Week 8: Liver Disorders Flashcards
What is Viral Hepatitis A? Discuss the pathology and manifestations.
Can be found in the feces, bile, and sera of infected individual. Is usually transmitted by fecal-oral route from lack of handwashing. Risk factors include crowded, unsanitary conditions and food and water contamination. Can be prevented through handwashing and use of gloves as well as administration of vaccines. Can also give immunoglobulin before exposure or early in incubation.
Incubation Phase: 30 days
Route of transmission: Fecal-oral, parenteral, sexual
Carrier state: negative
Severity: mild
What is Viral Hepatitis B? Discuss the pathology and manifestations.
Is usually transmitted parenterally and sexually, most commonly through maternal-infant transmission that occurs if mother is infected during the third trimester. Risk factors include immunosuppressed people or immunosuppressive drugs, hemodialysis, multiple blood transfusions, multiple sex partners, sharing needles, etc. Prevention includes vaccine, and immunoglobulin prophylaxis.
Current approved treatments are interferon injections or oral nucleoside analogues. Blood work needs to be closely monitored. For liver biochemistry and viral DNA levels.
Incubation phase: 60-180 days
Route of transmission: parenteral, sexual
Carrier state: positive
Severity: severe, may be prolonged or chronic
What is Viral Hepatitis C? Discuss the pathology and manifestations.
Usually transmitted parenterally, is responsible for most cases of posttransfusion hepatitis. It can also be implicated in infections related to IV drug use and human immunodeficiency viral infection (HIV). Co-infection with hep b is common. Approximately 80% of those with hepatitis C develop chronic liver disease.
Risk factors include HBV infection. There is no vaccine available, we can administer antiviral medications.
Primary objective of treatment is sustained virologic response which is an absence of viremia 12 weeks after completion of therapy.
Incubation phase: 35-72 days
Route of transmission: parenteral
Carrier state: positive
Severity: mild to severe - can develop into chronic
What is Non-Alcoholic Fatty Liver Disease? Discuss the pathology and manifestations
NAFLD is the infiltration of hepatocytes with fat, primarily in the form of triglycerides, that occurs in the absence of alcohol intake and inflammation. It is associated with polygenic susceptibility, obesity, insulin resistance, high levels of cholesterol and triglycerides that exceed metabolic capacity, metabolic syndrome, and type 2 diabetes mellitus.
Some individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH) with hepatocellular injury, inflammation, and with or without fibrosis. NASH can be difficulty to distinguish from alcohol-induced liver fibrosis. There are several noninvasive biomarkers to evaluate the progression of fibrosis in NASH. Results of liver function abnormal serologic studies include increased liver enzymes (ALT, AST, y-glutamyltransferase, bilirubin, and decreased serum albumin levels)
Exercise and coffee consumption are thought to be protective environmental factors.
NAFLD is usually asymptomatic and may remain undetected for years. Individuals with type 2 diabetes mellitus are at high risk for NASH, and assessment for NAFLD should be part of their care with consideration of bariatric surgery.
The most common cause of death among individuals with NAFLD is cardiovascular disease. Treatment is individualized and includes the use of behavioral modification, dietary counseling, and regular exercise. Pharmacotherapy with insulin sensitizers, vitamin E, and lipid-lowering drugs may be considered. Pioglitazone should be considered for those with NASH, especially if fibrosis is present.
What is Alcoholic Liver Disease? Discuss the pathology and manifestations.
Alcoholic Liver Disease is related to the toxic effects of alcohol, the formation of acetaldehyde, and coexisting liver disease. The spectrum of alcoholic liver disease includes alcoholic fatty liver, alcoholic steatohepatitis, and alcoholic cirrhosis with progression to hepatocellular carcinoma (HCC) in some cases. The progression of liver injury is related to the amount and duration of alcohol use, and the influence of associate diseases (e.g., obesity, metabolic syndrome, and viral hepatitis). Although alcoholic cirrhosis is the most prevalent of the various types of cirrhosis, the occurrence of cirrhosis among persons with alcoholism is relatively low.
Malnutrition contributes to the risk of complications and adverse outcomes associated with alcohol related liver disease. Chronic alcohol abuse results in a catabolic state with upregulation of inflammatory mediators that suppress appetite and cause intestinal dysfunction with malabsorption of nutrients and pancreatic insufficiency. The chronic inflammatory state and altered metabolic pathways associated with alcoholic liver injury and anorexia lead to a hypermetabolic state, protein energy, caloric, and micronutrient malnutrition. The malnutrition and loss of muscle mass accelerate liver decompensation and disease progression.
