Hepatobilary system Flashcards
1
Q
Hepatitis: What are the causes of hepatitis? (infectious and non infectious)
A
infectious:
- viral - most common
- bacterial
- fungal
- parasitic
non infectious
- alcohol
- drugs
- autoimmune
- metabolic diseases
2
Q
Hepatitis: What are the signs and symptoms of hepatitis?
A
Malaise
Jaundice - elevation of bile in the blood causes
Dark urine
Pale fatty stools
Serum & urine biochemistry, specific serological tests for HepA, B, C, D & E antibodies for viral hepatitis
3
Q
Hepatitis: What is the structure of a virus?
A
Consist of a strand of nucleic acid, either DNA or RNA, surrounded by a protective protein coat (the capsid).
Sometimes they have a further membrane of lipid, referred to as an envelope, surrounding the protein.
4
Q
Hepatitis: What is a complete virus called?
A
vision
5
Q
Hepatitis: What are the major hepatitis viruses?
A
- do we have to know this, ask
6
Q
Hepatitis: What is hepatitis A?
A
- RNA, belongs to group
Picornavirus - Genotypes I - VII.
- Four associated with human disease I-III & VII; most being I (80%) & III
Jejunum-blood-liver, bile faeces
2- week incubation followed
by 4-10 day prodrome. Resolves in few weeks
Vaccine – formalin-killed virus
7
Q
Hepatitis: What is the epidemiology of hepatitis A?
A
1.5 million cases worldwide; 6-7000 cases reported p.a. in UK
Children (3-5 years) often asymptomatic
Important in spread
- severity increases with age
8
Q
Hepatitis: Which antibody is produced the first time a host is exposed to an antigen?
A
IgM
IgM will eventually decline, and then the host produces IgG, which lasts much longer
9
Q
Hepatitis: Which antibody do you get in a secondary infection?
A
igG
Detection of IgM indicates acute or primary infection, IgG indicates past infection or immunity.
10
Q
Hepatitis: In which phase is hepatitis A infective?
A
Asymptomatic phase
11
Q
Hepatitis:What is chronic persistent hepatitis B?
A
Healthy carriers - can spread but no symptoms
12
Q
Hepatitis: What is a Dane particle?
A
The whole outer vision (capsule) which is infective of the hep b virus
13
Q
Hepatitis: What is HBE antigen used for?
A
Detect hep B infection
14
Q
Hepatitis: What does the surface antigen split off to form in hep B?
A
The tubular and spherical forms
15
Q
Hepatitis: What 4 genes are encoded by the hep B genome?
A
C, X, P, S
core protein - gene C
Dna polymerase - gene P
surface antigen - gene S
Gene x - regulatory?
16
Q
Hepatitis: how can enzymes be used to determine whether liver cells are abnormal?
A
Liver cells happen to have lots of AST, ALT, and GGTP inside them. When cells die or are sick the enzymes leak out causing the blood level of these enzymes to rise, which is a way of determining if the cells in question are sick.
17
Q
Hepatitis: What is laboratory diagnosis of hep B focused on?
A
detection of the hepatitis B surface antigen HBsAg
18
Q
Hepatitis: What antigen is also seen in the initial phase of hep b infection?
A
hbeag
19
Q
Hepatitis: What is high levels of hbeag an indication of?
A
HBeAg is usually a marker of high levels of replication of the virus.
The presence of HBeAg indicates that the blood and body fluids of the infected individual are highly contagious.
20
Q
Hepatitis: What is chronic infection of hep b characterised by?
A
persistence of HBsAg for at least 6 months (with or without concurrent HBeAg). Persistence of HBsAg is the principal marker of risk for developing chronic liver disease and liver cancer (hepatocellular carcinoma) later in life.
21
Q
Hepatitis: What is the epidemiology of hep b?
A
UK carriage approx. 0.1%
Carriage in Africa and Asia approx. 5%
Transmission; vertical, parenteral, sexual
>108 HBV/ml; 0.000001-0.00001ml blood;
Infection early in life > increased chance of chronicity
10% of chronic infection progress to chronic liver disease
Vaccine – genetically engineered HBsAg
22
Q
Hepatitis:What is hep D caused by?
A
a ‘defective’ RNA virus which coexists with HBV
23
Q
Hepatitis: What are the features of hep D?
A
Very small virus
Outer coat derived from HBsAg – cannot survive without HBV.
~5% HBV carriers are HDV positive.
24
Q
Hepatitis: What is the delta antigen of hep D used for?
A
Used for diagnosis
25
Hepatitis: What hepatitis virus can only occur with HBV?
Hep D
Infection co-incident with HBV
- HDV influenced by replication of HBV
- rarely progressive or chronic
Superinfection on HBV disease
- ideal for rapid HDV replication
- commonly chronic
15 million HDV cases worldwide
- mainly iv drug users in UK
26
Hepatitis:What are the viral features of hep C?
