Liver, biliary and pancreatic disease Flashcards
1
Q
Which strain of Ecoli is thought to be the most severe form? (Produces shigatoxin)
A
EO157
2
Q
An isolated rise in serum bilirubin with otherwise normal liver biochemistry is likely to be due to what?
A
Inherited defect in bilirubin metabolism - Gilbert’s disease
Haemolysis
Ineffective erythropoiesis
3
Q
What is the overall cause of high aminotransferases (AST, ALT)?
A
Liver cell damage e.g. acute hepatitis
4
Q
What can high levels of AST (aspartate aminotransferase) be seen in other than liver injury?
A
Myocardial infarction/ skeletal muscle damage. Is present in both heart and skeletal muscle as well as liver
5
Q
Which aminotransferase is a more specific measure of injury to the liver (ALT/AST)?
A
ALT
6
Q
Raised serum concentrations of alkaline phosphatase is seen in what?
A
Cholestasis (bile flow impaired)
Can also be increased in pregnancy, osteomalacia and growing children (as is also derived from placenta and bone)
7
Q
Gamma-GT serum concentration rises in what?
A
Alcohol abuse
Cholestasis (in parallel with alkaline phosphatase)
8
Q
Why may a prolonged prothrombin time occur in biliary obstruction?
A
Low concentration of bile salts (emulsify) results in poor absorption of vitamin K, which is essential - key in synthesising blood clotting factors inc. prothrombin
9
Q
What are the 4 main functions of the liver?
A
- Glucose and fat metabolism
- Detoxification and excretion
- Protein synthesis (albumin, clotting factors)
- Defence against infection (R-E system)
10
Q
Name some causes of acute liver failure
A
Viruses (A, B, EBV), drugs, alcohol, vascular, obstruction, congestion
11
Q
Name some causes of chronic liver failure
A
Alcohol, virus (B,C), autoimmune, metabolic (iron, copper)
12
Q
What is the term given to iron overload, and when is it most commonly seen?
A
Haemachromatosis
Seen in those with regular blood transfusions. Iron chelation is required
13
Q
How does acute liver injury present?
A
Malaise, nausea, anorexia, jaundice
14
Q
How does chronic liver injury present?
A
Ascites, oedema, haematemesis, melaena (varices), malaise, anorexia, wasting, easy bruising, itching, hepatomegaly, abnormal LFT’s
15
Q
What serum LFT’s give a relatively good index of liver function?
A
Serum bilirubin, serum albumin, prothrombin time
16
Q
What enzyme in the liver conjugates bilirubin?
A
Glucuronyl transferase
17
Q
What is Gilbert’s disease, and what causes it?
A
Congenital hyperbilirubinaemia, due to reduced glucuronyl transferase and therefore reduced conjugation of bilirubin –> High levels of unconjugated bilirubin build up. Often is asyptomatic but can appear jaundiced
18
Q
What type of jaundice is seen in haemolysis, and how would LFT’s appear?
A
Unconjugated bilirubin causes. All LFT’s would be normal other than increased unconjugated bilirubin
19
Q
How do the clinical symptoms differ in unconjugated jaundice and conjugated jaundice.
A
Unconjugated - jaundice, normal LFT
Conjugated - pale stool, dark urine, may itch (pruritis), abnormal LFT
20
Q
Give some causes of hepatic jaundice?
A
Hepatitis (viral, drug, immune, alcohol), ischaemia, neoplasm, CCF
21
Q
Give some causes of post hepatic jaundice?
A
Gallstones in bile duct, Mirizzi syndrome, stricture of CBD (malignant, ischaemic, inflammatory), blocked stent
22
Q
What is Mirizzi’s syndrome?
A
Gallstone becomes embedded in cystic duct or neck of gallbladder and compresses CBD or hepatic duct
23
Q
What are the two types of gallstone and how are they formed?
A
a) Cholesterol (70%) - cholesterol is held in solution by bile salts. So if excess cholesterol or reduced bile salt, they are formed
b) Pigment (30%) - consist of bilirubin polymers so are seen in chronic haemolysis and cirrhosis
24
Q
What are the risk factors for gallbladder formation?
