Case 9: Jay turns yellow

BODY IN HEALTH

 Anatomy/ histology/ innervation/ lymphatic/ blood supply of the liver

o Anatomy: The liver is the second biggest organ of the body, and it extends from the
right hypochondrium to the left hypochondrium. It is split into 4 lobes, on the
anterior surface the falciform ligament (lower free border is the ligamentum teres)
splits the liver into the left and right lobe. The caudate and quadrate lobes are seen
on the posterior surface. The falciform ligament attaches the liver to the anterior
abdominal wall; the coronary ligament attaches the liver to the diaphragm. The
inferior vena cava sits in a fossa on the left posterior surface on the liver, this is the
dividing line between the right lobe and the caudate lobe. The porta hepatis lies
within the hepatoduodenal ligament (thickening of the lesser omentum), just above
the quadrate lobe. The porta hepatis (triad) is the common bile duct, the portal vein
(joining of superior mesenteric vein and splenic vein) and the hepatic proper artery.
All the blood from the GI tract (rich in nutrients digested and absorbed by the GI
tract) comes to the liver (via the portal vein) to be detoxified (by Kupffer cells)
before going into the inferior vena cava. These vessels divide into smaller and
smaller vessels, ending in capillaries. These capillaries end in thousands of lobules of
the liver. Each lobule is composed of hepatocytes, and as blood passes through, they
are able to monitor, add, and remove substances from it. The blood leaves the liver
via the hepatic vein, and returns to the heart (to be oxygenated). The gall bladder
lies in a fossa in the right hepatic lobe.
o Histology:
 The major cell types are the hepatocyte that is an epithelial parenchymal cell. The
sinusoids are spaces in between the hepatocytes filled with mixed blood and
nutrients. The hepatocytes are arranged around a central vein, around the
hepatocyte lobules are triads (bile duct, portal venule, hepatic arteriole).
 Function of liver (regulation of energy, alcohol and drugs e.g. paracetamol, bile
production)
o Removing and excreting body wastes and hormones as well as drugs and foreign
substances: These substances enter the blood supply either through waste products
from metabolic processes or other foreign compounds. Enzymes in the liver alter
some toxins so they can be more easily excreted in the urine
o Synthesizing plasma proteins, including those necessary for blood clotting: most of
the 12 clotting factors are plasma proteins produced by the liver. If the liver is
damaged or diseased, it can take longer for the body to form clots. Other plasma
proteins produced by the liver include albumin which binds many water-insoluble
substances and contributes to osmotic pressure, fibrogen which is key to the clotting
process, and certain globulins which transport substances such as cholesterol and
iron
o Producing bile to aid in digestion: bile salts aid in fat digestion and absorption. Bile is
continuously secreted by the liver and stored in the gallbladder until a meal, when
bile enters the beginning of the small intestine.
o Producing immune factors and removing bacteria, helping the body fight infection:
the phagocytes in the liver produce acute-phase proteins in response to microbes.
These proteins are associated with the inflammation process, tissue-repair, and
immune cell activities
o Excretion of bilirubin: bilirubin is one of the few waste products excreted in bile.
Macrophages in the liver remove worn out red blood cells from the blood. Bilirubin
results from the breakdown of the haemoglobin in the red blood cells and is
excreted into bile by hepatocytes. Jaundice results when bilirubin cannot be
removed from the blood quickly enough
o Storing certain vitamins, minerals and sugars: the liver stores enough glucose in the
form of glycogen to provide a days’ worth of energy. The liver also stores fats, iron,
copper and many vitamins including vitamins A, D, K and B12.
o Processing nutrients absorbed from digestive tract: The liver converts glucose into
glycogen, its storage form. This glycogen can then be transformed back into glucose
if the body needs energy. The fatty acids produced by the digestion of lipids are used
to synthesize cholesterol and other substances. The liver also has the ability to
 convert certain amino acids into others (using enzymes such as aspartate
aminotransferase and alanine aminotransferase)
 Normal concentrations for serum bilirubin, alanine aminotransferase, aspartate
aminotransferase, alkaline phosphatase
o Conjugated bilirubin (in the liver bilirubin is conjugated with glucuronic acid by an
enzyme, making it water-soluble and excretable): less than 5.1 µmol/L
o Total bilirubin: 1.71 – 20.5 µmol/L
o Alanine aminotransferase: 7-56 IU/L
o Aspartate aminotransferase: 10-40 IU/L
o Alkaline phosphatase: 44-147 IU/L
 Overview of the adaptive immune system i.e. antibodies, cytokines, B and T cells

