Liver Flashcards
1
Q
What are the common causes of acute liver injury?
A
viral (A, B, EBV)
drugs
alcohol
vascular
obstruction
congestion
2
Q
What are the common causes of chronic liver injury?
A
alcohol
viral (B, C)
autoimmune
metabolic (iron, copper)
congestion
obstruction
3
Q
What are the presentations of acute liver injury?
A
malaise, nausea, anorexia, jaundice
rarer: confusion, bleeding, liver pain
4
Q
What are the presentations of chronic liver injury?
A
ascites, oedema, haematemesis (vomiting blood), malaise, anorexia, wasting, easy bruising, itching, hepatomegaly, abnormal LFTs
rarer: jaundice, confusion
5
Q
What is measured in Liver Function Tests?
A
serum bilirubin
albumin
prothrombin time
Serum liver enzymes: (give no index of liver function)
alkaline phosphatase
gamma-GT
transaminases (AST, ALT)
6
Q
What are the signs of cholestatic jaundice?
A
dark urine
pale stools
itching
abnormal LFTs
7
Q
What is the significance of very high AST/ALT levels in the blood?
A
Suggestive of liver disease
8
Q
What are the 3 types of gallstones?
A
Intrahepatic bile duct stones (hepatolithiasis)
- contain mainly brown pigment and cholesterol stones
Gallbladder stones (cholecystolithias)
- contain cholesterol (or black pigment) stones
Extrahepatic bile duct stones (choledocholithiasis)
- primary sontes mainly brown pigment stones, whereas secondary stones mainly cholesterol stones
9
Q
How are gallstones managed?
A
Gallbladder stones:
- Laparoscopic cholecystectomy
- Bile acid dissolution therapy (<1/3 success)
Bile duct stones:
- ERCP (Endoscopic retrograde cholangiopancreatography) with sphincterotomy and removal (basket or balloon), crushing (mechanical, laser..), stent placement
- surgery (large stones)
10
Q
What are the key presentations of gallbladder and bile duct stones?
A
Gallbladder:
Biliary pain, cholecystitis, sometimes obstructive jaundice
Bile duct:
Biliary pain, Obstructive jaundice, Cholangitis (inflammation of bile duct system) , Pancreatitis
11
Q
What are the types of Drug-induced liver injury?
A
- Hepatocellular (ALT >2 ULN, ALT/Alk Phos ≥ 5)
diclofenac, disulfiram, isoniazid, lamotrigine - Cholestatic (Alk Phos >2 ULN or ALT/Alk phos ≤ 2)
amoxicillin-clavulanate, cephalosporins, flucloxacillin, penicillin, sulfonamide, terbinafine - Mixed (ALT/Alk phos between 2 and 5)
carbamazepine, lamotrigine, phenytoin, sulfonamides
12
Q
Which drugs most commonly cause DILI?
A
Antibiotics (32-45%) - augmentin, flucloxacillin, penicillin, erythromycin
CNS Drugs (15%) - chlorpromazine, carbamazepine, valproate
Immunosuppressants (5%)
Analgesics/musculoskeletal (5-17%) - diclofenac
GI Drugs (10%) - PPIs
Dietary supplements (10%)
Multiple drugs (20%)
13
Q
How is paracetamol induced liver failure treated?
A
N-acetyl cysteine (NAC)
+ supportive treatment to correct coagulation defects, fluid/electrolyte imbalances, renal failure, hypoglycaemia, encephalopathy
14
Q
What are the indicators of severe paracetamol-induced liver failure?
A
late presentation (NAC less effective >24hrs)
acidosis (pH<7.3)
prothrombin time >70 sec
serum creatinine ≥ 300umol/l
80% mortality if no liver transplant
15
Q
What are the causes of ascites?
A
- Chronic liver disease (most) - hepatoma, TB, +/- portal vein thrombosis
- Neoplasia
- Pancreatitis, cardiac causes
16
Q
What is the pathophysiology of ascites?
