Common causes of esophagitis
Potassium chloride (KCl), aspirin, naproxen, ibuprofen, tetracycline, doxycycline, clindamycin, alendronate, quinidine, vitamin C, iron
Candida, HSV, CMV, Mycobacterium tuberculosis
Menetrier’s disease or chronic hypertrophic gastritis: It is characterized by excessive hyperplasia of the gastric mucosa. It is marked in the gastric fundus and body. On gross examination, the gastric rugal folds look prominent. Microscopic features include corkscrew shaped , hyperplastic gastric pits which become dilated forming cystic spaces, thickened mucosa, mild inflammatory infiltrate, atrophy of oxyntic glands, variable edema, hypertrophic muscularis mucosae and lymphoid follicles. It presents with dyspepsia, hematemesis and melena, hypoproteinemia, edema and hypochlorhydria. CMV infection may be associated. Some cases may progress to gastric adenocarcinoma.
Cushing’s ulcers: Peptic ulcers in head injury Curling’s ulcers: Peptic ulcers in burns Cameron ulcers: Peptic ulcers in hiatal hernia
Dermatitis herpetiformis: It presents as extremely itchy blisters (herpetic), eczematous rash with clusters of papules and vesicles seen on the extensor surface of the elbows, knees, buttocks, back or scalp. Scratch marks can be seen from intense itching. It is triggered by IgA deposits in skin formed against epidermal transglutaminase in celiac disease. Microscopy shows microabscesses filled with neutrophils and eosinophils. Remedy is with a gluten-free diet and dapsone.
Malabsorptive diarrhea: It is diarrhea associated with impaired nutrient absorption and digestion. It presents with bloating and pale, bulky, foul smelling, fatty stools (difficult to flush, tend to float). Malabsorptive diarrhea is seen in cystic fibrosis, celiac disease, intestinal bypass surgery, mesenteric ischemia, blind loop or small bowel bacterial overgrowth syndrome, pancreatic disease, Whipple disease and giardiasis.
Obturator sign: It is pain in RLQ on flexion and internal rotation of the hip. It is due to irritation of the obturator internus muscle by an inflamed pelvic appendix.
Psoas sign: It is pain in RLQ with extension of the right hip or with flexion of the right hip against resistance. It is caused by irritation of the iliopsoas muscle by an inflamed appendix. It may also be seen in psoas abscess or retroperitoneal hemorrhage.
Appendicitis with a mass in RLQ: The presence of a mass is suggestive of an abscess or phlegmon. Following rupture of the appendix, the omentum and surrounding bowel may adhere to it, in an effort to wall-off the perforation which can be palpated as an appendicular mass. If the patient is stable and a mass is seen on imaging, then conservative management is preferred with IV antibiotics and percutaneous or transrectal drainage of any localized abscess. This is followed by interval appendicectomy 4-8 weeks later.
Toxic megacolon or toxic colitis: It is a potentially fatal condition characterized by abnormal dilation of the colon from severe colitis. It presents with fever, abdominal pain and distension, nausea, vomiting,shock, diarrhea with/without blood and mucus, mental status changes and decreased bowel sounds. There is a high risk of perforation and peritonitis. It can occur as a complication of ulcerative colitis, less commonly in Crohn’s disease, or any other severe colitis from ischemia, infection, radiation, drugs like opioids and anticholinergics or pseudomembranous colitis. In UC, extension of inflammation into the muscularis layer and deeper into the colonic wall, along with tissue damage by neutrophil enzymes and increased local synthesis of nitric oxide lead to toxic megacolon. Imaging studies like X ray or CT scanning show colonic dilation, multiple air-fluid levels, >6cm dilation of the transverse colon. Endoscopy is contraindicated in suspected toxic megacolon due to high risk of perforation. Treatment involves supportive therapy, bowel rest, nasogastric tube, antibiotics (vancomycin and metronidazole), steroids and surgery like subtotal colectomy with ileostomy, sigmoidostomy or rectostomy. Not all cases need surgery.
