Disorders of the Liver and

Lobular Liver Lobule Microanatomy

 Hexagonal plates  Sinusoids  Hepatocytes  Triads

branch  Canaliculi

 Arteriole  Triad  Venuole  Arteriole  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 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  Providing the underlying framework remains

Cirrhosis

Cholestasis  Many things may lead to  Common features  Slowed bile excretion  Irreversible  Chronic inflammation  Intracellular  Scarring (fibrosis)  Drugs  Parenchymal loss  Viral  Regenerative nodules  By means of ducts  Altered vascularity  Drugs  Symptoms  Obstruction  Ascites  Gynecomastia   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  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

 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

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

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

 Asymptomatic infection  Women

 Acute hepatitis like a bad case of the flu  Chronic hepatitis

 Overt  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 Reye’s Syndrome

 Acute and chronic  Young kids  Acute hepatitis  Follows flu  Fatty liver ->  Cirrhosis  Got aspirin

 Liver and brain

 Fulminant

6 Acute 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

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

 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

 Malignant hepatocytes  Associated with  Hepatitis B  Cirrhosis  May be multiple foci

Cholangiocarcinoma

 Comes from bile duct  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  Chronic

 Presumed oxidative damage  Cancer

Pancreas

Acute

 Autodigestion  Acute inflammation  Enzyme activation  Fat necrosis with soaponification  Hemorrhage  Causes  Obstruction  Stone  Tumor  Alcohol  Complications   Shock

11 Soaponification

Pancreatic Pseudocyst

 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

 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 problem  This is what  Peripheral resistance diabetes becomes  Non-ketosis prone

13 Diabetic Vascular Changes

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