A
increased intrahepatic resistance
↓
Systemic vasodilation -> Portal hypertension
↓ ↓
↓ ascites <– low serum albumin
Secretion of:
- Renin-angiotensin
- Noradrenaline
- Vasopression
↓
Fluid retention
17
Q
What is the management for ascites?
A
- Fluid and salt restriction
- Diuretics (spironolactone +/- furosemide (helps to maintain normal potassium))
- large-volume paracentesis + albumin
- trans-jugular intrahepatic portsystemic shunt (TIPS)
18
Q
What is the effect of alcohol on the liver?
A
It changes the way that hepatocytes metabolise and produce fat.
Fat accumulation within hepatocytes is termed steatosis which can be large droplet (macrovesicular) or small droplet (microvesicular).
19
Q
What are the risk factors for Alcoholic hepatitis?
A
Female
Drinking pattern, binge
Quantity consumed
Obesity
HCV
Genetics
20
Q
What are the stages of progression to Alcoholic hepatitis?
A
Normal
↓ (90% of heavy drinkers)
Steatosis
↓ (20-40%)
Alcoholic steatohepatitis/fibrosis
↓ (8-20%)
Cirrhosis → (3-10%) Hepatocellular carcinoma
↓ (70%)
Alcoholic hepatitis
21
Q
What is portal hypertension?
A
High blood pressure in the portal system as a result of increased hepatic resistance and increased splanchnic blood flow.
22
Q
What are the causes of portal hypertension?
A
cirrhosis, fibrosis, portal vein thrombosis
23
Q
What are possible consequences of portal hypertension?
A
Varices (oesophageal, gastric…)
Splenomegaly
24
Q
What is the Lille score used for?
A
To assess the patient response to a liver transplant
Scores >0.45 predict a 6-month survival of 25%. Scores <0.45 predict a 6-month survival of 85%
25
What are the causes of acute worsening of chronic liver disease ('going off')?
Constipation
Drugs - sedatives, analgesics
- NSAIDs, diuretics, ACE blockers
Gastrointestinal bleed
Infection (ascites, blood, skin, chest …)
HYPO: natraemia, kalaemia, glycaemia ...
Alcohol withdrawal (not typically)
Other (cardiac, intracranial ...)
26
What are the reasons why liver patients are vulnerable to infection?
impaired reticulo-endothelial function reduced opsonic activity
leucocyte function
permeable gut wall
27
What causes coma in patients with CLD?
Hepatic encephalopathy (ammonia ...)
- infection
- GI bleed
- constipation
- hypokalaemia
- drug (sedatives, analgesics)
Hyponatraemia / hypoglycaemia
Intracranial event
28
What are 5 bedside tests for encephalopathy?
Serial 7’s (count down from 100 in 7s)
WORLD backwards
Animal counting in 1 minute
Draw 5 point star
Number connection test
29
What are some severe consquences of liver dysfunction?
Malnutrition
Coagulopathy
- impaired coagulation factor synthesis
- vitamin K deficiency (cholestasis)
- thrombocytopenia
Endocrine changes
- gynaecomastia
- impotence
- amenorrhoea
Hypoglycaemia (+/-)
30
Which drugs are used to treat liver disease?
Analgesia:
- sensitive to opiates
- NSAIDs cause renal failure
- paracetamol safest
Sedation:
- use short-acting benzodiazepines
(with care!!!)
Diuretics:
- excess weight loss - hyponatraemia
- hyperkalaemia
- renal failure
Antihypertensives:
- can often stop
- avoid ACE inhibitors
Aminoglycosides:
- avoid
31
What are the actions taken when liver patients 'go off'?
1 ABC: Airway, Breathing, Circulation
2 Look at chart
- vital signs, O2, BM(glucose), drug chart
3 Look at patient
- focus of infection? bleeding?
