Liver Path Flashcards

Question

Acute liver failure or fulminant hepatitis

Answer 1

occurs most commonly with HBV and HDV (in the U.S. with HAV and HBV) -A disasterous complication marked by a drop in transaminases (very little functional tissue left) and a prolonged prothrombin time

Answer 2

Persistence of abnormalities beyond 6 months is generally considered to be the definition of chronic hepatitis (see below) May occur with infection with HBV, HCV (most commonly) and HDV

Answer 3

HBV has the greatest association for progression to hepatocellular carcinoma (followed closely by HCV) HAV is the most common and HEV is the least common type of hepatitis in the U.S. In children, HAV is commonly encountered in day care centers HBV is the only DNA virus; the others are RNA viruses HAV and HEV are transmitted by fecal-oral, water, and food-borne routes

Answer 4

HBV, HCV, and HDV are transmitted by parental inoculation and by direct contact HAV is most likely to present with fever and jaundice, while HCV is least likely to present with these findings Both HAV and HEV have no carrier state or chronic state HCV is the mildest hepatitis type -However, it is the most common to progress to a chronic carrier state and chronic hepatitis -It is the most frequent cause of post-transfusion hepatitis

Answer 5

HDV is a defective RNA virus and requires HBV surface antigen in order to replicate in a hepatocyte - Immunization against HBV automatically protects against HDV infection as well - The transmission of both HBV and HDV at the same time is called coinfection and subsequent infection of a chronic carrier of HBV with HDV (a superinfection) results in disease ~30- 50 days later - Simultaneous HBV/HDV infections → 1 of 3 outcomes: * Acute severe hepatitis * Mild HBV hepatitis leading to fulminant disease * Leads to chronic progressive disease (80%) often culminating in cirrhosis

Answer 6

Include a mixed type of hyperbilirubinemia -CB fraction of 20-50% (rarely exceeding 10mg/dL) Markedly elevated transaminases (ALT>AST, 500-5000 U/L) Mildly elevated cholestasis enzymes (AP & GGT, <2.5 X normal) Hypoglycemia from impaired gluconeogenesis and peripheral atypical lymphocytosis are observed Prothrombin time is prolonged The urine is usually positive for both BR and urobilinogen (higher than normal) + Serologic tests for the major viruses

Answer 7

In most respects, is similar in all 5 major types Focal ballooning degeneration (hepatocyte swelling) and apoptosis are characteristic -The latter is responsible for the acidophilic bodies (Councilman bodies) commonly seen in liver biopsies Also see -Lymphocytic infiltrate (cytotoxic T cells), hypertrophy/hyperplasia of Küpffer cells, acinar disarray, portal tract inflammation Fatty change is not a feature of acute viral hepatitis except in in chronic hepatitis due to HCV

Answer 8

Bridging necrosis (and fibrosis)

Answer 9

Liver parenchyma showing hepatocytes with diffuse granular cytoplasm, so-called ground glass hepatocytes. Immunoperoxidase stain for HBsAg from the same case, showing cytoplasmic inclusions of viral particles

Answer 10

Defined as symptomatic, biochemical, or serologic evidence of continuing or replapsing hepatic disease for > 6 months with histologically documented inflammation and necrosis -Note that there are causes of chronic hepatitis other than viruses May occur in HBV (10%) or HCV (40-60 %) infection

Answer 11

The majority of patients with viral hepatitis are men who may or may not be symptomatic (fatigue, malaise, fever, jaundice) and who may present for the first time years later with ascites and terminal liver failure There is significant discordance between morphological subtypes and the prognosis -Mild lesions can to progress to severe ones and vice versa -The mildest type of chronic hepatitis is characterized by lymphocytic infiltration limited to the portal tracts with chronic “transaminitis” (elevated serum transaminases)

Answer 12

In the worst cases, the disease progresses to frank cirrhosis (see below) and to liver failure or to hepatocellular carcinoma Etiology (virus type) rather than the histologic pattern is the single most important factor determining the probability of developing progressive chronic hepatitis