Small enveloped SSRNA virus
Core of genetic material (RNA), surrounded by an icosahedral capsid
Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope - help it to attach to host cells of liver
27
Hepatitis: How is hep c released?
by budding
28
Hepatitis: What is hep c a member of? ( a family)
flaviviruses
29
Hepatitis: What is the epidemiology of HCV?
180 million carriers worldwide
- 5 million in Western Europe
- UK carriage ~0.08% (~40,000)
Transmission
- IV drug abuse needle sticks, tattoos, ear piercing
- -80% iv drug users infected
- Previously
- -blood products, haemodialysis, transplantation
minor routes - saliva; sexual; vertical
30
Hepatitis: Why is diagnosis of HCV unreliable?
antibody takes 6wk-6mnth to show up in blood) – 97% by 6mnth
31
Hepatitis: what is the treatment for HCV?
interferon a (interferes with replication) + Ribavirin (stimulates T cells to attack the virus)
32
Hepatitis: Why is there no vaccine for HCV?
Cure rate is dependent on the genotype, treatment history and presence of liver damage
re-infection can occur with the same type - lack of neutralising antibody
33
Hepatitis: Which types of HCV are the most common in the UK?
Types 1a and 1b
34
Hepatitis: What type of virus is hep E?
Rna hepevirus - 4 genotypes
35
Hepatitis: How is hep E spread?
Faecal-oral spread
36
Hepatitis: What is the average incubation period for hep E?
6 weeks
37
liver disease pathology: What is the most common cause of a lack of liver available to process things?
cirrhosis - end stage liver disease
38
liver disease pathology: What is the general mechanism of cirrhosis?
Damage to liver cells
inflammation to liver cells
mostly the cells regenerate
other pathway - healing by fibrosis
leading to cirrhosis
39
liver disease pathology: What are the causes of cirrhosis?
Anything that damages the liver and it is unable to recover
Hepatitis viruses - B, C, D, E
40
liver disease pathology: What are the consequences of cirrhosis?
jaundice
portal hypertension
ascites - abnormal buildup of fluid in the abdomen and increases BP due to low albumin production (water potential)
Heptocellular cancer - due to increased cell turnover during repair of the liver
41
liver disease pathology: What can block the outflow of bile from the liver?
Gall stones
42
GI pathology 1: What cellular changes occur in Barett's oesophagus?
turns from squamous into glandular mucosa (columnar lined lower oesophagus = Barett's) = metaplasia
43
GI pathology 1: What is metaplasia?
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
44
GI pathology 1: What is the stomach lined by?
Glandular epithelium with layer of mucin for acid buffering
45
GI pathology 1: What happens in Barrett's oesophagus?
Reflux of acid into oesophagus, squamous cells cannot adapt so die - left with acellular gap that causes pain
so squamous changes into glandular with mucin on top - protects against acid reflux
eventually producing dysplastic (pre cancerous) glandular epithelium
then neoplastic glandular epithelium
46
GI pathology 1: What are the differences in risk factors for squamous cell carcinoma and adenocarcinoma (oesophageal)
Squamous - alcohol and smoking
Adeno - obesity
47
GI pathology 1: Why are survival rates of oesophageal cancer not good?
Presents late
48
GI pathology 1: How does helicobacter gastritis occur?
helicobacter lives in the stomach mucin
attracting neutrophils from the capillaries which damage the lining cells
get ulcerations from the acid contacting
burning sensations in the stomach/ heartburn
49
GI pathology 1: What are the causes of gastric cancer?
Smoked foods
| pickled foods?
50
GI pathology 1: What cellular changes occur from HP, pernicious anaemia, smoked/pickled food diet?
Normal mucosa
intestinal metaplasia
genetic change causes dysplasia
genetic change causes intramucosal carcinoma
genetic change causes invasive carcinoma
51
GI pathology 1: What is gluten sensitive enteropathy coeliac disease?
Lack of villi/ atrophied villi reducing SA
crypt hyperplasia
hundreds of lymphocytes
allergic reaction to gluten in the blood
52
GI pathology 1: What is the mechanism of coeliac disease?
Immune reaction to gliadin protein in gluten
gliadin absorbed by gliadin peptide
another enzyme (TG) causes it to attach to HLA (antigen presenting cell) - causing toxic T cells to be produced and cause injury
53
GI pathology II: What is Crohn's disease?
produces aphthous ulcers
patchy inflammation/ulcers all the way through the gut
can get scarring in the bower's after long term - cobble stoned mucosa
drugs control inflammation well
most complications in the bowel
e.g. malabsorption, obstruction, perforation, fistula formation
54
GI pathology II: What is ulcerative colitis?
Only affects colon not mouth
not patchy inflammation - continuous inflammation
idiopathic
55
GI pathology II: What are the complications of ulcerative colitis?
