B5.024 - Big Case TML Flashcards
Describe the synthesis and metabolism functions of the liver
Synthesis - albumin, coagulation factors Metabolism - cholesterol synthesis/uptake, glucose production, glycogen storage, conversion of ammonia to urea, endogenous hormones, lipoproteins, AAs (non essential)
Biotransformation functions of the liver
Bilirubin - conjugation and excretion Drugs Ethanol
Immune function of normal liver
Reticule-endothelial formation Clearance of damaged cells, proteins, drugs, activated clotting factors Clearance of bacteria and antigens from portal circulation
What is stored in the liver
Glycogen Fats Iron Copper Vitamins A,D,K, B12
What are the two types of liver injury
Hepatocellular Coolest attic
What measures liver function
Albumin PT/INR Bilirubin
Liver function tests
Serum albumin - quantitative PT/INR - liver synthesizes the majority of coagulation factors (1, 2, 5, 7, 9, 10) so its an excellent predictor of liver dysfunction but NOT bleeding tendency Bilirubin
What tests suggest hepatocellular injury
ALT/AST Tells you about injury to hepatocytes
What tests suggest cholestatic injury
Alkaline phosphatase/bilirubin
What is cholestatic injury
Decrease bile flow to impaired secretion by hepatocytes Or Obstruction of bile flow through Indra or extra hepatic bile ducts
Acute causes of hepatocellular injury
Viral hepatitis Ischemia Autoimmune hepatitis Acetaminophen/toxins Drugs
Causes of acute cholestatic injury
Any biliary obstructive process PBC/PSC Drugs Sepsis
Markers of liver injury
ALT/AST Alk phos GGT Bilirubin
What is ALT
Alan in aminotransferase More specific for liver Located in hepatocyte cytosol
What is AST
Aspartate aminotransferase Present in liver, heart, skeletal muscle, kidney, brain, lungs, leukocytes In hepatocyte cytosol and all Mitochondria
What are ALT and AST markers for
Hepatic necrosis
What are normal values for AST/ALT
10-50
What causes highest elevation of AST/ALT
Over 1000 Acute viral hepatitis Toxin induced necrosis Ischemia Autoimmune hepatitis
What causes serum levels moderately elevated of AST/ALT
Chronic liver disease, neoplasms
Describe AST/ALT levels in acute biliary obstruction
Most have high levels initially which rapidly decline in 24-72 hours
Who gets alcoholic hepatitis
10-35% of drinkers who consume 30-50g of alcohol daily >5 years
Characterize alcoholic hepatitis
Inflammation and injury to liver; disease ranges from mild to severe More severe in females, European descent
Histo characteristics of alcoholic hepatitis
Ballooned hepatocytes Mallory desk hyaline Steatosis
What is the main enzyme responsible for the breakdown of ethanol
Alcohol dehydrogenase converts NAD—NADH and ethanol —Acetaldehyde
Increased ratio of NADH/NAD leads to what
Alcoholic fatty liver
What is the MEOS pathway
Microsomes ethanol oxidizing pathway - inducible p450 pathway CYP2E1: implicated in tolerance of various drugs in alcoholics and increased susceptibility to toxicity
What is perixosomal catalase
<2% of overall in Vito alcohol oxidation
What is alkaline phosphatase
Found in or near canalicular membrane Mainly present in liver, bone, placenta, intestine
Normal level of alkaline phosphatase
70-150 Less than 3x elevation in liver diseases 3-4x higher in infiltrative liver diseases or disease of bile duct
When is GGT useful
To determine if Alk phos is high from liver issues or bone/placenta
Where is GGT found
in bile duct epithelium and endoplasmic reticulum NOT IN BONE Sensitive indicator of cholestasis and poor specificity
Causes of acute liver injury
Drugs Toxins Ischemia Viral hepatitis
What are causes of chronic liver injury
Alcohol Autoimmune NAFL PSC/PBC Chronic viral hepatitis
What is jaundice
A medical condition with yellowing of the skin or whites of the eyes arising from excess of the pigment bilirubin and typically caused by obstruction of the bile duct, by liver disease or excessive breakdown of RBCs
Normal bilirubin v elevated
Normal 1 mg/dL Over 2-3 mg/dL needed to cause jaundice
How does blood flow through these structures
hepatic artery comes from aorta
portal vein brings nutrient rich blood from the GI tract