Answer 13

Occurs when hepatic insufficiency progresses from onset of symptoms to encephalopathy in 2-3 weeks (traditional definition says within 8 weeks) Fulminant viral hepatitis is the cause of 12% of cases of fulminant hepatic failure in the U.S. (HAV and HBV) Can be induced by hepatitis viruses A,B,C,D, and E Reactivation of chronic hepatitis B or acute herpesvirus infection are sometimes the cause Drug and other chemical toxicity make up 52% of fulminant hepatic failure -Particularly, acetominophen (10-15 g), isoniazid, antidepressants (MAOIs), halothane, methyldopa

Answer 14

In most cases, clinically significant liver compromise does not occur Can be classified as to whether blood flow into, through, or from the liver is impaired Impaired blood flow THROUGH the liver

Answer 15

Most commonly due to right heart failure Liver is enlarged Results in “nutmeg liver” -Has a mottled appearance

Answer 16

Is most commonly a result of chronic right heart failure Other causes include hepatic vein thrombosis, constrictive pericarditis, and tricuspid stenosis Bridging fibrosis between terminal hepatic veins (THVs) over time may produce “cardiac sclerosis” (cirrhosis)

Answer 17

may lead to hepatic hypoperfusion and hypoxia | Results in centrilobular (ischemic) necrosis

Answer 18

Associated with a hypercoagulable state most commonly secondary to polycythemia vera -Also due to paroxysmal nocturnal hemoglobinuria, oral contraceptives, and intra-abdominal cancers Prompt surgical treatment is required Mortality ranges form 50-90% Veno-occlusive disease (sinusoidal obstruction syndrome): -Associated with pyrrolizidine alkaloids, graft-vs-host reactions in bone marrow transplant patients, and hypervitaminosis A

Answer 19

Hepatic artery compromise - Liver infarction due to occlusion of the hepatic artery is rare owing to the double blood supply to the liver - However, hepatic artery thrombosis in a transplanted liver is likely to result in infarction - Portal vein obstruction and thrombosis

Answer 20

Currently, 67% of the population 18 yo and older drink alcohol >14 million Americans meet the criteria for alcohol (ethanol [EtOH]) abuse and/or dependence -Higher in men (11%) than women (4%) Classified as : 1. Fatty liver disease (most common; reversible) 2. alcoholic hepatitis (reversible, if person stops drinking) 3. cirrhosis (irreversible)

Answer 21

Alcohol abuse causes 200,000 deaths annually -Many are DUI related ~ 25 % of people with alcoholism have no liver disease, 30 % have fatty liver, 20 % have alcoholic hepatitis, and 25 % have cirrhosis Risk factors for developing the above changes: -The duration and magnitude of alcohol ingestion (regardless of kind, i.e., beer, wine, distilled spirits) *A daily intake of > 80g EtOH by ♂s and > 40g by ♀s for 10-20 years will likely result in cirrhosis *80 g of EtOH is present in a ½ pint of whiskey (80 proof or 40% EtOH), eight 12 oz. cans of beer (3.6% EtOH [wimpy beer]), or a liter of wine (12.5% EtOH)

Answer 22

Sex of the patient (females > males) -Women are more susceptible to liver damage than men, develop liver disease at an earlier age, and have a higher mortality rate in acute injury *Due to decreased gastric metabolism of EtOH (?) and differences in body mass (?) *♀ have lower gastric alcohol dehydrogenase activity so have higher blood levels than men when drinking the equivalent amount of EtOH Nutritional status -Protein-energy malnutrition (PEM) is commonly present in people with alcoholism -EtOH contains 7 kcal/g *However, it contains no vitamins, minerals, proteins, or fats (so has “empty” calories) *Since many people with alcoholism consume 30-50% of their calories as EtOH, the etiology of PEM is understandable Presence of coexisting HCV Certain genetic factors (IMPORTANT) -Genetic susceptibility has been established in families -Susceptibility to damage may relate to different types of enzymes used in the metabolism of alcohol

Answer 23

CNS abnormalities (e.g., Wernickes encephalopathy, Korsakoff’s psychosis; cancer (squamous cell cancer in the oropharynx, esophagus, or vocal cords); pancreatitis, thiamine and folate deficiency; peripheral neuropathy; fetal-alcohol syndrome; and congestive cardiomyopathy