Colon - blood loss, toxic dilation, some risk of cancer
joints - ankylosing spondylitis, arthiritis
eyes - iritis, uveitis, episcleritis
skin - erythema nodosum, pyoderma gangrenosum
liver - fatty change, chronic pericholangitis, sclerosing cholangitis
56
GI pathology II: What is diverticular disease?
outpouchings in the sigmoid colon into the fat layer - punched out
taking out colon often cures
too much pressure when squeezing from inside of the bowel probably due to a low fibre diet pushes mucosa out - can get infection
faeces out into the peritoneal cavity - can die from it - peritonitis
treated by high fibre diet
57
GI pathology II: What is happening to the incidence and mortality rates of colorectal cancer?
incidence increasing but mortality decreasing as treating earlier
58
GI pathology II: What is familial adenomatous polyposis?
normal colon but get thousands of adenomas in teens and early adult hood - polyps
get cancer in 20's - 30's
APC gene is the problem gene
59
GI pathology II: What are the cellular changes of colorectal cancer?
normal epithelium
adenoma
colorectoral adenocarcinoma
60
GI pathology II: What is the cellular mechanism of familial adenomatous polyposis?
APC gene bound to GSK
when beta catenin rise - binds to it and take sit away to be broken down - prevents getting high
mutation - no APC or faulty APC
beta catenin rises, can't remove this
moves through membrane and binds to the DNA - causes epithelial proliferation and causes adenoma
61
GI pathology II: What is hereditary nonpolyposis colorectal cancer? HNPCC
born with a mutation in one of the repair genes
then another mutation occurs during life time
2 hit system
get tumours elsewhere more often and don't respond as well to treatment
62
GI pathology II: What is resection coding?
R0 - tumour completely excised locally
• R1 - microscopic involvement of margin by tumour
• R2 - macroscopic involvement of margin by tumour
63
GI pathology II: What are the Dukes' stages and prognosis?
```
Dukes’ stage and prognosis
A - 95% 5 year survival
B - 75% 5 year survival
C - 35% 5 year survival
D - 25% 5 year survival
```
64
GI pathology II: What are the cellular stages of colorectal cancer?
prevention - low dose aspirin?
normal epithelium
endoscopic resection
adenoma
surgical resection
colorectal adenocarcinoma
chemotherapy palliative care
metastatic colorectal adenocarcinoma
65
Liver and Gall bladder disease: What does bile do?
helps emulsify fat
| changes pH into alkaline
66
Liver and Gall bladder disease: What are the functions of the liver?
Detoxification: Filters & cleans blood of waste products (drugs, hormones)
Immune functions: Fights infections and diseases (RE system)
Involved in Synthesis of clotting factors, proteins, enzymes, glycogen and fats (advanced cirrhosis patients go from having glycogen to being starved very quickly)
Production of bile & breakdown of bilirubin
Energy storage (glycogen and fats)
Regulation of fat metabolism
Ability to regenerate
67
Liver and Gall bladder disease: What is the metabolic role of the liver?
The liver maintains a continuous supply of energy for the body by controlling the metabolism of CHO and fats.
Its role varies during:
Fasting, absorption, digestion & metabolism
Multiple pathways
The liver is regulated by:
Endocrine glands eg pancreas, adrenal, thyroid
Nerves
68
Liver and Gall bladder disease: What are the types of liver disease?
acute vs chronic
acute - recovery
causes - viral, drugs, vascular e.g. clot
chronic - cirrhosis to liver failured
causes - alcohol, viral B/C, autoimmune, vascular metabolic
69
Liver and Gall bladder disease: How may acute liver injury present?
Asymptomatic
abnormal LFTs &coagulopathy
Malaise, nausea, anorexia
Jaundice
Confusion – think ALF !
Bleeding
Liver pain
70
Liver and Gall bladder disease: How may chronic liver injury present?
abnormal LFTs
hepatomegaly,
malaise, abdo discomfort
itching
```
Ascites, oedema
Haematemesis (varices)
Easy bruising (coagulopathy)
Jaundice
Confusion
Anorexia, wasting
```
71
Liver and Gall bladder disease: What are the serum liver function tests?
```
Albumin - tells you if liver is working
ALP – Alkaline phosphatase
GGT – gamma GT
ALT – Alanine Aminotransferase
AST – Aspartate Aminotransferase
Bilirubin - tells you if liver is working
Globulin
```
72
Liver and Gall bladder disease: What is jaundice due to?
High bilirubin (breakdown product of hmg)
73
Liver and Gall bladder disease: What are the causes of jaundice?
