Acute Liver Injury Flashcards
What does the Portal vein do?
It brings blood from the spleen and the intestines to the liver
What two vessels make up the dual blood supply to the Liver
- Portal vein (70%) blood from spleen, intestines and pancrease
- Hepatic artery
What is shock again?
Total body hypoperfusion
Budd Chiari Syndrome
A form of ischemic hepatitis due to hepatic vein thrombosis/
Patients with Budd Chiari suffer from what symptoms?
Tender Hepatomegaly, abdominal pain, Ascites
Due to blod backing up in the liver, poor flow
What is budd chiari most commonly due to>
Hypercoagulable state
Shock liver causes a rapid rise in —— to a peak 25-30 times normal
transaminases
Transaminases due to shock liver will fall when?
7-10 days after the episode (Billirubin also rises at this point)
What is the portal triad
Where venous (portal vein) and arterial (hepatic artery) mix. This mixture circulates along the sinusoids and drains into the central veins. The central veins will eventually fuse into the hepatic veins that drain into the Vena cava
What is so special about hepatic sinusoids?
They are lined by fenestrated endothelial cells that have neither a tight junctions not basement membranes meaning their is no barrier between the plasma and the hepatocytes
Kupffer cells do what
They sit between the fenestrated endothelial cells and nab (phagocytic) bacteria.
What role do Kupffer cells play in sepsis
Unfortunately, they release inflammatory cytokines and mediate sepsis.
What the fuck are Ito cells
fat storing cells that sit beneath the sinusoidal lining.
Also serve as multipotent mesenchymal cells that have the ability to differentiate into fibroblasts or myofibroblasts with chronic liver injury
Where and what is the “space of disse”
Located between the sinusoidal lining cells and the hepatocyte cell membrane.
Contains some extracellular matrix glycoproteins and occasional collagen fibrils
Bile is produced by what?
HEPATOCYTES
What is unique about the flow of bile?
It flows in a direction reverese to the afferent blood supply (Central to Portal)
Where do Hepatocytes secrete bile into?
Bile Canaliculi
What makes up the Bile canaliculi?
They are made up by the apposing lateral surfaces of two hepatocytes. Sealed by tight junctions and their are some actin filaments around them that provide peristaltic action to assist the bile in being secreted.
What are the most common types of drugs to cause liver injury
Antibiotics
Bile canaliculi eventaully drain where?
Bile Ductules which lie at the interface between the lobule and portal triad.
What are oval cells?
They are pluripotent stem cells that can divide into either ductal cells or hepatocytes.
What the hell is canalicular cholestasis?
this occurs when drugs ( or disease) interferes with the motility of the bile canaliculi and results in bile plugs.
What is hepatocellular cholestasis?
This occurs when the secretionof bile out of the hepatocyts is blocked
Chole =
BILE
3 types of pregnancy induced liver disease are?
1) HELLP (hemolysis, elevated liver enzymes, low platelets)
2) Acute fatty liver of pregnancy
3) Intrahepatic cholestasis of pregnancy
Which of the 3 pregnancy induced liver diseases is most common
Intrahepatic cholestasis of pregnancy (most common of the 3)
Intrahepatic cholestasis of pregnancy is caused by?
Epiallopregnenolone sulfate inhibition of farnesoid x receptor mediated bile acid reflux.
What is a clinical sign of intraheptic cholestasis of pregnancy
Maternal pruritis (itching)
Connection between psychoactive medications and liver injury?
Yeah….behind antibiotics, they are the most common type of drugs to cause liver injury
Three zones of the liver lobule are
Periportal, Midzonal, Central
In what order does blood flow through these lobules?
Periportal, then Midzonal, then central.
Centrolobular hepatocytes are generally last in the line of blood flow and thus often the first in line to suffer from hepatic injury/ischemia
Tylenol toxicity is likely when an adult takes how much?
Over 12 grams
Likely severe if an adult takes over 16 grams
First signs of tylenol toxicity>
Nausea, Vomitting, Palor, Sweating, Lethargy, Malaise
Between the 24 and 72 hour mark, someone suffering from Tylenol Toxicity will feel?
Fine usually
But….
After the 72 hour mark the original symtpoms of tylenol toxicity reappear along with Jaundice, Confusion, and bleeding
Hepatic Necrosis is classified by?
