deficiency more common than B12 deficiency
- dermatitis hepertiformis, epilepsy, myopathy, depression, paranoia, infertility, bone fractures/metabolic bone disease
Investigations
- anti-tTG antibody
- Mucosal biopsy: villous atrophy, crypt hyperplasia, increased plasma cells and lymphocytes
- low ferritin, Ca, albumin, cholesterol, carotene, B12 absorption
Management
- Dietary couselling: avoid wheat, barley, rye, (oats)
Prognosis
- increased risk of lymphoma, carcinoma
- risk of malignancy lowered by dietary gluten restriction
Crohn’s disease
Chronic transmural inflammatory disorder affecting from mouth to perianal region.
Features:
- Location: small bowel + colon in 50%
- Symptoms: post-prandial/colicky pain, fever, RLQ mass
- Endoscopic: ulcers, patchy lesions, pseudopolyps, cobblestoning
- Histologic: transmural distribution with skip lesions, focal inflammation, non-caseating granulomas, deep fissuring, apthous ulcerations, strictures
- AXR: cobblestone mucosa, frequent strictures and fistulas
- Complications: strictures, fistulas, perianal disease
- Increased risk of colon cancer
Extraintestinal manifestations
- Dermatologic: perianal skin tags, oral mucosal lesions, erythema nodusum, pyoderma gangrenosum
- Rheumatologic: peripheral arthritis and ankylosin spondylitis more common in Crohn’s, sacroiliitis
- Ocular: uveitis, episcleritis
- Hepatobiliary: cholelithiasis, primary sclerosing cholangitis
- Urologic: calculi, fistulae
Investigations
- Colonoscopy
- CT enterography (small bowel)
- elevated CRP
Management - Lifestyle: smoking cessation - Avoid anti-diarrheal agents during flareups - 5-ASA: sulfasalazine, mesalamine - Corticosteroids: prednisone - Immunosuppression: 6-mercaptopurineazathioprine, methotrexate - Immunomodulators: TNF-antagonist Surgery: reserved for complications
Prognosis
- highly variable course
- increased mortality with more proximal disease
Ulcerative colitis
Inflammatory disease affecting colonic mucosa anywhere from rectum to cecum, originates at rectum. Decrease risk in smokers.
Features
- Location: isolated to large bowel
- Symptoms: rectal bleeding, frequent small stools, pre-defectory urgency, tenesmus
- Endoscopic: continous diffuse inflammation, erythema, friability, loss of normal vascular pattern, pseudopolyps
- Histologic: mucosal distribution, continous disease, gland destruction, crypt abscess
- AXR: lack of haustra, strictures rare
- Complications: toxic megacolon
- increased risk of colon cancer
Extraintestinal manifestations
- Dermatologic: erythema nodusum 10%, pyoderma gangrenosum
- Rheumatologic: peripheral arthritis, ankylosin spondylitis and sacrolilitis
- Ocular: uveitis, episcleritis
- Hepatobiliary: primary sclerosing cholangitis
Investigations:
- sigmoidoscopy with mucosal biopsy
- colonoscopy to see extent of disease
- CT colonography if colonoscopy is contraindicated
Management
- 5-ASA: topical suppository very effective for distal disease, oral for mild-moderate disease
- Corticosteroids: remssion in acute disease, used as suppositories
- Immunosuppressants: IV cyclosporine or IV infliximab for servere UC, rapidly effective in a minority of patients. Azathioprine most commonly used to induce and maintain remission after steroid withdrawal
- Surgery: early in severe UC, aim for cure with colectomy
Complications
- more liver problems such as PSC
- greater risk of colorectal cancer
- toxic megacolon
Prognosis
- chronic relapsing problem in most patients
Irritable bowel syndrome
Functional bowel disease, onset of symptoms usually in young adulthood.
Criteria:
- > 12 weeks in the past 12 months of abdominal pain that has 2 out of 3 of the following:
- relieved with defecation,
- associated with change in stool frequency,
- associated with change in stool consistency
Investigations
- diagnosis of exclusion
Management
- reassurance, explanation
- stress reduction, relaxation therapy
- pain reduction: antispasmodic medication before meals, increase dietary fibre, TCA or SSRI
- diarrhea predominant: increase dietary fiber, loperamide, cholestyramine
- constipation predominant: exercise and increase dietary fibre, osmotic or other laxatives
Constipation
Passageof infrequent or hard stools with straining, bowel frequency <3/wk.