Alcoholic Fatty Liver Disease is the mildest form of alcoholic liver disease, and there may be no symptoms. It can be caused by relatively small amounts of alcohol and is typically reversible with the cessation of drinking. The fat deposition within the liver is caused primarily by increased lipogenesis, cholesterol synthesis, and decreased fatty acid oxidation by hepatocytes that occurs with increased alcohol metabolism.
The diagnosis of alcoholic steatohepatitis or cirrhosis is based on the individual’s history of alcohol use and clinical manifestations. The results of liver function tests are abnormal, and serologic studies show elevated levels of serum enzymes (i.e., alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase) and bilirubin, decreased levels of serum albumin, and a prolonged prothrombin time that is not easily corrected with vitamin K therapy. Liver biopsy can confirm the diagnosis of cirrhosis, but biopsy is not necessary if clinical manifestations of cirrhosis are evident.
There is no specific treatment for alcoholic steatohepatitis or cirrhosis. Rest, vitamin supplements, a nutritious diet, corticosteroids, antioxidants, drugs that slow fibrosis, and management of complications (e.g., ascites, GI bleeding, and encephalopathy) slow disease progression. Cessation of alcohol consumption slows the progression of liver damage, improves clinical symptoms, and prolongs life. Although the liver damage is irreversible, measures that halt the inflammation and destruction of liver cells prolong life, and many new drugs are being evaluated.
What is Liver Cirrhosis? Discuss the pathology and manifestations.
Cirrhosis is an irreversible inflammatory, fibrotic liver disease. Hepatitis C, alcohol-related liver disease, NAFLD, and hepatitis B are the most common causes.
Cirrhosis involves the replacement of normal healthy liver tissue with scare tissue. The process of cellular injury depends on the cause; however, not all pathologic mechanisms are clearly understood. Structural changes result from injury (e.g., viruses or toxicity from alcohol) and fibrosis, which is a consequence of infiltration of leukocytes, and release of inflammatory mediators with activation of stellate cells which transdifferentiate into fibrogenic myofibroblasts and promote fibrotic processes. Chaotic fibrosis alters or obstructs biliary channels and blood flow, producing jaundice and portal hypertension. New vascular channels form shunts, and blood from the portal vein bypasses the liver, contributing to portal hypertension, metabolic alterations, and toxin accumulation. The process of regeneration is disrupted by hypoxia, necrosis, atrophy, and ultimately, liver failure. The formation of fibrous bands and regenerating nodules distorts the architecture of the liver parenchyma and gives the liver a cobbly appearance. The liver may be larger or smaller than normal and is usually firm or hard when palpated.
Cirrhosis develops slowly over a period of years. Its severity and rate of progression depend on the cause. If toxins, such as alcohol metabolites, are involves, the rate of cell death and severity of inflammation depend on the amount of toxin present.
The pathophysiology of cirrhosis causes immune suppression and increases the risk for infection.
What is Acute (fulminant) Liver Failure? Discuss the pathology and manifestations.
Acute liver failure is a rare clinical syndrome resulting in severe impairment or necrosis of liver cells without preexisting liver disease or cirrhosis. It involves severe impairment or necrosis of liver cells without pre-existing liver disease of cirrhosis. Acetaminophen overdose is a leading cause of a cute liver failure. N-acetyl cysteine is an available treatment for detoxification and should be given as soon as possible, preferably within 16 hours after the acetaminophen was taken. Acute liver failure can also occur with concurrent liver disease, including complications of viral hepatitis, particularly hepatitis B virus infection.
Pathophysiology involves edematous hepatocytes and patchy areas of necrosis and inflammatory cell infiltrates disrupting parenchyma. The death of hepatocytes may be caused by viral or toxic injury or immunologic and inflammatory damage with necrosis and apoptosis.
Diangotics:
- LFTs (bilirubin, transaminases, ammonia)
- PT/INR
Acute liver failure usually develops 6 to 8 weeks after the initial symptoms of viral hepatitis or a metabolic liver disorder, or within 5 to 8 days of acetaminophen overdose.
Anorexia, vomiting, abdominal pain, and progressive jaundice are initial signs, followed by ascites, GI bleeding and hepatic encephalopathy.
Liver function tests reflect liver injury and show elevations in the levels of both direct and indirect serum bilirubin, serum transaminases, and blood ammonia. The prothrombin time is prolonged. Renal failure and pulmonary dysfunction can occur.
Treatment requires rapid evaluation and critical care. The hepatic necrosis is irreversible, and there can be significant mortality. Liver transplantation can be life saving. Artificial liver support systems can provide a bridge to transplantation or to allow the liver to recover.
What is portal hypertension?
