Gastrointestinal System Study Guide

GI Anatomy & Liver Function

GI Tract Overview

• Function: Digestion, absorption, elimination
• Blood supply: Celiac trunk (foregut), SMA (midgut), IMA (hindgut)
• GI tract is vulnerable to ischemia in shock states

Liver Functions

• Metabolism: Drugs, hormones, toxins
• Synthesis: Albumin, clotting factors, bile
• Storage: Glycogen, vitamins, iron
• Detoxification: Ammonia → Urea
• Bile production: Aids fat digestion

Liver Function Tests

• AST/ALT: Hepatocellular injury markers
• Alkaline Phosphatase/GGT: Cholestatic markers
• Bilirubin: Conjugated (direct) vs Unconjugated (indirect)
• Albumin: Synthetic function (chronic indicator)
• PT/INR: Synthetic function (acute indicator - clotting factors)

Pancreas Function

• Exocrine: Digestive enzymes (amylase, lipase, trypsin)
• Endocrine: Insulin (beta cells), Glucagon (alpha cells)

Acute Pancreatitis

Causes

• Most common: Gallstones (40%), Alcohol (40%)
• Other: Medications, ERCP, hypertriglyceridemia, hypercalcemia
• Mnemonic: I GET SMASHED

Clinical Presentation

• Severe epigastric pain radiating to back
• Nausea, vomiting, anorexia
• Abdominal tenderness, guarding, distension
• Grey Turner sign: Flank ecchymosis
• Cullen sign: Periumbilical ecchymosis
• These signs indicate retroperitoneal hemorrhage - severe disease

Diagnosis

• Lipase: Most specific (elevated 3x normal)
• Amylase: Elevated but less specific
• CT scan: For severity assessment, complications
• Ranson criteria, APACHE II for prognosis

Complications

• SIRS/Sepsis
• ARDS
• Acute kidney injury
• Abdominal compartment syndrome
• Pancreatic necrosis, pseudocyst, abscess
• Hemorrhage

Management

• NPO initially, then early enteral nutrition
• Aggressive IV fluid resuscitation
• Pain management
• Monitor for organ dysfunction
• ERCP if biliary cause with cholangitis
• Surgery for infected necrosis

GI Hemorrhage

Upper GI Bleed (UGIB)

• Source: Above ligament of Treitz (esophagus, stomach, duodenum)
• Presentation: Hematemesis (bright red or coffee ground), melena
• Causes: PUD (most common), varices, Mallory-Weiss tear, erosive gastritis
• Diagnosis: EGD within 24 hours

Lower GI Bleed (LGIB)

• Source: Below ligament of Treitz (colon, rectum)
• Presentation: Hematochezia (bright red blood per rectum)
• Causes: Diverticulosis (most common), angiodysplasia, cancer, hemorrhoids
• Diagnosis: Colonoscopy when prepared

Initial Management

• ABC assessment, hemodynamic stabilization
• Two large-bore IVs, fluid resuscitation
• Type and crossmatch, transfuse if Hgb <7 (or <8 with cardiac disease)
• Correct coagulopathy
• NPO, NG tube if concern for upper source
• PPI infusion for UGIB
• Consult GI for endoscopy

Variceal Bleeding

• Occurs in portal hypertension (cirrhosis)
• Massive, life-threatening hemorrhage
• Treatment: Octreotide (reduces portal pressure), PPI
• EGD with banding/sclerotherapy
• Balloon tamponade (Blakemore/Minnesota tube) if uncontrolled
• TIPS procedure for refractory bleeding
• Antibiotic prophylaxis (cirrhotic patients)

Hepatic Failure

Acute vs Chronic

• Acute liver failure: Rapid onset (<26 weeks) in previously healthy liver
• Causes: Acetaminophen toxicity (#1 in US), viral hepatitis, drug reactions
• Chronic liver failure: End-stage cirrhosis
• Causes: Alcohol, Hepatitis C, NAFLD