Etiology
- Idiopathic
- Medications side effects: narcotics, antidepressants
- Intestinal obstruction, fecal impaction,
- Metabolic: DM, hypothyroidism, hypercalcemia, hypokalemia, uremia
- Neurologic: intestinal pseudo-obstruction, Parkinson’s disease, multiple sclerosis
- Anal fissures, proctalgia
Features
- abdominal pain relieved by defecation, hard stools, straining and pain with defecation, flatulence, overflow diarrhea, tenesmus, abdominal distension
Investigations
- Imaging if necessary
- colon transit time
Treatment:
- dietary fibre for mild-moderate
- osmotic agents: lactulose, sorbitol
- enemas
Upper gastrointestinal bleed
Bleeding proximal to ligament of Treitz (suspensory ligament between duodenum and jejunum)
Etiology Above GE junction - epistaxis - esophageal varices 10-30% - esophagitis - esophageal cancer - Mallory-Weiss tear 10% Stomach - gastric ulcer 20% - gastritis 20% - gastric cancer Duodenum - ulcer in bulb 25% - aortoenteric fistula Coagulopathy Vascular malformation
Features
- hematochezia
- hematemesis
- coffee ground emesis
- melena
- occult blood in stool
Management
- stabilise patietn 1-2 large bore IVs, IVF, monitor
- send blood for FBC, group ad hold, PT, U&E, LFTs
- keep NBM
- consider NG tube to determine upper vs lower GI bleeding
- endoscopy, can use adrenaline injection and thermal hemostasis, or endoclips
- IV PPI, given to stabilise clot
- octreotide for variceal bleed
- consider IV erythromycin or metoclopramide to accelerate gastric emptying
Prognosis
- 80% stop spontaneously
- predictors of rebleeding: spurt, ooze, visible vessel, fibrin clot
- esophageal varices have a high rebleeding rate (55%) and mortality (29%)
Esophageal varices
Almost always due to portal hypertension, often accompanied by varices in the stomach.
Management
- Assess hemodynamic stability and resuscitate
- IV octreotide (splanchnic vasoconstriction, decrease portal collateral circulation and pressure)
- Endoscopic therapy, variceal ligation or sclerotherapy
Long-term treatment to decreased risk of recurrent bleed
- B-blocker
- Repeat EVL/sclerotherapy
- Nitrates
- Follow-up
Persistent or recurrent bleed
- Transjugate intrahepatic portosystemic shunt
- Balloon tamponade
- Liver transplant
Prognosis
- risk of bleeding 30% in first year
- risk of rebleeding 50-70%
Mallory-Weiss tear
Longitudinal laceration in gastric mucosa on lesser curvature near GE junction. Due to rapid increases in gastric pressure (vomiting, retching). Most suffer from alcohol abuse and hiatus hernia usually present
Features
- hematemesis + melena following retching
- can be fatal
Management
- 90% stop spontaneously
- if persistent, endoscopy with adrenaline injection + clips
Lower gastrointestinal bleed
Bleed distal to ligament of Treitez
Etiology
- diverticular (60% from right colon)
- vascular: angiodysplasia, anorectal (hemorroids, fissures)
- neoplasms: cancer, polyps
- inflammation: colitis, UC, infectious, radiation, ischemia
- post-polypectomy
Clinical feature
- hematochezia
- anemia
- occult blood in stool
Acute viral hepatitis
Viral hepatits lasting <6m
Features:
- flu-like prodrome may precede jaundice by 1-2wks: nausea, vomiting, anorexia, fatigue, myalgia, low-grade fever, arthralgia, urticaria
- 50% progress to icteric phaseL pale stools, dark urine 1-5d prior to icteric phase, hepatomegaly and RUQ pain, splenomegaly and cervical lymphadenopathy in 10-20% of cases
Investigations
- AST and ALT
- ALP and bilirubin minimally elevated
- viral serology
Treatment
- support hydration and diet
- hospitalisation: encephalopathy, coagulopathy, severe vomiting, hypoglycemia
Complications
- hepatocellular necrosis AST/ALT >10-20x normal
Hepatitis B
HBsAg - surface hep B antigen
HBeAG - envelope hep B antigen, indicates active viral replication
Anti-HBs - immunity or post resolved infection
Anti-HBe - in chronic HBV with suppressed HBV replication
Anti-HBc - IgM for acute infection which undergoes seroconversion to IgG in chronic or resolved infection.
