Chapter 2 Flashcards
How many Americans have chronic liver disease?
5.5 million
where is the liver located
RUQ of abdomen
the liver is the ___ solid organ in the body
largest
as little as ____ % of healthy liver tissue can regenerate into an entire liver
25%
what are the three categories of the structure of the liver
hepatic vascular system
biliary tree
hepatic lobules
how much blood is in the liver at any one time
500 ml or 13%
what type of blood does the hepatic artery bring to the liver
arterial (oxygenated) blood
what type of blood is brought to the liver by the portal vein
blood that has previously been through the small intestine and spleen.
venous blood0 abt 75% of blood entering liver, and contains the nutrients absorbed from the small intestine
what are sinusoids of liver
vascular channels in the liver where blood flows to be filtered
how does blood exit the liver
central vein -> hepatic veins -> empty into inferior vena cava
what is the biliary system
series of channels and ducts that transport bile from the liver into the small intestine
what produces bile and how is it secreted from the liver
hepatocytes create bile, then it is secreted from each lobe of the liver through the left and right hepatic ducts, which join to form the common hepatic duct
what two ducts meet to form the common bile duct
the common hepatic duct and the cystic duct from the gallbladder
what happens to bile in the gallbladder
it is stored until it is needed for the digestive process
how does bile re-enter the common bile duct
through the cystic duct, when enters the duodenum after combining with the pancreatic duct to form the ampulla a of Vater
the ampullary opening into the duodenum is controlled through the muscular sphincter of ____
Oddi
what is a hepatic lobule and how many are there in a normal liver
the structural unit of the liver, approx 100,000 in a normal liver
what is the primary purpose of the liver
maintain homeostasis
estimated 200 functions, although many not yet understood
what are some other functions of liver
detoxification
metabolism (convert glucose into energy and carbs to glucose and carbs and protein into fat)
synthesis of lipoproteins and cholesterol
synthesis of plasma proteins (manufacture of many essential blood components (albumin, fibrinogen, certain globulins)
synthesis of immune factors
digestive functions
excretion of bilirubin
storage (glucose in form of glycogen, fats, iron, copper, vitamins)
What are the issues that affect the usefulness of LFTs
- many tests nonspecific to liver, and abnml results can be associated with other disorders
- LFTs have low sensitivity and specificity
- results can be affected by outside factors (food intake, fasting, physical activity, meds, sample collection technique, splfcim transport, hemolysis)
- due to the liver’s large functional reserve capacity, as well as its regenerative capability, structural or functional damage can evade detection using blood testing
what are the aminotransferases
ALT/SGPT
AST/ SGOT
where is AST found
liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, erythrocytes
why is ALT a more specific marker for liver injury
highest level of ALT found in liver, with only small amounts in cardiac and skeletal muscle
what is LDH and its use in insurance setting
lactate dehydrogenase, present in most tissues of body, serves to determine the presence of a hemolyzed specimen
what are causes of GGT elevation
- can occur with even subclinical hepatocellular damage
- can be elevated in other conditions like renal failure, CAD, MI, pancreatic disease, DM.
- alcohol, meds (dilantin), nsaids, warfarin, statins
when are GGT elevations with alcohol present
with steady, heavy drinking over time, but not with binge drinking.
what is bilirubin
main bile pigment that is formed from the breakdown of hub in RBCs.
what is unconjugated hyperbilirubinemia caused by
- increased production of bilirubin (eg hemolytic anemia)
- decreased conjugation (eg Gilbert’s)
what is conjugated hyperbilirubinemia caused by
- decreased secretion of bile by liver (cirrhosis, hepatitis, primary biliary cirrhosis, drug-induced)
- cholestasis (biliary obstruction, choledocholithiasis, stricture, neoplasm, biliary atresia, sclerosis cholangitis)
what is alkaline phosphatase and where is it found
AP comprises a group of enzymes present in many tissues. primarily found in liver and bone, also present in kidney, intestine, lung and placenta
if AP is elev due to hepatic pathology, what other LFTs will also generally be elevated
GGT and/or bilirubin
what are the most common causes of AP elevations
- liver
- bone disease (Paget, osteosarcoma, bone mets from prostate cancer, other bone mets, fractures)
- malignant tumors
- renal disease (secondary hyperparathyroidism)
- primary hyperthyroidism
- polycythemia vera
- pregnancy
what is albumin
most important plasma protein
synthesized in liver
concern is low albumin, can be caused by heavy ETOH abusehypoalbuminemia not specific for liver disease
what is AFP
major protein in fetal seem. normal liver in non-pregnant adult does not product AFP. used as a tumor marker for hepatocellular carcinoma
can also be found with cirrhosis, viral hepatitis, other tumors.
