Hepatobiliary Pathology Flashcards
1
Q
describe the liver structure
A
- classic lobule
- roughly hexagonal
- consists of stacks of hepatocyte plates with intervening sinusoidal spaces
- the center of the lobule is a central vein
- portal triads at the angles of the hexagon
2
Q
where do the sinusoids drain
A
in the central vein
3
Q
what do the portal triads contain
A
- contains connective tissue with terminal branches of the hepatic artery, portal vein and bile duct
- contains lymphatic vessels and nerve
4
Q
describe the dual blood supply liver blood flow
A
- blood enters from the heaptic artery and the portal vein -> portal triads-> hepatic sinusoids ->central veins -> sublobular veins -> hepatic vein
5
Q
what makes up the portal triad
A
-arteriole
- bile duct
- portal vein
6
Q
what are the hepatocyte functions
A
- protein synthesis
- oxidation and conjugation of drugs, toxins
- lipid metabolism
- carbohydrate metabolism
- produces bile- an exocrine secretion
7
Q
what proteins are synthesized by the liver
A
albumin and other transport proteins, clotting factors, lipoprtoeins espcially VLDL
8
Q
how does the liver oxidize and conjugate drugs and toxins
A
makes substances not easily excreted by the kidney more hydrophilic, to enhnace excretion: hydroxylation, carboxylation and conjugation
9
Q
how does the liver do lipid metabolism
A
-stores or breaks down fatty acids from plasma
-synthesis and uptake of cholesterol
10
Q
describe carbohydrate metabolsim of the liver
A
either converts glucose to glycogen for carbohydrate storage, or breaks down glycogen to glucose for energy usage
11
Q
what do bile salts do
A
aid in emulsifying lipids in the GI tract
12
Q
what are the reversible changes in hepatocyte injury
A
- accumulation of fat (steatosis)
- accumulation of bilirubin
13
Q
what are the non reversible changes to hepatocyte injury
A
necrosis and/or apoptosis
- necrosis may follow hypoxia/ischemia and may be single cell death, zonal, regional
- necrosis or apoptosis may follow viral infection, toxin exposure, other inflammatory conditions
14
Q
what are the 2 outcomes following hepatocyte injury and describe each
A
- regeneration: by dividing hepatocytes near the site of injury or in more severe injuries by dividing stem cells
- scar formation: most often a result of chronic injury . may progress to sirrhosis wherein the liver is made up of nodules of regerenating hepatocytes surrounded by dense bands of collagen
15
Q
what are the causes of acute liver failure
A
- acetominophen ingestion
-autoimmune hepatitis - acute viral hepatitis
-other drugs/toxins
16
Q
what are the clinical features of acute liver failure
A
- nausea, vomting, jaundice, fatigue, encephalopathy, coagulation defects and icterus
- coagulopathy
- hepatorenal syndrome
17
Q
what is jaundice casued by
A
yellow coloration of the skin due to bilirubin retention and cholestasis
18
Q
what is icterus
A
discoloration of the sclera
19
Q
what is hepatic encephalopathy
A
symptoms ranging from behavioral abnormalities to confusion, stupor, coma and death
20
Q
what is the cause of hepatic encephalopathy
A
elevated ammonia levels which impair neuronal function and causes cerebral edema
21
Q
what is the histology for cholestasis
A
bile pigments within hepatocyte cytoplasm
22
Q
what is coagulopathy
A
bruising and bleeding
23
Q
what is hepatorenal syndrome
A
in patients without pre existing renal disease, acute liver failure can result in decreased renal perfusion leading to decreased urine output
24
Q
what is chronic liver failure and describe it
A
- cirrhosis
- diffuse transformation of the liver into regenerative hepatocyte nodules surrounded by bands of dense fibrous connective tissue- scar
25
what are the most common causes of chronic liver failure
-chronic hepatitis B
- chronic hepatitis C
- nonalcoholic fatty liver disease
- alcohol relatde liver disease
26
describe cirrhosis
- it does not indicate the presence of a specific disease, it is a common final pathway of a number of chronic liver diseases
- not all chronic liver disease results in cirrhosis and not all cirrhosis results in end stage liver disease
27
what is portal hypertension
increased portal vascular resistance, portosystemic shunts may develop
28
what are ascites and what causes it
- increased fluid in the peritoneal space
- primarily due to portal hypertension
29
what is viral hepatitis caused by
hepatotrophic vrisues A, B, C, D, and E
30
describe hepatitis A, transmission, symptoms, and diagnosis
- usually benign and self limited
- ingestion of contaminated food/water from fecal- oral route of transmission
- symtpoms: fever, fatigue, decreased appetite, jaundice at 2-12 weeks of infection
- does not cause chronic hepatitis
- diagnosis: detection of IgM antibodies
31
describe hepatitis B