Answer 24

alcohol →alcohol dehydrogenase → acetaldehyde + NADH + H+ →aldehyde dehydrogenase→ acetate + NADH + H+ → acetyl-CoA Alcohol dehydrogenase metabolizes alcohol in the cytosol, while acetaldehyde dehydrogenase metabolizes acetaldehyde (toxic to cells) in the mitochondria Acetaldehyde is the major toxic product responsible for most of the damage that occurs in the liver (see below) - Asian people may have a defect in the latter enzyme, which leads to a buildup of acetaldehyde in the blood (they get sick faster) -This is similar to the effect of Antabuse (disulfiram) which inhibits the enzyme Other individuals have an enzyme that metabolizes alcohol faster

Answer 25

Refers to the presence of IRREVERSIBLE DIFFUSE FIBROSIS in the liver with or without the formation of regenerative nodules Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver -With continuing fibrosis, the liver is subdivided into nodules of regenerating hepatocytes surrounded by scar tissue (cirrhotic state) Cirrhosis may begin with a micronodular pattern (< 3 mm nodules) and end with a predominantly macronodular pattern (>3 mm nodules) with a mixed pattern in between Alcoholic cirrhosis tends to have a micronodular pattern

Answer 26

The characteristic diffuse nodularity of the surface reflects the interplay between nodular regeneration and scarring. The greenish tint of some nodules is due to bile stasis. A hepatocellular carcinoma is present as a budding mass at the lower edge of the right lobe (arrow, lower left of figure).

Answer 27

Alcoholic liver disease is the most common cause of cirrhosis (~ 65%) in the United States -Followed by macronodular (postnecrotic) cirrhosis secondary to chronic active viral hepatitis (HBV, HCV, HDV; 10-30%) Other causes include Wilson’s disease, -antitrypsin deficiency The most common cause of death is rupture of esophageal varices (a complication of portal hypertension) Complications associated with cirrhosis, in general, relate to the development of hepatocellular failure, portal hyper-tension, and progression to hepatocellular carcinoma

Answer 28

Most severe consequence of liver disease 80-90% of hepatic functional capacity must be affected before hepatic failure occurs -Balance may tipped toward failure by intercurrent disease that places a demand on the liver (e.g., GI bleeding, infection, electrolyte disturbance, severe stress [surgery or heart failure]) May be seen in the setting of fulminant hepatic failure (FHF) related to drug use (e.g., acetaminophen) and viral infections most commonly (e.g., HBV) and chronic liver disease (e.g., cirrhosis) FHF, by definition, is acute liver failure (massive hepatic necrosis) associated with hepatic encephalopathy occurring within a few weeks of symptoms of hepatic dysfunction -The major difference between FHF and chronic liver disease as a cause of hepatocellular failure is the short duration of onset in FHF and the absence of portal hypertension (which may be a feature of chronic liver disease) Chronic liver disease is the endpoint for chronic hepatitis ending in cirrhosis Hepatic dysfunction without necrosis -Hepatocytes are unable to perform normal metabolic functions *Observed in Reye’s syndrome, tetracycline toxicity, and acute fatty liver of pregnancy

Answer 29

Multiple coagulation defects are commonly present in hepatocellular failure owing to inability of hepatocytes to synthesize coagulation factors -The prothrombin test is the best monitor of these deficiencies and is not corrected by intramuscular injection of vitamin K Hypoalbuminemia from decreased albumin synthesis reduces plasma oncotic pressure (predisposing to pitting edema and ascites) Severely impaired liver function renders patients highly susceptible to failure of multiple organ systems

Answer 30

Is a reversible metabolic disorder associated with diffuse slowing of brain waves on an electroencephalogram and clinical evidence of encephalopathy Clinical findings in early stages of encephalopathy consist of alterations in the mental status examination, somnolence, disordered sleep rhythms, and asterixis (inability to sustain posture, flapping tremor) As encephalopathy progresses, the patient becomes less arouseable, asterixis worsens, incontinence occurs, and eventually coma and death take place

Answer 31

Is defined as renal failure with severe liver disease with no intrinsic abnormality demonstrable in the kidneys The etiology is unknown -Vasoconstriction of renal vessels (by endothelin-1) with decreased blood flow to the cortex plus preservation of tubular function is a proposed mechanism The condition improves with reversal of liver failure The kidneys at autopsy are grossly normal and histologic evidence of tubular necrosis is absent Patients have oliguria with the usual proportionate increase in the serum blood urea nitrogen and creatinine