4 Tests
- FBC, U&E, blood cultures, ascitic fluid clotting, LFTs …
32
WHat are the causes of CLD?
Alcohol
Non Alcoholic Steatohepatitis (NASH)
Viral hepatitis (B, C)
Immune
- autoimmune hepatitis
- primary biliary cirrhosis
- sclerosing cholangitis
Metabolic
- haemochromatosis
- Wilson’s
- a1 antitrypsin deficiency…
Vascular
- Budd-Chiari
33
WHat are the causes of CLD?
Alcohol
Non Alcoholic Steatohepatitis (NASH)
Viral hepatitis (B, C)
Immune
- autoimmune hepatitis
- primary biliary cirrhosis
- sclerosing cholangitis
Metabolic
- haemochromatosis
- Wilson’s
- a1 antitrypsin deficiency…
Vascular
- Budd-Chiari
34
What are the investigations for chronic liver disease?
Viral serology - hepatitis B surface antigen, hepatitis C antibody
Immunology
- autoantibodies - AMA, ANA, ASMA, coeliac antibodies
- immunoglobulins
Biochemistry
- iron studies
- copper studies - caeruloplasmin, 24hr urine copper
- a1-antitrypsin level
- lipids, glucose
Radiological investigations - USS / CT / MRI
35
What are the possible causes of hepatitis?
- Viral (A,B,C, CMB, EBV)
- Drug-induced
- Autoimmune
- Alcoholic
36
what is primary biliary cholangitis?
A form of autoimmune hepatitis (liver inflammation) affecting the small bile ducts.
37
What are the presentations of PBC?
- Asymptomatic lab abnormalities
- Itching and/or fatigue
- Dry eyes
- Joint pains
- Variceal bleeding
- Liver failure; ascites, jaundice
38
What is the treatment for PBC?
- Ursodeoxycholic acid (reduces intestinal absorption of cholesterol)
- Colestyramine (prevents bile absorption in the gut + can help with pruritis)
- Liver transplant in end stage liver disease
- Immunosuppression
39
What is primary sclerosing cholangitis?
An autoimmune condition where the intrahepatic or extrahepatic ducts become strictured and fibrotic. This causes an obstruction to the flow of bile out of the liver and into the intestines.
Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts.
Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.
40
What autoimmune disease is strongly linked to PSC?
Over 70% of PSC patients have inflammatory bowel disease
41
What are the risk factors for PSC?
Male
Aged 30-40
Ulcerative Colitis (IFD)
FHx
42
What are the key presentations of PSC?
Jaundice
Chronic right upper quadrant pain
Pruritis
Fatigue
Hepatomegaly
43
What is the gold standard test for PSC?
Magnetic resonance cholangiopancreatography (shows bile duct lesions or strictures)
44
What is haemochromatosis?
An iron storage disorder resulting in excessive total body iron and deposition of iron in tissues
45
What is the cause of haemochromatosis?
In most cases (90%) it is caused by autosomal recessive mutation of human haemochromatosis protein gene on chromosome 6 which is important in regulating iron metabolism
46
What are the symptoms of haemochromatosis?
Chronic tiredness
Joint pain
Pigmentation (bronze/slate grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
47
What are the investigations for Haemochromatosis?
Serum ferritin
Transferrin saturation
Genetic testing
Liver biopsy with Perl's stain
CT abdomen
MRI
48
What is the management for haemochromatosis?
Venesection
Monitoring serum ferritin
Avoid alcohol
Genetic counselling
Monitoring and treatment of complications
49
What is a1-antitrypsin deficiency ?
A condition caused by an abnormality in the gene for a protease inhibitor called a1-antitrypsin which results in inability to export it from the liver. A1AT protects tissues by inhibiting the neutrophil elastase enzyme which digests connective tissue and so deficiency results in tissue damage particularly to the liver and lungs.
50
What are the CAGE questions?