what does prothrombin time measure
rate of conversion from prothrombin to thrombin after activation of the extrinsic coagulation pathway
what is CDT
carbohydrate-deficient transferrin
helps detect heavy alcohol consumption
what is hemoglobin-associated acetaldehyde (HAA) assay
specific confirmation test that distinguishes alcohol-related from non-alcohol-related liver enzyme elevations
it is a major metabolite of ethanol
what use do X-rays have in evaluating liver disease
add little value
on occasion, calcification d/t gallstones, cysts or scarring
can identify calcified tumors or vascular lesions
what 3 purposes can tumor markers be used for
making a diagnosis of cancer
determining prognosis
monitoring effectiveness of cancer treatment
most coagulation factors are synthesized by the ______
liver
what does the prothrombin time measure
the rate of conversion of prothrombin to thrombin after activation of the extrinsic coagulation pathway
deficiency of what results in prolonged PT? and what is the measurement of PT useful in?
deficiency of one or more of the liver-produced coagulation factors
PT measurement is useful in assessing the severity and prognosis of acute liver disease
what are some non-hepatic causes of prolonged PT times
vit K deficiency, coagulopathies, inherited deficiency of a coagulation factor, or meds that antagonize the PT complex (warfarin)
changes to CDT occurs when individuals consume how much alcohol
usually more than 4-5 drinks per day for 2 weeks or more
What is HAA
hemoglobin-associated acetaldehyde assay
a specific confirmation test that distinguishes alcohol-related from non-alcohol-related liver enzyme elevations
it is a major metabolite of ethanol
excessive alcohol intake causes ________ to be chronically present at elevated levels in the blood
acetaldehyde. at these high levels, it attaches to blood proteins, creating elev HAA
what is the initial radiological study of choice for many hepatobiliary disorders
ultrasound because it is inexpensive, non-invasive, and portable.
what test is becoming the preferred technique for imaging of the hepatobiliary system
CT, except for GB, which is better imaged with US
which test can identify between hepatic masses, cystic vs solid and identify abscesses
CT
which test is important for characterization and staging of liver lesions seen on other tests and is test of choice for confirming vascular lesions (hemangiomas)
MRI
what is FibroScan and what are its advantages and disadvantages
noninvasive procedure using US, determine severity of fibrosis, less expensive than liver bx, immediate results. limitations: limitations in people with ascites, morbid obesity, large amounts of chest wall fat, less reliable in people with low grade fibrosis and those with acute liver inflammation
what is the most accurate test to confirm dx of specific liver diseases
liver bx
what are the indications for liver bx
- eval abnm diagnostic findings and hepatosplenomegaly
- confirm dx and determination of prognosis
- confirm suspected hepatic neoplasm
- dx of cholestatic liver dz
- eval of infiltrative or granulomatous dz
- eval and staging of chronic hepatitis
- identification and staging of alcoholic liver dz
- eval of effectiveness of treatment of liver disorders
what is the major limitation of liver bx
sampling error due to adequacy and/or location of the specimens obtained
define fatty liver and its range of severity
when 5% of the liver mass is made of fat
range from mild steatosis (fatty liver) to inflammation (Steatohepatitis), to fibrosis and cirrhosis
hepatic steatosis can be caused by
- increased peripheral mobilization of fatty acids into the liver
- increased hepatic synthesis of fatty acids
- impaired hepatic catabolism of fatty acids
- impaired synthesis and excretion of VLDL from liver
- necroinflamamtory changes
what is the most common etiology of chronically elevated LFTs in the US
NAFLD is replacing alcohol and viral hepatitis as the most common etiology
what are the causes of NAFLD
poorly controlled diabetes insulin resistance metabolic syndrome HLD obesity acute starvation post-bariatric surgery medications (amiodaraone, valproate, corticosteroids, calcium channel blockers, salicylates, high-dose estrogen'tamoxifen)
ferritin levels are increased in ____ to ____% of individuals with NAFLD and transferrin saturation is elev in ____ to ____%
20 to 50%
5 to 10%
as the disease progresses from simple steatosis to NASH, what will be present on liver bx?
steatosis inflammation Mallory bodies (eosinophilic cytoplasmic aggregates of protein) glycogen nuclei fibrosis cirrhosis
what is treatment for NAFLD
modification of risk factors to prevent progression
weight loss, dietary modifications
tighter HLD and diabetes control
NASH develops into fibrosis or cirrhosis within ______ years in 10-49% of cases. approx ____% of people die within ten years a a result of cirrhosis
within 5-10. yrs
10-40%
mortality and morbidity risk of people with NAFLD extends beyond cirrhosis/liver failure because they are at increased risk for…
MI
stroke
diabetes
and their complications, because they also more likely suffer from obesity, HLD, insulin resistance, HTN, and/or atherosclerosis
what % of the American population consumes ETOH at least occasionally
75%
what % of alcohol users abuse alcohol or are alcohol dependent
10%
the pathology of alcoholic liver injury comprises 3 major components. what are they?
fatty liver
alcoholic hepatitis (steatohepatitis)
cirrhosis
fatty liver is present in over ____% of binge and chronic drinkers?