- clinical vourse varies widely: acute hepatitis with clearance and recovery, nonprogressive chronic hepatitis, progressive chornic hepatitis leading to cirrhosis, fulminant hepatitis with massive liver necrosis , asymptomatic carrier state
- HBV associated chronic hepatitis incurs an elevated risk for hepatocellular carcinoma
32
what is the prevalance of hepatitis B and what countries have it more
2 billion
- africa and asia
33
what is the transmission and testing for hep B
- parenteral transmission- vaccine is 95% effective
- detection of HBsAg, anti- HBcag, HBV DNA by PCR
34
what is the histology for hep B
ground glass
35
describe hepatitis C, transmission, diagnosis and treatment
- affects ~170 million people worldwide
- parenteral route of transmission
- acute infection is generally asymptomatic (85% of time), but 80-90% of infected people develop persistent chronic infections leading to cirrhosis in about 20% over 2-3 decades
- diagnosis: HCV RNA
- treatable: antiviral combination therapy can cure 95% of infections
36
where does inflammation usually occur in hep C infections
portal triad
37
describe hepatitis D, diagnosis
- dependent on HBV for its life cycle to progress
- parenteral route of transmission
- diagnosis by detecting HDV RNA
- coinfection: clinically indistinguishable from HBV infection, usually self limited
- superinfection: HBV carrier exposed to HDV, resulting in either severe acute hepatitis or exacerbation of chronic HBV
38
describe Hepatitis E- transmission and diagnosis
- enterically transmitted by fecal-oral
- usually produces acute, self limited hepatitis
- zoonotic, with animal reservoirs
- diagnosis: IgM, HEV RNA
39
descrbe bacterial infections of the liver
- ascending infections involving the biliary tract
- seeding via blood S. aureus and salmonella typhi
- liver abscesses
40
describe parasitic infectinos of liver
- worms- schistosomiasis, liver flukes, echinococcus
- enteamoeba histolytica
41
what is autoimmune hepatitis
- presence of autoantibodies
- responds to immunosuppression
- may be a genetic predisposition
- may be associated with other autoimmune diseases
42
what are examples of autoantibodies in autoimmune hepatitis
antinuclear antibodies (ANA), anti smooth muscle antibodies (ASMA)
43
what is the remission percentage of patients with autoimmune hepatitis
90%
44
what is the morphology of autoimmune hepatitis
- necrosis and inflammation
- may lead to cirrhosis
45
what are the patterns of injury due to drugs and toxins
- fatty change
- fibrosis
- cholestasis
- necrosis
46
what causes fatty change of liver
alcohol
- methotrexate
- tetracycline
47
what causes fibrosis of the liver
- alcohol
- methotrexate
48
what causes cholestasis
chlorpromazine
49
what causes necrosis
acetominophen, carbon tetrachloride, mushroom toxins (amanita phalloides - death cap)
50
what are the drug reaction types
- predictable/ intrinsic
- unpredictable/idiosyncratic
51
what are the predictable drug reactions and another name for predictable drug reactions
acetaminophen
- intrinsic
52
what are the unpredictable drug reactions and another name for unpredictable drug reactions
chlorpromazine
- idiosyncratic
53
describe fatty liver disease - alcohol and non alcohol realted
-both feature varying degrees of steatosis, steatohepatitis, gradually increasing fibrosis which may eventually progress to cirrhosis
54
what is steatohepatitis and what stain is used to see it
symptoms and lab abnormalities develop in the setting of an already fatty liver
- malaise, anorexia, upper abdominal discomfort
- masson trichrome stain
55
what is NAFLD associated with
becoming increasingly common
-associated with type 2 DM, obesity, hyperlipidemia, and HTN
56
what percentage of deaths from cirrhosis are from excessive alcohol consumption
40-50%
57
what are the metabolic liver diseases
- hemochromatosis
- wilson disease
- alpha 1 anti trypsin deficiency
58
what is hemochromatosis and what stain is used to identify it
- excessive absorption of iron, deposited in liver, pancreas, heart and other organs
- may be acquired
- usually hereditary with loss or impairment of regulatory control of intestinal iron absorption
- mutation of HFE gene most common
- prussian blue stain
59
what does tissue deposition of hemosiderin lead to
gradually increasing fibrosis
- iron deposition in other organs can lead to fibrosis and atrophy of other organs in addition to changes in skin pigmentation
60
describe wilson disease
- autosomal recessive: loss of function mutation of ATP7B leading to imapired copper excretion in bile and failure to incorporate copper into ceruloplasmin
- increased unbound copper in the circulation causes hemolysis
- accumulation of toxic levels of copper in organs, pricipally liver brain and eye
61
what is the morphology of wilson disease and what stain is used to identify it