Clinical Manifestations

• Jaundice (elevated bilirubin)
• Coagulopathy (decreased clotting factor synthesis)
• Ascites (portal hypertension, low albumin)
• Hepatic encephalopathy (ammonia accumulation)
• Hepatorenal syndrome

Hepatic Encephalopathy

• Caused by ammonia and other toxins not cleared by liver
• Stages: Confusion → Asterixis → Somnolence → Coma
• Precipitants: GI bleed, infection, constipation, meds, electrolyte imbalance
• Treatment: Lactulose (reduces ammonia absorption)
• Rifaximin (gut antibiotic)
• Identify and treat precipitant

Other Complications

• Spontaneous bacterial peritonitis (SBP): Infection of ascitic fluid
• Diagnosis: >250 PMNs/mm³ in ascitic fluid
• Treatment: Ceftriaxone or fluoroquinolone
• Hepatorenal syndrome: Renal failure from splanchnic vasodilation
• Very poor prognosis without liver transplant
• Coagulopathy: Bleeding AND clotting risk

Drugs Causing Acute Liver Failure

• Acetaminophen (most common cause)
• NSAIDs, Aspirin
• Isoniazid, Rifampin
• Amiodarone
• Statins
• Herbal supplements (Herbalife, Hydroxycut)
• Illicit drugs: Cocaine, MDMA, Methamphetamine
• Alcohol

Abdominal Compartment Syndrome

Definition

• Sustained intra-abdominal pressure (IAP) >20 mmHg WITH organ dysfunction
• Normal IAP: 5-7 mmHg
• Intra-abdominal hypertension: IAP >12 mmHg

Risk Factors

• Massive fluid resuscitation
• Abdominal trauma/surgery
• Pancreatitis
• Ileus, bowel obstruction
• Ascites
• Burns

Organ Effects

• Cardiac: Decreased venous return, decreased CO
• Respiratory: Elevated diaphragm, decreased compliance, hypoxia
• Renal: Decreased renal perfusion, oliguria
• GI: Decreased perfusion, bacterial translocation
• CNS: Increased ICP

Diagnosis & Treatment

• Measurement: Bladder pressure via Foley catheter
• Technique: Instill 25 mL saline, measure at end-expiration
• Treatment: Decompress abdomen
• - NG suction, rectal tube
• - Paracentesis if ascites
• - Surgical decompression if refractory
• Avoid excessive crystalloid resuscitation

Nutrition & Refeeding

Enteral vs Parenteral

• Enteral nutrition preferred: "If the gut works, use it"
• Benefits: Maintains gut integrity, reduces infection, cheaper
• Start within 24-48 hours in most ICU patients
• Parenteral (TPN): Only if enteral contraindicated or inadequate
• TPN risks: Line infection, hyperglycemia, liver dysfunction

Refeeding Syndrome

• Occurs when malnourished patients are fed too aggressively
• At risk: Anorexia, alcoholism, prolonged NPO, malabsorption
• Pathophysiology: Insulin surge → intracellular shift of electrolytes

Refeeding Electrolyte Changes

• Hypophosphatemia (HALLMARK - most dangerous)
• Hypokalemia
• Hypomagnesemia
• Fluid retention

Refeeding Complications

• Respiratory failure (diaphragm weakness)
• Cardiac arrhythmias, heart failure
• Seizures
• Rhabdomyolysis
• Death if severe

Prevention & Treatment

• Identify at-risk patients
• Start feeding slowly (10-20 kcal/kg/day initially)
• Give thiamine BEFORE feeding (prevents Wernicke)
• Monitor and replace phosphorus, potassium, magnesium
• Advance calories gradually over 5-7 days

EN & TPN Contraindications

Enteral Nutrition (EN) Contraindications

• Complete bowel obstruction - mechanical blockage prevents formula passage
• Severe ileus - paralyzed gut cannot move contents, risk of aspiration
• Major upper GI bleeding - active bleeding may worsen with feeding
• Intractable vomiting - cannot retain formula
• Severe diarrhea - malabsorption and electrolyte losses
• GI ischemia - compromised blood flow, feeding could worsen ischemia
• High-output GI fistula - significant losses prevent adequate absorption
• Severe hemodynamic instability on high-dose vasopressors (relative)

