Gastroenterology - Hepatology Flashcards
1
Q
List the functions of the liver.
A
Metabolic function:
- stores glycogen
- releases glucose
- absorbs fats, fat soluble vitamins (A, D, E, K) and iron
- cholesterol synthesis
Stores bile salts:
- dissolves dietary fats
Conjugates billirubin:
- breakdown product of haemoglobin
Synthesises most clotting factors
Detoxification:
- drug excretion / activation (CYP 450)
- alcohol breakdown
Immune function:
- Kupfer cells engulf antigens
Manufactures proteins:
- albumin
- binding proteins
2
Q
What are the risk factors for liver disease?
A
- blood transfusion (esp. before 1990)
- IVDU
- sexual exposure
- medications
- FHx of liver disease, diabetes or IBD
- obesity
- alcohol use
- foreign travel
3
Q
What are the features of acute liver disase?
A
- no pre-existing liver disease
- resolves within 6 months
For example:
- hepatitis A
- EBV
- drug induced liver injury
4
Q
What are the features of chronic liver disease?
A
- asymptomatic
- persists past 6 months
- may lead to cirrhosis and its complications
For example:
- alcohol use
- hepatitis C
- autoimmune disease
5
Q
What are some signs of liver disease that could be identified upon examination?
A
- spider naevae
- clubbing
- palmar erythema
- ascites
6
Q
How can liver disease be investigated?
A
- FBC (thrombocytopenia sensitive marker of liver fibrosis)
- ALT (hepatocyte damage)
- ALP (cholestatic damage; concurrent rise in GGT confirms ALP in liver in origin)
- billirubin, albumin and INR are markers of synthetic function
7
Q
Give some causes of hepatitic liver disease (ALT > 500).
A
- viral
- ischaemia
- toxins (e.g. paracetamol)
- autoimmune
8
Q
Give some causes of hepatitic liver disease (ALT 100-200).
A
- non-alcoholic steatohepatitis
- autoimmune hepatitis
- chronic viral hepatitis
- drug induced liver injury
9
Q
Give some causes of cholestatic liver disease (dilated ducts).
A
- gallstones
- malignancy
10
Q
Give some causes of cholestatic liver disease (non-dilated ducts).
A
- alcoholic hepatitis
- cirrhosis (e.g. alcohol, PSC, PBC)
- drug induced liver injury (e.g. abx)
11
Q
What is hepatitis?
A
Inflammation of the liver, which can range from chronic and low level inflammation, to acute and severe inflammation.
12
Q
What are the causes of hepatitis?
A
- alcohol hepatitis
- non-alcoholic fatty liver disease
- viral hepatitis
- autoimmune heptatitis
- drug induced hepatitis (e.g. paracetamol overdose)
13
Q
Presentation of hepatitis.
A
- abdominal pain
- fatigue
- pruritis
- myalgia / arthralgia
- n+v
- jaundice
- fever
14
Q
What are the biochemical findings that are consistent with hepatitis?
A
Hepatic picture:
- elevated AST / ALT
- proportionally less of a rise in ALP
- hyperbillirubinaemia (conjugated and unconjugated)
15
Q
What is the most common viral hepatitis worldwide?
A
Hepatitis A - although fairly rare within the UK.
16
Q
What type of virus is Hepatitis A?
A
RNA virus
17
Q
How is Hepatitis A transmitted?
A
Faecal-oral route, usually by contaminated food or water.
18
Q
Presentation of Hepatitis A.
A
- n+v
- anorexia
- jaundice
19
Q
Why do patients with hepatitis A commonly have pale stool?
A
Hepatitis A can cause cholestasis, meaning less stercobillin reaches the rectum causing pale stool.
Urine becomes darker as urobillogen accumulates and is excreted by the renal route.
20
Q
Treatment of Hepatitis A.
A
Resolves without treatment within 1-3 months.
Management is usually basic analgesia.
Vaccination is available to reduce the chance of developing infection.
21
Q
What type of virus is Hepatitis B?