Answer 32

with an inability to degrade hormones such as estrogens, 17ketosteroids (dehydroepiandrosterone and androstenedione), and aldosterone - Hyperestrinism in a male is the result of failure to metabolize estrogens and 17-ketosterolds (which are converted bv aromatases to estrogen in adipose cells) - Signs of hyperestrinism are gynecomastia, palmar ervthema, spider angiomas, testicular atrophy (which decreases spermatogenesis), and a female distribution of hair (sparse axillary hair, lack of hair ascending to the umbilicus

Answer 33

Males with hepatocellular failure have reduced free testosterone levels owing to hyperestrinism, which increases the synthesis of sex hormone-binding globulin (SHBG) by the liver SHBG has a higher affinity for testosterone than for estrogen -Hence the serum levels of testosterone are lowered -Low testosterone levels result in sexual impotence Furthermore, if the patient is an alcoholic, alcohol will decrease testosterone synthesis by interfering with the ability of luteinizing hormone to bind with Leydig's cells (the site of testosterone synthesis) in the testicles -Alcohol also directly decreases the release of luteinizing and follicle-stimulating hormones from the anterior pituitary

Answer 34

with retention of salt and water is due not only to faulty metabolism of aldosterone by the liver but also to a reduction in cardiac output with subsequent stimulation of the renin-angiotensin-aldosterone system -Contributes to pitting edema and ascites owing to retention of salt and water

Answer 35

Is a consistent metabolic abnormality in liver failure The toxic products from impaired hepatic detoxification overstimulate the respiratory center increasing the clearance of C02 Hypoglycemia commonly occurs owing to a decrease in gluconeogenesis and glycogen stores in the liver Malabsorption may occur as a result of the inability to synthesize primary bile acids or salts

Answer 36

Is a consistent feature of chronic liver failure Its pathogenesis is multifactorial (see below) In cirrhosis (the most common cause of ascites), the development of portal hypertension leads to an increase in portal vein hydrostatic pressure and leakage of a transudate into the abdominal cavity Additional factors that contribute to the production of ascites are: -Decreased oncotic pressure (hypoalbuminemia) -An increase in hepatic lymph formation due to intrasinusoidal obstruction (fibrosis) with subsequent leakage from the capsular surface, and -Secondary hyperaldosteronism

Answer 37

Alcohol is singled out as the most common cause of fatty liver (steatosis) Unlike the other types of alcohol-related liver disease, it may develop after only a single overindulgence of alcohol The liver becomes diffusely enlarged and has a yellowish-brown appearance -Individual hepatocytes are enlarged by a single fat droplet that pushes the nucleus to the periphery of the cell (macrovesicular steatosis vs. microvesicular steatosis in which many small fat droplets are present in the cell but do not displace the nucleus) Initially, the fatty change is primarily in zone III around THV, but with more prolonged alcohol intake it eventually diffuses throughout the liver In general, fatty livers produce mild elevation of transaminases and cholestasis enzymes, but jaundice is uncommon The lesion is reversible once alcohol is discontinued

Answer 38

most commonly associated with bouts of heavy drinking in excess of 100 g/d for more than one year Morphology -Grossly, the liver is enlarged and tender -Microscopically, there is fatty change, Mallory’s bodies (alcoholic hyaline), a neutrophilic infiltrate (viral hepatitis has a lymphocyte infiltrate), intrahepatic cholestasis in zone III areas, and perivenular fibrosis Clinically, patients have a low-grade fever, jaundice, and ascites and may even progress to hepatic encephalopathy (see above)

Answer 39

Include a transaminasemia with AST (< 500 U/L) > ALT, elevated cholestasis enzymes (GGT is disproportionately increased owing to enzyme induction by alcohol), and an elevated total bilirubin

Answer 40

Consist of a macrocytic anemia (which is either due to direct alcohol effect on the RBC membrane [round target cells] or to folate deficiency [more common]), absolute neutrophilic leukocytosis, and abnormal coagulation tests (prolonged prothrombin time) Approximately 20% die of hepatic failure, and 30% of those who survive develop alcoholic cirrhosis Alcoholic hepatitis is reversible if the patient totally abstains from alcohol