Parenteral Nutrition (TPN) Contraindications

• Ability to feed enterally - if gut works, use it first
• Hyperosmolality - patient cannot tolerate the osmotic load
• Severe hyperglycemia - PN significantly impacts blood glucose
• Severe electrolyte imbalance - must correct before starting TPN
• Volume overload - TPN contains significant fluid
• Inadequate IV access - requires dedicated central line
• Expected duration <5-7 days (generally not worth TPN risks)

Why Enteral Preferred Over Parenteral

• Maintains gut mucosal integrity and barrier function
• Reduces bacterial translocation risk
• Lower infection rates compared to TPN
• More cost-effective
• Supports gut immune function (GALT)
• Stimulates gut hormones and motility

TPN Monitoring Requirements

• Blood glucose: Every 4-6 hours initially (hyperglycemia common)
• Electrolytes: Daily initially, then 2-3x weekly when stable
• LFTs: Weekly (TPN-associated liver dysfunction)
• Triglycerides: Weekly if receiving lipid emulsions
• Central line site: Daily assessment for infection
• Fluid balance: Daily weights, intake/output

Special Considerations

• Refeeding risk: Start TPN at reduced rate in malnourished patients
• Critical illness: May need modified formulas (lower glucose, higher protein)
• Renal failure: Adjust electrolytes, may need specialized formulas
• Liver failure: Monitor closely for worsening hepatic function
• Do NOT abruptly stop TPN - risk of rebound hypoglycemia

Hepatic Failure Diagnostics

Elevated Lab Values in Hepatic Failure

• PT/INR: Prolonged due to decreased synthesis of vitamin K-dependent clotting factors
• AST/ALT: Elevated from hepatocellular damage (released from injured hepatocytes)
• Alkaline Phosphatase (ALP): Elevated, especially in cholestatic conditions
• LDH: Non-specific marker of tissue damage, elevated in liver injury
• Bilirubin: Elevated due to impaired conjugation and excretion (causes jaundice)
• Ammonia: Elevated due to impaired hepatic detoxification (leads to encephalopathy)
• Lactate: Elevated from impaired clearance and tissue hypoperfusion
• Urobilinogen: Elevated from hemolysis or impaired liver uptake
• Amylase/Lipase: May be elevated with biliary involvement

Decreased Lab Values in Hepatic Failure

• Platelets (<150,000): Due to hypersplenism, bone marrow suppression, or consumption
• Fibrinogen: Reduced hepatic synthesis (increases bleeding risk)
• Albumin: Decreased synthesis (causes edema, ascites, fluid shifts)
• Total Protein: Reflects overall impaired liver synthetic function
• RBCs: May be decreased from bleeding or bone marrow effects
• Sodium: Dilutional hyponatremia common
• Potassium: Often decreased from various mechanisms
• Phosphorus: May be depleted in acute liver failure
• Blood Glucose: Hypoglycemia from impaired gluconeogenesis and glycogenolysis

Coagulation Impairment in Liver Failure

• Liver produces factors II, VII, IX, X (vitamin K dependent)
• Also produces fibrinogen, factor V, and other proteins
• PT/INR is sensitive acute indicator of synthetic function
• Factor VII has shortest half-life - first to decrease
• Paradoxical: Both bleeding AND clotting risk in liver failure
• Do not "correct" INR unless actively bleeding or procedure needed

Clinical Implications for Critical Care

• Elevated ammonia: Monitor for hepatic encephalopathy, asterixis
• Coagulopathy: Implement bleeding precautions, careful with procedures
• Low albumin: Affects drug binding, contributes to third-spacing
• Electrolyte shifts: Frequent monitoring and careful replacement
• Hypoglycemia risk: Regular glucose monitoring essential
• Lactate trends: Prognostic marker and indicator of perfusion