A
Fat, female, fertile
25
What is the management for a gallstone in both the gallbladder and bile duct if symptomatic?
Gall bladder = Laproscopic cholecystectomy
| Bile duct = ERCP (endoscopic retrograde cholangio-pancreatography)
26
What is the main cause for acute liver failure?
Drug induced liver injury (DILI)
27
Drugs that are the possible cause of liver injury?
Antibiotics, CNS drugs, immunosuppressants, analgesics, GI drugs, dietary supplement
28
What enzyme in the body converts the reactive toxic paracetamol intermediate to a stable metabolite?
Glutathione transferase
29
What drug is used to increase the availability of glutathione transferase in a paracetamol overdose?
N-acetyl-cysteine (NAC)
30
What factors indicate a poor prognosis in paracetamol overdose and potential requirement for transplant?
1. Late presentation (over 24 hours)
2. Acidosis
3. Prothrombin time > 70 sec
4. Serum creatinine >=300mmol/l
31
What is melaena and what causes it?
Black tar like faeces associated with upper gastrointestinal bleeding
32
What is the most common cause of ascites?
Chronic liver disease (cirrhosis)
33
What is ascites?
Build up of fluid in peritoneal cavity
34
Outline pathogenesis of ascites
Nitric oxides from liver damage (cirrhosis) cause peripheral arterial vasodilation. Sympathetic nervous system, and renin angiotensin system try to compensate for this and increase secretion of NA, as well as aldosterone and vasopressin. Salt and water retention.
The resulting oedema is localised in the peritoneal cavity due to the portal hypertension caused by the cirrhosis. Low serum albumin also contributes
35
What is the management for ascites?
1. Diuretics - begin spironolactone and move to furosemide. Must be careful to not remove too much fluid too quickly as transfer of fluid from ascitic to vascular compartment only 700ml/day. If do too fast will get hypokalaemia and encephalopathy
2. Paracentesis
36
Give 3 causes of portal hypertension?
1. Cirrhosis
2. Fibrosis
3. Portal thrombosis
37
What are the consequences of portal hypertension?
Increased hepatic resistance and therefore increased splanchic blood flow means that varices form (oesophageal or gastric) and splenomegaly may occur
38
What are the main sites of infection for liver patients?
SBP (ascites), septicaemia, pneumonia, skin (cellulitis), UTI
39
Cirrhotic patient with ascites BP and sats start to fall, general malaise. What test would be done, and what is the significance of this test being positive?
Diagnostic aspiration. Neutrophil count of 250 or over suggests spontaneous bacterial peritonitis and empirical antibiotic therapy given
40
What bacteria is the most common cause of SBP?
E.coli
41
Name 4 key consequences of liver dysfunction
1. Malnutrition
2. Coagulopathy - vitamin K deficiency
3. Endocrine changes (gynaecomastia, impotence, amenorrhoea)
4. Hypoglycaemia
42
What are the main causes of chronic liver disease?
1. Alcohol
2. NAFLD (Non alcoholic steatohepatitis)
3. Viral (B,C)
4. Autoimmune
5. Metabolic
6. Vascular
43
What is NASH commonly associated with?
Obesity, type 2 diabetes, hypertension, hyperlipidaemia
44
Autoimmune hepatitis is commonly seen in what patients?
Young and middle aged women
45
How will a patient with autoimmune hepatitis present?
Chronic liver disease signs: Palmar erythema, spider naevi, hepatosplenomegaly and jaundice
or anorexia, malaise, nausea and fatigue.
40% will present with acute hepatitis
46
What is the treatment for a patient with autoimmune hepatitis?
Prednisolone +- azathioprine
47
AMA (anti mitochondrial antibody) will be increased in?
Primary biliary cirrhosis and other autoimmune liver conditions (AIH, sclerosing cholangitis)
48
Name 3 autoimmune causes of chronic liver disease.
1. Autoimmune hepatitis
2. Primary biliary cirrhosis
3. Sclerosing cholangitis
49
What does ASMA stand for and what is it raised in?
Anti-smooth muscle antibody
Raised in autoimmune condition
50
How does primary biliary cirrhosis present?
1. Asymptomatic lab abnormalities
2. Itching +- fatigue
3. Variceal bleeding
4. Possibly dry eyes and joint pain
51
How do varices occur and what are they?