A
DNA virus
22
Q
How is Hepatitis B transmissed?
A
Direct contact with blood or bodily fluids (e.g. sexual intercourse, sharing needles).
Vertical transmission (mother to child through pregnancy and delivery).
23
Q
What do the following viral markers indicate in hepatitis B?
a) HBsAg
b) HBeAg
c) HBcAb
d) HBsAb
e) HBV DNA
A
a) surface antigen, suggestive of active infection
b) E antigen, marker of viral replication and suggestive of high infectivity
c) core antibodies, suggestive of past or current infection
d) surface antibody, suggestive of vaccination or past or current infection
e) direct count of the viral load
24
Q
Which viral markers should be tested for when screening for Hepatitis B?
A
- HBcAb (previous infection)
- HBsAg (active infection)
Note IgM (acute) and IgG (chronic) versions of HBcAb can indicate whether previous infection was acute or chronic.
If these are positive, do further testing for HBeAg and viral load.
25
Describe the vaccination programme for Hepatitis B.
Vaccination to Hepatitis B is included as part of the 6 in 1 vaccination for infants.
The vaccine requires 3 doses at different intervals.
Involves injecting the HBsAg - patients tested for HBsAb to confirm their response to vaccine.
26
What is the management of Hepatitis B?
- prophylactic vaccination
- low threshold for screening
- screen for other blood born viruses
- refer for specialist management
- notify Public Health England
- stop smoking and alcohol
27
What type of virus is Hepatitis C?
RNA virus
28
Describe the disease course of Hepatitis C.
- 25% clear the virus independently
- 75% do not clear, and infection becomes chronic
Chronic infection associated with liver cirrhosis and hepatocellular carcinoma.
29
How is Hepatitis C detected?
Hepatatis C antibody is screening test.
Hepatitis C RNA testing can confirm diagnosis, calculate viral lobe and assess for genotype.
30
Management of Hepatitis C?
- low threshold for screening
- screen for other blood born viruses
- refer for specialist management
- notify PHE
- stop smoking and alcohol
Medical management using direct acting antivirals (DAA) tailored to specific viral genotype.
31
What type of virus is Hepatitis D?
RNA virus
32
Pathophysiology of Hepatitis D.
Only survive in patients with Hepatitis B, as it attaches to the HBsAg to survive.
Hepatitis D increases the risk of complications and disease severity of Hepatitis B, but is very rare in the UK.
33
What type of virus is Hepatitis E?
RNA virus
34
How is Hepatitis E transmitted?
Faecal oral route
35
Presentation of Hepatitis E?
Mild illness, with the virus cleared within a month and no treatment required.
36
Autoimmune hepatitis causes
a) acute
b) chronic
disease?
a) acute
37
Describe
a) Type 1 autoimmune hepatitis
b) Type 2 autoimmune hepatitis
a) occurs in adults, typically presenting in post-menopausal women with fatigue and features of liver disease upon examination.
b) occurs in children and young adults, presenting with acute hepatitis and jaundice.
38
Give the autoantibodies associated with Type 1 autoimmune hepatitis.
- ANA
- anti-actin
- anti-SLA
39
Give the autoantibodies associated with Type 2 autoimmune hepatitis.
- anti-LKM1
- anti-LC1
40
How is autoimmune hepatitis treated?
- high dose prednisolone
- azathioprine
- liver transplant in end-stage liver disease*
*Note autoimmune hepatitis can recur in transplanted livers, so is not necessarily curative.
41
Give the steps of alcoholic liver disease.
Chronic and excessive alcohol consumption leads to:
1. Alcohol related fatty liver: drinking leads to a build up of fat in the liver. If drinking stops, this process reverses within around 2 weeks.
2. Alcoholic hepatitis: chronic alcohol consumption causes inflammation within the liver. Permanent abstinence may allow reversal of mild alcoholic hepatitis.
3. Cirrhosis: irreversible scarring of the liver.
42
Department of Health, 2016, gives which recommendations on alcohol consumption?
