Final Study Hepatobiliary System.pdf

Hepatobiliary System Liver Functions • • • • Gallbladder Functions • Digestive Endocrine Hematologic Excretory Pancreas Functions • • Storage Digestive Endocrine Liver Liver Functions o o o o o Synthesis and Storage of amino acids, proteins, vitamins, and fats Detoxification Blood Circulation...

Hepatobiliary System Liver Functions • • • • Gallbladder Functions • Digestive Endocrine Hematologic Excretory Pancreas Functions • • Storage Digestive Endocrine Liver Liver Functions o o o o o Synthesis and Storage of amino acids, proteins, vitamins, and fats Detoxification Blood Circulation & Filtration Bile Drainage Blood Glucose Regulation Liver Injury The liver is highly metabolically active and receives a large percentage of the blood circulation. Because of this, it can be a big target for injury. Types of Liver Injury Toxic Infectious • • E t O H M e d • • Neoplastic V i r a l B a • Metabolic P r i m a r y • Circulatory NonAlco holic fatty liver disea se • B u d d C h • s ( A P A P * ) A f l a t o x i n s Fungal toxins From food • I n d u s t r i a l t o x i n s • c t e r i a l P a r a s i t i c • S e c o n d a r y 28.8M Adults • Hepa tolen ticula r dege nerat ion • Hem ochr omat osis • Alph a-1 Antit rypsi n Defic iency • • i a r i s y n d r o m e H e p a t i c V e n o O c c l u s i v e D i s e a s e I s c h e m i c H e p a t i t i s *APAP = Acetaminophen (Tylenol); leading cause of acute liver failure Types of Liver Injury Damage Inflammation Degeneration • • Hepati tis Usuall y viral • • Normal Hydropic Hydro pic (water y) Toxins FattyETOH, Obesit y, T2DM Necrosis • Necrosis Fibrosis Diffu se or focal • Sever e, chro nic injur y Fibrosis Progression of Liver Disease The liver responds remarkably well to injury. Repairs can be made through regeneration (up to a point). The liver has enormous functional reserve and must suffer a marked decline of capacity before becoming symptomatic (~10% normal function remaining). Fatty Liver Disease Steatosis or fatty degeneration (accumulation of triglycerides in liver cells) Reversible or may progress to steatohepatitis (NASH) (inflammation + fatty degeneration) Increases risk of hepatocellular carcinoma. Risk Factors • • • • Excessive alcohol intake (causes alcoholic fatty liver disease) Diabetes (causes non-alcoholic fatty liver disease) Obesity (causes non-alcoholic fatty liver disease) High triglycerides (causes non-alcoholic fatty liver disease) Cirrhosis Patterned, irreversible fibrosis of the entire liver. Characterized by dense fibrous tissue and unique cellular architecture. Causes ~31,000 deaths annually (1.2%) Etiology Hep C Virus (HCV) (26%) Alcoholic Liver Disease (21%) • HCV+ Alcoholic Liver Disease (15%) • Cryptogenic Cirrhosis (18%) Associated with steatosis (NAFLD) • Hepatitis B Virus (HBV) (15%) • Miscellaneous (5%) • • Effects • • • Variable Decreased hepatic function Portal HTN Hepatic failure Most severe consequence of liver disease Prevalence • • • Causes • Chronic liver disease Hepatitis or ETOH abuse • Massive hepatic necrosis Fulminant viral hepatitis Drugs and chemicals (APAP, mushroom poisoning) • Hepatic Dysfunction w/o overt necrosis Acute fatty liver of pregnancy Tetracycline toxicity Reye syndrome ~44,358 deaths annually May follow sudden or chronic injury 80-90% loss of functional capacity Signs & Symptoms • • • • Jaundice Portal HTN Ascites Fetor hepaticus "Liver breathe" • Hypoalbumi nemia • Hypoglycemi a • Hyperammo nemia • Bleeding disorders Signs in Men Signs in Women • • • • • Gyneco mastia Impoten ce Testicula r