bile duct transports bile derived from hepatocytes to the gallbladder
Describe the flow of broken down RBCs through the circulation to excretion
What is the main enzyme responsible for the breakdown of bilirubin
Heme oxygenase breaks down heme into biliverdin
What do you need to know when evaluating jaundice
Is it conjugated or non conjugated
What are causes of pre hepatic and hemolytic jaundice
extrinsic causes external to blood cells
intrinsic defects in red blood cells
Differential for genetic causes of pre hepatic hyperbilirubinemia
indirect
spherocytosis
sickle cell
thalassemia
G6PD deficiency
wilsons disease
Autoimmune causes of indirect hyperbilirubinemia
hemolytic anemia
drug induced
Infectious, trauma, drug causes of indirect hyperbilirubinemia
Malaria
extravascular blood loss
dapsone
rifampin
What is G6PD deficiency
genetic x linked disorder
mutation in G6PD gene
normal function is to produce compounds which prevent ROS build up in RBCs
in deficiency, ROS build up can cause hemolytic anemia
Explain the epidemiology of G6PD deficiency
makes it more difficult for malaria to infect RBCs
Hepatitis A transmission, incubation period, natural Hx
fecal oral
28 days
98% chance complete recovery
symptoms and biochemical abnormalities should resolve over the next few days
in one or 2 months, her anti-HAV should convert from IgM to IgG
Management of hepatitis A
supportive care
good handwashing
close household contacts should receive serum immune globulin
What is physiologic jaundice
increased enterohepatic circulation of bilirubin
lack intestinal flora to convert bilirubin conjugates
decreased hepatic levels of UDP glucuronosyltransferase actvity
meconium has a lot of bilirubin
Breast milk jaundice
unknown cause, persists after physiologic
from 2-12 weeks
dont stop breastfeeding
Breast feeding jaundice
decreased hepatic levels of UDP glucuronosyltransferase activity, more pronounced in premature infants
not enough milk: keep trying or supplement
Treatment of physiologic jaundice
hydration
adequate nutrition
bili lights
exchange transfusion
How does phototherapy work
bili lights change the internal hydrogen bonds of the bilirubin molecule to create forms that can be excreted into bile or urine without glucuronidation
What is kernicterus
severe unconjugated hyperbilirubinemia
yellow staining of the basal ganglia, hippocampus, cerebellum, and nuclei of the floor of the fourth ventricle
clinically: high pitched cry, hypotonia, vomiting, hyperpyrexia, sluggish, seizures, paresis of gaze, death
Differential for post hepatic hyperbilirubinemia
congenital - biliary atresia
malignancy - HCC, pancreatic, lymphoma, cholangiocarcinoma
infectious - clonorchis, opisthorchis
antatomic obstruction - mirizzi syndrome, gallstones
What is mirizzi syndrome
when a gallstone in the cystic duct becomes so large it obstructs the common hepatic duct
Risk factors for HCC
Cirrhosis - 80%
HBV
HCV
NAFLD
M>W
Dx and treatment of HCC
CT or MRI
AFP
treatment ; TACE, tumor ablation, surgical resection, liver transplant
What is cirrhosis
the end result of chronic hepatic inflammation
defined histologically by hepatic fibrosis, regenerative nodule formation
Complications of cirrhosis
- Loss of hepatocytes
- Portal hypertension and portal systemic shunting
- Hematologist abnormalities
Portal hypertension manifestations
ascites
verices
hepatic encephalopathy
hepatorenal syndrome
What is hepatic encephalopathy
derangment of mental function caused by acute liver failure or by cirrhosis with portal systemic shunting
cirrhotic liver fails to detoxify portal blood toxins, which then interact with the CNS
Grades of hepatic encephalopathy
1 - trivial lack of awareness, euphoria/anxiety, shortened attention
2 - lethargy or apathy, minimal disorientation, subtle personality changes, inappropriate behavior
3 - somnolence to semi stupor but responsive to verbal stimuli, confusion
4 - coma
Hepatorenal syndrome
oliguria, increased BUN and Cr, concentrated ruin in a patient with decompensated chronic liver disease
ascites
tubular function INTACT
no glomerular injury
similar to intravascular volume depletion
Hematologist complications of cirrhosis
anemia
thrombocytopenia
leukopenia
