L12- GIT Pathology VI (liver) Flashcards
describe structure of liver lobule and acinus
(acinus is half a lobule)
- central vein
- surrounded by 6 portal triads
- triads: hepatic artery, portal vein, bile duct
- Zone 1 near periphery, Zone 3 surrounds central vein
- Zone 3 most susceptible to hypoxia
Note- blood flow is outside in; bile flow is inside out
list the cells of the liver
-Hepatocytes: thin plates/cords 1-2 cells thick
- endothelial cells (blood)
- Kupffer cells (liver macrophages)
- stellate cells (perisinusoidal / ito cells): stores fat / vitE
track the movement of bile (from production until it reaches intrahepatic ductules)
1) excreted by hepatocytes
2) into bile canaliculi
3) canals of Hering
4) bile ducts
list the general clinical features of liver disease
- RUQ pain
- jaundice
- anorexia
- pruritus
- fever
- mental confusion
- easy bruising
list the lab investigations for the liver
- Serum Bilirubin: conjugated, unconjugated
- Transaminases: ALT, AST, ALP/ALK, GGT
- Serum Albumin
- AFP
- serum ammonia
- ceruloplasmin
LFT result indicating alcoholic liver disease….
AST:ALT >2
LFT result indicating viral hepatitis….
AST:ALT <1
LFT result indicating cholelithiasis (biliary obstruction)….
elevated ALP, GGT
LFT result indicating HCC….
(hepatocellular cancer)
α-fetoprotein (AFP)
LFT result indicating hepatic failure….
elevated ammonia
LFT result indicating Wilson’s disease….
dec Ceruloplasmin (Cu carrier)
Indicate the *liver disease with the following LFT results:
- (1) elevated GGT, ALP
- (2) elevated ALP alone
- (3) elevated GGT alone
- (4) AST:ALT > 2
- (5) AST:ALT < 1
1- cholestasis / biliary obstruction 2- infiltrative diseases / metastasis, congestive diseases via RHF 3- alcohol use 4- alcoholic liver disese 5- viral hepatitis
Indicate the *liver disease with the following LFT results:
- (1) inc AFP
- (2) dec serum albumin
- (3) dec ceruloplasmin
- (4) inc PT
- (5) inc NH3+
1- HCC 2- chronic liver disease 3- Wilson's disease 4- acute or chronic liver disease 5- hepatic failure
list the radiographic techniques used to investigate liver disease
Visualization of biliary tree:
- ERCP (endoscopic retrograde cholangiopancreatogram): diagnostic, therapeutic
- MRCP (magnetic resonance cholangiopancreatogram): diagnostic
Other:
- MRI, CT, US
- liver biopsy
chronic liver disease is defined as lasting longer than…..
6 mos
= chronic hepatitis
describe how severity of liver disease is determined
*Morphological pattern of hepatocyte
- reversible / self-limiting injury: normal function returns after removing offending agent
e. g. fatty degen. via EtOH, cholestasis
-irreversible damage / fibrosis + progressive = cirrhosis
describe the 2 types of hepatocellular injury
- Ballooning: large hepatocytes w/ regularly clumped cytoplasm
- Feathery: fine, foamy cytoplasm due to detergent action of bile salts
describe the morphological features of hepatic injury
- Hepatocellular injury (ballooning, feathery)
- Necrosis: focal, bridging, massive
- Apoptosis: councilman bodies / acidophil bodies
- Regeneration: hepatocyte cord thickening, mitosis, acinar change (rosettes)
- Fibrosis
list the types of steatosis and their causes
Macrovesciular steatosis: alcohol, NASH, malnutrition
Microvesicular steatosis: acute fatty liver of pregnancy, Reye syndrome, drugs, obesity, DM
describe Macrovesicular Steatosis (+ causes)
Large Droplet: single fat vacuole, displaces nucleus to periphery
Small droplet: multiple fat vacuoles (not as fine as microvesicular)
Causes: alcohol, NASH / NAFLD (non-alcoholic steatohepatitis / non-alcoholic fatty liver disease), malnutrition
describe Microvesicular Steatosis (+ causes)
-multiple fine vacuoles, nucleus is central
Causes: acute fatty liver in pregnancy, Reye syndrome, drugs, obesity, DM
Signs of Liver Disease seen in acute and chronic conditions
- icterus / jaundice
- hepatomegaly
- RUQ pain / tenderness
- peripheral edema
Signs of Liver Disease seen in only chronic conditions
- splenomegaly (portal HTN)
- palmar erythema
- spider angiomas
- gynecomastia + testicular atrophy (men)
- Dupuytren contracture (hand fibrosis contracts ulnar nerve digits)
- parotic enlargement
- clubbing
- white nails (leukonychia)
- muscle wasting
Jaundice:
- defined as (1)
- presence in the eye is (2), and will be seen clinically with (3) lab values
- accumulation of (3) also leads to (4) in newborns
- (5) / (6) describe the results of retaining two other substances
1- skin yellowing 2- scleral icterus 3- bilirubin >2.0 mg/dL 4- kernicterus (neonatal jaundice => brain damage) 5- cholesterol --> skin xanthomas 6- bile salts --> pruritus
list the classifications of jaundice
- pre-hepatic
- hepatic
- post-hepatic
list the causes of pre-hepatic jaundice
excess production of bilirubin:
- hemolytic anemia
- inc blood resorption from hemorrhage
- ineffective erythropoiesis
list the causes of post-hepatic jaundice
impaired bile flow:
- gallstones, head of pancreas cancer, extra hepatic bile ducts
- biliary atresia (neonates)
list the causes of hepatic jaundice
- reduced uptake: drugs, diffuse liver disease
- impaired conjugation (neonates)