Zone and Extent. Central zone, Midzone, Periportal zone
Extent:
Focal- few cells affected in random distribution
Confluent- large cell groups
Bridging- necrosis extends between lobules
Massive- necrosis involves 75% of the liver or more
Acetaminophen injury generally induces necrosis in which zone?
Central
Mushrooms injure what zone?
Mid-zone
Phosphorous compounds injure what zones?
Periportal
Autoimmune hepatitis is very similar in presentation to viral hepatitis, but the treatment is different. How do you tell it apart?
There will be diagnostic antibodies
MOST COMMON= anti-nuclear
Second most common= anti- smooth muscle
MCC of acute liver injury is:
Alcohol
What is the AST/ALT ratio in Alcoholic Hepatitis
around 2…KNOW THIS…also know that this is unique because most causes of liver injury lead to more ALT than AST…ALcohol is the exception
Make a toAST to alcohol
KNOW»» AST rarely gets above 300. So if you have super high levels think something else
Histological characteristics of Acute Liver Injury
- Ballooning Degeneration
- Steatosis
- Mallory Bodies
- Feathery Degeneration
- Apoptosis
- Acute Inflammation
Most common age range for alcoholic hepatitis
40-60
What causes the ballooning degeneration of hepatocytes
First off, ballooning degeneration is not exclusive to alcoholic hepatitis. It can be caused by a variety of things.
Hepatocytes become swollen with Na and H2O because ATP levels are depleted and the Na-K pump fails
Steatosis =
Fatty change
More specifically, the accumulation of lipid in the hepatocyte cytoplasm
What are the two types of steatosis?
1) Macrovesicular- More common, due to decreased lipoprotein synthesis and impaired secretion of lipids.
2) Microvesicular- Impaired mitochondrial beta-oxidation of fatty acids for ATP synthesis.
What causes MACRO-vesicular steatosis?
Due to decreased lipoprotein synthesis with resultant IMPAIRED SECRETION OF LIPIDS
What causes micro-vesicular steatosis
impaired mitochondrial beta oxidation of fatty acids for ATP synthesis
Micro-vesicular steatosis seen most commonly in what conditions?
acute fatty liver of pregnancy, Reye syndrome, multiple hornet stings, mixed with macro-vesicular in alcoholic hep
Micro- ARM….acute fatty liver of pregnancy, Reye syndrome, mixed with macro in alcoholic hepatitis
Reye’s syndrome
Aspirin toxicity in kids
KNOW…Micro-vesicular steatosis is less common and less reversible than
macro-vesicular steatosis
What might you notice about mitochondria in microvesivular steatosis?
They are greatly enlarged
What are Mallory Bodies?
aggregates of intermediate filaments (cytokeratins)
Most commonly seen in alcoholic hepatits and NASH
Microscopic triad of alcoholic hepatitis is
Mallory Bodies, Steatosis, Neutrophils
With severe intracellular cholestasis, what occurs
hepatocytes swell and the cytoplasm becomes wispy…called feathery degeneration
Feathery Degeneration is associated with what?
Billiary obstruction by stones, tumors, or granulomas
What is the most common form of cdell death in hepatic viral infections
Apoptosis
Most common pattern of drug-induced liver injury is what?
Hepatocellular
Canalicular cholestasis vs hepatocellular cholestasis
Canalicular cholestasis - when something (drug or disease) interferes with the movement of bile through the canaliculi
Hepatocellular cholestasis- when something interferes with the secretion of bile INTO the canaliculi
Cholestatic liver disease will do what to biliribuin and alk phos levels?
Severely elevate them
Ballooning degeneration common in acute or chronic liver disease?
Acute
Alcoholic hepatitis shows what type of steatosis?
Micro and Macrovesicular
Remember macrovesicular is caused by decreased lipoprotein synthesis and impaired secretion of lipids whereas micro is caused by impaired beta oxidation of fatty acids by macrophages.
What is feathery degeneration associated with?
Severe intracellular cholestasis, hepatocytes swell and the cytoplasm becomes wispy.
What does feathery degeneration imply
Bad news, it means that damage is severe.
Most commonly seen with biliary obstruction by stones, tumors, or granulomas
High levels of alk phos=
obstruction
Most common mechanism of cell death in liver viral infections
apoptosis
