CH11

the hilum

dual blood supply:
arterial oxygenated blood through hepatic
venous through portal vein

fixed phagocytes and serves as the main scavengers of foreign and internal particulate

lining the lobular blood space and sinusoids of the liver

bacteria and blood cell fragments

converted into urobilinogen and reabsorbed into the portal circulation and returned to the liver

stored in gall bladder

excretory, metabolism, synthesis

brings bile into the into intestines to mix with food and pancreatic enzymes

CHO, fats, lipids

plasma, transport, and coagulation proteins (NOT Ig)

blood enters liver (through portal)

Kupffer cells

AST and ALT

alkaline phosphatase

various metabolites: carbs, lipids, proteins derived from the food or peripheral storage sites

accumulation of ammonia and other presumptive neurotoxins in the intestines

substances may act on the brain possibly causing coma and hepatic encephalopathy

causes dilated arterioles surrounded by dilated capillaries known as spider nevi

testicular atrophy (loss of libido) and gynecomastia

alcoholic pts with cirrhosis
also attributed to hyperestrinism

jaundice, hepatitis, cirrhosis
toxic/metabolic hepatic injury
disease of extrahepatic bile ducts, gallbladder (gallstones)
tumors
hepatitis encephalopathy
hormone disturbances

fluid that is made and released by the liver and stored in the gallbladder

help with digestion;
breaks down fats into fatty acids to be taken into digestive tract

jaundice

low pressure venous system; results in portal HTN

formation of ascites or splenomegaly

block in portal blood flow

between portal and systemic venous circulation

opens and forms venous dilatation called varices

esophagus
anal canal
paraumbilical region
retroperitoneal
intrahepatic (patent ductus venosus)

distention of Glisson's capsule is typical of CHF, tumors, and hepatitis

RBCs uptake, process, and excretion bilirubin released from aged RBCs

Glisson's capsule
bilirubin
plasma proteins
viruses

detox or modifies many drugs, hormones, cytokines, and biologically active metabolites

readily replaced by new hepatocytes derived from the remaining healthy cells

arteriovenous anastomoses

portal blood bypasses liver and gets into systemic circulation

metabolites, hormones, toxic subs, ammonia in the blood do not get detoxified

from the breakdown of senescent RBC with a minor contribution from degradation of tissue heme-containing proteins

serum albumin (and delivered to liver)

by hepatocellular uptake and glucuronidation by glucuronosyltransferases in hepatocytes

generate monoglucuronides;
become water soluble and readily excreted into bile

gut bacteria deconjugates and degrades bilirubin into urobilinogen

excreted in feces (stercobilinogen) with some reabsorption and reexcretion into bile

taken up by the phagocytic cells in spleen

hemoglobin is degraded into heme and globin

heme loses iron and is transformed into pigment bilirubin

blinds to albumin (not water soluble); gets conjugated in the liver (to glucuronide)

when bound to glucuronide

gets excreted into bile and into intestine, contributing to digestion of dietary fats

converted by bacteria into urobilinogen to be reabsorbed;
most is recirculated in the liver, small portion excreted in urine

hyperbilirubinemia

yellow sclera of eyes

accumulation of bilirubin (or its conjugates) in body tissues, producing jaundice (icterus)

heme from aged RBC

spleen and liver

converted into bilirubin (unconjugated) and binds to albumin to be taken up by liver and excreted in bile

hemolysis and Gilbert's Disease

disturbances in the excretion of bilirubin that has been conjugated to glucuronide in liver cells

brown and foamy

hemolysis
hematoma
Gilbert's Disease
Increased unconj. Bilirubin

common autosomal dominant genetic defect in hepatic conjugation of bilirubin

viral hepatitis
alcoholic liver disease
drug-induced liver disease

liver cell necrosis and destruction of the liver and liver parenchyma

both conjugated and unconjugated bilirubin

obstruction of bile flow (increased bili)
gall bladder carcinoma
bile cannot reach intestine
biliary stones

gallstones in common bile duct
carcinoma of head of pancreas
carcinoma of common bile duct

acholic (clay colored)

biliary stones and acholic feces

hemolysis, hematoma, Gilbert's Disease

viral hepatitis
alcoholic liver disease
drug-induced liver disease

gallstones
carcinoma of the pancreas / bile duct

produce a mix of predominantly conjugated hyperbilirubinemia due to reflux of conjugates back into plasma

hepatic (mixed) and post hepatic (obstructive) jaundice

primarily sclera, skin, and mucous membranes

diffuses into tissues and binds to various organs

unconjugated bilirubin (leading to brown urine)

hepatotropic hepatavirus A B C D E

only affecting the liver

dark urine
ALT and AST increases
can progress to chronic hepatitis

EBV, CMV, herpes virus, viruses causing childhood viral diseases, yellow fever virus (tropics)

acute infection with resolution
can progress into chronic hepatitis

1. Preicteric
2. icteric
3. convalescent

weak, nausea, vomit, dark and foamy urine

jaundice, increased liver enzymes (AST & ALT?)