Abnormally high blood pressure in the portal venous system caused by resistance to blood flow. Pressure in this system is normally 3mm Hg; portal hypertension is an increase to at least 10 mm Hg.
portal hypertension is caused by disorders that obstruct or impede blood flow through any component of the portal venous system or vena cava. Intrahepatic causes result from vascular remodeling with shunts, thrombosis, inflammation, or fibrosis of the sinusoids, as occurs in cirrhosis of the liver, biliary cirrhosis, viral hepatitis, or schistosomiasis (a parasitic infection). Posthepatic causes occur from hepatic vein thrombosis or cardiac disorders that impair the pumping ability of the right side of the heart. This causes blood to collect and increases pressure in the veins of the portal system. The most common cause of portal hypertension is fibrosis and obstruction caused by cirrhosis of the liver.
Portal hypertension is often diagnosed at the time of variceal bleeding and confirmed by upper GI endoscopy and evaluation of portal venous pressure. The individual usually has a history of jaundice, hepatitis, alcoholism, or cirrhosis.
What is ascites?
Ascites is the accumulation of fluid in the peritoneal cavity. Ascites traps body fluid in the peritoneal space, from which it cannot escape. Ascites reduces the amount of body fluid available for normal physiologic functions. Cirrhosis is the most common cause of ascites, but other causes include heart failure, constrictive pericarditis, abdominal malignancies, nephrotic syndrome, and malnutrition.
Several factors contribute to the development of ascites, including portal hypertension, splanchnic vasodilation, decreased synthesis of albumin by the liver, splanchnic arterial vasodilation, and renal sodium and water retention. Portal hypertension causes capillary hydrostatic pressure to exceed capillary osmotic pressure, pushing water into the peritoneal cavity. Portal hypertension also increases the production of hepatic lymph, which “weeps” into the peritoneal cavity. Reduced serum albumin levels reduce capillary oncotic pressure adding to the fluid shift.
The accumulation of ascitic fluid causes abdominal distention, increased abdominal girth, and weight gain. Large volumes of fluid (10 to 20L) displace the diaphragm and cause dyspnea by decreasing lung capacity.
Some peripheral edema is usually present. Dilutional hyponatremia may be noted because of excess fluid volume. Approximately 10% of individuals with ascites develop bacterial peritonitis, either spontaneously or because of paracentesis, which causes fever, chills, abdominal pain, decreased bowel sounds, and cloudy ascitic fluid.
Overflow theory: capillary hydrostatic pressure > capillary osmotic pressure and this results in water moving to peritoneal cavity.
Underfill theory: increased hepatic sinusoidal hydrostatic pressure and decreased plasma oncotic pressure with weeping oh lymph fluid from the surface of the liver. Then decreased plasma volume activates ADH and RAAS = volume overload.
Forward theory: both circulating nitric oxide and carbon monoxide lead to splanchnic vasodilation. Decreased systemic vascular resistance overcomes compensatory cardiac output. Stimulation of baroreceptors activates renal sodium retention. Combined portal hypertension and splanchnic vasodilation = fluid transudation and lymph formation = ascites.
Treatment:
- dietary salt restriction and potassium-sparing diuretics, vasopressin receptor-2 antagonists are effective for dilutional hyponatremia
- albumin
- monitor for hyponatremia and hypokalemia
- paracentesis
- treat bacterial peritonitis
- peritoneovenous shunt and trans-jugular intrahepatic portosystemic shunt (TIPS) may be offered
- Liver transplant
What is hepatic encephalopathy?
Hepatic encephalopathy (portal system encephalopathy) is a complex neurologic syndrome characterized by impaired behavioral, cognitive, and motor function. The syndrome may develop rapidly during acute fulminant hepatitis or slowly during the course of cirrhosis and the development of portal hypertension or after portosystemic bypass or shunting.
Liver dysfunction and the development of collateral vessels that shunt blood around the liver to the systemic circulation permit toxins absorbed from the GI tract and normally removed by the liver, to accumulate and circulate freely to the brain. The accumulated toxins alter cerebral energy metabolism, interfere with neurotransmission, and cause edema. The most hazardous substances are end products of intestinal protein digestion, particularly ammonia, which cannot be converted to urea by the diseased liver.
he digestion of blood from leaking or ruptured varices adds to the amount of ammonia present in systemic blood, as does the action of ammonia-forming bacteria in the colon. Ammonia that reaches the brain is metabolized to glutamine, with osmotic disturbances and alterations in cerebral blood flow that interfere with neurotransmitters and cause astrocyte edema or cytotoxic edema and oxidation. Disruption of the blood-brain barrier causes vasogenic edema and contributes to astrocytes swelling, brain edema, and intracranial hypertension. Excessive amounts of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter from intestinal flora, may contribute to reduced levels of consciousness. Infection, systemic inflammation, hemorrhage, and electrolyte imbalance (including zinc deficiency), constipation, and the use of sedatives and analgesics can precipitate hepatic encephalopathy in the presence of liver disease.