Do not regularly drink more than 14 units per week, spread evenly over 3 or more days and not more than 5 units per day.
Pregnant women should avoid alcohol completely.
Any level of alcohol consumption increases the risk of cancers, particularly breast, mouth and throat.
43
Which questioning technique can be used to screen for harmful alcohol use?
CAGE questions:
1. Have you ever thought you should CUT down?
2. Do you get ANNOYED at others commenting on your drinking?
3. Do you ever feel GUILTY about drinking?
4. Do you EVER drink in the morning to help your hangover or nerves?
The Alcohol Use Disorders Identification Test (AUDIT) is a questionnaire developed by WHO to screen people for harmful alcohol use.
44
What are the complications of chronic alcohol use?
- alcoholic liver disease
- cirrhosis
- hepatocellular carcinoma
- alcohol dependance and withdrawal
- Wernicke-Korsakoff syndrome
- pancreatitis
- alcoholic cardiomyopathy
45
What are the signs of liver disease that may be identified upon examination?
- jaundice
- hepatomegaly
- spider naevi
- palmar erythema
- gynaecomastia
- bruising (abnormal clotting)
- ascites
- caput Medusae
- asterixis (decompensated liver disease)
46
How should alcoholic liver disease be investigated?
- FBC (raised MCV)
- LFTs (elevated ALT, AST and GGT; low albumin due to reduced synthetic function; hyperbilirubinaemia in cirrhosis)
- elevated prothrombin time due to reduced synthetic function
- U&Es deranged in hepatorenal syndrome
Fibroscan is ultrasound used to assess degree of cirrhosis.
Endoscopy to assess for and treat oesophageal varices.
CT and MRI can look for fatty infiltration, hepatocellular carcinoma, hepatosplenomegaly and ascites.
47
Management of alcoholic liver disease?
- stop drinking permanently
- detoxication regime
- nutritional support with vitamins (e.g. thiamine) and high protein diet
- steroids
- treat complications of cirrhosis
- refer for liver transplant in severe disease
48
What are the symptoms of alcohol withdrawal at the different times after alcohol consumption ceases?
6-12 hours
12-24 hours
24-48 hours
24-72 hours
6-12 hours: tremor, sweating, headache, craving, anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: delirium tremens
49
What is delirium tremens?
A medical emergency associated with alcohol withdrawal, with a mortality of 35% if untreated.
Symptoms arise within 24-72 hours after alcohol consumption is ceased.
50
Pathophysiology of delirium tremens.
Alcohol stimulates GABA and NMDA receptors in the brain, having an inhibitory effect on the electrical activity within the brain.
Chronic alcohol use results in the GABA system being down-regulated and NMDA being up-regulated.
When alcohol is removed from the system suddenly, GABA under-functions and NMDA over-functions causing extreme excitability of the brain, with excess adrenergic activity.
51
Presentation of delirium tremens.
Symptom onset within 24-72 hours after alcohol cessation:
- acute confusion
- severe agitation
- delusions and hallucinations
- tremor
- tachycardia
- hypertension
- hyperthermia
- ataxia
- arrhythmias
52
How is alcohol withdrawal managed?
Chlordiazepoxide is a benzodiazepine used to combat the effects of alcohol withdrawal, given orally as a reducing regime titrated to the required dose based upon local alcohol withdrawal protocol.
Intravenous high dose B vitamins, and oral thiamine, should be co-prescribed.
53
Pathophysiology of Wernicke-Korsakoff syndrome (WKS)?
Chronic alcohol excess leads to poor absorption of thiamine, causing thiamine deficiency. This leads to:
1. Wernicke's encephalopathy
which complicates into...
2. Korsakoffs syndrome
54
Features of Wernicke's encephalopathy?
- confusion
- oculomotor disturbances
- ataxia
Wernicke’s encephalopathy is a medical emergency and has a high mortality rate if untreated. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.
55
Features of Korsakoffs syndrome?
- memory impairment
- behavioural changes
Korsakoffs syndrome is often irreversible and results in patients requiring full time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.