Bowel Obstruction

Understanding Bowel Obstruction

• Definition: Blockage preventing normal passage of intestinal contents
• Results in proximal bowel dilation and distension
• Can occur in small bowel (more common) or large bowel
• Untreated obstruction can progress to strangulation and necrosis
• Medical emergency if signs of ischemia or perforation develop

Small Bowel Obstruction (SBO)

• Most common cause: Adhesions from prior abdominal surgery
• Other causes: Hernias (incarcerated), tumors, Crohn disease, intussusception
• Proximal SBO: Early vomiting, minimal distension
• Distal SBO: Delayed vomiting, significant abdominal distension
• Complete obstruction: No flatus or bowel movements
• Partial obstruction: Some passage of gas or stool

Large Bowel Obstruction (LBO)

• Most common causes: Colorectal malignancy, volvulus (sigmoid or cecal)
• Volvulus: Twisting of bowel segment on its mesentery
• Diverticular disease can cause stricture formation
• Presents with progressive distension, constipation, abdominal pain
• Closed-loop obstruction: Risk of perforation if ileocecal valve competent

Diagnostic Approach

• Plain abdominal radiographs: Dilated loops, air-fluid levels, cutoff point
• CT abdomen/pelvis: Gold standard - identifies location, cause, and complications
• Look for transition point where dilated bowel meets collapsed bowel
• CT findings concerning for ischemia: Wall thickening, pneumatosis, portal venous gas
• Labs: Electrolyte abnormalities, elevated lactate suggests ischemia

Management Principles

• NPO status - bowel rest essential
• Nasogastric tube to low intermittent suction for decompression
• Aggressive IV fluid resuscitation - significant third-spacing occurs
• Electrolyte replacement (potassium, magnesium commonly depleted)
• Pain management with careful opioid use
• Surgery indicated for: Complete obstruction, strangulation, perforation, or failure of conservative management
• Adhesive SBO often resolves with conservative treatment (48-72 hours trial)

Bowel Perforation

Pathophysiology of Perforation

• Full-thickness breach of gastrointestinal wall
• Intestinal contents leak into peritoneal cavity
• Triggers rapid bacterial peritonitis and systemic inflammatory response
• Progression to sepsis and septic shock if untreated
• Mortality increases significantly with delayed diagnosis

Common Causes

• Iatrogenic: Endoscopy, colonoscopy, PEG tube placement, paracentesis
• Peptic ulcer disease: Perforated gastric or duodenal ulcer
• Diverticular disease: Ruptured diverticulum
• Penetrating trauma: Stab wounds, gunshot wounds
• Foreign body ingestion or insertion
• Ischemic bowel: Necrosis leading to perforation
• Malignancy: Tumor erosion through bowel wall

Clinical Presentation

• Severe acute abdominal pain - often sudden onset
• Rigid or board-like abdomen (peritonitis)
• Rebound tenderness and involuntary guarding
• Fever and tachycardia (SIRS response)
• Hypotension in advanced cases (septic shock)
• Absent bowel sounds
• Patient may be unable to lie still

Diagnostic Findings

• Upright CXR or abdominal X-ray: Free air under diaphragm (pneumoperitoneum)
• CT abdomen: Most sensitive - detects small amounts of free air and fluid
• Oral contrast extravasation confirms perforation location
• Labs: Leukocytosis, elevated lactate, metabolic acidosis
• Some perforations may be contained and not show free air

Emergency Management

• Immediate NPO status
• Large-bore IV access, aggressive fluid resuscitation
• Broad-spectrum IV antibiotics covering gram-negative and anaerobes
• Nasogastric tube decompression
• Emergency surgical consultation - exploratory laparotomy
• Surgical repair: Primary closure, resection with anastomosis, or ostomy
• Post-op ICU admission typically required

Gallbladder Disease

Gallbladder Anatomy & Function

• Reservoir for bile produced by the liver
• Concentrates and stores bile between meals (30-60 mL capacity)
• Bile released through cystic duct into common bile duct when fat enters duodenum
• Cholecystokinin (CCK) triggers gallbladder contraction
• Bile emulsifies fats for digestion and absorption