90%
a smaller % of heavy drinkers will progress from fatty liver to _________ followed by _________
alcoholic hepatitis followed by cirrhosis
what % of alcoholics will develop alcoholic hepatitis
10 - 20%
what are the 7 risk factors for alcoholic liver disease
- quantity of alcohol consumed
- female gender
- hepatitis C
- genetic variability in alcohol-metabolizing enzymes
- malnutrition
- co-exposure to drugs or toxins
- immunologic dysfunction
is fatty liver reversible if alcohol is stopped?
what about cirrhosis?
fatty liver can be reversed
cirrhosis cannot
what 5 criteria are used to determine a dx of cirrhosis
- pronounced, insufficiently repaired necrosis of the parenchyma
- diffuse connective tissue proliferation
- varying degrees of nodular parenchymal regeneration
- loss and transformation of the lobular structure within the liver as a whole
- impaired intrahepatic and intra-acinar vascular supply
what are the major causes of cirrhosis
alcohol chronic infection (hepatitis B, C, D) cholestasis (biliary cirrhosis) autoimmune hepatitis chemical agents venous congestion (Budd-chiari syndrome) homeochromatosis NASH
with cirrhosis, the structural changes in the liver cause … (Symptoms)
jaundice portal hypertension esophageal varices ascites spontaneous bacterial peritonitis hepatorenal syndrome hepatic encephalopathy coagulopathy
describe jaundice
hyperbilirubinemia
yellowish discoloration of skin, conjunctiva, mucous membranes
what % of people with cirrhosis will develop esophageal varices
50% will develop within 2 years of dx, and 70-80% within 10 years
why is the mortality rate high with vatical bleed
the hemorrhage is typically massive. each episode is life threatening
what % of ascites occurs in the setting of cirrhosis
85% of cases
50% of those with ascites will die within ____ years
2
what are causes of ascites other than alcohol
other liver diseases malignancy heart failure infection pancreatitis
what is portal HTN
abnormally high pressure in the portal circulation
clinically significant portal HTN is present tin ___% of those with cirrhosis
60%
what are the major clinical manifestations of portal HTN
hemorrhage from gastroesophageal varices
splenomegaly with hypersplenism
ascites
acute and chronic hepatic encephalopathy
what is hepatorenal syndrom
development of acute renal failure in individuals with advanced chronic liver disease and fulminant hepatitis, who have portal HTN and ascites
at least 40% of individuals with cirrhosis and ascites will develop HRS within 5 years. what is HRS characterized by?
- marked decrease in GFR and renal plasma flow in the absence of other identifiable causes of renal failure
- marked abnormalities in systemic hemodynamics
- activation of endogenous vasoactive systems
what is hepatic encephalopathy characterized by
disturbances in consciousness and behavior
personality changes
fluctuating neurologic signs
asterisks (“flapping tremor”)
distinctive EEG changes
in severe cases, irreversible coma and death can occur
what is the leading cause of chronic hepatitis cirrhosis, and hepatocellular carcinoma worldwide
hepatitis B
what ranks 2nd (after cirrhosis) as cause of fatal liver disease
metastatic tumor (such as from breast, lung, gastrointestinal, and genitourinary cancers)
what is Wilson’s disease
rare, autosomal recessive inherited disorder of copper metabolism
what does Wilson’s disease affect
liver, brain, kidneys, eyes, joints
what is cholangitis
localized or diffuse inflammatory changes affecting the intrahepatic and extra hepatic bile ducts
what is primary sclerosis cholangitis
chronic cholestatic liver disease of unknown etiology that primary affects young to middle-aged males.
primary sclerosis cholangitis is frequently found in association with _______
inflammatory bowel disease, particularly UC and chron’s colitis.
