Liver Disease, Cirrhosis & Hepatic neoplasms Flashcards
There are two main types of Liver Abscesses
○ Pyogenic Hepatic Abscess
○ Amebic Hepatic Abscess
____ means “involving the formation
of pus.” Amebic abscesses are technically
not “pus”-filled, but rather filled with
necrotic debris
“Pyogenic”
T/F Immunocompromise is a significant risk factor for both types of hepatic abcesses
T
Pyogenic abcesses epidemiology
most commonly occur in patients at
least 50-60 years of age, but
can occur at any age.
■ Diabetes and Hepatobiliary
disease are risk factors
Amebic Hepatic Abscess epidemiology
most common in tropical climates
and in areas with poor sanitation.
■ Most often seen in young
males (7-12 times higher)
Pathophysiology of pyogenic abcesses
○ Bacteria invade the liver by:
■ Ascending the bile ducts (Ascending Cholangitis)
OR
■ Spread from the GI tract via the Portal Vein
● Often following peritonitis
Most common pathogens causing pyogenic abcesses
E coli, Klebsiella pneumoniae
Pathophysiology - Amebic abscesses
Amebic abscesses are caused by Entamoeba histolytica after ingestion of a
cyst in contaminated water or food.
○ Trophozoites reach the liver through the portal system.
○ They replicate in hepatic cells and can
lead to a collection of “anchovy-like”
fluid comprised of necrotic tissue.
Hepatic Abscesses S/S & differentiating the two types
○ Pain in the right upper quadrant or epigastric region
○ Jaundice is commonly present as well
○ Hepatomegaly and tenderness over the liver are common but not always present
Pyogenic abscesses
○ Fever is usually present
Amebic abscesses
○ Initially, most patients are asymptomatic,
but then progress to abdominal pain and
fever
○ Often a history of recent/current diarrhea
and may have traveled to an endemic area
Diagnosis - Hepatic Abscesses
○ Leukocytosis (about 75%) and elevated ALT and AST common.
○ Ultrasound is the recommended initial diagnostic imaging study
○ CT and MRI can be used in gaining a more detailed view.
Specific diagnostic testing for pyogenic abscesses
Blood cultures are positive
in 50-100% of Pyogenic
abscess cases.
Specific diagnostic testing for amebic abscesses
○ Serology tests for Entamoeba Histolytica antibodies confirms the diagnosis of amebic abscess. (if neg. and concerned, recheck 1 week!!!)
○ Stool O&P testing reveals ameba in
about 1/4 of these patients
Treatment - Pyogenic abscesses
● Metronidazole + Duel Antibiotic combo*
● Antibiotics continue for at least 2-3
weeks.
● Drainage is performed, via percutaneous
or endoscopic ultrasound-guided needle
aspirations. This is used for treatment as
well as determining pathogens
Treatment - Amebic abscesses
● Amebic abscesses: Metronidazole
+/- a luminal agent is treatment of
choice
Signs of Chronic Liver Disease
● Portal Hypertension
● Caput Medusae
● Esophageal Varices
● Ascites: Increased hydrostatic pressure & Decreased oncotic pressure
● Coagulopathy
● Thrombocytopenia –> splenomegaly
● Hypoalbuminemia
● Hyperbilirubinemia→Jaundice
● Spider Angioma
Serum ascites albumin gradient (SAAG) =
serum albumin level - ascitic fluid albumin level
■ Greater than 1.1 g/dL (meaning low albumin in the ascitic fluid) indicates
likely portal hypertension (97%) (transudative process).
↑Hydrostatic Pressure:
Fluid is pushed out of the vessels = proteins aren’t expelled
↓ Oncotic Pressure:
Lower albumin levels in the blood → water expelled to increase relative serum albumin
Hepatic Encephalopathy
Hepatic encephalopathy is a syndrome
sometimes observed in patients with
cirrhosis, characterized by acute
personality changes, intellectual
impairment, neuromuscular changes,
and decreased level of consciousness.
Etiology of hepatic encephalopathy
● This is caused by multiple mechanisms, but elevated Ammonia levels are believed to be the most common cause.
○ Ammonia is normally broken down & metabolized by themliver, so elevated levels of the toxin can occur with cirrhosis.
● It is believed that Ammonia alters the permeability of the BBB, allowing
neurotoxins to enter and causing neurologic malfunction.
