Liver, Biliary Tract, Pancreas Pathophysiology Semiology (PDF)

LIVER, BILIARY TRACT, PANCREAS Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus November 2023 LIVER PORTAL HYPERTENSION Portal Hypertension • Definition – Increase in the blood pressure around the liver • the portal venous syste...

LIVER, BILIARY TRACT, PANCREAS Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus November 2023 LIVER PORTAL HYPERTENSION Portal Hypertension • Definition – Increase in the blood pressure around the liver • the portal venous system • Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver difference between the wedged 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 12 13 HVPG and esophageal varices • • • • HVPG > 10mmHg: varices development HVPG > 12mmHg: high risk of variceal bleeding HVPG > 16mmHg: high risk of death HVPG > 20mmHg: high risk of treatment failure and rebleeding • HVPG increase -> 1mmHg: 3% increase of risk of death for the following 19 months 15 16 17 18 CIRRHOSIS Cirrhosis - Definition • Diffuse process with fibrosis and nodule formation replacing the normal hepatic parenchyma • It is the end result of the fibrogenesis that occurs with chronic liver injury Cirrhosis Etiology • The two most common causes in the United States – alcoholic liver disease – hepatitis C • On average about 27,000 deaths per year • Patients with cirrhosis are susceptible to a variety of complications • Reduced life expectancy Cirrhosis - Etiology 23 Alcoholic Liver Disease Cirrhosis • The clinical diagnosis of alcoholic liver disease, using a combination of physical findings, laboratory values, and clinical presenation, is relatively accurate • However, liver biopsy can be justified in selected cases, especially when the diagnosis is in question • In addition to confirming the diagnosis, liver biopsy is also useful for ruling out other unsuspected causes of liver disease, better characterizing the extent of the damage, providing prognosis, and guiding therapeutic decision making Alcoholic Liver Disease Physical Examination Constitutional •Fever Skin •Spider angioma •Parotid and lacrimal gland enlargement •Palmer erythema •Jaundice •Decreased body hair •Gynecomastia Musculoskeletal •Dupuytren’s contracture •Clubbing •Muscle wasting Genitourinary •Testicular atrophy Abdomen •Hepatomegaly or small shrunken liver •Splenomegaly •Ascites •Hepatic tenderness Neurologic •Asterixis •Confusion, stupor 26 Alcoholic Liver Disease Laboratory Findings Liver synthetic function •Hyperbilirubinemia (usually conjugated) •Prolonged prothrombin time •Hypoalbuminemia Liver enzyme levels •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels elevated, usually < 300 U/L; AST/ALT ratio ~ 2:1 Hematologic •Anemia •Leukocytosis or leukopenia •Thrombocytopenia •Increased serum globulin levels Metabolic •Elevated blood ammonia level •Hyperglycemia •Respiratory alkalosis •Hypomagnesemia •Hypophosphatemia •Hyponatremia •Hypokalemia 28 Dupuytren’s contracture 29 30 31 32 Parotid gland enlargement 33 Cirrhosis - Complications • • • • • • Ascites Spontaneous Bacterial Peritonitis Hepatorenal syndrome Variceal hemorrhage Hepatic Encephalopathy Hepatocellular carcinoma Ascites • Accumulation of fluid within the peritoneal cavity • Most common complication of cirrhosis • Two-year survival of patients with ascites is approximately 50 percent • Grading • Grade 1 — mild; detectable only by US • Grade 2 — moderate; moderate symmetrical distension of the abdomen • Grade 3 — large or gross ascites with marked abdominal distension Ascites – Physical Examination • The word ascites is of Greek origin (askos) and means bag or sac • Pathologic fluid collection within the abdominal cavity • Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL, depending on the phase of their menstrual cycle Ascites • Signs of portal hypertension and chronic liver disease • Jaundice, palmar erythema, spider angiomas • The liver may be difficult to palpate but if palpable often enlarged • The puddle sign may be present when as little as 120 mL of fluid is present • When peritoneal fluid >500 mL ->shifting dullness or bulging flanks • Fluid-wave sign is notoriously inaccurate. 