through contaminated needles and multiple sec partners

portal tracts

cell-death apoptosis
ballooning (reversible)
degeneration (granularity / ballooning)

inflammation / fibrosis extending from portal tracts into the body,
loss of architecture when regenerated,
ballooning degeneration,
eosinophilic bodies

when eosinophilic bodies present

a dying hepatocyte is seen shrinking down to form an eosinophilic councilman body

disruption of lobular architecture,
aggress inflam and fibrosis with liver cell death,
fibrous tissue forms connective bridge between adjacent portal tracts

portal tract inflammation accompanied by spilling of inflammatory cells across the limiting plate (interface hepatitis) and all the way into the lobule

bridging fibrosis forming conn tissue bridges between adjacent portal tracts (or centrilobular areas)

ground glass cells, contains surface ags in the ER

collapse of liver parenchyma with viral hepatitis;
conn tissue of many portal tracts collapsed together

chronic liver disease

loss of normal liver structure and function;
irreversible fibrosis and nodules

alcohol
hep B C D
hereditary metabolic disease
autoimmune disease
drugs
biliary obstruction
cryptogenic (unknown)

hemochromatosis
Wilson's disease
alpha1-antitrypsin deficiency

primary biliary cirrhosis
primary sclerosing cholangitis
autoimmune hepatitis

cystic fibrosis
gallstones

necrosis of liver cells
repair by fibrosis
regeneration of liver cells (nodules)

necrosis followed by fibrous tissue ingrowth from portal tracts

nodule regeneration
smaller liver
irregularly-shaped liver
cirrhosis

results from diseases of biliary tree (autoimmune), affecting bile ducts

after prolonged partial or complete obstruction of bile flow

mechanically occlude the duct and may cause chronic inflammation

liver infected (HBV / HCV) hepatotropic viruses
alcohol abuse leading to fatty transformation of the liver (which appears yellow)

smooth surface in gross examination

microscopically

appearance of nodules on the surface of the liver throughout parenchyma

due to extensive fibrosis

firm, yellow, increased in ;
Mallory bodies and fat droplets

liver cell necrosis, fibrous tissue ingrowth from portal tracts

liver cell injury,
chronic inflammation,
progressive,
irreversible

destruction of underlying architecture,
fibrosis,
attempts to regenerate,
vascular reorganization leading to shunting,
repeat

because of oxidation of bile into biliverdin, a green pigment

accumulation of iron

irreversible
chronic inflam
scarring (fibrosis)
parenchymal loss
regenerative nodules
altered vasculature
possible cryptogenic

in alcoholic cirrhosis (along with fat droplets)

around central vein extending outward to the portal tracts with increasing severity

intracytoplasmic fat

fibrosis in characteristic perisinusoidal pattern

peritoneal transudate or edema limited to abdominal cavity

hydroperitoneum

presence of fat droplets and Mallory-denk bodies in liver cells

bleeding
hematemesis
hyperestrinism
hepatic encephalopy
ascites resulting in hyperaldosterone
hepatorenal syndrome
hyperbilirubinemia (conjugated)
prolonged PTT
AST and ALT increase
anemia
leukocytosis / leukopenia
thrombocytopenia
increased globulin levels
testicular atrophy and impotence
abnormal VIT absorption

exsanguination from bleeding esophageal varices

reduced clotting factors
thrombocytopenia

spider nevi
palmar erythema
gynecomastia
testicular atrophy
loss of ovulation

phytoestrogen in alcohol and direct inhibition of testosterone by ethanol disrupts estrogen to testosterone ratio

hypoperfusion of kidneys
Na+ retention can produce renal failure

ascites

splenomegaly
trapping of WBC and RBC in the spleen

hypoalbuminemia, prolonged PTT, loss of detox function, endocrine symptoms due to decreased metab or hormones

reduced production of albumin
(hypoalbuminemia, reduced oncotic pressure of plasma);
hypovolemia,
portal HTN,
reduced fluid circulating triggers

hydroperitoneum / ascites

increased transudation of fluid into abdomen cavity

accumulation of fluid in abdomen cavity

will resume normal function;
may be infected due to ascites, leading to bacterial peritonitis

results in portal hypertension

ascites, splenomegaly, anastomoses

vessels in liver are blocked; blood cannot flow properly

leads to development of large, swollen veins (varices) within the esophagus, stomach, rectum, or umbilical area

obstruction of bile duct causes jaundice; block bile ducts lead to bile buildup in liver; jaundice develops due to increasing level of bilirubinemia

circ widen; increasing pressure in anastomoses, becoming varicosities that can bleed and rupture in 3 areas