what is the only effective therapeutic option for end-stage liver disease from PSC
liver transplant
what are the 2 types of biliary cirrhosis
primary - chronic, progressive. unknown etiology possibly autoimmune
secondary - result of prolonged bile duct obstruction, narrowing or closure, most commonly caused by PSC, also by bile duct strictures, tumors, biliary atresia, cystic fibrosis
what is Gaucher’s dsiease
most common lipid storage disease, caused by gene mutation
what are the 3 clinical forms of gaucher’s disease
- type 1- non-neuronopathic, common in Ashkenazi jews
- type 2 - infantile, death within first year of life
- type 3- juvenile or subacute neuronopathic less severe
what is reye’s syndrome
almost exclusively children, usually after viral illness, associated with use of aspirin during the illness
functions of the liver include all of the following EXCEPT:
- storing iron
- destroying damaged WBC
- removing toxin
- synthesizing cholesterol
destroying damaged WBC
All of the following statements the Hepatitis B surface antigen (HBsAg) are correct EXCEPT:
- it is the easiest marker of acute infection
- it measure the viral load
- it appears before onset of symptoms
- it clears by the convalescence stage of infection
it measure the viral load
what are the medical treatments for hep C
interferon alpha and ribavirin
NAFLD can be caused by all of the following EXCEPT
- obesity
- HTN
- metabolic syndrome
- insulin resistance
HTN
what are the primary factors that affect prognosis in hereditary hemochromatosis?
early diagnosis
compliance to treatment
what are the primary causes of death from hereditary hemochromatosis
hepatocelluar carcinoma complications or cirrhosis (liver failure portal HTN, bleeding from esophageal varices) cardiomyopathy CHF, arrhythmias complications of DM bacterial and viral infections
what are the infectious etiologies of hepatitis
viral
bacterial
fungal
parasitic organisms
what are the causes of noninfectious hepatitis
medications
toxins
autoimmune disorders
all hepatitis viruses are RNA viruses except _____ which is a _____ virus
hepatitis B is a DNA virus
what are the two methods of transmission of viral hepatitis
enteric (oral-fecal)
blood-borne
which types of hepatitis are enterically transmitted
HAV and HEV
which types of hepatitis are blood-borne
HBV, HCV, HDV
are blood-borne or enteric ally transmitted hepatitis viruses associated with persistent infection, viremia and chronic liver disease
blood-borne
how is chronic hepatitis defined
persistent infection for at least 6 months
how many people become infected with hep B in the US each year
200,000-300,000
which type of hepatitis is the world leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwode
hep b
approx ____% of the world’s population has chronic HBV infection
5%
how is hep b transmitted
exposure to infectious blood or body fluids
what are the stages of hep b
- incubation period - between 15-180 days, avg 60-90 days
- prodromal stage - lasts from few days up to 2-4 wks, with non-specific symptoms (malaise, myalgia, GI and flu-like symptoms)
- clinical stage - defined by the presence of jaundice (icterus) and hepatomegaly, lab values vary significantly, depending on the degree of severity and course taken, can last 3-6 wks
- convalescence phase- all labs normalize within 4-6 months
describe stages of progression to liver failure (from chronic hep b)
fibrosis -> cirrhosis -> liver failure
what is the earliest marker of acute infection with hep b
HBV surface antigen (HBsAg), appears before onset of symptoms or elevation of LFTs
Should HbsAg clear before the convalescence stage of acute infection?
yes
HBsAg (surface antigen) persistence for more than 6 months indicates progression to ______ or ______
carrier state or chronic HBV
what is HBeAg a marker for
HBV e antigen (HBeAg) is a marker for highly infectious state and active viral replication
should HBeAg clear by the convalescence stage of acute infection?
yes
persistence of HBeAg for more than 10 weeks suggests progression to _____
chronic state
HBV core antibody (HBcAb or anti-HBcAb) indicates exposure to ______ and _____
exposure to HBV and viral replication
which hep b serology test persists for life
HBcAb (HBV core antibody)
HBV surface antibody (HBsAb or anti-HBsAb) represents _____
cure from acute infection and immunity from future infection
which hep b serology test, if present with persistent pos HBsAg, but neg HBeAg, represents chronic carrier state
HBsAb
which two hep b serology tests, if present together, represent immunity as a result of vaccine
HBcAb abd HBsAb
why is HBV DNA, or viral load, useful for
assessment of those with chronic HBV as candidates for antiviral treatment and to track response to treatment
what antiviral agents are currently being used for hepatitis
lamivudine, adenovirus, entecavir, interferon alfa, pegylated interferon alfa
do most infected individuals clear the hepatitis c virus?
no
how do most new HCV infections occur in US
60% in individuals who use IV drugs
<20% through sexual exposure
about how many people are infected with hcv
4 million, with 2.7 million having chronic infection
what are the stages of hep c
- incubation (6-12 wks)
- acute (mild symptoms if any)
- chronic HCV develops in 70-80% of people. symptoms usually absent until substantial scarring of liver occurs