Gallstone Formation (Cholelithiasis)

• Formed from supersaturation of bile with cholesterol or bilirubin
• Cholesterol stones: Most common (75-80% in Western populations)
• Pigment stones: Associated with hemolysis, cirrhosis, biliary infections
• Risk factors "5 Fs": Female, Forty, Fertile, Fat, Family history
• Additional risks: Rapid weight loss, TPN, pregnancy, certain medications
• Many patients asymptomatic - stones discovered incidentally

Biliary Colic vs Cholecystitis

• Biliary colic: Intermittent stone impaction in cystic duct
• Pain: Right upper quadrant or epigastric, radiates to right scapula
• Typically after fatty meals, resolves within hours
• Acute cholecystitis: Sustained cystic duct obstruction with inflammation
• Murphy sign positive: Inspiratory arrest during RUQ palpation
• Cholecystitis may progress to gangrenous or perforated gallbladder

Complications of Gallstones

• Choledocholithiasis: Stone in common bile duct
• Cholangitis: Infected bile duct - medical emergency (Charcot triad)
• Charcot triad: Fever, RUQ pain, jaundice
• Reynolds pentad: Charcot triad plus altered mental status and hypotension
• Gallstone pancreatitis: Stone obstructs ampulla of Vater
• Gallbladder perforation with biliary peritonitis

Diagnosis & Treatment

• Right upper quadrant ultrasound: First-line imaging
• HIDA scan: Assesses cystic duct patency if ultrasound equivocal
• Labs: Elevated WBC, LFTs elevated if CBD involvement
• Treatment: Laparoscopic cholecystectomy (gold standard)
• ERCP: For common bile duct stones before or after cholecystectomy
• Supportive care: NPO, IV fluids, pain management, antibiotics if infected

Mesenteric Ischemia

Overview of Mesenteric Ischemia

• Insufficient blood flow to intestines causing ischemic injury
• Superior mesenteric artery (SMA) most commonly involved
• SMA supplies small intestine and right colon
• Time-critical emergency: "Pain out of proportion to exam" is classic finding
• High mortality rate if bowel infarction develops (>50%)

Types of Acute Mesenteric Ischemia

• Arterial embolism (50%): Most common - usually from cardiac source
• Risk factors: Atrial fibrillation, recent MI, valvular disease
• Arterial thrombosis (25%): Chronic atherosclerosis with acute occlusion
• These patients often have history of "intestinal angina" (postprandial pain)
• Non-occlusive mesenteric ischemia (NOMI): Low-flow states (shock, vasopressors)
• Mesenteric venous thrombosis: Hypercoagulable states, portal hypertension

Clinical Presentation

• Severe periumbilical or diffuse abdominal pain
• Pain severity disproportionate to physical findings (early)
• Nausea, vomiting, diarrhea (may be bloody)
• Later: Peritonitis, absent bowel sounds, abdominal distension
• Often elderly patients with cardiac risk factors
• Rapid deterioration to sepsis and shock with infarction

Diagnostic Evaluation

• CT angiography: Test of choice - identifies occlusion and bowel viability
• Findings: SMA cutoff, bowel wall thickening, pneumatosis, portal venous gas
• Labs: Elevated lactate (late finding), leukocytosis, metabolic acidosis
• D-dimer often elevated but nonspecific
• Plain films: May show ileus pattern, "thumbprinting" (mucosal edema)
• Conventional angiography: Therapeutic capability for intervention

Management Approach

• Aggressive IV fluid resuscitation
• Broad-spectrum antibiotics for bacterial translocation
• Anticoagulation with heparin (unless contraindicated)
• Surgical consultation - urgent laparotomy often needed
• Endovascular options: Catheter-directed thrombolysis, thrombectomy
• Surgery: Embolectomy, bypass, or bowel resection for necrosis
• Second-look laparotomy at 24-48 hours common
• May require multiple surgeries, ostomy creation

