Disorders of the Liver and Pancreas
Lobular Liver Lobule Microanatomy
Hexagonal plates Sinusoids Hepatocytes Triads
Bile duct branch Canaliculi
Arteriole Triad Venuole Arteriole Blood flows from periphery to Venuole
Central vein Bile Duct Branch Space of Dissé
Bile Formation
Hemoglobin breakdown Conversion in liver to water soluble form
Bilirubin Serum levels help diagnose lever disease
Excretion in bile
Some is reabsorbed
1 Zonal Pattern of Injury Liver Injury, The Basics
Peripheral Lots of stuff injures the liver. Middle It’s the great detoxifier Central Chronic injury Triadal Fibrosis Limiting plate Regeneration Piecemeal necrosis Providing the underlying framework remains
Cirrhosis
Cholestasis Many things may lead to cirrhosis Common features Slowed bile excretion Irreversible Chronic inflammation Intracellular Scarring (fibrosis) Drugs Parenchymal loss Viral infection Regenerative nodules By means of ducts Altered vascularity Drugs Symptoms Obstruction Ascites Gynecomastia Esophageal varices Splenomegaly Caput medusae
Cirrhosis Cirrhosis Many things may lead to cirrhosis Common features Irreversible Irreversible Chronic inflammation Scarring Scarring (fibrosis) Botched regeneration Parenchymal loss Vascular rearrangements Regenerative nodules Caput medusae -> Altered vascularity Symptoms Ascites -> Ascites Low albumin Gynecomastia Venous portal hypertension Esophageal varices Splenomegaly Caput medusae
2 Common Etiologies Cirrhosis
Inherited Stellate cell Pigmentary becomes real Post necrotic important Chronic viral Normally stores Nutritional vitamin A Lymphocytes turn him into a collagen making machine
Sequence of Events
Liver cell injury Cycle of chronic inflammation Destruction of underlying architecture Fibrosis Attempts to regenerate Vascular reorganization leading to shunting Repeat cycle Progressive Irreversible
Parasitic
There are several Schistosomiasis
Clonorchis sinensis
3 Inflammation of Liver Viral Hepatitis
Generally taken to mean hepatic specific viruses. Very common, lots of things do it. Histologic features common to most Toxins and drugs Acute Bacteria Necrosis of random liver cells Cholangitis Councilman bodies = bright pink dead cells Diffuse liver cell swelling Abscesses Bile stasis Viruses Portal (triadal) inflammation EBV Chronic pattern = persistence or relapse for 6 months CMV Chronic and acute inflammation Hepatic specific Piecemeal necrosis Parasites Bridging necrosis Autoimmune cirrhosis
Acute Viral Hepatitis
Chronic or Persistent Hepatitis Hepatitis A
‘Infectious hepatitis’ Food handlers Virus in stool Seafood Self limiting No chronic state No cirrhosis No carrier state History and serology IgM IgG Maybe virus
4 Hepatitis B Chronic Hepatitis B
‘Serum hepatitis’ Sexually transmitted Blood borne Infrequently a person Longer incubation develops chronic Common in Asia infection with B. Most get over it fine Leads to cirrhosis Immunologic damage Less common Chronic progressive Fulminant failure and death Cirrhosis Chronic carrier state
Hepatitis B Outcomes Hepatitis C
Delta Agent Hepatitis C
Very high rate of persistence Incomplete virus Needs hepatitis B to Long incubation period replicate Cirrhosis The two together cause terrible disease. Fulminant loss of liver
Can become infected later if you are a carrier of hepatitis B
5 Hepatitis Outcomes Autoimmune Hepatitis
Asymptomatic infection Women
Acute hepatitis like a bad case of the flu Chronic hepatitis
Overt Jaundice No viral markers
Carrier state May lead to cirrhosis
Fulminant liver death
Chronicity, +/- cirrhosis
Abscesses Drug and Toxin
Bacterial Too many to list Parasitic Direct hepatocyte toxicity Blood borne Biliary paralysis Ascends ducts Conversion to a truly toxic agent