Answer 41

Is a chronic active hepatitis type most commonly seen in young and perimenopausal women (female predominance [78%]) Viral serological markers are absent IgG and gammaglobulin levels are >1.5 times normal Autoimmune hepatitis has an insidious onset and usually presents with jaundice (80%), hepatosplenomegaly (50-80%), diarrhea (30%), and signs of other autoimmune disorders (e.g., autoimmune hemolytic anemia, Hashimoto’s thyroiditis) Autoimmune hepatitis has no direct relationship to systemic lupus erythematosus (SLE) other than a positive antinuclear antibody (ANA) test (50-80%) and a positive LE prep (15%; neutrophil with phagocytosed altered DNA) Additional laboratory abnormalities include a positive anti-smooth muscle antibody (75%) and positive anti-liver/kidney/microsome autoantibodies Responds to immunosuppressive therapy However, in a significant number of patients, the disease progresses to cirrhosis (40%)

Answer 42

``` Portal hypertension (PH) is secondary to obstruction to normal blood flow It may be the result of prehepatic obstruction (e.g., portal vein thrombosis), intrahepatic obstruction (e.g., cirrhosis, the most common cause), or posthepatic obstruction (e.g., Budd-Chiari syndrome, venoocclusive disease) PH results in retrograde blood flow owing to increased intrasinusoidal pressure hampering blood flow into the liver ```

Answer 43

Is obstruction to the flow of bile May be intra- or extra-hepatic in origin One of the most important consequences of cholestasis is the exclusion of bile from the intestine In order of decreasing percentage, bile contains salts, electrolytes, phospholipids, proteins, cholesterol, and conjugated bilirubin The primary bile acids (cholic and chenodeoxycholic acid) are synthesized from cholesterol (CH) -Approximately 50% of CH is eliminated from the body each day by its conversion to primary bile acids

Answer 44

hereditary hyperbilirubinemias (e.g., Dubin-Johnson syndrome), biliary atresia drug use (e.g., oral contraceptives), viral hepatitis (early cholestatic phase) neonatal cholestasis, alcoholic hepatitis, primary biliary cirrhosis

Answer 45

Is more common than intrahepatic cholestasis May be caused by: -Choledocholithiasis (the most common cause) -Carcinoma of the head of the pancreas (second most common cause) -Carcinoma of the bile ducts, inflammatory strictures, biliary atresia, primary sclerosing cholangitis, and parasitic diseases Grossly, the liver is enlarged and has a diffuse greenish discoloration

Answer 46

Clinically, patients have complaints of jaundice and pruritis (which often precedes jaundice and is due to bile salt deposition in the skin) Physical examination -Frequently reveals skin xanthomas and xanthelasmas from increased cholesterol deposition in macrophages -Clay colored stools are noted on rectal examination, and the urine is a dark orange color Laboratory abnormalities -Consist of a mild to moderate transaminasemia, markedly increased cholestasis enzymes (5-20 times normal) and high serum cholesterol levels

Answer 47

Is a patchy obliterative inflammatory fibrosis of the large bile ducts that leads to strictures and cholestasis Is associated with inflammatory bowel disease (most commonly ulcerative colitis) in 50-70% of cases It is more common in males than females The walls of the intra-and extrahepatic ducts are markedly thickened (concentric fibrosis) and the lumens are narrowed, producing areas of stricture altering with bead-like dilatations An obstructive enzyme pattern often predates signs and symptoms of the disease (e.g., jaundice, pruritis) in 85% of cases Secondary biliary cirrhosis and liver failure usually occur in 10-12 years Cholangiocarcinoma may also occur

Answer 48

PBC is a progressive disease characterized by autoimmune destruction of small interlobular bile ducts and bile duct radicals in the portal triads - It has a 10/1 female to male ratio and frequents middle age (40-50 yo) - Is often associated with other autoimmune diseases such as Sjogren’s syndrome, rheumatoid arthritis, CREST syndrome, Hashimoto’s thyroiditis, and renal tubular acidosis - The pathogenesis involves the production of antimitochondrial antibodies to epithelial antigens in bile duct epithelium - It progresses through four stages: * The fourth stage is characterized by cirrhosis and absence of bile ducts in the above-mentioned areas of inflammation

Answer 49

Pruritus without jaundice is the earliest sign of the disease The cholestasis enzymes are also markedly elevated Antimitochondrial antibodies are present in the serum (90% of cases) and increased IgM levels (95%), both of which are markers for the disease and often prompt a liver biopsy Anti-smooth muscle antibodies and rheumatoid factor are also increased in 65% and 70% of cases, respectively Cholestatic jaundice is a late finding and correlates with the decrease in the number of bile ducts in the liver that are available to deliver bile to the intestine Serum CH levels are markedly elevated and commonly produce xanthelasmas and skin eruptions Malabsorption from decreased bile acids complicates the nutritional status of the patient Renal tubular acidosis with potassium wasting offers a difficult metabolic problem to manage Cirrhosis, portal hypertension, and liver failure invariable occur within 5-10 years of symptoms Liver transplantation offers further longevity to those with end-stage disease