Abdominal Compartment Syndrome

Understanding Abdominal Compartment Syndrome

• Definition: Sustained intra-abdominal pressure (IAP) >20 mmHg WITH new organ dysfunction
• Intra-abdominal hypertension (IAH): Sustained IAP >12 mmHg
• Normal IAP: 5-7 mmHg in critically ill patients
• Affects 50-80% of critically ill patients (IAH); up to 50% develop ACS
• Unrecognized ACS has extremely high mortality

Risk Factors

• Massive fluid resuscitation (crystalloid-induced visceral edema)
• Abdominal trauma and damage control surgery
• Severe burns with aggressive fluid therapy
• Acute pancreatitis with significant inflammation
• Abdominal surgery, particularly with packing
• Ascites, liver transplantation
• Mechanical ventilation with high PEEP (>10 cmH2O)
• Obesity, elevated head of bed position

Systemic Effects

• Cardiovascular: Decreased venous return, reduced cardiac output
• Respiratory: Elevated diaphragm, decreased compliance, hypoxia
• Renal: Compressed renal vessels, oliguria progressing to AKI
• GI: Bowel ischemia, bacterial translocation to bloodstream
• Hepatic: Impaired portal flow, decreased lactate clearance
• CNS: Elevated ICP from impaired venous drainage

Clinical Recognition

• Tense, distended abdomen (most common finding)
• Progressive oliguria despite adequate fluid resuscitation
• Increased peak airway pressures, difficulty ventilating
• Hemodynamic instability requiring escalating vasopressor support
• Elevated JVD, peripheral edema
• Signs of hypoperfusion: Cool extremities, altered mental status, lactic acidosis
• Patients often sedated and unable to report symptoms

Diagnosis - Bladder Pressure Measurement

• Gold standard: Urinary bladder pressure measurement
• Simple, minimally invasive, and accurate
• Patient supine, instill 25 mL sterile saline via Foley
• Measure at end-expiration with transducer at symphysis pubis
• Grade I IAH: 12-15 mmHg
• Grade II IAH: 16-20 mmHg
• Grade III IAH: 21-25 mmHg
• Grade IV IAH: >25 mmHg
• ACS = Grade III-IV IAH + organ dysfunction

Management Strategy

• Prevention: Judicious fluid resuscitation, damage control resuscitation
• Medical management: NG tube decompression, sedation, paracentesis for ascites
• Optimize abdominal wall compliance: Avoid high head-of-bed elevation
• Neuromuscular blockade may temporarily improve compliance
• Diuretics or ultrafiltration if volume overloaded
• Surgical decompression: Decompressive laparotomy with open abdomen
• Temporary abdominal closure devices (VAC/wound vac)
• Staged abdominal closure once edema resolves

Acute Abdominal Trauma

Mechanisms of Injury

• Blunt trauma: Motor vehicle collisions (most common), falls, assaults
• Penetrating trauma: Stab wounds, gunshot wounds
• Solid organs (spleen, liver) most vulnerable to blunt injury
• Hollow viscus (bowel) more commonly injured in penetrating trauma
• Significant force can cause deceleration injuries (mesenteric tears)

Clinical Assessment

• Kehr sign: Left shoulder pain - suggests splenic injury with diaphragm irritation
• Seat belt sign: Linear abdominal bruising - high suspicion for internal injury
• Grey Turner sign: Flank ecchymosis - retroperitoneal hemorrhage
• Cullen sign: Periumbilical ecchymosis - intraperitoneal or retroperitoneal bleeding
• Abdominal distension, guarding, rebound tenderness suggest peritonitis
• Hemodynamic instability: Hypotension, tachycardia indicate significant bleeding

Diagnostic Evaluation

• FAST exam (Focused Assessment with Sonography for Trauma): First-line in unstable patient
• Detects free fluid in peritoneum and pericardium
• CT abdomen/pelvis with IV contrast: Gold standard for stable patients
• Identifies solid organ injury grade, active bleeding, bowel injury
• Diagnostic peritoneal lavage (DPL): Largely replaced by FAST and CT
• Serial H/H and physical exams for observation patients

