Diseases of the Hepatobiliary System Flashcards
Anatomy of the liver
The liver, which weighs 1200-1500 g in the average adult, is divided into 2 main lobes, the right and the left lobes.
The liver has a dual blood supply, deriving blood from the hepatic artery (ex the celiac artery) (gives oxygenated blood from the heart) and from the portal vein (gives deoxygenated blood from the GI tract)
Bile leaves the liver via the right and left hepatic ducts which join to form the common hepatic duct; this then becomes known as the common bile duct (CBD) after it is joined by the cystic duct, which drains the gallbladder. The CBD is joined by the pancreatic duct just before it enters the duodenum at the ampulla of Vater; the ampulla is guarded by the sphincter of Oddi.
Even if the cystic duct is blocked, bile can still enter the gallbladder via small tiny ducts
Histology of the liver
The liver is divided into hexagonal lobules.
- At the centre of each lobule is the central vein aka terminal venule which joins the hepatic veins.
- At the periphery (corner) of the lobules are the portal tracts, each of which contains a branch of the hepatic artery (in red, brings oxygenated blood), portal vein (in blue, deoxygenated blood from GI tract) and bile duct (empties out of the liver).
The lobules comprise the parenchyma of the liver and consist of anastamosing sheets or cords of liver cells (hepatocytes).
- Between these cords are vascular sinusoids.
Arterial and venous blood enters the liver via the hepatic artery and portal veins, flows through the sinusoids during which it washes over the hepatocytes, and then exits through the central veins into the hepatic veins and vena cava.
At each portal tract, there is blood going in, and bile going out
- blood trickles between hepatocytes to reach the central vein
- bile goes in the opposite direction. It is secreted by hepatocytes and travels outwards towards the portal tract where it drains at the biliary system (bile duct)
Liver functions
- Metabolic
- The liver plays a role in both glucose and lipid physiology.
- Excess blood glucose is stored in the liver as glycogen.
- Glucose is released into the blood through glycogenolysis
- through gluconeogenesis, the liver produces glucose from amino acids.
- During fasting, the liver converts free fatty acids to triglycerides which are secreted in the form of lipoproteins. - Synthetic
- With the exception of immunoglobulins, most serum proteins (such as albumin, clotting factors, complement, iron and copper binding proteins) are synthesized in the liver. - Storage
- The liver is an important storage site for glycogen, triglycerides, iron, copper and lipid- soluble vitamins. - Catabolic
- Endogenous substances such as hormones and serum proteins are catabolized by the liver to maintain a balance in their level
- Exogenous substances such as drugs are also catabolized by the liver. - Excretory
- The main excretory product is bile which is important for fat absorption in the small intestine.
THE COMMON HEPATOTROPIC VIRUSES
Viral hepatitis is inflammation of the liver caused by viruses
- these viruses can be those that exert their sole effect on the liver, OR viruses that produce liver damage as part of systemic infection, in which the liver is only one of several organs/systems affected e.g. cytomegalovirus or Epstein Barr virus.
Hepatitis A, B, C, D
Hepatitis A
Hepatitis A typically causes mild or asymptomatic hepatitis.
The virus is spread by the fecal-oral route (person-person or via contaminated food or water).
Epidemics are quite common, and there is a high rate of infection with oro-anal sexual practices.
Serology is used in diagnosis — anti-HAV IgM is indicative of current infection, while anti-HAV IgG is indicative of past infection.
In those with symptoms, the illness is usually mild and self-limited, although protracted or relapsing hepatitis can occur on occasion.
Very few patients develop fulminant hepatitis, and chronic hepatitis does NOT occur (or is extremely rare).
There is no carrier state.
- (A carrier is an asymptomatic individual who harbors – and can therefore transmit – a virus but may not have clinical disease; a carrier may also have asymptomatic chronic hepatitis.)
Hepatitis B
Hepatitis B infection is a major world-wide problem
- an estimated 2 billion people have been infected
- 400 million people have chronic infection worldwide. (75% of these are in SEA)
- The carrier rate is particularly high (~20%) in South- East Asia.
- It is estimated that there are 300,000 new cases/year in the U.S. and 3,000/year in Canada.
In infected persons, HBV is present in all body fluids except feces; spread occurs by parenteral routes and close contact, including sexual activity.
- Transplacental (vertical) spread also occurs.