Subtle changes in personality, memory loss, irritability, disinhibition, lethargy, and sleep disturbances are common initial manifestations of hepatic encephalopathy. Symptoms then can progress to confusion, disorientation to time and space, asterixis, slow speech, bradykinesia, stupor, convulsions, and coma, which are less frequent. Coma is usually a sign of liver failure and ultimately results in death.
Treatment:
- correction of fluid and electrolyte imbalances
- managing cerebral edema with hypertonic saline
- mannitol or hypothermia
- dietary proteins
- prevent ammonia absorption in the colon
- reduce gut ammonia with lactulose
What is jaundice?
Jaundice, or icterus, is a yellow or greenish pigmentation of the skin caused by hyperbilirubinemia (plasma bilirubin concentrations greater than 2.5 to 3mg/dL). Hyperbilirubinemia and jaundice can result from (1) extrahepatic (posthepatic) obstruction to bile flow, (2) intrahepatic obstruction, or (3) prehepatic excessive production of unconjugated bilirubin (i.e., excessive hemolysis of red blood cells).
Obstructive jaundice can result from extrahepatic or intrahepatic obstruction. Extrahepatic obstructive jaundice develops if the common bile duct is occluded. Occlusion may be from a gallstone, tumor, or inflammation. If occluded, bilirubin conjugated by the hepatocytes cannot flow through the obstructed common bile duct into the duodenum. Therefore bilirubin accumulates in the liver and enters the bloodstream, causing hyperbilirubinemia and jaundice.
Intrahepatic (hepatocellular) obstructive jaundice involves disturbances in hepatocyte function and obstruction of bile canaliculi. The uptake, conjugation, or excretion of bilirubin can be affected with elevated levels of both conjugated and unconjugated bilirubin. Obstruction of bile canaliculi diminishes flow of conjugated bilirubin into the common bile duct.
Prehepatic obstruction involves the excessive production of bilirubin from excessive hemolysis of red blood cells.
What is hepatorenal syndrome?
HRS is functional renal failure that develops as a complication of advanced liver disease. The renal failure is not caused by primary renal disease or other extrinsic factors but rather by portal hypertension, cardiac impairment, and other circulatory alterations associated with advanced liver disease, such as cirrhosis or fulminant hepatitis with portal hypertension and decreased systemic vascular resistance. HRS is characterized by reduced renal blood flow and glomerular filtration rate.
What is Alcoholic steatohepatitis?
It is a precursor of cirrhosis characterized by increased hepatic fat storage, inflammation, and degeneration and necrosis of hepatocytes. The inflammation and necrosis caused by alcoholic steatohepatitis stimulate the irreversible fibrosis characteristic of the cirrhotic stage of disease.
What is Alcoholic Cirrhosis?
Is caused by the toxic effects of alcohol metabolism in the liver, immunologic alterations, inflammatory cytokines, oxidative stress from lipid peroxidation, malnutrition, and an ongoing cycle of liver injury and regeneration. Alcohol is transformed to acetaldehyde; excessive amounts are toxic and significantly alter hepatocyte function and activate hepatic stellate cells, a primary cell involved in liver fibrosis. Enzyme and protein synthesis may be depressed or altered, and hormone and ammonia degradation is diminished. Kupffer cell (macrophage) activation attracts neutrophils promoting inflammation, endotoxins accumulate from translocation of gut bacteria, and cell-mediated immunity is suppressed. Cellular damage initiates an inflammatory response that, along with necrosis, results in activation of hepatic stellate cells and excessive collagen formation. Fibrosis and scarring interspersed with regenerating nodules alter the structure of the liver and obstruct biliary and vascular channels. Eventually hepatocytes lose their ability to regenerate with progression to liver failure.
Fatty infiltration causes no specific symptoms or abnormal liver function test results. The liver is usually enlarged and may be found during a routine examination.
The clinical manifestations of alcoholic steatohepatitis can be mild or severe. Nonspecific symptoms include fatigue, weight loss, and anorexia Manifestations of acute illness include nausea, anorexia, fever, abdominal pain, and jaundice. Cirrhosis is a multiple-system disease and causes hepatomegaly, splenomegaly, ascites, portal hypertension, GI hemorrhage, hepatic encephalopathy, and esophageal varices. Anemia results from blood loss, malnutrition, and hypersplenism. Pulmonary syndrome and HRS are usually late complications. Toxic effects of alcohol also can cause testicular atrophy, reduced libido, azoospermia, and decreased testosterone levels in men. Premenopausal women with cirrhosis experience anovulation or irregular ovulation related to alterations in hormone metabolism.
What is included in the porta of the liver?
The hepatic portal vein, the hepatic artery, and the hepatic duct.