Answer 50

Occurs in response to chronic obstruction of the bile ducts May occur in cystic fibrosis (focal biliary cirrhosis) owing to inspissated* bile blocking the bile ducts, common bile duct stones or strictures, and parasitic diseases involving the bile ducts *made or having become thickened in consistency (blocked with inspissated bile)

Answer 51

A condition resembling alcohol-induced liver disease but occurs in patients who are not (or claim not) to be heavy drinkers Men and women are equally affected Strong associations with obesity, dyslipidemia, hyperinsulinemia, and insulin resistance and overt Type 2 diabetes Patients are largely asymptomatic with abnormal biochemical laboratory tests Biopsy shows steatosis -Steatohepatitis (nonalcoholic steatohepatitis or NASH) with multifocal inflammation is an intermediate form of liver damage May account for up to 70% of chronic hepatitis of “unknown” cause

Answer 52

Excess hemosiderin in the liver may be inherited (hemochromatosis) or secondarily acquired (hemosiderosis) Hereditary Hemochromatosis -Is an autosomal recessive disease with an HLA-A3 inheritance pattern (70%) *Is the most common genetic disease (1/200) in the United States -People who are homozygous for the disease have an increase in a membrane iron-binding protein on the mucosal cells of the small intestine -Leads to excessive absorption of iron -The male-to female ratio is 10/1 -The deposition of iron is predominantly parenchymal rather than in fixed macrophages (a late manifestation of the disease)

Answer 53

Occurs more commonly in men and postmenopausal women Women of reproductive age rarely demonstrate signs or symptoms owing to the loss of blood during menses and childbearing Symptoms include fatigue, joint pain (patients develop degenerative arthritis), abdominal discomfort (hepatomegaly) impotence in males and secondary amenorrhea in women (hypothalamic and gonadal involvement), and cardiac arrhythmias Signs consist of skin hyperpigmentation (stimulation of melanocytes by iron and iron itself are responsible), hepatosplenomegaly (micronodular cirrhosis in 100% with portal hypertension), signs of hypothyroidism, malabsorption (pancreatic exocrine deficiency), diabetes mellitus (a late finding of “bronze diabetes” [hyperpigmentation plus diabetes]), and cardiomegaly (restrictive cardiomyopathy) Hepatocellular carcinoma may occur in 30% of cases

Answer 54

Are those of iron overload, mainly an increase in serum iron, percent saturation, and ferritin and a decrease in total iron-binding capacity (increased iron stores decrease liver synthesis of transferrin) Percent saturation > 62% in males or > 50% in females plus a serum ferritin greater than twice normal (often > 500 g/L) are typical Direct DNA testing for two abnormal gene loci on chromosome 6 is recommended in patients so affected and as a screen for family members The confirmatory test is a liver biopsy with quantitation of iron Phlebotomy is the mainstay of treatment Hepatocellular carcinoma is the leading cause of death in hemochromatosis

Answer 55

Is an acquired iron overload disease Occurs with hemolytic anemias associated with ineffective erythropoiesis which is treated with multiple transfusions (usually > 100); drinking well water containing excess iron; and eating food cooked in iron pots (e.g., among the Bantus in Africa [a genetic susceptibility exists]) Iron deposits primarily in fixed macrophages in the liver, bone marrow, and spleen, but it can enter parenchymal cells as well as later in the disease Particularly common in alcoholic liver disease -Represents alcohol-induced redistribution of iron (total body iron is not significantly increased)

Answer 56

Is an autosomal recessive disease characterized by a defect in copper excretion into bile and accumulation of toxic levels of copper in the liver, eye, and brain A gene defect in a copper-transporting ATPase occurs on chromosome 13 The excess free copper is stored in the liver -There it produces acute hepatitis that progresses to chronic active hepatitis and postnecrotic cirrhosis Ceruloplasmin (a copper-binding protein)is an excellent screen for the disease -Chronic liver disease reduces the synthesis of ceruloplasmin Unbound free copper spills over into the plasma and deposits in other organs such as Descemet’s membrane in the eye (forming a Kayser-Fleischer ring) and the lenticular nuclei in the brain -The combination of low ceruloplasmin level plus Kayser-Fleischer ring in the eye is diagnostic for Wilson’s disease -Degeneration of the lenticular nuclei produces signs of spasticity, dysarthria, and tremors

Answer 57

In Wilson’s disease, the total copper concentration is decreased, owing to decreased ceruloplasmin, the free copper level is increased, as is urinary excretion and the copper content of the liver The confirmatory test is a liver biopsy with quantitation of copper Treatment with penicillamine, a copper-chelating agent, improves symptoms but does not reverse cirrhosis

Answer 58

Is an autosomal recessive disease characterized by either abnormally low AAT levels in the plasma or defective secretion of AAT secondary to abnormal protein folding in the ER AAT is a protease inhibitor that is predominantly synthesized in the liver

Answer 59