Cirrhosis leads to portal hypertension in the liver, and the rerouting of blood through small vessels in oesophagus and stomach. These vessels may become large and swollen.
52
What is the safest analgesic to prescribe in liver disease and why?
Paracetamol
NSAIDs cause renal failure and these patients are very sensitive to opiates
53
What drugs are capable of causing renal failure in liver disease?
NSAIDS, ACE inhibitors, diuretics, aminoglycosides
54
What are the main causes of renal failure in liver disease?
Drugs, infection, GI bleeding, myoglobinuria, renal tract obstruction
55
What is the cause of hepatic encephalopathy?
Build up of 'toxic' substances including ammonia. Bypass the liver via collaterals and gaining access to the brain.
Ammonia is produced by the breakdown of dietary protein by gut bacteria
56
What are the most common precipitating factors of hepatic encephalopathy?
1. Infection
2. GI bleed
3. Constipation
4. Hypokalaemia
5. Drug (sedative/analgesic)
57
Main cause of coma in patients with liver disease?
Hepatic encephalopathy. Also, hyponatraemia and hypogylcaemia
58
What is the basic management of a patient with hepatic encephalopathy?
1. Treat underlying cause
2. Laxatives - lactulose. Decreases colonic pH and reduces absorption of ammonia
3. Antibiotics reduce number of bowel organisms
4. Initially protein restricted
59
When taking a history of a patient with suspected chronic liver disease, what would you cover in the history?
1. PMH - alcohol problems, biliary surgery, autoimmune disease, blood products
2. Social - sexual, alcohol
3. Drug history
4. Family history
60
What is a normal prothrombin time?
12-16s
61
What is a normal value for ALP?
39-117
62
Normal values for ALT and AST?
ALT - 5-40U/L
| AST- 12-40U/L
63
What are main types of hepatitis?
1. Viral (A,B,C,CMV,EBV)
2. Drug-induced
3. Autoimmune
4. Alcoholic
64
How is disease severity in hepatitis measured (2 factors)?
Prothrombin time and serum bilirubin
65
What are the pathological features of hepatitis?
1. Liver cell necrosis
| 2. Inflammatory cell infiltration
66
How long must there be sustained inflammatory disease of the liver for it to be classed as chronic hepatitis?
6 months
67
How does a patient with acute hepatitis often present?
- Jaundiced
- Enlarged liver
- Raised ALT (hepatocellular damage)
68
What is steatosis and why does it occur? How would laboratory tests appear?
'Fatty liver' - macrovesicular droplets of triglyceride in hepatocytes.
Regular alcohol use for a few weeks onwards causes this.
Laboratory tests appear normal other than raised gamma-GT and elevated MCV
69
What is the cardinal sign of alcoholic hepatitis?
Rapid onset of jaundice
Other signs and symptoms: Nausea, anorexia, RUQ pain, encephalopathy, fever, ascites and tender hepatomegaly
70
Histological appearance of hepatocytes in alcoholic hepatitis?
- Steatosis
- Contain amorphous eosinophilic material (Mallory bodies) surrounded by neutrophils
- May be fibrosis and foamy degeneration of hepatocytes
71
What would an increased serum creatinine mean for a patient with alcoholic hepatitis?
Ominous - may predict development of hepatorenal syndrome
72
How would you expect AST and ALT levels in alcoholic hepatitis to present?
Both elevated but disproportionate rise is AST (AST:ALT >2)
73
Will platelet count be high or low in alcoholic hepatitis?
Low - thrombocytopenia due to bone marrow hypoplasia and or hypersplenism due to portal hypertension
74
What test and investigation would be done in suspected biliary obstruction
1. US
| 2. ALP
75
How would you treat hepatitis (v.vague)?
Steroids (e.g. prednisolone)
76
If AMA and ASMA +ve, ALP high but AST and ALT normal, as well as albumin and bilirubin levels being normal, what is the most likely diagnosis?
Primary biliary cirrhosis or primary sclerosing cholangitis
77
Primary biliary cirrhosis affects who?
Mainly women 40-50 age group
78
What causes PBC?