BODY IN DISEASE

 Virology of Hepatitis:
o Hepatitis B is a DNA virus, it replicates within infected liver cells (hepatocytes). The
virus attaches to the hepatocyte membrane and the core particles enter. The core
particles then release its DNA and DNA polymerase into the hepatocyte nucleus.
From within the nucleus the hepatitis B DNA causes the liver cell to produce, surface
hepatitis B antigens, DNA polymerase, Hepatitis Be antigens, and other proteins.
o DNA polymerase causes the liver cell to make copies of hepatitis B DNA. Versions of
the hepatitis B virus are constructed by the liver cell. These copies of the virus are
then released from the liver cell membrane into the blood stream and from there
can infect other liver cells and thus replicate effectively.
 Types of Hepatitis B:
o Acute hepatitis B infection: last less than 6 months (can be symptomatic or
asymptomatic) and the infected person can pass the virus on during this time. The
immune system likely can clear acute hepatitis B from the body; the person should
recover in a few months. Most people who get hepatitis B as adults have an acute
infection, but can lead to chronic infection (10% of people infected with hepatitis B
develop chronic infection)
o Chronic hepatitis B infection: lasts longer than 6 months. It lingers because the
immune system can’t fight off the infection. Chronic hepatitis B infection may last a
lifetime, possibly leading to serious illness such as cirrhosis and liver cancer.
 Causes and symptoms of Hepatitis (B)
o Symptoms usually develop 2-3 months after exposure to the hepatitis B virus. Many
people infected in adulthood will not experience any symptoms and will fight off the
infection without realising they had it.
o Symptoms of hepatitis B can include:
 Tiredness
 General aches and pains
 Fever
 ORAL MANIFESTATIONS: Dry mouth, lichen planus, sialadentitis
 General sense of feeling unwell
 Loss of appetite
  Nausea and vomiting
 Stomach aches
 Jaundice
 Dark urine and pale/grey faeces
o Hepatitis B infection is caused by the hepatitis B virus (HBV). The virus is passed from
person to person through blood, semen or other body fluids
 What is the difference between Hepatitis B and Be antigens?
o Hepatitis B surface antigen (HBsAg) is a protein on the surface of the hepatitis B virus
(HBV); it can be detected in high levels in serum during acute or chronic HBV
infection. The presence of HBsAg indicates that the person is infectious. The body
normally produces antibodies to HBsAg as part of the normal immune response to
infection. HBsAg is the antigen used to make Hepatitis B vaccine.
o Hepatitis Be antigen (HBeAg) a secreted product of the nucleocaspid gene of the
hepatitis B virus that is found in serum during acute and chronic hepatitis B
infection. Its presence indicates that that the virus is replicating and infected person
has high levels of HBV.
 How do symptoms arise (generalised itching, joint pain, and jaundice, darker urine and
paler faeces)?
o Jaundice is associated with newly acquired or acute hepatitis B infection. It is a more
severe symptom of an acute HBV infection. Jaundice is due to an accumulation of
bilirubin, a yellow pigment, in the blood and tissues. The liver is responsible for
controlling the levels of bilirubin.
o If the liver is having problems performing basic, yet essential functions, yellow skin,
eyes, dark urine and itching (pruritus) may all be due to inability to filter excess
bilirubin.
o Rheumatic complications of HCV happen as a result of the body's immune system
fighting the virus. In patients with HCV, because the virus is continually multiplying,
the immune system is continually fighting the virus, resulting in system-wide
inflammation and the joint and muscle complications of HCV.
 How Hepatitis B is transmitted, risk factors, epidemiology?
o Hepatitis B can be spread by:
 A mother to her new-born baby, babies of infected mothers are vaccinated
immediately after birth to help prevent infection
 Injecting drugs and sharing needles and other drug equipment, such as
spoons and filters
 Having sex with an infected person without using a condom
 Having a tattoo, body piercing or medical or dental treatment in an
unhygienic environment with unsterilized equipment
 Having a blood transfusion in a country where blood is not tested for
hepatitis B
 Sharing toothbrushes or razors contaminated with infected blood
 Needle stick injury
 The blood of someone with hepatitis B getting into an open would, cut or
scratch
 o Risk factors include:

 Have unprotected sex with multiple sex partners or with someone who's
infected with HBV

 Share needles during IV drug use

 Are a man who has sex with other men

 Live with someone who has a chronic HBV infection

 Are an infant born to an infected mother

 Have a job that exposes you to human blood

 Travel to regions with high infection rates of HBV, such as Asia, the Pacific
Islands, Africa and Eastern Europe

 What is the significance of the raised enzyme levels?

o ALT and AST are enzymes produced in liver cells that can be detected in the blood
stream. The normal range for ALT is between 0-40. When liver cells are damaged
these enzymes are released and elevated levels are detected in serum. The value of
ALT in the blood stream is generally taken to be an indicator of the damage that
hepatitis causing to liver cells. However damage may be occurring with little or no
elevation of ALT (this is especially true for hepatitis C and people with end
stage liver disease).
 Other common pathologies of the liver
o Hepatits A
o Hepatitis C
o Hepatits D (delta hepatitis, this can only survive in the presence of Hepatitis B virus)
o Hepatitis E (a virus transmitted through the faeces of an infected person)
o Heptatis F +G
o Cryptogenic (caused by a virus as yet unidentified)
o Yellow Fever
o Epstein Barr Virus
o Cytomegalovirus
o Alcohol
o Hemochromatosis
o Wilson’s Disease
 Complications of Hepatitis:
o Scarring of the liver (cirrhosis) – inflammation associated with Hepatitis B infection
can lead to extensive liver scarring, which may further impair the liver’s ability to
function
o Liver cancer – people with chronic hepatitis B infection have an increased risk of liver
cancer
o Liver Failure - Acute liver failure is a condition in which the vital functions of the liver
shut down
o Extrahepatic conditions – kidney disease or rheumatological disorders
PTPC

 Treatment and prevention for Hepatitis B

o Treatment: this depends on how long and severe the infection is:
 Acute hepatitis B does not usually require specific treatment, but may
require treatment to relieve symptoms
 Rest
 Over the counter analgesics (e.g. ibuprofen or paracetamol) to
relieve stomach aches
 Maintain a cool, well ventilated environment, loose clothing avoid
hot baths to relieve the itching
 Medication such as metoclopramide, to stop nausea, and
chlorphenamine to reduce itching (these can be prescribed by
doctor when necessary)
 Chronic hepatitis B is often treated with medication to keep the virus under
control
 Antiviral medication (tenofovir or entecavir): if the liver is not
functioning well, or peginterferon alpha-2a is not suitable or not
working, a doctor may recommend antiviral medication instead
 Peginteferon alpha-2a: if the liver is still functioning fairly well, first
treatment offered is usually peginteferon alpha-2a. This stimulates
the immune system to attach the hepatitis B virus and regain control
over it. It’s usually injected once a week for 48-weeks
o Prevention: vaccination for those who may come into contact with those hepatitis
(men who have sex with men, babies of mothers with hepatitis, healthcare
providers, people planning to travel to areas with high hepatitis B infection rates),
using disposable or highly sterilised instruments (that may be use to handle bodily
fluids)
 Any contraindications of Hepatitis B medications with dental work
o Drugs to avoid
 Tetracyclines, erythromycin, aminoglycosides, metronidazole, NSAIDs
 What is the role of the British Liver trust?
o They are a registered charity funded by donations. They: support patients and
families living with liver disease, campaign to improve awareness, fund research into
liver disease and lobby for improved services for patients, support health care
professionals to deliver high standards of care and support
 How do virological tests work?
 Long term management of living with Hepatitis B
 What procedures are in place for dentists to protect themselves against Hepatitis B?
o Cross infection control measures:
 Masks, gloves, barriers (rubber dam when necessary), correct sterilisation
protocols, disinfection of all surfaces (virus can live outside of the body for a
week)
o Immunisation with Hepatitis B vaccination
o Consultation with patients doctor on what they can and can’t have (drug-wise)