Hepatisis Flashcards
What is the functional unit of the liver an dhow does this relate to blood flow/hepatitis
Lobule!
Blood enters from the triads, exits from the central vein
Most blood flows into the liver via the portal vein, which collects bloood from the entire GI tract
Remaining blood is oxygenated blood supplied by portal artery (20%)
These vessels continue to bifurcate—> small venues and arterioles ultimately terminating in the sinusoids which are small blood vessels with fenestrated endothelium (ie there are holes) that are lined by hepatocytes
These terminate in the central vein, from which the blood exits. A lobule has a central vein in the center, around which like spokes of a wheel are the portal traits. Each triad has a branch of the portal vein, a branch of the hepatic artery, and a small bile duct (triad)
Blood enters in the triad, flows through the sinusoids to the central vein, then exits the liver
Hepatocellular necrosis around the portal triad, where inflammation occurs not usually infectious because lots of things cause inflammation in the liver
What is hepatitis
Hepatic inflammation/injury
Hepatic cell necrosis (cell death)
May be acute or chronic; diverse etiologies;
- bacterial, fungal, parasitic infections
- immune disorders
- metabolic diseases
- lack of perfusion/oxygenation
- toxic injury (medications, toxins, herbals, alcohol)
- viral infections
Inflammation is around the portal triads
Many things can cause hepatitis, most not due to viral infection
Viral hepatitis
Numerous viruses can infect the liver
However the term viral hepatitis is reserved for those viruses that target the liver specifically - they are hepatotropic
Hepatitis viruses are lettered sequentially:
- Hepatitis A
- Hepatitis B
- Hepatitis C
- hepatitis D
- hep E
- non A/ nonB - old term used for viral hepatitis of unknown origin
While all hepatitis viruses cause hepatitis, the viruses themselves are quite differnet. The severity of their symptoms can vary in frequency and severity
Acute Hepatitis -symptoms
Frequency nad severity varies with virus
Mechanism is the same: immune-mediated damage to infected hepatocytes
Less specific sx—> more specific sx
Fever fatigue malaise nausea vomiting—> abdominal pain—> right upper quadrant abdominal pain—> hepatomegaly—> jaundice (icteric phase) with dark urine, pale stools, puritus (itchy skin), sclera icterus
Fulminant hepatitis- massive hepatic necrosis leading to death a rare outcome
- HEV causes this most commonly, followed by HAV and less frequently by HBV and HCV
NB hep A, B and C all cause an acute illness characterized by nausea, malaise, jaundice. Symptoms dont distinguish these viruses nor do they tell you that the hepatitis is due to a virus infection eg alcoholic cirrhosis is very common
Jaundice
Yellow discoloration of the skin, sclera, and mucus membranes
Sclera icterus (white of the eyes are yellow)
Due to systemic retention of pigmented bilirubin in tissues
Puriritus-itchy skin
You need to know about bilirubin because you can measure it - an important lab test
Bilirubin - breakdown product of hemoglobin
Conjugated = direct
Unconjugated = indirect
Total bilirubin = direct + indirect
Bilirubin not soluble; binds to albumin aand is transported to the liver
Conjugation occurs in liver, improves solubility
Erythrocytes are destroyed by macrophages in the spleen and bone marrow releasing hemoglobin which is degraded to heme; the globin is metabolized to its constituent amino acids while heme is converted into unconjugated bilirubin in macrophages of the spleen and bone marrow, bound to plasma albumin and transported to the liver
In the liver it is conjugated with glucuronic acid making it water soluble for excretion in the bile
Conjugated is most hepatic causes
Also hemolytic anemia, EHEC, malaria etc
Bilirubin metabolism and elimination
Jaundice can result from increased production, decreased excretion or both
Pre hepatic causes (mostly unconjugated bilirubin, indirect)
- increased bilirubin production (hemolytic anemia’s)
- reduced hepatocellular uptake (drugs interferences with transport systems)
- impaired conjugation (diffuse hepatocellular disease, hepatitis)
Post hepatic causes
(Mostly conjugated bilirubin, direct)
Decreased hepatocellular excretion - Dublin Johnson syndrome
Impaired bile flow
- biliary obstruction
More than one mechanism can operate to produce jaundice
Normally unconjugated bilirubin contributes more to the total serum bilirubin than the conjugated form since the later is produced n the liver and secreted into the bile
In addition to impaired bilirubin metabolism, death of hepatocytes releases various enzymes
Serum level of these enzymes (called Liver Function Tests) reflects the severity of disease
Follow LFTs over time to monitor disease progress
- ALT (alanine aminotransferase): more specific for liver abnormalities than other enzyme tests, high ALT suggests viral rather than alcohol hepatitis
- AST (aspartate aminotransferase): less specific, since AST present in muscle and other tissues, this is a mitochondrial enzyme also present in heart, muscle, kidney and brain and so is less specific for liver disease, in many cases of liver inflammation the ALT and AST activities are elevated in a 1:1 ratio
- AP (alkaline phosphatase): again less specific, but is indicative of bile cut injury, liver and non liver related disease elevated
- GT (gamma glutamate transpeptidase: often elevated in those who use alcohol or other liver toxic substances to excess
Chronic Hepatitis - symptoms
See image of cirrhosis end stage liver slide 13
If acute infection isnt cleared, patient may develop chronic hepatitis
Caused only by hep B and C with variable frequency
Can be
- asymptomatic (chronic p ersistent hepatitis)
- symptomatic (chronic active hepatitis; CAH)
Can lead to bad outcomes:
- cirrhosis (refers to the way the liver scars due to damage)