Progressive destruction of intrahepatic bile ducts causing cholestasis and leading to cirrhosis
Individuals are genetically susceptible but thought that the disease expression results from environmental trigger (possibly infective)
79
What is the single most common presenting complaint in primary biliary cholangitis?
Pruritis with or without jaundice
80
How will liver biochem appear in primary biliary cirrhosis?
Often normal other than raised ALP, gamma GT and raised serum AMA/ASMA
81
What does the Mayo Clinic prognostic score use to predict survival in non transplanted patients with PBC?
1. Serum albumin
2. Serum bilirubin
3. Prothrombin time
82
PBC is linked to other autoimmune disorders such as?
Sjogren's syndrome, scleroderma, RA
83
What is Sjogren's syndrome?
Autoimmune disease whereby body attacks glands that secrete fluid so get dry eyes and mouth
Often seen in PBC
84
3 treatments of cholestatic itch?
1. Rifampicin (antibiotic)
2. Opiate antagonist
3. UV light
85
What is primary sclerosing cholangitis?
Chronic cholestatic liver disease characterized by progressive obliterating fibrosis of intra and extrahepatic ducts leading to cirrhosis
86
What is the cause of primary sclerosing cholangitis?
Unknown
87
Patients with primary sclerosing cholangitis often (75%) have what disease also?
Ulcerative colitis (may be asymptomatic)
88
How does a patient with PSC present (including LFTs)?
Jaundice, itching, pain (+- rigors)
ALP and gamma GT will be raised
89
What is the treatment of a patient with primary biliary cirrhosis or primary sclerosing cholangitis?
Ursodeoxycholic acid (unclear benefits in PSC) and transplant in PSC
90
What condition in around 1/10 will lead to cholangiocarcinoma?
Primary sclerosing cholangitis
91
What is haemachromatosis?
Autosomal recessive genetic disorder by which there is uncontrolled intestinal iron absorption in upper small intestine with deposition in liver, heart, pancreas.
Eventually leads to fibrosis
92
What are the two missense gene mutations that lead to haemochromatosis ?
C282Y and H63D (on HFE gene)
93
How is haemochromatosis diagnosed?
- Raised serum ferritin (>500ug/L) and transferrin saturation . Serum iron also elevated
- Confirmed by HFE genotyping and liver biopsy (serum ferritin >1000)
94
If cirrhosis is present in a patient with haemochromatosis, what does it increase the risk of?
Hepatocellular carcinoma
95
What is the management of a patient with haemochromatosis?
Venesection (500ml of blood removed twice weekly until iron stores normalised) can take up to 2 years
96
What is the main cause of hepatocellular carcinoma?
Cirrhosis
97
What patients are at increased risk of hepatocellular carcinoma?
1 HIGH Hepatitis B,C and haemochromatosis
| 2. LOWER cirrhosis from alcohol or autoimmune disease
98
How does hepatocellular carcinoma present?
Decompensation of liver disease, weight loss, ascites, abdominal pain
99
What marker do 50% of patients with hepatocellular carcinoma produce?
Alpha-fetoprotein
100
What are the risk factors for non alcoholic fatty liver disease?
Obesity, hyperllipidaemia, diabetes, hypertension
101
What is the treatment for NAFLD?
Treatment of risk factors and transplantation for end stage disease
102
How does alpha-1 antitrypsin deficiency lead to cirrhosis?
2% of ppn carry Z allele for gene which means can't export alpha-1 antitrypsin from the liver. Protein retention n the liver can lead to liver disease and lack of in the blood leads to emphysema due to the lack of regulation of proteases in the lung
103
What is Wilson's disease and what does it lead to?
Metabolic autosomal recessive disorder by which there is decreased secretion of copper into the biliary system so copper accumulates in the liver leading to fulminant hepatic failure and cirrhosis, parkinsonism (basal ganglia deposition), cornea (Kaiser-Fleischer rings) deposition and in the renal tubules.
104
How is Wilson's disease diagnosed and treated?
Diagnosed - low serum copper, increased 24 hour urinary excretion of copper, increased copper of liver biopsy
Treatment - penicillamine, trientine (chelate) or zinc to reduce copper absorption
105
What is a transjugular intrahepatic portosystemic shunt usually used for?