Epidemiology
- 4 phases of chronic hepatitis B
1. Immune tolerance: extremely high HBV-DNA, presence of viral replication (HBeAg) due to little immune control, ninimal immune mediated liver damage
2. Immune clearance: falling but still elevated HBV-DNA levels, HBeAg positive and immune mediated attack on liver
3. Immune control: lower HBV-DNA, HBeAg negative, anti-HBe positive, normal LFTs due to immune control without immune-mediated liver damage
4. Immune escape: elevated HBV-DNA, HBeAg negative, anti-HBe positive, LFTs high characterised by progressing disease and liver fibrosis
Management
- Counseling: 40% of men will die from HBV related complications
- Tratment goal reduce HBV-DNA to undetectable levels; interferon, tenofovir
- Blood and sexual precautions
- Vaccinate against Hep A
Complications
- liver fibrosis
- co-infection with Hep D (requires HBsAg for entry)
Hepatitis C
RNA virus, blood-borne transmission.
Risks: IVDU, blood transfusion prior to 1992, tattoos
Diagnosis
- anti-HCV and HCV-RNA in serum
Management
- Blood-borne precautions
- Vaccinate for Hep B and A
- Alcohol avoidance
- a-interferon + ribavirin
- Sustained remission: undetectable HCV-RNA 6 months off treatment
Hepatitis C
RNA virus, blood-borne transmission.
Risks: IVDU, blood transfusion prior to 1992, tattoos
Diagnosis
- anti-HCV and HCV-RNA in serum
Management
- Blood-borne precautions
- Vaccinate for Hep B and A
- Alcohol avoidance
- a-interferon + ribavirin
- Sustained remission: undetectable HCV-RNA 6 months off treatment
Prognosis
- 80% become chronic (of those 20% evolve to cirrhosis)
- risk of hepatoma increases if cirrhoic
- can cause cryoglobulinemia
Other hepatitis viruses
HDV
- infectious only in the presence of Hep B
HEV
- fecal-oral route
- 10-20% mortality in pregnancy
CMV
EBV
Yellow fever
Autoimmune chronic active hepatitis
Extramanifestations of :
- sicca, Raynaud’s thyroiditis, Sjogrens, arthralgias
- hypergammaglobulinemia
Management
- Steroids + azathioprine
Drug induced liver disease
Acetaminophen
- metabolised by CYP P450
- requires 10-15g in healthy or 4-6g in alcoholics/anticonvulsant users
- first 24h: nausea, vomiting
- 24-48h: asyptomatic but ongoing hepatic necrosis resulting in increased LFTs
- >48h: continued hepatic necrosis
Management
- oral activated charcoal
- N-acetylcysteine most effective if given 8-10h of ingestion
Chlorpromazine
- cholestasis in 1% after 4 wks
Isoniazid
- elevated transaminases but <1% develop clinically significant disease
Methotrexate
- causes cirrhosis with increased risk in pre-existing liver disease
Amiodarone
- same as alcoholic hepatitis
Others
- azoles
- statins
- methyldopa
- phenytoin
- rifampicin
- sulfonamides
Wilson’s disease
AR defect in copper metabolism. Decreased biliary excretion of copper plus decreased incorporation of copper into ceruloplasmin
Features:
- Liver: acute heaptitis, fulminant liver failure, chronic active heaptitis, cirrhosis, low risk of hepatocellular carcinoma
- Eyes: Kayyser-Fleischer rings
- CNS: basal ganglia (Parkinsonism), cerebellum (dysarthria, dysphagia, ataxia), cerebrum (psychosis, affective disorder)
- Kidneys: Fanconi’s syndrome (PT transport defects), stones
- Blood: intravascular hemolysis
- Joints: arthritis, bone demineralisation, calcifications
Investigations Screening - reduced serum ceruloplasmin - Kayser-Fleischer rings - increased urinary copper excretion Gold standard: - increased copper on liver biopsy
Treatment
- Penicillamine: chleates copper, poorly tolerated
- Trientine: chelates copper
- Zinc: impairs copper excretion/decreases copper absorption from gut
- Tetrathiomolybdate perferred if neurological involvement
- Screen relatives
- Liver transplant in severe cases
Hemochromatosis
Excess iron storage, causes multiorgan system dysfuction with total body stores increased to 20-40g
Etiology:
- Primary: AR gene, increase iron absorption
- Secondary: parental iron overload (transfusions), chronic hemolytic anemia, excessive iron intake
Features
- Liver: cirrhosis 30%, HCC 200x risk
- Pancreas: diabetes, chronic pancreatitis
- Skin: bronze or grey
- Heart: dilated cardiomyopathy