liver: variable- fatty change, hepatitis (acute or chronic) ultimately cirrhosis
- eye: Kayser- Fleischer rings - deposits of copper in the limbus of the cornea
- copper stain
62
what are the clinical features of wilson disease
- acute/chronic liver disease or neurophsychiatric signs may be presenting factors
- diagnoses by decreased serum ceruloplasmin, increased hepatic copper content, increased urine copper
- treamtnet: copper chelation therapy; zinc based therapy nhibits copper uptake in the gut
63
describe alpha 1 anti trypsin deficiency
- autosomal recessive, mutations resulting in misfolding and loss of function of alpha-1 AT which normally inhibits proteases
- alpha-1AT synthesized mainly by hepatocytes- the abnormal form accumulates in hepatocytes -> apoptosis
- before they die hepatocytes accumulate cytoplsamic globular inclusions
- may progress to hepatitis and eventually cirrhosis
64
describe the clinical presentation of alpha 1 AT and the stain used to identify it
- only effective tx for severe liver disease is transplant
- the lung is also often involved resulting in emphysema
- periodic acid-Schiff stain
65
what are the benign hepatic tumors
- focal nodular hyperplasia
- cavernous hemangioma
- hepatocellular adenoma
66
what are the maligant hepatic tumors
- hepatocellular carcinoma (HCC)
- tumors metastatic to the liver - more common
67
describe focal nodular hyperplasaia
- may be single or multiplt
- develop in non cirrhotic liver
- result from focal chronic hypoperufsion of an area of the liver reuslting in scarring and compensatory hyperperfusion -> focal hepatocyte hyperplasia
- most common in younger women ages 20-50
68
describe hepatocellular ademona
- usually arises in a non cirrhotic liver
- most common in reproductive age women stimulated by estrogen
- sheets of sheets of hepatocytes normal to atypical
- rare cases progress to malignancy
69
describe cavernous hemangioma
- most common benign liver tumor
- tumor of benign blood vessles, variably dilated
70
describe hepatocellular carcinoma
-incidence varies widely throughout the world- highest in eastern asia and sub saharan african
- expossure to HBV and aflatoxin - aspergillus flavus- markedly increases risk of HCC
- incidence of HCC in western countries is rising mainly due to increased HCV
- chronic liver diseases are the most common setting for HCC development
- main risk factors include: HBV, HCV, aflatoxin exposure and increasinly NAFLD
71
what is the histology of hepatocellular carcinoma
the neoplastic liver cells grow with distorted architecture, forming thickened cords and pseudoglandular spaces
72
where is the gallbladder located
inferior and adherent to the liver
73
what is the function of the gallbladder
- concentrate, store and excrete bile
- receives dilute bile from the common hepatic duct
- in response to hormones from enteroendocrine cells or to parasympathetic stimulation the gallbladder contracts and delivers bile to the duodenum via the cystic duct and the common bile duct
74
what are the layers of the gallbladder wall
- mucosa
- muscularis externa
- connective tissue/adventitia
- serosa
75
describe the gallbladder mucosa
- contains epithelium and lamina propria
- occasional mucous glands near the neck
- surface epithelium is simple columnar
76
describe the surface epithelium of the gallbladder mucosa
- resembles intestinal absorptive cells
- apicolateral junctional complexes
- short microvilli
- complex lateral plications surrounding intercellular spaces
77
describe gallstones
- affects 10-20% of adults in the US
- two types of stones: cholesterol stones and pigment bile salt sontesw
78
what are the cholesterol stone risk factors
- dyslipidemia
- female
- insulin resistance
- gallbladder stasis
79
what are the pigment stone factors
- chronic hemolysis- malaria, sickle cell
- biliary infection
- various GI disorders, chron disease
80
describe gallbladder carcinoma
- occurs at older age with slight female predominance
- usually not resectable at the time of diagnosis
- mean 5 year survivial approximately 5-12%
- though to arise primarily in a background of chronic gallbladder inflammation
81
how does cholestasis appear on histology
bile pigments within hepatocyte cytoplasm
82
what is the typical histology for a hepatitis C infection
chronic inflammation of a portal tract
83
what is the typical resemblance physically and histologically of a focal nodular hyperplasia
central stellate scar on the tumor
- histologically: can resemble cirrhosis but is a focal lesion
84
what is the histological appearance of hepatocellular adenoma
cords of hepatocytes are seen surrounding an artery without portal tracts
85
what is the histological presentation of a hepatocellular carcinoma
- neoplastic liver cells grow with distroted architecture
- form thickened cords and pseduoglandular spaces