56
What is non alcoholic fatty liver disease (NAFLD)?
The alcohol-independent fatty infiltration of the liver, progressing to hepatitis and cirrhosis.
57
What are the stages of NAFLD?
1. Non-alcoholic fatty liver disease
2. Non-alcoholic steatohepatitis
3. Fibrosis
4. Cirrhosis
58
Risk factors for NAFLD.
- obesity
- poor diet
- physical inactivity
- T2DM
- hypercholesterolaemia
- smoking
- hypertension
59
What steps should be taken in the management of a patient presenting with abnormal LFTs without a clear cause?
Perform a non-invasive liver screen:
- ultrasound liver
- hepatitis B and C serology
- autoantibodies
- immunoglobulins
- alpha-1 antritrypsin levels
- ferritin and transferrin saturation
60
How is NAFLD investigated?
Enhanced liver fibrosis (ELF) blood test is first line and indicates fibrosis of the liver if elevated.
NAFLD fibrosis score can be used as an alternative if ELF blood test is unavailable.
Fibroscan is the third line investigation.
Liver ultrasound to confirm diagnosis of hepatic steatosis, however cannot indicate the severity, function or presence of fibrosis.
61
How is NAFLD managed?
- weight loss
- exercise
- smoking cessation
- control of diabetes, blood pressure and cholesterol
- avoid alcohol
Refer patients with liver fibrosis to a liver specialist where they may treat with vitamin E or pioglitazone.
62
What is liver cirrhosis?
The result of chronic inflammation of the liver, where hepatocytes become fibrosed and nodules of scar tissue form within the liver.
63
What are the common causes of liver cirrhosis?
- alcoholic liver disease
- non-alcoholic fatty liver disease
- hepatitis B
- hepatitis C
64
What are the signs of liver cirrhosis?
- jaundice (hyperbilirubinaemia)
- hepatomegaly
- splenomegaly (secondary to portal hypertension)
- spider naevi
- palmar erythema
- gynaecomastia
- bruising
- ascites
- caput Medusae
- asterixis
65
How is liver cirrhosis investigated?
- deranged LFTs
- U&Es (hyponatraemia due to fluid retention in severe disease)
- ELF blood test
- ultrasound
- FibroScan
- endoscopy
- CT / MRI
- liver biopsy
66
How is liver cirrhosis managed?
- ultrasound and AFP every 6/12 to screen for HCC
- endoscopy every 3 years in patients without known varices
- high protein, low sodium diet
- consideration of liver transplant
67
What are the complications of liver cirrhosis?
- malnutrition
- portal hypertension > varices > variceal bleeding
- ascites
- hepato-renal syndrome
- hepatic encephalopathy
- hepatocellular carcinoma
68
How does liver cirrhosis cause malnutrition?
Fibrosis of hepatocytes deplete the metabolic functions (glycogenesis and glycogenolysis) of the liver, and thus the body begins to rely upon the protein-stores within the body for energy.
This leads to muscle wasting and weight loss.
69
How can malnutrition in liver cirrhosis be managed?
- regular meals
- low sodium
- high protein and high calorie diet
- avoid alcohol
70
Which two veins converge to form the portal vein?
Superior mesenteric vein
Splenic vein
Portal vein delivers blood to the liver
71
Pathophysiology of varices?
Liver cirrhosis reduces elasticity of the liver, increasing hydrostatic pressure and resistance upon the veins within the liver.
This results in increased back pressure into the portal system, resulting in portal hypertension. The sites at which the portal system anastamoses with the systemic venous system then become swollen and tortuous (ie. varices).
72
At which sites do varices occur?
- gastro oesophageal junction (GOJ)
- ileocaecal junction
- rectum
- anterior abdominal wall via the umblical vein (caput medusae)
Varices do not cause symptoms or problems until they start bleeding. Due to the high blood flow through varices, once they start bleeding patients can exsanguinate (bleed out) very quickly.
73
How are stable varices treated?