Used to screen for harmful alcohol use
C- Cut down? (ever thought you should reduce alcohol intake)
A - Annoyed? (annoyed at other for comments re drinking)
G - Guilty? (guilt about drinking)
E - Eye opener? (morning drinking to help hangover/nerves?)
51
What are the signs of alcoholic liver disease?
Jaundice
Hepatomegaly
Spider Naevi
Palmar Erythema
Gynaecomastia
Bruising – due to abnormal clotting
Ascites
Caput Medusae – engorged superficial epigastric veins
Asterixis – “flapping tremor” in decompensated liver disease
52
What are the investigations for ALD?
FBC (↑MCV), LFTs (↑ALT + AST, ↑GGT), Clotting (↑prothrombin), U+Es
USS
Endoscopy
CT/MRI
Liver biopsy
53
What is the management for ALD?
STOP DRINKING permanently
Nutritional support + high protein diet
Steroids
Treat complications (portal hypertension, varices, ascites)
Liver transplant in severe disease (+alcohol abstinence)
54
What is NAFLD?
Non-alcoholic fatty liver disease
= Overarching term for conditions caused by a build-up of fat in the liver not caused by heavy alcohol use.
55
What are the risk factors for NAFLD?
obesity
Hypertension
T2DM
FHx
Endocrine disorders
Drugs (NSAIDs, amiodarone)
Smoking
High cholesterol
56
What is the pathophysiology of NAFLD?
Hepatosteatosis → Non alcoholic steatohepatitis → Fibrosis → Cirrhosis
57
What are the key presentations for NAFLD?
Typically asymptomatic (initial findings incidental)
Very severe → signs of liver failure
58
What are the investigations for NAFLD?
USS abdo
Bloods (deranged LFTs, ↑prothrombin, ↓albumin, ↑bilirubin)
FBC - thrombocytopenia, hyperglycaemia
59
What is the management for NAFLD?
Lose weight
Control risk factors (statins, metformin, ACE-i)
Vitamin E (improves histological steatotic/fibrotic liver appearance)
60
What are the potential complications of NAFLD?
HE, ascites, HCC, portal hypertension, oesophageal varices
61
What are ALT and AST?
Alanine aminotransferase and aspartine aminotransferase are transaminases. These are liver enzymes released into the blood as a result of inflammation of the liver cells.
62
What is the difference between acute and chronic hepatitis?
Acute = infection cleared within 6 months
Chronic = infection prolonged beyond 6 months
63
What causes hepatitis A?
a picoRNA virus transmitted via faecal-oral spread which replicates in the liver and is excreted in the bile
64
What are the risk factors for hep A?
Overcrowding
poor sanitation
shellfish
travel
65
What are the key presentations of Hep A?
Malaise, nausea + vomiting and fever in prodromal phase (1-2 wks)
Jaundice, dark urine + pale stools, hepatosplenomegaly following this
66
What are the investigations for Hep A?
Bloods - ↑ESR + leukopenia
LFTs - bilirubin ↑ when icteric (jaundiced)
HAV serology - HAV IgM = acutely infected
67
What is the management of Hep A?
supportive (basic analgesia)
vaccination
68
What is the cause of Hep B?
a dsDNA virus which infects hepatocytes
69
What are the transmission routes for Hep B?
- Needles
- Sexual
- Vertical (mother to baby)
- Horizontal
70
What are the risk factors for Hep B?
IV drug abuse
MSM (men who have sex with men)
Dialysis patients
Healthcare workers
71
What are the key presentations of Hep B?
SImilar to hep A
1-2 week prodrome
deepening jaundice, dark urine, pale stools
Hepatosplenomegaly
Urticaria
Arthralgia
72
What are the investigations for Hep B?
Serology:
Surface antigen (HBsAg) – active infection
E antigen (HBeAg) – marker of viral replication and implies high infectivity
Core antibodies (HBcAb) – implies past or current infection
Surface antibody (HBsAb) – implies vaccination or past or current infection
Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load
73
What is the treatment for Hep B?
vaccination for prevention
s/c pegylated interferon alpha 2A (antiviral agent)
74
What causes Hep C?
ssRNA virus
75
What is the prognosis for Hep C?