Pre-hepatic
- Haemolysis (increased substrate)
```
Hepatic (intrinsic liver disease)
- Cirrhosis
- Infiltration of the liver by tumours
- Acute hepatitis
(viral, alcoholic, autoimmune, drug-induced)
```
Post-hepatic (obstruction of biliary outflow)
- Gallstones
- External compression: pancreatitis, lymphadeno-pathy, pancreatic tumour, ampullary tumour
74
Liver and Gall bladder disease: What are the causes of chronic liver disease?
Most common
NAFLD & NASH
Alcohol
Viral hepatitis (B, C)
Less common
Auto-immune
- autoimmune hepatitis
- primary biliary cirrhosis
- Primary sclerosing cholangitis
Metabolic
- Haemochromatosis
- Wilson’s - overload of copper
- alpha1 antitrypsin deficiency…
Vascular
- Budd-Chiari
- Portal vein thrombosis
Drugs
- Amiodarone
- Chemotherpay
75
Liver and Gall bladde disease: What are the risk factors for non alcoholic fatty liver disease?
diabetes, obesity, hypertension, dyslipidaemia = metabolic syndrome
76
Liver and Gall bladder disease: What are the stages of fatty liver disease?
Fatty liver - deposits of fat cause enlargement
Liver fibrosis - scar tissue forms
Cirrhosis - growth of connective tissue destroys liver cells
77
Liver and Gall bladder disease: Compare and contrast hep B and hep C
```
Hepatitis B
DNA Virus
Reads in hepatocyte genome
Persists in liver even if no in longer in blood
Can reactivate
Mainly transmitted via intercourse/vertically
Early infection: chronicity
Vaccination available
Longterm treatment
```
```
Hepatitis C
RNA virus
Mainly transmitted through IVDA; needles blood products
Once cleared = cleared
Reinfection possible – no immunity
Time limited treatment
well tolerated, 90 % cure
No vaccination
```
78
Liver and Gall bladder disease: What are the stages of chronic liver disease?
```
NCPH = non-cirrhotic portal hypertension
Often due to vascular problems in the liver
Tolerating bleeding well and clotting generally intact;
Relatively rare (patients generally aware)
```
Pre-cirrhotic
No effect on dental work
May be asymptomatic
Liver cirrhosis
Compensated & decompensated
79
Liver and Gall bladder disease: what is the difference between compensated and decompensated liver cirrhosis?
Compensated
Invisible
Blood can be normal
Risk low
Decompensated
Visible
Abnormal blood tests
Risks high
80
Liver and Gall bladder disease: What is the prognosis of cirrhsis worsened by?
Malnutrition
Variceal bleeding
Infection (SBP)
Renal failure
81
Liver and Gall bladder disease: What are the complications in chronic liver disease?
Acute:
- GI bleeding Portal
- Ascites hypertension
- Jaundice
- Hepatic Encephalopathy
- Renal impairment
- Coagulopathy
- Infection
Chronic:
- Malnutrition
- Bone disease
82
Liver and Gall bladder disease: What are the signs and symptoms of chronic liver disease?
```
Palmer erythema
Spider naevi
Gynaecomastia
Leuconychia
Clubbing
Jaundice
Ascites
hepatic encephalopathy
```
83
Liver and Gall bladder disease: How do you recognise HE?
Confusion
Altered behaviour
Coma
Collateral history
```
How test for HE
Serial 7s: 100 - 93 – 86 – 79 – 72 – 65
“baby hippopotamus”
5-star drawing
Number connection test
Ammonia level (>50) – poor correlation
```
84
Liver and Gall bladder disease: How do you treat liver disease?
Symptomatic - Diuretics
Nutrition support
Supplements
Propranolol
```
Specific
Antiviral
Immunosuppression
Relieving obstruction
Venesection
```
85
Liver and Gall bladder disease: What are the dental considerations in liver diseasE?
Comprehensive medical and dental histories
Appropriate laboratory investigations
Full blood count (FBC)
Prothrombin Time (PT)
LFTs (and U&Es)
Consultation with and/or to referral to physician(s) prior to dental treatment
Minimization of soft tissue trauma during dental procedures
Consideration of hospital setting for advanced surgical procedures or severely coagulopathic patients
Potential for increased bleeding in patients with liver disease
Coagulopathy
Thrombocytopenia
Be aware of infection risks and consider extra precautions if higher risk of injury (double gloves)
Hep B vaccination
Caution should be used in prescribing medications that are metabolized in the liver and/or impair haemostasis
- Anaesthetics - Local (amides) and General (halothane) - anaethetist
- Antiplatelet (aspirin) stop 7 days before dental surgery/extraction
- Increased DILI with Flucloxacillin and Co-Amoxyclav
- Sedatives (long-acting benzodiazepines, barbiturates)
Potential for increased drug toxicity in patients with advanced liver disease
- Caution should be used in prescribing medications metabolized in the liver
- AVOID NSAIDs
- Paracetamol – safest pain killer in liver disease
- Opiates – slow and low