Pituitary: hypogonadotrophic hypogonadism (impotence, amenorrhea)
- Joints: arthralgia, chondrocalcinosis
Investigations Screening - Transferritin saturation >50% - Serum ferritin >400ng/mL - HFE gene analysis Liver biopsy HCC screening if cirrhosis
Treatment
- Phlebotomy weekly then life long maintenance every 2-6m
- Deferoxamine if phlebotom contraindicated
Alcoholic liver disease
Types
- Fatty liver: always reverisble if alcohol ceased
- Alcoholic hepatitis (35%): usually reversible if alcohol stopped
- Cirrhosis: 10-15%, potentially irreversible
Pathophysiology
- ethanol oxidation to acetaldehyde, impairs lipolysis
- inflammation and fibrosis
Features
- > 2-3 drinks/d in females and >3-6 drinks/d in men for >10yrs leads to cirrhosis in about 10-20%
- Fatty liver: mildly tender hepatomegaly, mildly increased transaminases
- Alcoholic hepatitis: variable severity, feels unwell, may have low grade fever, RUQ discomfort, increased WBC
- INR and bilirubin predicts mortality
Treatmet
- Alcohol cessation: AA, disulfiram, naltrexone, acamprosate
- thiamine supplements
- prednisone for those with elevated INR and bilirubin
Prognosis
- fatty liver: complete resolution after cessation of alcohol
- alcohol hepatitis mortality 70% in 5yrs if alcohol continued, drops to 30% with cessation
Non-alcoholic fatty liver disease
Insulin resistance leading to hepatic steatosis
Features:
- asymptomatic
- may present with fatigue, malaise and vague RUQ discomfort
- elevated LFTs, AST/ALP <1
- US echogenic liver
Management
- gradual weight loss
- optimisation of therapy for diabetes hyperlipidaemia, hypertension
Prognosis
- most die from cardiovascular or cerebrovascular disease
- better prognosis than alcoholic hepatitis
Chronic hepatitis
Increase in serum transaminases for >6m
Etiology
- fatty liver
- viral
- drugs
- autoimmune
- genetic
Treat underlying cause
Cirrhosis
Liver damage characterised by diffuse distortion of the basic architecture and replacement with scar tissue.
Compensated cirrhosis: asymptomatic and can last for 10-20yrs with normal life expectancy
Decompensated cirrhosis: liver failure, ascites, variceal bleed
Etiology
- fatty liver
- chronic viral hepatitis
- hemochromatosis
- a1-antitrypsin deficiency
- primary biliary cirrhosis
- chronic hepatic congestion: cardiac cirrhosis, hepatic vein thrombosis
- Idiopathic
- rare: Wilson’s disease
Features
- encephalopathy, fetor hepaticus
- xanthelasma, sclera icterus, jaundice, spider angioma, bruising
- gynaecomastia, loss of sexual hair, testicular atrophy
- muscle wasting, ankle oedema,
- palmer erythema, Dupytren’s contractures, leuckonychia, clubbing
- esophageal varices, melena, splenomegaly,
- caput medusa, umbilical hernias, ascites, hemorroids
Diagnosis
- liver biopsy
- fall in PLT, rise in INR, fall in albumin, rise in bilirubin
- CT for varices, nodular liver, ascites
- gastroscopy: varices, portal gastropathy
Management
- treat underlying cause
- decrease insults
- follow patient for complications
- liver transplantation
Complications
- Hematologic: pancytopenia from hypersplenism, decreased clotting factors
- Variceal bleeds: resusitation, antibiotics prophylaxis, octreotide with endoscopic band ligation
- Renal failure: pre-renal, acute tubular necrosis, hepatorenal syndrome
Portal hypertension
Pressure gradient between hepatic vein pressure and wedged hepatic vein pressure >5mmHg
Pathophysiology
- pre-sinusoidal: portal vein thrombosis, sarcoidosis
- sinusoidal: cirrhosis, alcoholic hepatitis
- post-sinusoidal: RHF, hepatic vein thrombosis, veno-occlusive disease, constrictive pericarditis
Complications
- GI bleed from varices
- ascites
- hepatic encephalopathy
- thrombocytopenia
- renal dysfunction
- sepsis
- arterial hypoxemia
Managment
- beta-blocker decrease bleed risk from varices
- nitrates decrease portal hypertension
- tranjugular intrahepatic portosystemic shunt
Hepatic encephalopathy
Acute neuropsychiatric syndrome secondary to liver disease. Portosystemic shunt arond hepatocytes, increase level of systemic toxins (ammonia, mercaptans, fatty acids, amino acids)
Precipitating factors:
- nitrogen load: GI bleed, protein from food, renal failure