1/4 make full recovery
3/4 contract chronic hep C
76
How is Hep C transmitted?
Most commonly via needles in IVDU, limited vertical + sexual transmission
77
what are the key presentations of hep C?
often acutely asymptomatic, few patients with influenza-like symptoms
present later with chronic liver signs + hepatosplenomegaly
78
What are the serology results for Hep C?
HCV RNA = current infection/diagnoses acute infection
HCV Ab = presents within 4-6 weeks of infection
79
What is the treatment for Hep C?
Curable with direct acting antivirals (DAA): oral ribavirin + NS5A-I/NS5B-I
Liver transplantation for end-stage liver disease
80
What percentage of Hep C cases progress to chronic liver failure?
30%
81
what is the cause of hepatitis D?
ssRNA virus combined with hep B infection
82
How is hep D transmitted?
exposure to infected blood and serous body fluids; and contaminated needles, syringes, blood and plasma product transfusions
83
Why is Hep D dependent on Hep B?
It is an incomplete virus and uses HBV to assemble itself
84
What are the symptoms of Hep D?
Mild illness - abdo pain, fatigue, pruritis, fever, muscle aches, n/v, jaundice
85
What is the cause of Hep E?
ssRNA virus
86
What risk factors are associated with Hep E?
Undercooked pork
contaminated water
87
What is the pathophysiology of Hep E?
Self-limiting acute hepatitis but can cause chronic disease in immunosuppressed individuals and fulminant liver failure which is high risk in pregnant women
88
What are the key presentations of Hep E?
Mild illness (abdo pain, fatigue, pruritus, fever, muscle aches, nausea/vomiting, jaundice)
89
What are the investigations for Hep E?
Serology (HEV IgM = acute infection)
90
What is the management for Hep E?
Supportive treatment, self-limiting
91
What is autoimmune hepatitis?
rare cause of chronic hepatitis
92
What is the cause of autoimmune hepatitis?
Exact cause is unknown but thought to be associated with a genetic predisposition and triggered by environmental factors such a viral infection that causes a T cell-mediated response against the liver cells
93
What are the risk factors for autoimmune hepatitis?
Female
Other autoimmune disease
Viral hepatitis
HLA DR3 or DR4
94
What are the two types of autoimmune hepatitis?
T1: occurs in adults and typically affects women in their late 40s/50s, presents around or after menopause with fatigue and features of liver disease on examination
T2: occurs in children and typically teenagers or patients in their early twenties present with acute hepatitis with high transaminase and jaundice
95
What are the presentations of autoimmune hepatitis?
Mild illness (abdo pain, fatigue, pruritus, fever, muscle aches, nausea/vomiting, jaundice)
96
What is the gold standard investigation for autoimmune hepatitis?
Liver biopsy
97
What is the management for autoimmune hepatitis?
High dose corticosteroids (prednisolone)
Immunosuppressants (azathioprine)
Hep A+B vaccination
Liver transplant may be required in end stage liver disease
98
What are the infectious causes of acute hepatitis?
Viral: hepatitis A, B+/- D, C+E, human herpes viruses, influenza, SARS-CoV-2
Non-viral: spirochaetes (leptospirosis, syphilis), mycobacteria (M. tuberculosis), Bacteria (bartonella), parasites (toxoplasma)
99
What are non-infectious causes of acute hepatitis?
Drugs
Alcohol
Other toxins / poisoning
Non-alcoholic fatty liver disease
Pregnancy
Autoimmune hepatitis
Hereditary metabolic causes
100
What is liver cirrhosis?
The replacement of normal liver cells with fibrosis (scar tissue) forming nodules of scar tissue within the liver
101
what are the most common causes of liver cirrhosis?