Creates a shunt between portal vein and hepatic vein, to treat portal hypertension which frequently causes ascites, and stomach or oesophageal varices.
Can also be used in Budd Chiari syndrome to restore hepatic venous drainage
106
What are the main underlying causes of Budd-Chiari syndrome?
Hypercoaguable state - myeloproliferative disorders, malignancy, oral contraceptives, inherited thrombophilias
107
What is Budd-Chiari syndrome?
Occlusion of hepatic vein which causes stasis and congestion within liver leading to hypoxic damage and necrosis of hepatocytes
108
Causes of chronic liver disease?
Alcohol, NASH, viral (B,C), autoimmune, vascular, metabolic
109
Name 3 viral causes of hepatitis other than the Hep viruses?
EBV, CMV, Yellow fever, influenza, adenoviruses, coxsackie B
110
Which of the hep viruses causes chronic hepatitis?
B (and D), C
E can be chronic in immunosuppressed
111
Which of the Hep viruses is most infectious?
B
112
Which of the hep viruses is spread by faeco-oral transmission?
A & E
113
Which of the hep viruses is most common?
A
114
What is the treatment of Hep A?
SUPPORTIVE
| Is self limiting
115
What is the treatment of hep B?
1. Pegylated interferon-alpha
| 2. Antivirals (Tenofovir, entecavir)
116
What is the treatment of hep C?
1. Direct acting antivirals (NS5B polymerase inhibitor) - Sofosbuvir
2. IFN - alpha / RIBAVIRIN
117
What is the treatment of hep D?
1. Peg IFN-alpha
| 2. Antivirals (Adefovir)
118
What is the treatment of Hep E?
Self limiting so --> SUPPORTIVE
| If chronic - Ribavirin
119
What are the risk factors for developing Hep A?
Travel, shellfish, food handlers
120
What are the risk factors for developing Hep B/C/D?
IV drug user, healthcare worker, sex worker
121
What are the risk factors for developing Hep E?
Contaminated water, poor sanitation, farm animals
122
How long is the incubation time for Hep A and E?
2-6wks
123
How long is the incubation time for Hep B,C,D?
Hep B and D - 1- 6months
| Hep C - Shorter than this slightly
124
Hep D requires what for assembly?
HBsAg
125
You are 100% immune after infection with what Hep virus?
A
126
What is the main potential complication of acute Hep viruses? And what are they?
A and E
| Fulminant hepatitis
127
Symptoms in HBV can last how long?
6-12 weeks
128
Which Hep virus is there neither a vaccine nor PEP?
Hep C
129
Give the 3 stages in preventing Hep C?
1. Screen blood products
2. Lifestyle modification e.g. Needle exchange
3. Universal precaution for handling body fluids
130
Hepatitis D only exists in the presence of Hep B. Which form of Hep B infection (acute/chronic) causes a super infection with Hep D leading to increased risk of fulminant hep and increased progression of liver disease?
Chronic !!
131
What are the two standard precautions in place to prevent Hep E spread?
Food hygiene and animal husbandry
132
What are the 3 serious potential consequences of chronic infection with Hep B/C/D?
Cirrhosis, HCC (hepatocellular carcinoma) and cholangiocarcinoma
133
What percentage of adults that are infected with Hep B virus develop chronic disease?
10%
134
Hep B replicates where?
In hepatocytes
135
Give the 4 phases of chronic HBV and describe the HBeAg/Ab levels at these points?
1. Immune tolerance - HBeAg produced
2. Immune clearance - HBeAg seroconversion (becomes -ve)
3. Inactive HBV carrier - HBeAb
4. Reactivation ^ALT and ^HBV levels
136
Main functions of the liver?
1. Glucose and fat metabolism
2. Detoxification and excretion of toxins
3. Protein synthesis (albumin and clotting factors)
4. Defence against infection (RE system)
137
What are the causes of portal hypertension?
1. Cirrhosis
2. Fibrosis
3. Portal vein thrombosis
4. Hepatoma
5. TB
138
What are the two main factors that contribute to ascites formation?
1. Portal hypertension
| 2. Low albumin
139
How long must an acute hepatitis last before it is classed as chronic?
6 months