atrophy Female hair distributi on • • Irregular menses Palmar erythem a Spider telangie ctasia Fulminant Hepatic Failure Rapidly progresses to hepatic failure and encephalopathy (weeks) Primarily caused by acetaminophen overdose (46%) Other Causes • • • • • • Hep A & B (10%) Heat stroke Acute fatty liver of pregnancy Wild mushroom poisoning Adverse reactions to drugs Autoimmune diseases Jaundice / Icterus Excess bilirubin in the blood Prehepatic Jaundice • • Hepatic Jaundice • Hematoma reabsorption Hemolytic anemia • • • Posthepatic Jaundice • Defective liver functioning Viral hepatitis Drug interference Cirrhosis • • Portal HTN Etiology • • • Sluggish hepatic blood flow Congested drainage of GI tract Splenomegaly Symptoms • Anorexia • Ascites • Varices Esophageal Gastric Biliary obstruction Gallstones Pancreatic cancer Hemorrhoidal Ascites Most common complication of cirrhosis >500ml of free fluid within the peritoneal cavity Increased hydrostatic pressure and decreased oncotic pressure Indicates advanced liver disease 50% 2-year survival rate Hepatic Encephalopathy Complex neuropsychiatric syndrome caused by hepatic failure or severe chronic liver disease. A build-up of metabolic wastes in the blood can lead to mild confusion, lethargy, stupor, or coma. Liver Function Tests Tests for… Comprehensive Metabolic Panel Enzymes Bilirubin Produced during normal clearance of RBCs • Proteins Albumin and plasma proteins • Coagulation tests • Hepatitis virus antigens and antibodies • Autoimmune antibodies Calcium Carbon dioxide Chloride Creatine Potassium Sodium Glucose Albumin Blood urea nitrogen (BUN) • Total bilirubin • Total protein • Alanine aminotransferase (ALT) • Alkaline phosphatase (ALP) • Aspartate aminotransferase (AST) Red = Liver function test • • • • • • • • • • • Alcoholic Liver Injury Reversible (until you reach cirrhosis) Pathogenesis • • • Direct cellular toxicity Toxic metabolic products Alteration of lipid metabolism Effects • • • • Inflammation Increased fat storage Collagen synthesis Neutrophil infiltration Can lead to… • • • • • Fatty change Acute hepatitis Chronic hepatitis with portal fibrosis Cirrhosis Chronic liver failure Hepatitis #1 cause of acute hepatitis → Viral #1 cause of chronic hepatitis → Viral #2 cause of chronic hepatitis → Alcohol Acute Viral Hepatitis Phases 1) Incubation • • Usually lasts a few weeks Peak period of infectivity 2) Symptomatic Pre-Jaundice Phase • • • • Malaise Fatigability Nausea Anorexia 3) Symptomatic Jaundice Phase • Jaundice appears and other symptoms fade 4) Convalescence • • • Jaundice fades Infectivity declines Antibodies appear in blood 5) Carrier • HCV>>HBV Common Associated Viruses Virus Transmission Hepatitis Virus A Oral-fecal contamination Hepatitis Virus B Blood-borne (Needle stick) / Sexually / Vertically Hepatitis Virus C Blood-borne (Needle stick) / Sexually / Congenital Hepatitis Virus D Co-infection with HBV; Can put fetus at risk in pregnant women Hepatitis Virus E Oral-fecal contamination Cytomegalovirus Epstein-Barr Virus Summary Virus Epidemiology Vaccine Acute Failure Chronic Cancer Annual Mortality Treatment HAV ~37,700 new cases in 2019 in U.S. Yes <1% No No 225 Supportive HBV ~20,700 new cases and ~1.59M chronic cases in U.S. in 2019 Yes <1% ~3.5% <1% ~3,000 Antivirals HCV ~57,500 new cases and ~2.5M chronic cases in U.S. in 2019 No No 75-85% 1-5% 14,242 Antivirals Hepatitis A Virus Family • • Picorn avirida e family Nonen velope d (+)ssR NA Clinical Manifestations Tx Prevention • • Acute, viral hepati tis • Asymp tomati c (90% of infected children) Pa lli