Alcoholic liver disease
Non-alcoholic fatty liver disease
Hep B, hep C
102
What are the rarer causes of liver cirrhosis?
autoimmune hepatitis, PBC, haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cystic fibrosis, drugs (e.g. amiodarone, methotrexate, sodium valproate
103
What are the risk factors for liver cirrhosis?
Alcohol misuse
Intravenous drug use
Unprotected sex
Obesity
104
What are the key presentations of cirrhosis?
Jaundice (caused by raised bilirubin)
Hepatomegaly
Splenomegaly
105
What are the signs of cirrhosis?
Spider naevi (telengiectasia with a central arteriole and small vessels radiating away)
Palmar erythema (caused by hyperdynamic circulation)
Gynaecomastia + testicular atrophy in males
Bruising
Ascites
Caput medusae (distended paraumbilical veins due to portal hypertension)
Asterixis (flapping hand tremor in decompensated liver disease)
106
What are the investigations for cirrhosis?
enhanced liver fibrosis blood test
bloods
liver biopsy (GS)
USS
fibroscan
endoscopy
CT/MRI
107
What are the treatment options for cirrhosis?
High protein, low sodium diet
Consider liver transplant
Manage complications (malnutrition, portal hypertension, varices, ascites, carcinoma)
108
What is jaundice?
yellowing of the skin/eyes due to accumulation of conjugated/unconjugated bilirubin
109
what is pre-hepatic jaundice?
Excessive breakdown of RBCs overwhelm's the liver's ability to conjugate bilirubin which results in unconjugated hyperbilirubinaemia
110
What is intrahepatic jaundice?
Also known as hepatocellular jaundice. Dysfunction of the hepatocytes results in inability to conjugate bilirubin . This leads to unconjugated hyperbilirubinaemia. When the liver is cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction.
==> both unconjugated + conjugated bilirubin in the blood = 'mixed picture'
111
what is post-hepatic jaundice?
Obstruction of biliary drainage so that the bilirubin which is not excreted will be conjugated, leading to conjugated hyperbilirubinaemia.
112
What are the causes of pre-hepatic jaundice?
haemolytic causes:
- Haemolytic anaemia
- Gilbert’s syndrome
- Criggler-Najjar syndrome
- sickle cell
- G6PDH deficiency
- autoimmune haemolytic anaemia
- thalassaemia
- malaria
113
What are the causes of intrahepatic jaundice?
Alcoholic liver disease
Viral hepatitis
Iatrogenic, e.g. medication
Hereditary haemochromatosis
Autoimmune hepatitis
Primary biliary cirrhosis or primary sclerosing cholangitis
Hepatocellular carcinoma
114
What are the causes of post-hepatic jaundice?
Intra-luminal causes, such as gallstones
Mural causes, such as cholangiocarcinoma, strictures, or drug-induced cholestasis
Extra-mural causes, such as pancreatic cancer or abdominal masses (e.g. lymphomas)
115
What is Courvoisier sign?
Painless jaundice + palpable gallbladder
Most likely pancreatic cancer (or cholangiocarcinoma)
60-70% occur at head of the pancreas
116
What is Charcot triad?
fever, RUQ pain, jaundice
117
What is Reynold Pentad?
sign of obstructive ascending cholangitis --> dever, RUQ pain, jaundice (Charcot triad) + confusion/AMD, hypotension
118
What is Murphy sign?
RUQ tenderness; ask paitent to take breath in while pressing RUQ; will see them wince/stop inspiring normally => indicates cholecystitis
119
What is hepatic encephalopathy?
Neuropsychiatric syndrome caused by acute or chronic advanced hepatic insufficiency and or portosystemic shunt. Manifests as a wide spectrum of neurological or psychiatric abnormality ranging from subclinical alterations to coma.
120
What are 7 risk factors for hepatic encephalopathy?