Hepatic Encephalopathy is generally treated with _____
Lactulose, which pulls
Ammonia into the lumen of the intestine and helps to excrete the toxin
through the feces. Lactulose is a laxative and initiates diarrhea
____ is a physical exam finding that can
be present in several different forms of
metabolic encephalopathy, including
Hepatic Encephalopathy.
Asterixis
○ Patient should have arms extend
outright, with palms out and fingers to
the ceiling. Will be unable to keep hands
still, with “flapping tremor.”
Spontaneous Bacterial Peritonitis
● SBP is a significant complication of liver disease where the ascitic fluid becomes spontaneously infected with a bacterial pathogen.
● Most of the time, the source of the bacteria is not identifiable and the development is unexpected
and spontaneous.
● Most common presentation is acute abdominal pain and fever in a patient with ascites.
Spontaneous Bacterial Peritonitis Tx
● Emergent diagnostic paracentesis is required so that a peritoneal fluid analysis and culture can be performed.
An _____ in the ascitic fluid is the best predictor of Spontaneous Bacterial Peritonitis
elevated neutrophil count
_____ is defined as iron overload
Hemochromatosis
Hemochromatosis
● Hereditary Hemochromatosis is caused by a genetic changes that leads to the accumulation of iron in vital organs, and iron toxicity.
● A decreased expression or activity of Hepcidin, the principal iron regulatory releasing hormone, which normally inhibits iron absorption by enterocytes of the
gut
● Ultimately, the disease results in increased iron absorption from the duodenum → Iron overload
Hemochromatosis - pathophysiology
○ Hemochromatosis is characterized by increased accumulation of iron, in
the form of Hemosiderin, in the liver, pancreas, heart, adrenal glands,
testicles, pituitary, and kidneys.
○ Cirrhosis often develops as the iron causes liver cell death and fibrosis.
S/S hemochromatosis
○ Symptoms often do not develop until around 40 in males, postmenopause in women (50’s).
○ Early symptoms include fatigue and arthralgias.
○ Later symptoms include severe arthropathy, hepatomegaly, hepatic
dysfunction, and skin hyperpigmentation or “Bronze skin”.
○ Once liver failure begins, all the signs and symptoms of cirrhosis are possible, including the complications.
Dx of Hemochromatosis
■ Mild to moderately elevated Liver Enzymes
■ Elevated plasma iron: Usually >50% Transferrin saturation
○ Testing for HFE (called Homeostatic Iron Regulator) protein mutation is indicated for any patient with evidence of Iron overload, and will be diagnostic.
○ Liver biopsy to assess for cirrhosis, iron deposition
Management of hemochromatosis
○ The ultimate goal of treatment is to remove iron stores before the
overload leads to irreversible organ damage.
○ Frequent phlebotomy is the first-line treatment of Hemochromatosis-related iron overload.
○ Joints often need surgically replaced and liver transplant is often needed for cirrhosis that was not prevented by phlebotomy.
Wilson’s Disease
(hepatolenticular degeneration)
● Rare autosomal recessive disorder
● It usually manifests before the age of 35.
● There are over 300 different genetic mutations of the Wilson gene on
Chromosome 13 that can lead to the disease
Wilsons disease pathophysiology
○ The genetic mutation causes a defect in
the copper transporter ATP7B.
○ This results in the accumulation of copper
throughout the body, and especially in the
liver, due to the inability to fully clear the
copper from the blood.
○ The disease is characterized by excessive absorption of copper from the small intestine and decreased excretion of copper by the liver
Wilson’s Disease - S/S
○ Tends to present as liver disease and/or neuropsychiatric disease in young
adults, most commonly under the age of 35 years.
○ Neurologic manifestations are related to copper deposition in the basal ganglia
and can appear similar to Parkinsonism, often preceded by personality changes
or new behavioral concerns.
● Signs and Symptoms- Kayser-Fleischer Rings
What is this called and what is it found with?
Kayser-Fleischer Rings found with wilson’s disease
Wilson’s Disease Diagnosis
○ Serum ceruloplasmin levels are low in 90% of Wilson’s patients.
○ Urinary copper excretion is greater than 100 mcg/d in 24 hours.
○ Brain MRI may reveal increased signal in the
basal ganglia or midbrain on certain
sequences.
Management of wilson’s disease
○ The mainstay of treatment is lifelong use
of chelating agents (making water soluble)
○ Otherwise, treatment is focused on optimizing liver function and treating the complications that arise if cirrhosis has developed.