30-40% of people get acute hepatitis
- the rest don’t get symptoms
Rate of chronic hepatitis or cirrhosis is 5-10%
Blood and body fluid borne disease
- high conc in blood, serum, and wound exudates
- moderate conc in semen, vaginal fluid, and saliva
- low conc in urine, sweat, tears and breastmilk
Spread if by parenteral, close contact, sexual, and vertical
At risk are recipients of blood transfusions and blood products, IV drug abusers, health care workers (including dentists), and those on hemodialysis or who practise oro-anal sex.
A variety of serum antigens and antibodies occur in hepatitis B infection making serology useful in diagnosis.
- The various antigens and antibodies appear in the serum in a specific order, and therefore can be useful to assess a patient’s stage of disease as well as prognosis.
- For example, HBSAg (surface antigen) is the first marker to appear in the blood, followed by HBEAg (E antigen), HBCAb (core antibody), HBEAb (E antibody) and HBSAb (surface antibody).
- The presence and timing of serum markers may provide important clinical information, e.g. persistence in the blood of HBSAg or HBEAg for longer that 6 months or 4 months respectively implies that the disease has become chronic.
- HBSAb is an antibody that “normally” persists for life and confers protection to HBV for life; it is the basis for the vaccine.
- HBSAg indicates active infection
Hepatitis B has low conc in breastmilk
Histologically
- hepatocyte with fluffy pink cytoplasm is smooth appearance and is called groundglass hepatocyte means that the hepatocyte is infected with hepatitis B
Outcome of infection with HBV
Subclinical disease with clearing of the virus and complete recovery (most individuals, approx. 65%)
Acute hepatitis (approx. 25%)
- 99% recover
- 1% develop fulminant hepatitis resulting in death or transplant
Chronic hepatitis (5-10%)
- approx. 1% of these recover
- approx. 20% develop cirrhosis
- 2-3% develop hepatocellular carcinoma
Asymptomatic carrier state (5-10%)
Hepatocellular carcinoma (HCC) (risk is increased 200X over the general population).
Hepatitis C
This virus accounts for the majority (80-90%) of parenterally transmitted, post-transfusion and sporadic hepatitis in the general population.
It is a major problem in Canada with about 5,000 new cases reported per year and a total of approximately 240,000 infected persons.
Transmission is similar to hepatitis B.
- Of all patients with hepatitis C, approximately 5-10% have a history of blood transfusion; most of the remainder will have acquired the virus from some form of parenteral transmission.
- The commonest source of hepatitis C is in populations engaged in IV drug abuse and related practices.
- Needle stick transmission is less “efficient” than HBV
As with hepatitis B, most patients have subclinical disease and a small number have an acute, self-limiting disease.
- few have acute hepatitis
- Fulminant hepatitis is rare.
- Of those infected, the majority (80%) will develop chronic hepatitis; progression usually takes many years, measured in decades.
- The carrier state is also more common than with hepatitis B (80%).
Cirrhosis occurs in approx. 20% of patients with chronic hepatitis.
There is an increased risk of HCC (200X). (Hepatocellular carcinoma)
Serological diagnosis is made via the presence of anti-HCV antibodies or using PCR to detect viral RNA.
Treatment options include the use of interferon and related drugs. There is NO vaccine.
Hepatitis D
This virus is an important modifier of both acute and chronic hepatitis B.
HDV is a DEFECTIVE virus that can only replicate in the presence of HBV.
Can take the form of acute or chronic hepatitis
The virus is transmitted parenterally or intravenously
The clinical presentation depends on whether the virus was acquired concurrently with hepatitis B (co-infection) or after (super- infection), and can take the form of acute or chronic hepatitis.
CIRRHOSIS
Cirrhosis is an end stage in the evolution of many chronic liver diseases including viral hepatitis.
It is a DIFFUSE process in which there is deposition of fibrous tissue (FIBROSIS) and conversion of the normal architecture into REGENERATIVE NODULES.
CIRRHOSIS - Etiology
What can cause cell death?
Infections - HBV, HCV, schistosomiasis
Drugs & toxins - alcohol, methotrexate, amiodorone, etc.
Metabolic – NAFLD/NASH, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, etc.
Autoimmune - primary biliary cirrhosis etc.
Biliary obstruction - calculi, sclerosing cholangitis etc.
Cardiovascular disease (Vascular) - veno-occlusive disease, Budd-Chiari syndrome, right heart failure (cardiac cirrhosis) etc.
Miscellaneous - neonatal hepatitis syndromes, etc.
Cryptogenic
CIRRHOSIS - Pathogenesis
3 major mechanisms common to all etiological causes combine to create cirrhosis - cell death, fibrosis and regeneration.