- dec excretions: drugs, transporter deficiency (related to impaired conjugation)
- impaired bile flow –> bile duct obstruction
Cirrhosis defining characteristics
- bridging fibrous septa
- parenchymal nodules created by regeneration
- diffuse liver involvement
NOTE- end stage result of many liver diseases are irrespective of primary etiology
define Cirrhosis classification
based on nodule size:
- Micronodular, <3mm nodules
- Macronodular, >3mm nodules
list the disease types that can cause Cirrohosis
Hepatic diseases: viral / autoimmune hepatitis, steatohepatitis (alcoholic/NASH)
Biliary diseases: primary biliary cholangitis, primary sclerosing cholangitis (UC)
Metabolic diseases: hereditary hemochromatosis, Wilson’s disease, AAT deficiency
Cyptogenic / Idiopathic
describe the clinical features of cirrhosis
(possibly silent / asymptomatic)
- portal HTN –> ascites, splenomegaly, varices
- liver failure
-inc risk of HCC
what are the consequences of portal HTN (often seen in liver disease, e.g. cirrhosis)
- ascites
- hepatic encephalopathy
- congestive splenomegaly –> thrombocytopenia
- portosystemic shunts: esophageal / gastric varices, hemorrhoids in rectum, retroperitoneum affected, caput medusae of abdominal wall
(1) is the most common infectious disease of the liver, caused mostly by (2), although (3) infections can involve the liver
1- viral hepatitis
2- Hepatitis A, B, C, D, E
3- EBV (infectious mononucleosis), CMV, yellow fever
HepA:
- (1) genome
- causes (acute/chronic) hepatitis
- commonly affects (3), spreading via (4) route
- (5) incubation period
1- non-enveloped (+)ssRNA (picornavirus family) 2- acute (no chronic disease) 3- children (unvaccinated) 4- fecal-oral 5- 2-6 wks
HepA:
- diagnosis either requires (1) or (2)
- (3) does not occur with hepA virus
1- IgM anti-HepA at onset
2- IgG after few months
3- carriers
HepB:
- (1) genome
- aka (2), explain
- (3) transmission
- (4) incubation period
1- enveloped dsDNA
2- serum hepatitis b/c present in all body fluids
3- blood transfusion, sex, IV drug use, needle stick injuries
4- 4-26 wks
discuss the distribution of HepB complications post-acute infections
healty carriers, 5-10%
subclinical disease, 60-65% (–> recovery)
acute hepatitis, 20-25% (–> recovery, rarely fulminant/death)
perisistent infection, 4% (–> most recover, some advance to chronic HepB –> cirrosis / —> HCC / death)
HepB Histology:
- (1) general hepatocyte appearance
- (2) intracellular characteristic
- immunostaining for (3) is necessary to confirm its abundant presence in cells, include color
- (4) is a key trait of chronic hepatitis
1- ground-glass
2- large pale, finely granular pink cytoplasmic inclusions (H&E)
3- HepB surface Ag, brown
4- portal tract expansion via lymphoid follicle
HepC:
- (1) genome
- causes mostly (acute/chronic) hepatitis
1- enveloped (+)ssDNA (flavivirius)
2- both, high propensity for chronic infections
discuss the distribution of HepC complications post-acute infections
- resolution, 15%
- chronic hepatitis, 85% (–> either stable disease or cirrohosis with its complications)
- fulminant, rare
explain HepD infection
-what needs to occur for infection, which method is more dangerous
-its a defective RNA virus
-becomes infective when encapsulated by HBsAg (hepatitis B surface Ag)
OR
-co-infection with HepB (more dangerous = superinfection)
HepE:
- (1) genome
- causes mostly (acute/chronic)
- (3) transmission, mostly affecting (4) people
- possibly fatal in (5) population
- (6) is a popular complication
1- non-envelope 2- mostly acute 3- enteric (endemics) 4- immunosuppressed (post-liver transplant Pts) 5- pregnant 6- cholestasis
what are the clinical results of viral hepatitis
1- asymptomatic infection
2- carrier state
3- acute hepatitis
4- chronic hepatitis
5- fulminant hepatitis
Autoimmune hepatitis:
- more in (males/females)
- involves Ig(2) against (3) in adults or (4) in children
- responds to (5)
1- females
2- IgG
3- anti-nuclear / anti-smooth muscle Abs (type I)
4- anti-LKM (liver kidney microsomal) Abs (type II)
5- immuno-suppressive therapy
Autoimmune hepatitis histological description (hepatitis type and defining cells)
focal lobular hepatitis w/ prominent plasma cells
list the patterns of alcoholic liver disease
- hepatic stenosis
- alcoholic hepatitis (steatohepatitis)
- variable amounts of fibrosis –> can progress to cirrhosis
(micronodular cirrhosis –> progresses to macronodular)
NAFLD = (1):
- (2) Sxs
- (3) risk factors
1- nonalcoholic fatty liver disease
2- asymptomatic OR mild elevation of serum transferases, may lead to cirrhosis
3- obesity, insulin resistance, DM, hyperlipidemia
NAFLD = (1):
-similar presentation to (2- include features)
1- nonalcoholic fatty liver disease
2- alcoholic liver disease:
- steatosis
- steatohepatitis = ballooning, Mallory hyaline
- fibrosis around central vein
- may progress to cirrhosis
fulminant hepatitis definition
- acute liver disease, rapid progression
- encephalopathy develops w/in 8 wks
-pathology: massive necrosis, submassive necrosis
liver necrosis:
- (1) general appearance
- confluent necrosis in (2) region
1- small, bile-stained, soft, congested
2- periventricular region