ati ve • Sani tati on Hyg ien e Inac tiva ted viru s vac cine Ga mm aglo buli n sho t • • • Hepatitis B Virus CTLs eliminate infected cells Family Clinical Manifestations • • Pararet rovirus Envelo ped dsDNA (+)RT • Acu te, viral hep atiti s Tx Prevention • • Interf eron thera py Antivi ral • Su b u ni t va • • Partiall y doublestrande d • medic ation s Ful min ant hep atic failu re (rar e) Chr onic hep atiti s (10 %) cc in e Cirrhosis Carcinogenic • • • Outcomes 40k new infections annually in the US 3k deaths annually 1 healthcare worker dies each day from HBV Hepatitis C Virus CTLs eliminate infected cells Family Acute Infection • • • Flav iviri dae fam ily Env elo ped (+)s sRN A Ma ny gen • Asym ptoma tic • Mild hepati tis (15%) • Spont aneou s resolu tion 10-50% of cases Chronic Infection • • • • Cirrho sis (1030%) Liver failure Hepat ocellul ar carcin oma Portal HTN Tx • • Int erf er on th era py An tivi ral me ds oty pes Chronic Viral Hepatitis Viral hepatitis proven by liver biopsy Findings • • • • Enlarged, tender liver Splenomegal y Palmar erythema Spider angiomas Palmar erythema Spider angiomas Reye's Syndrome Fatty liver & Encephalopathy <15yoa ~2 cases annually in the US (very rare) Causes • • Symptoms Vir al inf ect ion + As pir in us e No as • • • • Findings Stup or Coma Vomi ting Conv ulsio ns • • Tx Hepato megaly Hypogl ycemia • Inf usi on of glu cos e, pla sm a, and ma pir in bef or e 15 yo a! nni tol Poo r pro gno sis (50 % mo rtal ity rat e) • Hepatocellular Carcinoma Relatively rare in the US Usually metastatic cancers of the colon, lung, and breast Risk Factors • • Alpha-Fetoprotein • Viral hepatitis (HBV & HCV) Aflatoxins • Elevated in 70% of cases Correlates with tumor burden Dx • Biopsy Hepatolenticular Degeneration ("Wilson's Disease") Impaired excretion of hepatic copper Etiology • • Areas of Accumulation Autoso mal recessi ve 1:30,00 0 Possible Complications • • • Liv er Bra in Oth er org ans Findings • Low serum ceruloplas min concentra tion (reduced transport into the liver for processing) • High levels of copper in urine Tx • Chela tion Neuropsychiatric disorders Cu disrupts neurotransmission • Kayser-Fleischer rings Cu deposition in cornea Other causes (Acute hepatitis, fulminant hepatitis, chronic active hepatitis, cirrhosis) • Gallbladder Gallbladder Functions o o o Store and concentrate bile Emulsify fat Secretion stimulated by fat in the duodenum Gallstones Gallstones are supersaturated bile caused by gallbladder stasis. Gallbladder attacks occurs when the gallbladder is blocked but tries to contract, leading to spasm. Prevalence • • 20% of US adults over 40 75% are cholesterol Risk Factors • • • • Elevated estrogen levels (F>M 2:1) Obesity Advancing age (>40) Comorbidities (Diabetes, cirrhosis) Tx • Diet • • Medication Surgery ↓Cholesterol Pancreas Functions Exocrine • • • • Proteases Lipase Amylase Protease inhibitors Pancreatic Diseases Usually limited to exocrine components of the organ. Endocrine • • Insulin Glucagon o o Digestive function diseases caused by premature activation of protease enzymes or obstruction of the common bile duct. Pancreatic malignancies are often asymptomatic for years before being caught. About 57k cases annually in the US, with an 80% mortality rate. Pancreatitis Acute Pancreatitis • • • Short-lived Usually resolves 50% related to gallstones Chronic Pancreatitis • • • Does not resolve itself Progressive destruction of the pancreas 60% related to alcoholism Potential Complications • • • • Bleeding Tissue damage Infection Blood borne distribution of digestive enzymes