- hepatocellular carcinoma (malignant cancer, often induced by hepB or C but never A
Cirrhosis Liver
13 + 14
Bridging fibrosis in core biopsy
- fibrous bands connecting portal triads
As liver becomes cirrhosis it shrinks in size, externally it appears modular and is quite firm to the touch
- shrunken, micronodular, firm to touch
As it becomes cirrhosis, it becomes more difficult to pump blood through it—> elevated portal pressures
Liver cirrhosis- bridging fibrosis (bands of births scar tissue that connect the portal triads
Major cause of cirrhosis are chronic alcohol abuse, hep C, hep B
Cirrhosis
Rigid non compliant liver results in portal hypertension
Resulting symptoms just follow the anatomy —> increased venous pressure throughout leads to fluid transduction (ascites)
Increased pressure in the portal system: things back up - spleen enlarged, pressure in the venous system is increased and as a result fluid leaks out due to hydrostatic pressure giving rise to ASCITES (fluid in abdominal space)
Other outcomes ar hemorrhoids a nd esophageal varies - engorged veins in the lower esophagus, which if torn can lead to massive and life threatening blood loss since there is nothing to stop the bleeding
Classic presentation of cirrhosis
Patient who vomits copious amounts of bright red blood (suggests upper GI tract bleed and this is a medical emergency)
Cirrhosis also has metabolic consequences
Causes portal hypertension (—> varices, large spleen etc and ascites) and hepatic insufficiency (—> jaundice and hepatic encephalopathy)
Decreased clotting factors: coagulopathy
Decreased glycogen storage: hypoglycemia
Increased ammonia: hepatic encephalopathy (liver is not detoxifying blood insufficiently, you get high ammonia levels)
Hepatitis A virus
RNA picornavirus
- small
- RNA positive strand
- single serotype worldwide
- nonenveloped - quite stable outside the body
- acute disease and asymptomatic infection ONLY! No chronicity
- no cytopathic; symptoms result from immune-mediated destruction of virus infected cells, typical acute infection lifestyle
Spread by fecal oral route only and is acid stable; causes acute infections; infection confers life long immunity; there is a vaccine; infection is usuallly symptomatic, usually self-limited. Damage to the liver is from the immune response
Hep A virus pathogenesis
Enters bloodstream through oropharynx, replicates in GI tract then viremia spreads to liver
Virus produced and released into bile, and then shed into stool for about 10 days before symptoms appear
HAV replicates slowly in liver and is not cytopathic
Liver pathology due to immune response directed against virus-infected cells
Hep A virus: epidemiology
Affects 1.4 million worldwide annually
Common cause of acute haptitis
Enteric transmission
- spread person to person via fecal oral route
- acquired from contaminated food and water
- stable in fresh and salt water for long periods: shellfish common source- contaminated water; as filter feeders they concentrate the virus
Infection confers immunity
HAV outbreaks usually originate from a point source (daycare center, water supply, restaurant)
Spreads readily - infected people are contagious before they are symptomatic
Get HAV vaccine before traveling
HAV infection rates have decreased in the US by > 90% in recent years
Due to vaccine1!!
Since children are normally asymptomatic they play an important role in the sprea dof community outbreaks where virus is spread between close contacts
Now most outbreaks are associated with contaminated food
Mechanisms of food borne spread of HAV
1) clean food may be contained by a food handler who is incubating HAV
2) food may be contaminated at its source, eg shellfish harvested from waters contaminated with sewage or crops irrigated with contaminated water
Maternal-fetal Transmission and parenteral Transmission through blood transfusions are NOT major risk factors for HAV transmission (but HBV and HCV are)
Recent HAV outbreaks
Frozen strawberries in Virginia
Frozen scallops from the Philippines—> HAV outbreaks in several stages including sushi chain
Hep A virus; clinical sx
Acute self-limited- no chronic infection, no association with cancer; > 80% adults symptomatic
Symptoms occur abruptly 15-50 days post exposure, intensify for 4 - 6 days before icteric (jaundice phase)
- incubation is around 1 month and a duration of around 1 month
Infection usually asymptomatic in children
Hepatomegaly in 80%
Jaundice 70% adults, 15% children
Less common = splenomegaly, rash
Fulminant hepatitis rare 1 - 3 per 100
Hep A virus Diagnosis
Clinical symptoms/signs, their timing and identification of aknown infected source
Lab findings:
- increase in LFTs/bilirubin
Detect: serum HAV igM
- enzyme immunoassay
- 100% with acute HAV
- remain + for 3 - 6 months
IgG antibodies
- early in convalescence
- prior exposure to HAV (or vaccine)
- remain detectable for decades, 85% of individuals who are infected with HAV have a full clinical and biochemical recovery within 3 months, and all by 6
IgM is gold standard for diagnosing acute infection
HAV Treatment/control
Treatment: supportive since HAV is self limited
Full recovery within 3 months most common
Maintenance of sanitary conditions
- handwashing, cooked foods, avoid impure water
HAV vaccine
- two inactivated HAV vaccines available
- indications: travel, chronic liver disease
- recommended for children as routine immunization
HBV
Genome covered by the core antigen (HBcAg) which is surrounded by a lipid envelope and the surface Ag (HBsAg)
- HBsAg can assemble into subviral particles, not infectious but more common than virus in the blood of infected people
Another viral protein, called E antigen (HbeAg) is secreted from infected cells and can be detected in patient sera
HBsAg forms the basis of the vaccine that you have received
HBV has a partially dsDNA genome
- makes new DNA from viral RNA by using reverse transcriptase