``` In general, liver disease is more likely to develop when AAT cannot be secreted from the hepatocytes Pulmonary disease (panacinar emphysema) is more likely to occur with low concentrations of functional AAT in the serum that are unrelated to a defect in secretion by the liver Liver transplantation is the only option for AAT deficiency-induced cirrhosis All family members should be phenotyped to identify candidates for liver or pulmonary disease ```

Answer 60

``` Lysomomal Storage Diseases Hypertriglyceridemia Glycogen storage diseases Lipofuscin Amyloidosis ```

Answer 61

These are NEITHER NEOPLASMS NOR VARIANTS OF CIRRHOSIS Focal nodular hvperplasia presents as a spontaneous mass lesion -It has a 2/1 female-to-male ratio and no identifiable cause -Grossly, there is a central stellate scar with wagon-wheel radiation to the periphery -Bile ducts actively proliferate in the fibrous tissue -It has no malignant potential and rarely causes intraperitoneal hemorrhage Nodular regenerative hyperplasia -Associated with the development of portal hypertension and its attendant clinical manifestations

Answer 62

``` Cavernous Hemangiomas Liver cell (hepatic) Adenomas ```

Answer 63

Are the most common overall benign tumor of the liver Occur directly beneath the capsule and should not be mistaken for metastatic tumors blind percutaneous biopsies should not be performed on them (they will bleed) They rarely are of clinical importance Imaging studies confirm the diagnosis

Answer 64

Usually occur in women of childbearing age They are highly vascular tumors and are associated with: -The use of oral contraceptives -Anabolic steroids, and -Rarely, von Gierke's glycogen storage disease They have a tendency to rupture during pregnancy (20% mortality) Imaging studies confirm the diagnosis They rarely transform into a hepatocellular carcinoma (notable exception is von Gierke's disease)

Answer 65

Metastatic tumors constitute the most common form of cancer of the liver Common metastatic tumors come from: -Primary carcinomas located in the lung (most common cause) -Gastrointestinal tract (second most common cause [esophagus, stomach, pancreas, and colon]), and breast -Malignant lymphomas and malignant melanomas also frequently metastasize to the liver Carcinoembryonic antigen (CEA) is used as a marker for recurrence of colorectal and pancreatic cancers The CT scan is the most accurate imaging technique for detecting metastases

Answer 66

Is the most common primary cancer of the liver Is five times more common in men than in women Peaks around 60 years of age >85% of HCC occurs in countries with high rates of chronic HBV infection

Answer 67

In general, cirrhosis is the most common cause (75-90%) -Specifically, postnecrotic cirrhosis secondary to HBV (aflatoxins [produced by the fungus Aspergillus flavus] Other causes -Chronic alcoholism -HBV is followed closely by pigment cirrhosis (hemochromatosis) and HCV -Less common causes include oral contraceptive use, smoking, AAT deficiency, and von Gierke's disease