Angiodysplasia (vascular ectasia) of the colon: It is a vascular malformation most commonly found in the cecum and ascending colon. It is a common cause of painless, lower gastrointestinal bleeding in the elderly. Lesions may be single or multiple. They are associated with chronic renal disease, aortic stenosis, von Willebrand disease, scleroderma etc. It is diagnosed by endoscopy, enteroscopy and angiography which shows a vascular tuft and early opacification of the draining veins. Technetium 99m or Tc sulfur colloid scan can detect active bleeding from angiodysplasia. Microscopically, clusters of dilated blood vessels are seen in the mucosa and submucosa. It is treated with endoscopic coagulation, angiographic embolization or right colectomy, depending on the severity. Bleeding stops spontaneously in most cases.
Jaundice in the newborn period: Most cases of newborn jaundice are physiological. Catabolism of hemoglobin is high in the newborn period due to which more bilirubin is produced. Due to relative immaturity of hepatic glucuronyl transferase enzyme, the levels of unconjugated bilirubin are elevated. Physiological jaundice is first seen on days 2-4 after birth and resolves by 2 weeks. Jaundice is considered pathologic if it presents within the first 24 hours after birth, the total serum bilirubin level rises by more than 5 mg per dL/day or is higher than 17 mg/dL or an infant has signs and symptoms suggestive of serious illness. Unconjugated bilirubin carries a high risk of CNS damage by depositing in the basal ganglia and brainstem nuclei . It can present as encephalopathy which may progress to kernicterus. Bilirubin encephalopathy presents with jaundice, lethargy, high-pitched cry, and poor feeding. Kernicterus is a more severe form presenting as opisthotonus, cerebral palsy, hearing loss, paralysis of upward gaze and mental retardation. The management of mild neonatal jaundice is by increasing breast feedings, supplemented with formula feeding if needed; cases with high elevations of serum bilirubin should be treated with phototherapy and exchange transfusion. CNS symptoms must be treated emergently with exchange transfusion.
Cut-off levels for starting phototherapy in newborns*
Age | Bilirubin level |
25-48 hours | 15 mg/dl |
49-72 hours | 18 mg/dl |
>72 hours | 20 mg/dl |
* In sick infants with jaundice, phototherapy should be started even if bilirubin levels are lower
Obesity
Hyperlipidemia
Diabetes Mellitus
Alcoholic liver disease
Starvation
Severe malnutrition
Pregnancy
Hypoxia
Toxins like carbon tetrachloride, chloroform, aflatoxins
Medications like aspirin, halothane, steroids, amiodarone, diltiazem, tamoxifen
Biopsy shows microvesicular steatosis in the initial stages and then macrosteatosis. Hepatocytes are ballooned with lipid deposits in the cytoplasm and nucleus is pushed to the periphery. Mallory bodies are present. It is seen as a vacuole in H and E sections and stained red with Sudan III and Oil Red-O.
Alcohol metabolism increases NADH in the liver resulting in an increased NADH/NAD ratio. This leads to increased ketogenesis and fatty acid synthesis and decreased beta oxidation of fatty acids.
Sterol regulatory element-binding proteins or SREBPs are a family of transcription factors that regulate the enzymes responsible for the synthesis of cholesterol, fatty acids and triglycerides in liver and other tissues. Ethanol increases SREBP regulated transcription of the protein SREBP 1 and hepatic triglyceride synthesis.
Alcohol also inhibits PPAR alpha activity. PPAR alpha is a nuclear hormone receptor and stimulates oxidation of fatty acids.
Alcohol inhibits the synthesis of phosphatidylcholine thereby inhibiting VLDL synthesis. As a result, triglyceride secretion from the liver in the form of VLDL is interrupted.
Cirrhotic cardiomyopathy: Impaired systolic function, diastolic dysfunction and prolonged QT interval in the absence of primary cardiac disease; raised BNP and proBNP and troponin; defect in beta receptor activity, myocyte apoptosis, increased nitric oxide and carbon monoxide. Liver transplant is definitive treatment.