38 Stages of ascites • Diuretic-responsive ascites • Refractory ascites • Hyponatremia •Refractory ascites • Hepatorenal syndrome (HRS) Each stage reflects a more deranged circulatory state. Spontaneous bacterial peritonitis (SBP) • Most common type of bacterial infection in hospitalized cirrhotic patients Hepatic Encephalopathy Pathophysiology ⚫ Cerebral vasomotor dysfunction ⚫ Oedema secondary to ammonia toxicity ⚫ Inflammation due to SIRS ⚫ Putative benzodiazepine-like molecules Hepatic Encephalopathy Pathophysiology ⚫ ⚫ ⚫ Ammonia as a key factor in the pathogenesis of HE. ⚫ Portal ammonia is derived from both the ⚫ urease activity of colonic bacteria and the ⚫ de-amidation of glutamine in the small bowel. The intact liver clears almost all of the portal vein ammonia, converting it into glutamine and preventing entry into the systemic circulation. Ammonia- astrocyte swelling in brain 43 Hepatic Encephalopathy Pathophysiology 45 Hepatic Encephalopathy Pathophysiology Stages of Hepatic Encephalopathy West-Haven Scale Grade Presentation 0 Lack of detectable changes in personality or behavior. Asterixis absent. I Trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Euphoria or depression. Asterixis can be detected. II Lethargy or apathy. Disorientation. Inappropriate behavior. Slurred speech. Obvious asterixis. III Gross disorientation. Bizarre behavior. Semi-stupor to stupor. Asterixis generally absent. IV Coma. Stages of Hepatic Encephalopathy West-Haven Scale Hepatic Encephalopathy Signs and symptoms • • • • Abnormal behavior Cognitive function abnormalities Level of consciousness Neuromuscular function • Sleep disorders – Insomnia, lethargy • Bradykinesia • Asterixis • Absence of focal semiology 50 Hepatic Encephalopathy Asterixis • Inability to maintain a position, which is demonstrated by jerking movements of the outstretched hands when bent upward at the wrist. • The tremor is caused by abnormal function of the diencephalic motor centers in the brain, which regulate the muscles involved in maintaining position. Hepatic Encephalopathy Triggering factors • • • • • • • Constipation Bleeding Infection (SBP, UTI) Electrolytic disorders Portal vein thrombosis Worsening liver disease HCC 53 JAUNDICE Jaundice (icterus) a condition of yellow discoloration of the • Skin • Conjunctivae • Mucous membranes resulting from widespread tissue deposition of the pigmented metabolite bilirubin Jaundice can result from • an increase in bilirubin production • or a decrease in hepatobiliary elimination of bilirubin Bilirubin metabolism Pre-hepatic (hemolytic) Hepatic (hepatocellular) Post-hepatic (cholestatic or obstructive) Unconjugated Hyperbilirubinemia Causes • ▲ bilirubin production PREHEPATI|C • hemolysis • ineffective erythropoiesis • blood transfusion • resorption of hematomas • ▼decreased hepatocellular uptake of unconjugated bilirubin • ▼ bilirubin conjugation Drugs • rifampin • cyclosporine A Autosomal inherited disorders Gilbert’s Type I Crigler-Najjar Type II Crigler-Najjar Dubin-Johnson Rotor’s UNCONJUGATED MIXED/CONJUGATED Clinical presentation (except from jaundice) Diagnostic approach Therapeutic approach DEPENDS ON THE PROBLEM Obstructive Jaundice i.e. bile duct obstruction • Choledocholithiasis • Pancreatic head cancer • Choloangiocarcinoma therapy is typically directed at relieving the obstruction (ERCP or surgery) Non-obstructive Jaundice i.e. liver disease optimal treatment is directed toward the underlying cause • cessation of ethanol • discontinuation of the offending drug • administration of antiviral therapy for hepatitis • immunosuppressive agents for autoimmune hepatitis BE CAREFUL JAUNDICE CHOLESTASIS Cholestasis • defined as stagnation, or at least a marked reduction, in bile secretion and flow • can be due to a functional impairment of the hepatocytes in the secretion of bile and/or due to an obstruction at any level of the excretory pathway of bile, from the level of the hepatic parenchymal cells at the basolateral (sinusoidal) membrane of the hepatocyte to the ampulla of Vater in the duodenum • marked bile acidemia with