Management Approach

• Hemodynamic stabilization: Large-bore IV access, crystalloids, blood products
• Massive transfusion protocol for severe hemorrhagic shock
• Non-operative management: Most blunt solid organ injuries (spleen, liver)
• Angioembolization for active bleeding without peritonitis
• Surgical exploration: Hemodynamic instability, peritonitis, hollow viscus injury
• Damage control surgery: Abbreviated laparotomy for severely injured patients
• ICU monitoring with serial exams and imaging

Drug-Induced Liver Injury (DILI)

Overview of Drug-Induced Hepatotoxicity

• Leading cause of acute liver failure in developed countries
• Can be dose-dependent (predictable) or idiosyncratic (unpredictable)
• Dose-dependent: Damage correlates with amount ingested (acetaminophen)
• Idiosyncratic: Occurs unpredictably, not dose-related (immune-mediated)
• Latency period varies from days to months after drug exposure
• Often diagnosed by exclusion of other causes

Common Hepatotoxic Medications

• ACETAMINOPHEN: #1 cause of acute liver failure - dose-dependent toxicity
• Maximum safe dose: 4g/day (less in alcoholics or liver disease)
• Antibiotics: Amoxicillin-clavulanate, isoniazid, rifampin, sulfonamides
• Antiepileptics: Phenytoin, carbamazepine, valproic acid
• Cardiovascular: Amiodarone, statins, labetalol
• NSAIDs: All can cause hepatotoxicity, especially with chronic use
• Antifungals: Ketoconazole, itraconazole

Other Hepatotoxic Substances

• ALCOHOL: Chronic use causes fatty liver, hepatitis, cirrhosis
• Recreational drugs: MDMA (ecstasy), cocaine, methamphetamine
• Herbal/supplements: Herbalife, Hydroxycut, green tea extract, kava
• Anesthetic agents: Halothane, isoflurane (rare)
• Psychiatric medications: MAOIs, tricyclic antidepressants
• Immunosuppressants: Methotrexate, azathioprine
• Chemotherapy agents: Gemtuzumab and others

Clinical Patterns of DILI

• Hepatocellular injury: Predominant ALT elevation (ALT >3x ULN)
• Cholestatic injury: Predominant ALP elevation with jaundice
• Mixed pattern: Both hepatocellular and cholestatic features
• R-ratio helps classify: ALT/ULN divided by ALP/ULN
• R >5 = hepatocellular | R <2 = cholestatic | R 2-5 = mixed
• Hepatocellular pattern has worse prognosis

Acetaminophen Toxicity

• Toxic dose: >150 mg/kg or >7.5-10g in adults
• Mechanism: Depletes glutathione, toxic metabolite (NAPQI) accumulates
• Phase 1 (0-24h): Nausea, vomiting, anorexia - may appear well
• Phase 2 (24-72h): Rising LFTs, RUQ pain, coagulopathy develops
• Phase 3 (72-96h): Peak liver injury, possible fulminant hepatic failure
• Phase 4: Recovery or death (if untreated severe toxicity)

Management of Acetaminophen Toxicity

• N-Acetylcysteine (NAC): Antidote - replenishes glutathione
• Most effective if given within 8 hours of ingestion
• Still beneficial up to 24+ hours in severe cases
• Rumack-Matthew nomogram: Guides treatment based on level and time
• IV NAC protocol: 150 mg/kg over 1 hour, then infusion
• Oral NAC: 140 mg/kg loading, then 70 mg/kg every 4 hours x17 doses
• Activated charcoal if presenting within 4 hours
• Liver transplant evaluation for fulminant hepatic failure

General DILI Management

• STOP the offending medication immediately
• Supportive care: IV fluids, monitor for complications
• Check INR - coagulopathy indicates severe synthetic dysfunction
• Monitor for hepatic encephalopathy (ammonia level, mental status)
• Avoid other hepatotoxic medications
• NAC may benefit non-acetaminophen DILI (controversial)
• Liver transplant evaluation if criteria met (Kings College Criteria)
• Report to FDA MedWatch for suspected DILI