- propanolol (reduce portal hypertension)
- elastic band ligation of varices
74
What is transjugular intra-hepatic porosystemic shunt (TIPS)?
Interventional radiologist inserts a wire under X-ray guidance into the jugular vein, down the vena cava, and into the liver via the hepatic vein.
A connection is made through the liver tissue, between the hepatic vein and the portal vein - a stent is placed here. This relieves the pressure in the portal system and varices.
75
How are bleeding oesophageal varices managed?
Resuscitation:
- terlipressin causes vasoconstriction and slows bleeding
- correct coagulopathy with vitamin K and FFP
- prophylactic broad spectrum antibiotics
- consider intubation and intensive care
Urgent endoscopy required to allow for obliteration or ligation of varices.
76
Pathophysiology of ascites in liver cirrhosis?
Portal hypertension and hypoalbuminaemia causes a transudative exudate, as Starling's forces favour fluid moving from the capillaries into the peritoneal cavity.
This causes a drop in circulating volume, which is detected by the kidneys as a reduced renal blood flow. They subsequently release renin, leading to aldosterone secretion and reabsorption of fluid and sodium in the kidneys.
77
How is ascites managed?
- aldosterone antagonists (e.g. spironolactone)
- paracentesis (ascitic tap or drain)
- low sodium diet
78
What is spontaneous bacterial peritonitis?
A complication of ascites, in which an infection develops in the ascitic fluid and peritoneal lining without any clear cause.
Has a mortality of around 20%.
79
Presentation of spontaneous bacterial peritonitis.
- asymptomatic
- fever
- abdominal pain
- ileus
- hypotension
- deranged bloods (raised WCC, CRP, creatinine, metabolic acidosis)
80
Which organisms most commonly cause primary bacterial peritonitis?
- Escherichia coli
- Klebsiella pneumoniae
- Gram positive cocci (e.g. Staphylococcus and Enterococcus)
81
How is spontaneous bacterial peritonitis managed?
- ascitic culture
- IV cephalosporin (e.g. cefotaxime)
82
What is hepatorenal syndrome?
Liver cirrhosis causes portal hypertension, in which the portal blood vessels dilate. This leads to a loss of blood volume in other areas of circulation, including a reduced renal blood flow.
This leads to hypotension in the kidneys, which is detected by the macula densa and subsequently stimulates granular cells to release renin, activating RAAS.
While RAAS attempts to raise blood pressure, sympathetic input causes renal vasoconstriction and consequent ischaemia. This leads to a rapid deterioration of kidney function.
83
What is hepatic encephalopathy?
Cirrhosis reduces the metabolic function of the liver, meaning it cannot detoxify many waste products, such as ammonia.
Ammonia concentrates within the blood, and crosses the blood brain barrier. Hyperammonaemia within the CNS can cause a range of neurological symptoms.
84
Give the features of
Grade 1
Grade 2
Grade 3
Grade 4
hepatic encephalopathy.
Grade 1: psychomotor slowing, constructional apraxia, poor memory, reversed sleep pattern.
Grade 2: lethargy, disorientation, agitation and asterixis
Grade 3: droswiness
Grade 4: coma
85
How is hepatic encephalopathy managed?
- laxatives (e.g. lactulose) promote excretion of ammonia
- antibiotics (e.g. rifaximin) reduces number of intestinal bacteria producing ammonia
- nutritional support (e.g. NG tubes)
86
What are the indications for liver transplant?
- acute liver failure (e.g. acute viral hepatitis, paracetamol overdose)
- chronic liver failure
87
Give some contraindications to liver transplantation.
- significant comorbidities (e.g. severe kidney or heart disease)
- excessive weight loss and malnutrition
- active hepatitis B, hepatitis C or other infection
- end stage HIV
- active alcohol use*
*Approx 6 months of alcohol abstinence required to be eligible for liver transplant.
88
Outline the surgical techniques for liver transplantation.
'Rooftop' or 'Mercedes Benz' incision is made along the lower costal margin for open surgery, with the liver subsequently excised. The new liver is implanted and connected.