- drugs: narcotics, CNS depressants
- electrolyte disturbance: hypokalemia, alkalosis, hypoxia, hypovolaemia
- infection
- deteriorating liver function
Stages
I: apathy, restlessness, slowed intellect
II: asterixis, lethargy, drowsiness, disorientation
III: stupor, hyperactive reflexes, extensor plantar response
IV: coma
Investigations
- rule out non-liver related neuropsychiatric disease
Treatment
- treat underlying precipitating cause
- decrease nitrous generation: decrease dietary protein to 50g/d, lactulose, antibiotics (metronidazole)
Ascites
Fluid in peritoneal cavity
Portal hypertension related (serum ascites albumin gradient >11g/L)
- cirrhosis
- chronic hepatic congestion: RHF, Budd-Chiari
- massive liver metastases
- myxedema
Non-portal hypertension related serum ascites albumin gradient <11g/L)
- peritoneal carinomatosis
- TB
- pancreatic disease
- serositis
- nephrotic syndrome
Diagnosis
- Abdo US
- physical exam (detectable when >500mL)
Treatmetn
- non-refractory ascites: Na restriction, diuretics
- refractory ascites: therapeutic paracentesis, IV albumin, TIPS
Complications
- bacterial peritonitis: IV ceftriaxone, IV albumin
Fulminant hepatic failure
Previously normal liver, rapid <8wks development of jaundice followed by hepatic encephalopathy
Etiology
- drugs: acetaminophen
- viral: hep B
- ischemic
- idiopathic
Management
- correct hypoglycaemia
- monitor level of consciousness, prevent GI bleeding with PPI
- consider liver biopsy
- liver transplant
Jaundice
Features
- dark urine, pale stools: suggests rise in conjugated bilirubin, post-hepatic obstruction
- pruritus: chronic disease
- abdominal pain: biliary tract obstruction
- painless jaundice in elderly: pancreatic cancer
- kernicterus: rarely seen in adults due to BBB
Investigations
- Bilirubin, LFTs
- US for bile duct obstruction
- Direct bile duct visualisation:
- MRCP - non-invasive
- ERCP - invasive, therapeutic intervention
- percutaneous transhepatic cholangiography - if ERCP fails
Unconjugated hyperbilirubinemia
1) Overproduction: hemolysis, ineffective erythropoiesis
2) Decreased hepatic uptake: Gilbert’s syndrome, drugs (rifampicin)
3) Decreased conjugation: drug inhibition (chloramphenicol), Gilbert’s syndrome, neonatal jaundice
Conjugated hyperbilirubinemia
1) Impaired hepatic secretion: hepatocellular disease, drug induced cholestasos (COC, chlorapromazine), primary biliary cirrhosis, primary sclerosing cholangitis, sepsis, post-operative
2) Extrahepatic biliary obstruction: intraductal (gallstones, biliary stricture, parasites, malignancy, sclerosing cholangitis), extraductal (malignancy, metastases in peri-portal nodes, inflammation)
Gilbert’s syndrome
Mild decrease in glucuronyltransferase activity leading to defective conjugation of bilirubin. Affects 7% of population, AD inheritance.
Features
- presents in teens-20’s often incidental finding
- intermittent jaundice with increased serum unconjugated bilirubin
Sclerosing cholangitis
Inflammation of biliary tree leading to scarring and obliteration.
Etiology
- Idiopathic: most common, associated with IBD (more common in UC), more commonly seen in men, common indication for liver transplant
- Secondary: long-term choledocholithiasis, cholangiocarcinoma, surgical/traumatic injury, contiguous inflammatory process, post- ERCP, HIV
Features
- insidious, may present with fatigue and pruritus
- may present with signs of episodic bacterial cholangitis secondary to biliary obstruction
Diagnosis:
- increased ALP, mildly increased AST
- p-ANCA and elevated IgM
- ERCp shows narrowing and dilatations of bile dusts
Complications
- repeated bouts may lead to complete biliary obstruction with secondary hepatic failure
- increased incidence of cholangiocarcinoma
Management
- image bile duct MRCP af least annually for early detection of cholangiocarcioma
- endoscopic sphincterotomy, biliary stent
- antibiotics for cholangitis, drainage for pus
- liver transplant
Primary biliary cirrhosis
Chronic inflammation and fibrous obliteration of intrahepatic ductules. Likely autoimmune (Sjogren’s, scleroderma, CREST, RA, thyroiditis). Mainly affects middle-aged women.