Alcoholic Liver Disease Reye’s Syndrome
Acute and chronic Young kids Acute hepatitis Follows flu Fatty liver -> Cirrhosis Got aspirin
Liver and brain
Fulminant liver failure
6 Acute Alcoholic Hepatitis Alcoholic Cirrhosis
About 15-20% of alcoholics Micronodular pattern, so called ‘hobnails’ Liver cell necrosis Increased portal pressures Balloon degeneration
Neutrophils Mallory bodies
Alcoholic and Non-Alcoholic Fatty Liver Disease
Non Alcoholic • DM • Obesity • Metabolic syndrome • Even kids
Pigmentary
Other Types of Cirrhosis Iron Oxidative injury
Scarring
Congenital problem with excessive absorption
7 Wilson’s Disease Alpha-1 Anti-trypsin Deficiency
Copper metabolism Absence of transport protein Neutralizes proteases and elastases Builds up in various organs Made in the liver Can’t finish the process Cirrhosis Constipated cells fill up Brain degeneration with partially completed Corneal ring anti-trypsin
Causes cell death and scarring
Emphysema
Intrahepatic Biliary Disease
Drug related
Bile stasis
Inflammation Scarring
Primary conditions of the biliary tree
Autoimmune, often leading to cirrhosis
Sometimes associated with other conditions
Primary Biliary Cirrhosis Primary Biliary Cirrhosis
Women Granulomatous destruction of medium sized bile ducts High serum cholesterol Xanthomas Cirrhosis Antimitochondrial antibodies Sicca syndrome Dry eyes & mouth Scleroderma Rheumatoid arthritis All autoimmune in nature
8 Primary Sclerosing Cholangitis
Concentric fibrosis of smaller bile ducts Onionskin
Seen with ulcerative colitis
No antibodies No other problems, like Sicca syndrome
Vascular Related Hepatic Infarct
Congestion Infarcts Cirrhosis altered vascularity of liver
Pregnancy Related Eclampsia
HELLP syndrome Hepatic enzymes Low platelets
Eclampsia
High blood pressure Fatty liver May be life threatening
9 Tumors of the Liver
Hyperplasia vs. true tumor
Estrogens
Benign vs. malignant
Primary vs. metastatic
Bowel
Lung Kidney
Breast
Metastatic Cancer Hepatocellular Carcinoma
Malignant hepatocytes Associated with Hepatitis B Cirrhosis May be multiple foci
Cholangiocarcinoma Gallstones
Comes from bile duct epithelium Ethnicity Adenocarcinoma Age Much desmoplasia Not associated with the stuff seen in hepatocellular cancer Sex Fatty foods
Cholesterol and mixed stones
Pigmentary stones Obstruction
Painful Infection
10 Gallstones Cancer of Gallbladder
Chronic irritation of gallstone Chronic cholecystitis
Presumed oxidative damage Cancer
Pancreas
Acute Pancreatitis
Autodigestion Acute inflammation Enzyme activation Fat necrosis with soaponification Hemorrhage Causes Obstruction Stone Tumor Alcohol Complications Pseudocyst Shock
11 Acute Pancreatitis Soaponification
Pancreatic Pseudocyst Chronic Pancreatitis
Extensive fibrosis Calcifications
Cystic fibrosis
Cystic Fibrosis Pancreatic Cancer
Often advanced at the
Inherited problem of time of discovery. chloride pump Adenocarcinoma Thick mucus From ductal epithelium
Clogs Spreads to liver Bowel Not hormonally active Pancreas Painless jaundice Fibrosis
Malabsorption Bronchi
12 Islet Cell Insulin Secretion and Peripheral Utilization Tumors
Insulin secreting Hypoglycemic episodes
Zollinger-Ellison
Glucagonomas VIPomas
Type I Diabetes Type I Diabetes
Lack of insulin Trigger leads to autoimmune destruction of islets Trigger causes autoimmune destruction of beta cells.
Ketosis prone
Glycosylated Type II Diabetes Proteins
Small vessel Insulin release vascular disease problem This is what Peripheral resistance diabetes becomes Non-ketosis prone
13 Diabetic Vascular Changes
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