89
How should a patient be managed following liver transplantation?
- lifelong immunosuppression (e.g. azathioprine, tacrolimus)
- lifestyle advice (e.g. alcohol and smoking abstinence)
- monitoring for cancer
- monitoring for disease recurrence
90
What are the signs of liver transplant rejection?
- abnormal LFTs
- fatigue
- fever
- jaundice
91
What are the main types of liver cancer?
- hepatocellular carcinoma (~80%)
- cholangiocarcinoma (~20%)
92
Risk factors for hepatocellular carcinoma?
- viral hepatitis (B and C)
- alcohol
- non alcoholic fatty liver cidsease
- other chronic liver disease
Patients with liver cirrhosis are screened for HCC, using USS and AFP every 6 months.
93
Presentation of liver cancer.
- weight loss
- abdominal pain
- anorexia
- n+v
- jaundice
- pruritis
Note liver cancer remains asymptomatic for a long time, with patients becoming symptomatic in more severe disease. This delays presentation and makes prognosis poor.
94
Tumour marker for hepatocellular carcinoma.
AFP
95
Tumour marker for cholangiocarcinoma.
CA19-9
96
How should suspected liver cancer be investigated?
- tumour markers (AFP / CA19-9)
- liver ultrasound
- CT / MRI for staging
- ERCP for biopsy in cholangiocarcinoma
97
How is HCC managed?
- surgical resection of early disease (curative)
- kinase inhibitors (e.g. sorafenib) inhibit proliferation of cancer cells
- resistant to chemo and radiotherapy
- palliative care
98
How is cholangiocarcinoma managed?
- surgical resection of early disease (curative)
- ERCP to place a stent in bile duct to allow for drainage of bile (symptomatic)
- resistant to chemo and radiotherapy
99
What is primary sclerosing cholangitis (PSC)?
Intrahepatic and extrahepatic ducts become strictured and fibrotic, causing obstruction to flow of bile out of the liver and into the intestines.
Chronic bile obstruction eventually leads to hepatitis, fibrosis and cirrhosis.
100
Cause of PSC?
Unknown, however 70% of cases associated with ulcerative colitis.
101
Risk factors for PSC.
- male
- age 30-40
- ulcerative colitis
- family history
102
Presentation of PSC.
- jaundice
- chronic right upper quadrant pain
- pruritis
- fatigue
- hepatomegaly
103
Investigations for PSC.
- LFTs (elevated ALP; cholestatic)
- autoantibodies (e.g. p-ANCA, ANA, aCL)
GOLD STANDARD for diagnosis is MRCP - MRI of the liver, bile ducts and pancreas.
104
Complications of PSC.
- acute bacterial cholangitis
- cholangiocarcinoma
- colorectal cancer
- cirrhosis
- biliary strictures
- fat soluble vitamin deficiency (A, D, E, K)
105
What is the management of PSC?
Liver transplant curative.
ERCP to dilate and stent strictures.
Monitoring for complications.
106
Outline the role of ERCP in PSC.
Endoscope inserted into the throat > oesophagus > stomach > duodenum > sphincter of Oddi > ampulla of Vater > bile ducts.
Once in the bile ducts, X-rays and radiocontrast can be used to identify any strictures, which can then be dilated and stented during the same procedure.
107
Pathophysiology of primary biliary cirrhosis (PBC)?
Autoimmune inflammation of the small bile ducts within the liver, causing cholestasis.
Back-pressure of bile obstruction leads to fibrosis, cirrhosis and liver failure.
108
Which ducts are affected first in PBC?
Intralobar ducts, AKA Canals of Hering.
109
Presentation of PBC.
- fatigue
- pruritis
- jaundice
- GI disturbances and abdominal pain
- pale stool
- xanthoma and xanthelasma
- signs of cirrhosis and failure
110
How is PBC diagnosed?
- ALP raised
- AMA raised
- ANA raised
- ESR raised
- IgM raised
Liver biopsy is used in diagnosing and staging the disease.