Features
- asymptomatic
- pruritus, fatigue
- chronic: jaundice, melanosis, cholestasis signs
- end-stage: hepaticellular failure, portal hypertension, ascites
- high incidence of osteoporosis
Investigations
- increased ALP, GGT
- positive anti-mitochondrial antibodies
- increased serum cholesterol
- liver biopsy confirmation
Treatment
- ursodiol, colchicine, methotrexate
- cholestyramine
- Ca and vitamin D for low bone density, bisphosphenates for severe osteoporosis
- monitor for thyroid disease
- liver transplant if severe disease
Ascending cholangitis
Infection of biliary tree. Stasis in biliary tract due to obstruction or stricture, infection originates in duodenum and spreads hematogenously from portal vein. Bacteria: E. coli, Klebsiella, Enterobacter, Enterococcus
Features
- Charcot’s triad: fever, RUQ pain, jaundice
- Reynol’s Pentadwith suppurative cholangitis: fever, RUQ pain, jaundice, hypotension, altered mental status
Diagnosis
- increased WBC, increased ALP and bilirubin
- blood cultures
- abdominal US
Treatment
- drainage via ERCP
- antibiotic therapy: broad spectrum metronidazole + ceftriaxone, carbapenem monotherapy
Acute pancreatitis
Etiology
- Idiopathic
- Gallstones 45%
- Ethanol 35%
- Tumours
- Scorpion stings
- Microbiology: mycoplasma, campylobacter, TB, mumps, rubella, varicella, viral hepatitis
- Autoimmune: SLE, polyarteritis nodosa, Crohn’s
- Surgery/trauma: ERCP
- Hyperlipidemia, Hypercalcemia, Hypothermia
- Emboli/ischemia
- Drugs/toxins: asathioprine, mercaptopurine, furosemide, estrogens, valproate, antibiotics
Pathology
- mild: peripancreatic fat necrosis, interstitial edema
- severe: extensive peri-pancreatic and intra-pancreatic fat necrosis, parenchymal necrosis, multiorgan failure
Features:
- epigastric pain, constant, radiates to back, improve leaning forward
- tender rigid abdomen, guarding
- nausea, vomiting
- abdominal distension, paralytic ileus
- jaundice
- Cullen’s/Grey-Turner’s signs
- tetany, transient hypocalcemia
- hypovolaemic shock
- acute respiratory distress syndrome
Investigations
- amylase and lipase
- ALT raised strongly suggests biliary pancreatitis
- increased WBC, glucose, low calcium
- AXR, US for biliary tree, CT with IV contrast, ERCP/MRCP if uncertain cause
Prognosis
- usually benign, self-limiting course
- severe may lead to shock, pulmonary oedema, multi-organ dysfunction, GI ulceration, death
Ranson's criteria Admission - Glucose >11 mmol/L - Age >55 - LDH >350 IU/L - AST >250 IU/L - WBC >16 x 10^9/L
During first 48hr
- Calcium <2mmol/L
- Hematocrit drop >10%
- Oxygenation arterial <60 mmHg
- Base deficit >4 mmol/L
- BUN rise >1.8 mmol/L
- Sequestration >6L
Treatment
1) hemodynamic stability
2) analgesia
3) oxygen
4) stop progression of damage
5) treats local and systemic complications
Late complications
- pseudocysts
- infected necrosis/abscesses
- bleeding
- splenic and portal vein thrombosis
- rare: diabetes, pancreatic duct damage
Chronic pancreatitis
Irreversible damage to pancreas by: pancreatic cell loss, inflammation, fibrosis
Etiology
- Alcohol: causes a large proportion (>90%) of chronic pancreatitis, decreases pancreatic secretion, toxic effect on acinar cells and stimulates fibrosis
- Cystic fibrosis
- Severe protein-calorie malnutrition
- Hereditary
- Idiopathic
Features
- early: recurrent attacks of severe abdominal pain
- late: malabsorption syndrome, diabetes, calcification, jaundice, weight loss, ascites, GI bleed
Investigations:
- increase in serum glucose and ALP
- AXR: pancreatic calcifications
- US: calcification, dilated pancreatic ducts, pseudocysts
- MRCP
- fecal elastase test for exocrine function
Management
- total alcohol abstinence
- enzyme replacement
- analgesics
- time
- endoscopy for sphincterotomy, surgery
- steatorrhea: pancreatic enzyme replacement, restrict fat