- Cell death is usually the initiating factor and has to occur continuously over a long period of time to induce cirrhosis.
- There are many causes of cell death including, amongst other factors, alcohol and drugs. - Fibrosis is a repair mechanism that follows cell death, although fibrogenesis can probably be initiated directly without the intervention of cell death and inflammation.
- Regeneration completes the reparative process.
- Regeneration is influenced by a variety of hormones, including insulin and glucagon, by cytokines and by polypeptide growth factors.
CIRRHOSIS - Complications
There are several adverse consequences of cirrhosis; these include mechanical effects with abnormal shunting of blood, and functional effects, with failure to perform normal physiological functions of the liver.
Abnormal blood flow:
- This leads to portal hypertension with secondary dilation of veins at the base of the esophagus (esophageal varices)
- these varices can rupture leading to hematemesis.
- Portal hypertension also causes splenomegaly and ascites.
Parenchymal insufficiency:
- This manifests with impaired protein synthesis, inadequate deactivation of drugs and hormones, jaundice, clotting abnormalities and hepatic encephalopathy.
- decreased liver function results in bleeding when it fails to make clotting factors
- Hepatocellular carcinoma can occur as a late complication.
ALCOHOLIC LIVER DISEASE
Alcohol is one of many toxins that can adversely affect the liver.
There are 3 major forms of alcoholic liver disease - steatosis (fatty change) due to deranged lipid metabolism, alcoholic hepatitis and cirrhosis:
- Steatosis - the earliest manifestation of alcoholic liver injury, usually disappears 2-4 weeks after abstinence. It is typically macrovesicular. It means fat in the liver
- histologically: pink hepatocytes with purple nuclei, big white fat droplet circles within the cytoplasm of hepatocytes. no inflammation - Alcoholic hepatitis (steatohepatitis) - a form of hepatitis with a triad of steatosis, inflammation and the presence of Mallory bodies in liver cells (liver cell damage). It is elevated liver enzymes
- histologically: hepatocytes with fat droplets. Small pruple dots are inflammatory cells, meaning there is inflammation. Mallory denk body is dark plump pink material, indicates hepatocyte damage caused by fat - Cirrhosis - most often due to alcohol abuse in the Western world and caused by persistent hepatitis.
- histologically: CT stain where fibrosis is blue. In alcoholic or fatty liver diseases, there is a pattern of fibrosis called Perry Cellular Fibrosis where the fibrosis instead of just forming large bands around nodules of hepatocytes, the fibrosis will form fine fibrous strands around individual hepatocyes; looks like chicken wire
Steatosis alone is associated with few symptoms or signs of liver disease, whereas patients with hepatitis have non-specific symptoms with elevated aminotransferases, alkaline phosphatase and jaundice. Hepatocellular carcinoma develops in 5-15% of patients with alcoholic cirrhosis; alcohol may act as a promoter or co-carcinogen related to induction of microsomal enzymes.
How much alcohol causes liver disease?
Short term ingestion of 80 g alcohol (8 beers) leads to mild, reversible changes e.g. steatosis
Chronic ingestion of 80-160 g/day produces a borderline risk for severe injury
Chronic daily ingestion of >160 g/day x 10-20 years has a more consistent association with severe injury
10-15% of alcoholics develop cirrhosis
Fatty liver disease
Fatty liver is the most common liver abnormality in North America and up to 25% of the population are affected.
Fatty liver disease is considered to be the hepatic expression of the metabolic syndrome. Its increase in prevalence has occurred in association with increasing OBESITY rates.
Metabolic syndrome is a cluster of metabolic abnormalities that are risk factors for CV disease
- it is the association of insulin resistance with truncal obesity, diabetes mellitus, dyslipidemia and systemic hypertension
The 2 main morphologic types of non-alcoholic fatty liver disease (NAFLD) are…
1. NAFL (non-alcoholic fatty liver)
- steatosis without hepatocellular injury
2. NASH (non-alcoholic steatohepatitis)
- steatosis with inflammation and hepatocellular injury with or without fibrosis
NAFL and NASH are the #1 cause of liver disease in Western countries
NAFL and NASH are the most common cause of elevated liver enzymes and possibly the most common reason for liver transplant
Not all patients with NAFL progress to NASH and cirrhosis (estimated 10-20% will progress).
- But 15-25% of patients with NASH will progress to cirrhosis.
- The risk of cirrhosis is increased if other liver disease is also present (e.g., HCV).