Answer 68

Grossly, there is invariably a background of cirrhosis with unifocal or multifocal nodular masses representing HCC Microscopically, there is prominent vessel invasion (portal and hepatic veins) and the presence of bile in neoplastic cells (a reliable finding)

Answer 69

Patients present with fever (liver cell necrosis), abdominal pain, weight loss, and an abdominal mass Clinical deterioration in a known cirrhotic, increasing abdominal girth (ascites), bloody ascitic fluid, and a sudden rise in serum GGT and AP are highly predictive of HCC Additional laboratory abnormalities include an increase in α-fetoprotein (75-90%; usually > 500 ng/mL) and an increase in AAT Ectopic hormone relationships consist of secondary polycythemia (due to erythropoietin production by the tumor) and hypoglycemia related to production of an insulin-like factor

Answer 70

CT scanning and angiography (of the hypervascular mass) are the best diagnostic combination for detection of HCC HCC spreads directly in the liver first and then to regional lymph nodes and the lungs Vaccination against HBV should decrease the incidence of HCC Patients survive an average of 6 months after the diagnosis is confirmed

Answer 71

Gallstones (calculi) and cholecystitis are the most frequent diseases involving the gallbladder Occur in 10-20% of adult men and 20-40% of adult women Calculi most commonly precipitate in the gallbladder but may also develop in the common bile duct (CBD) Cholesterol (80%) and pigment (bilirubin calcium salts) stones (20%) are the two main types

Answer 72

Include: biliary "colic" in the right upper quadrant (distention of the wall due to impaction of a stone in the cystic duct or CBD) and abdominal distention with bloating 30 minutes after eating (particularly fatty foods) Complications associated with stone formation consist of: -Obstruction (e.g., in the cystic duct or CBD) -Acute cholecystitis (stone impacted in cystic duct) -Biliary fistula (which produces gallstone ileus) -Chronic cholecystitis -Acute pancreatitis, and -A predisposition to gallbladder cancer Ultrasonography is the gold standard test for the diagnosis of stones and duct dilatation

Answer 73

Is a female-dominant disease Is most commonly the result of an impacted stone (90%) in the cystic duct -The obstructed duct blocks the efflux of bile, resulting in secondary chemical irritation of the mucosa, which in turn predisposes to bacterial invasion as a secondary event in 80% of cases In addition, the inflammation surrounding the impacted stone obstructs blood vessels (producing distal ischemia)

Answer 74

mucosal damage and the potential for bacterial infection -Escherichia coli is the most common microbial pathogen Rarely, acalculous ( no stones) cholecystitis can result from primary infection with Salmonella typhi and staphylococci, in the setting of systemic vasculitis, severe atherosclerotic ischemic disease, and acquired immunodeficiency syndrome with biliary tract infection -Early diagnosis is crucial to prevent a fatal outcome

Answer 75

Gross appearance -The gallbladder is enlarged, congested, and covered with a fibrohemorrhagic exudate -The wall of the gallbladder is thickened, edematous, and focally hemorrhagic Microscopically, there are collections of neutrophils in the wall and the mucosa is replaced or covered by a thick exudate complications

Answer 76

Empyema (accumulation of pus in the gallbladder), gangrenous necrosis, and perforation are potential

Answer 77

Patients develop an acute onset of a constant, dull, aching right upper quadrant pain (the pain is not colicky, so “biliary colic" is a misnomer) that occurs within 15-30 minutes of eating The pain frequently radiates to the right scapula or right shoulder Shaking chills and fever are commonly present Right upper quadrant tenderness on palpation after deep inspiration is known as Murphy's sign Jaundice may occur and should alert the clinician to the possibility of a stone in the CBD

Answer 78

Elevated cholestasis markers (AP and GGT) in some cases, and An absolute neutrophilic leukocytosis with a shift to the left An elevated serum amylase suggests associated pancreatitis The natural history of acute cholecystitis depends on whether or not the obstruction is relieved, with 90% resolving over 3-7 days May require cholecystectomy

Liver Path Flashcards

(102 cards)