Liver Cirrhosis
Cirrhosis is the 9th leading causes of death in the US and is the end result of
chronic, repeated, or severe hepatocellular injury
Liver Cirrhosis - epidemiology
○ Fatty Liver Disease is becoming more common.
○ Alcohol is one of the strongest risk factors for cirrhosis
Liver Cirrhosis - Pathophysiology
○ Chronic inflammation and disease of the liver ultimately leads to hepatocellular death.
○ The hepatocellular injury leads to
intercellular fibrosis and atrophy of
the liver.
○ In some cases, nodular
regeneration occurs, resulting in a
nodular, shrunken liver.
Liver Cirrhosis S/S
○ May remain asymptomatic for years,
although most have symptoms from the
causative disease
○ Symptoms can include: Fatigue, weakness,
insomnia, muscle cramps, weight loss,
anorexia, nausea/vomiting, decreased libido.
Liver Cirrhosis Diagnosis
○ Lab studies are often minimally abnormal until late in cirrhosis.
○ Previously elevated AST and ALT may normalize or even become low as
Cirrhosis develops
○ Ultrasound, CT, and/or MRI can be used to
evaluate the size of the liver
● A liver biopsy is often performed to confirm various diagnosis.
What will a Liver Biopsy show in cirrhosis?
● The histologic appearance in cirrhosis is that of fibrosis and nodules.
○ Findings that identify the underlying cause may not be present.
○ Alternatively, the biopsy could be diagnostic for underlying causes
of cirrhosis, like alcoholic liver disease, NASH, etc.
When is liver biopsy unsafe?
○ Because of the high risk of bleeding, liver
biopsy is not safe if the INR is greater than
1.6 or if the platelet count is under 60,000.
Management of liver cirrhosis
○ Abstinence from alcohol is a key component of treatment.
○ Otherwise, treatment is generally focused on complications as they
arise, such as treating ascites and hepatic encephalopathy.
○ A low salt diet
○ Liver transplant is curative if your patient qualifies.
■ MELD scoring
MELD Score
● MELD = Model for End-Stage Liver Disease
○ A well-developed scoring system used to assess the severity of chronic liver disease.
○ MELD-Na includes Sodium into calculation and is more specific
● This evidence-based scoring system has proven useful for determining
prognosis and prioritizing for receipt of a liver transplant.
● Using a complex logarithmic formula, it uses the patient’s dialysis status,
serum Bilirubin, serum Creatinine, INR and Na to predict survival.
Hepatocellular Carcinoma (HCC)
● HCC is a malignant neoplasm that arises
from the parenchymal cells of the liver.
● It is very important to remember that
metastatic tumors to the liver are by far the
most common hepatic neoplasms, but HCC
is the aggressive primary hepatic neoplasm
80% of all HCCs are associated with ____
Cirrhosis
Hepatocellular Carcinoma epidemiology
○ Because of its link to Chronic Hepatitis C, HCC represents one of the
fastest growing cause of cancer deaths in the US.
○ The incidence of HCC is expected to increase dramatically in the coming
decades secondary to the dramatic increase in NAFLD and NASH.
Hepatocellular Carcinoma - pathyphysiology
○ The exact pathophysiology or pathogenicity of HCC has not been
definitively determined.
■ It is clearly a multifactorial event and occurs after extensive
hepatic damage and disease.
S/S Hepatocellular carcinoma
○ Symptoms from the HCC generally develop later when the patient
suddenly begins to deteriorate clinically.
■ Example: Cachexia, weakness, and sudden weight loss in a cirrhotic
patient that was previously stable.
○ Any time a cirrhotic patient (remember-usually a small, atrophic liver)
develops an enlarging, potentially tender liver, it is HCC until proven
otherwise.
■ Rapidly expanding abdominal mass is possible
Dx of hepatocellular carcinoma
○ Sudden and sustained elevation in serum Alkaline Phosphatase in a
patient that was previously stable is a common lab finding.
○ Alpha-Fetoprotein levels are elevated in
70% of HCC. (AFP is not liver specific)
○ CT and MRI are the preferred
imaging studies- reveal a mass.
○ Liver Biopsy is diagnostic, although
seeding by needle is a concern.
Hepatocellular Carcinoma management
○ Overall, transplantation remains the best
option for patients with HCC.
○ 1-year survival rate is 23% and 5-year survival rate is 5%