Hepatopulmonary syndrome: It is a syndrome characterized by hypoxia, pulmonary vasodilation and liver dysfunction seen in cirrhosis. Liver transplant may help mild to moderate cases.
Portopulmonary hypertension: It is defined as pulmonary hypertension as a result of portal hypertension. There is risk of pulmonary vascular thrombosis. Treatment is with epoprostenol, bosentan, ambrisentan, sildenafil, iloprost, liver transplant.
+ Hepatorenal syndrome also
Complication | Management |
Bleeding varices | Control bleeding with sclerotherapy, band ligation (preferred); treat hypotension and hypovolemia; octreotide, terlipressin or vasopressin; TIPSS or surgical shunts; temporary balloon tamponade with Sengstaken-Blakemore tube; beta blockers like propranolol or nadolol for prophylaxis |
Ascites | Diuretics (furosemide or spironolactone), low sodium diet (limit salt intake to 2000mg/dl, not less), paracentesis, TIPSS |
Spontaneous bacterial peritonitis | Treat ascites, iv antibiotics |
Renal failure | Treat hypovolemia, maintain adequate hydration, stop diuretics, give albumin infusions, add terlipressin or midodrine and octreotide in hepatorenal syndrome |
Encephalopathy | Lactulose, oral Rifaximin, neomycin, metronidazole; treat underlying infections, bleeding, limit protein intake up to 1.5 g/kg/day, correct electrolytes, avoid sedatives, use probiotics |
Site | Vessels involved |
Lower esophagus | Esophageal branch of left gastric vein with esophageal branches of azygous/hemiazygous vein |
Umbilicus | Paraumbilical vein which drains into left branch of portal vein with superficial epigastric vein (systemic) |
Rectal | Superior rectal (portal) with middle and inferior rectal (systemic) |
Points | 1 | 2 | 3 |
Encephalopathy | None | Minimal | Advanced |
Ascites | Absent | Controlled | Refractory |
Bilirubin (mg/dl) | <2 | 2-3 | >3 |
Albumin (g/L) | >35 | 28-35 | <28 |
Prothrombin (sec) | <4 (<1.7) | 4-6 (INR 1.7-2.2) | >6 (INR >2.2) |
* Also called CTP or Child-Turcotte-Pugh scoring system
From the above table, patients are grouped into three classes. Higher class or score indicates more severe liver disease.
Class A: Patients scoring <7 points, better prognosis
Class B: Patients scoring 7-9 points, bad prognosis
Class C: Patients scoring > or = 10 points, worse prognosis
The actual MELD score is then calculated using the following formula.
MELD = 3.8 X log e(total bilirubin [mg/dL]) + 11.2 X log e(INR) + 9.6 X log e(creatinine [mg/dL])
Patients with MELD scores above 40 have >71% mortality in the next 3 months. Patients with MELD score at or above 19 should be referred for liver transplant evaluation. Those with MELD scores >12 should be started prophylaxis for SBP.
UNOS or United Network for Organ Sharing lays down criteria that determines which patients get priority for liver transplant. They are as follows:
Status 1: Patients with acute severe disease who are in ICU with acute liver disease with a life expectancy without a liver transplant of fewer than 7 days, or who recently received a liver transplant and that failed. Status 1 patients get highest priority.
MELD or PELD (pediatric) score: Predicts mortality risk within a 3 month period. Priority is given to patients with higher MELD scores and longer time on the waiting list.
Priority is given first to status 1, followed by higher score on MELD or PELD.
Current untreated infections like SBP
Advanced, undertreated cardiopulmonary disease
Alcohol or substance abuse
Secondary metastases to liver
Hepatocellular carcinoma is not a contraindication to liver transplant except in advanced stages.
Each of the above criteria carries 1 point
Score < 3 mortality 0-3% Score >= 3 mortality 11-15% Score >= 6 mortality 40% or higher
Alternatively, APACHE II scoring system can be used. A score higher than 8 indicates severe pancreatitis.