cannot be absorbed

lower esophagus
hemorrhoidal plexus
periumbilical areas of anterior abdominal wall

serious metabolic consequences and corresponding clinical symptoms

clouded mentation and distinct neurologic symptoms

ammonia and putative neurotoxins absorbed from the intestine (hepatic coma)

formation of varices in the rectal vein, submucosal vein, esophagus, and paraumbilical inferior epigastric vein

lower part of esophagus dilated veins prone to bleeding (common cause of death)

ascites due to collection of fluid in peritoneal cavity as a result of decreased reabsorption of capillary fluid

ascites, splenomegaly, anastomoses

hemorrhoids, esophageal varices, caput medusae

increased RBC destruction, anastomoses, varices, hepatic encephalopathy

fatty liver, increase FA synthesis

progression to alcoholic hepatitis

fever, FA, leukocytosis, abdominal pain, jaundice

steatohepatitis

cirrhosis

converts alcohol to acetaldehyde, then to dehydrogenase

alcohol dehydrogenase and acetaldehyde dehydrogenase

produces TNF; induces mitochondria to increase production of ROS

inflammation and fibrosis

Mallory's hyaline (aka alcoholic hyaline)

in conjunction with chronic alcoholism

globules are aggregates of intermediate filaments in the cytoplasm resulting from hepatocyte injury

fat droplets and Mallory-denk bodies

liver enzymes (increase in fatty acid synthesis and decrease fatty acid oxidation)

cytokeratin aggresomes;
eosinophilic inclusions in degenerating hepatocytes

neutrophils

chicken wire fibrosis (sinusoidal, perivenular, and occasionally periportal)

fever
increase in WBC
jaundice

thickening and scarring (fibrosis) of the liver

advanced form on non-alcoholic fatty liver disease

a. nonalcoholic fatty liver (NAFL) stenosis
b. nonalcoholic steatohepatitis with inflammation (NASH)
c. cirrhosis

prevalence of obesity coupled with rising adoption of sedentary lifestyle is a major factor influencing growth of NASH

abnormal accumulation of triglycerides, reversible, soft, yellow, greasy

liver inflammation and damage caused by buildup of fat in liver

obesity

larger liver with more fatty change

excess fat causes insulin resistance and inflammatory signals;
pancreas has to produce more in order to maintain normal glucose

lobular structure
fibrous septa
central vein to portal regions
portal tract to portal tract
hepatic parenchyma
hepatocyte regeneration of micronodules

no normal lobular architecture; central veins are hard to find

divides hepatic parenchyma into modules;
initially delicate and extend through sinusoids

liver becomes more fibrotic, loses fat and shrinks ;
ischemic necrosis and fibrous obliteration of nodules create broad expanses of scar tissue

parenchyma shows extensive fatty change

Gilbert's Disease
Hemochromatosis
Wilson's Disease
Αlpha1-antitrypsin disease
Panacinar Emphysema

benign recurrent jaundice with unconjugated bilirubin

excessive accumulation of iron in many organs, cirrhosis, bronze diabetes

excessive accumulation of copper;
seen in liver, eye, CNS, cirrhosis

accumulation of AAT, cirrhosis
liver cells contain cytoplasmic globules composed to alpha1-antitrypsin;
deficiency is due to autosomal recessive disorder that is related to the presence of PIZ allele of the gene that encodes for alpha1-antitrypsin

air spaces distal to the terminal bronchioles; emphysema due to a1-AT deficiency in lower part of lungs and anterior margins

genetic disorder that manifests as pulmonary emphysema, liver cirrhosis, and rarely as the skin disease panniculitis

low serum levels of AAT, main protease inhibitor (PI) in human serum

development of resp symptoms, emphysema, airflow obstruction early in adult life;
additional risk facts=environmental factors

development of acute or chronic liver disease;
prolonged jaundice after birth, abnormal liver enzymes, cirrhotic liver at age 50

1. autoimmune hepatitis
2. primary biliary cirrhosis
3. primary sclerosing cholangitis

young women, other autoimmune diseases;
abs: ANA, ant-smooth muscle

middle aged women, chronic jaundice, hypercholesterolemia
abs: AMA

men <40 years old, ulcerative colitis, no specific abs

destruction of intrahepatic ducts

constriction of extrahepatic and intrahepatic ducts

chemicals found in bile

hemangioma and hepatocellular adenoma

hepatocellular carcinoma, Cholangiocellular carcinoma of liver, carcinoma of extrahepatic bile ducts, gallbladder carcinoma

enlarger liver with multiple nodules with depressed central area, umbilicated appearance

AST, ALT, HCV and HBsAg or anti HBcAb, ALP elevation

ALP elevation

glutamyl transpeptidase (GGTP)

antimitochondrial ab

antinuclear abs (ANAs) and smooth muscle abs

iron and genetic studies

copper studies

alpha1-AT fractionation and other studies