normal to slightly elevated bilirubin levels) Cholestatic jaundice can thus be classified depending upon the level of obstruction to bile flow Intrahepatic (functional) • a disease involving the liver parenchymal cells INTRAHEPATIC and/or the intrahepatic bile ducts • intralobular (disease of liver parenchymal cells and transporter molecules) • extralobular (disease involving intrahepatic bile ducts) EXTRAHEPATIC Extrahepatic (obstructive) • excretory block outside of the liver, along with the extrahepatic bile ducts BILIARY TRACT GALLSTONE DISEASE intrahepatic cholelithiasis Choledocholithiasis Biliary colic • Characteristic symptoms of gallbladder stones • Episodic attacks of severe pain in the right upper abdominal quadrant or epigastrium for at least 15-30 min with radiation to the right back or shoulder • Positive reaction to analgesics How is a patient with biliary colic treated? • NSAIDs (e.g. diclofenac, indomethacin) ± • spasmolytics (e.g. butylscopolamine) and opioids (e.g. buprenorphine) CHOLECYSTITIS Signs and symptoms of cholecystitis •Severe pain in your upper right or center abdomen •Pain that spreads to your right shoulder or back •Tenderness over your abdomen when it's touched •Nausea •Vomiting •Fever Cholecystitis signs and symptoms often occur after a meal, particularly a large or fatty one CHOLANGITIS Cholangitis syndromes • complex end-stage hepatobiliary disorders • a wide range of abnormalities fall into the diagnostic criteria for cholangitis • inflammation and fibrosis of the hepatobiliary system that is characterized by eventual narrowing and obstruction of the bile ducts Therapeutic interventions for obviating the obstructive lesions in biliary hepatic ducts is the primary approach for management of cholangitis liver transplantation? especially in patients with progressed disease. etiology and pathogenesis of various forms of cholangitis are heterogeneous may be triggered by both genetic and acquired mediators may also present as a primary immune condition divided into three main categories • primary sclerosing cholangitis (PSC) • secondary cholangitis • immune cholangitis Acute Cholangitis is characterized by infections involving the biliary system and leading to inflammation and obstruction of the biliary ducts Signs and Symptoms Charcot’s triad • Jaundice • Fever ± rigors • Right upper quadrant abdominal pain Reynolds’ pentad • Charcot’s triad • Confusion • Shock ULTRASOUND Abdominal • In a patient with a recent history of biliary pain Endoscopic (or MRI) • In case of strong clinical suspicion of gallbladder stones and (-) abdominal ultrasound What is the recommended treatment for bile duct stones? • Endoscopic Retrograde Cholangiopancreatography (ERCP) • Endoscopic sphincterotomy and stone extraction • Intraoperative ERCP or laparoscopic bile duct exploration in combination with cholecystectomy • Extracorporeal shock wave, electrohydraulic or laser lithotripsy may be performed In case of failed standard stone extraction Laparoscopic bile duct exploration Extracorporeal shock wave, electrohydraulic or laser lithotripsy SEMIOLOGY (PANCREAS) Dr. Konstantinos Ekmektzoglou Lecturer School of Medicine European University Cyprus November 2020 PANCREATITIS Diagnosis of acute pancreatitis (2 of the following 3 features) • abdominal pain consistent with acute pancreatitis • serum lipase activity (or amylase activity) at ≥ 3 times greater than ULN • characteristic findings of acute pancreatitis on CT/MRI/US Clinical presentation AP (based on imaging findings) Interstitial edematous pancreatitis (IEP) • more common • non-necrotizing inflammation of the pancreas Necrotizing pancreatitis • necrosis may involve either the pancreatic parenchyma or the peripancreatic tissues Clinical presentation History (CAN GIVE YOU IMPORTANT CLUES) Abdominal pain Nausea and vomiting Specific abdominal findings • Grey Turner’s sign • Cullen’s sign IEP APFC NP ANC Treatment • Fluid resuscitation • Antibiotics? • Nutrition • Specific treatment of biliary acute pancreatitis • Invasive (radiological, endoscopic, or surgical) interventions Complications of CP Complications of CP