Hypovolaemia
GI bleeding
Constipation
Excessive protein intake
Hypokalaemia
Hyponatraemia
Metabolic alkalosis
121
What are the key presentations of hepatic encephalopathy?
Mood, sleep or motor disturbances
Advanced neurological deficits (confusion, drowsiness → coma/unconsciousness)
122
What are the investigations for hepatic encephalopathy?
LFTs
Arterial/venous blood gas
urine toxin screen
abdo USS
123
What are the differentials for hepatic encephalopathy?
Brain tumours, subdural haematoma, acute stroke, meningitis
124
What is the management for hepatic encephalopathy?
Supportive care + reversal of precipitating factors + LACTULOSE
Rifaximin considered for patients with persistant symptoms
125
What is pancreatic cancer?
Adenocarcinoma of exocrine pancreas (99% cases).
126
What are the risk factors for pancreatic cancer?
Smoking
FHx
Other hereditary cancer syndromes
Chronic sporadic pancreatitis
Diabetes mellitus
Obesity dietary factors (↑alcohol intake, low folate and high meat + fat intake)
127
What percentages of pancreatic cancers affect the head, body and tail of the pancreas?
60% head
25% body
15% tail
128
What are the key presentations of pancreatic cancer?
head = Courvoisier sign (painless jaundice + palpable gallbladder) + pale stool, dark urine
body = epigastric pain radiating to back, relieved by sitting forward
129
What are the investigations for pancreatic cancer?
Pancreatic protocol CT
Abdo USS (1st line for body/tail cancer)
LFTs
Pancreatic protocol CT (GS)
PT, FBC, Cancer antigen, ERCP, PET scan, biopsy
130
What are the differentials for pancreatic cancer diagnosis?
Chronic pancreatitis, bile duct stones, ampullary carcinoma, cholangiocarcinoma
131
What is the treatment for pancreatic cancer?
Very poor prognosis (5yr survival = 3%)
Surgery + post-op chemo if no metastases
Otherwise palliative care
132
What is HCC?
Hepatocellular Carcinoma = Primary cancer arising from hepatocytes in predominantly cirrhotic liver
133
What are the risk factors for HCC?
Cirrhosis
Chronic hep B infection
Chronic Hep C cirrhosis
Chronic alcohol abuse
Diabetes
Obesity
FHx
Older age
134
What are the most common sites of HCC metastases?
lymph nodes, bones, lungs via haematogenous spread (hepatic/portal veins)
135
What are the key presentations of HCC?
Hepatomegaly
Abdominal distention
oesophageal /gastric variceal bleeding
RUQ abdo pain
136
What are the treatment options for HCC?
Surgical resection of tumour
Liver transplant (inly real cure)
137
What are the investigations for HCC?
May show ↑serum AFP
Abdo USS
CT
138
What is cholangiocarcinoma?
Cancer arising from the bile duct epithelium, can be divided depending on their location in the biliary tree: intrahepatic or extrahepatic
139
What are the risk factors for cholangiocarcinoma?
Age >50 yrs
Parasitic fluke worms
Cholangitis
Choledocholithiasis (stones in CBD)
Cholecystolithiasis (stones in gallbladder)
Ulcerative colitis
PSC
Cirrhosis
ALD
Hep B or C infection
HIV
140
What are the presentations of cholangiocarcinoma?
Abdo pain, jaundice, weight loss, pruritus, fevers
Courvoisier sign (more common with pancreatic cancer)
141
What are the investigations for cholangiocarcinoma?
Bloods: ↑CEA, ↑CA19-9, LFT = ↑bilirubin and ALP
Abdo USS + CT
ERCP (GS) - also treats by stenting structures on biliary tree
biopsy
142
What is the management for cholangiocarcinoma?
Majority of cases inoperable as patients present very late
If operable: partial liver resection
If inoperable liver transplant
143
What are the 3 main biliary tract diseases?
Gallstones, cholecystitis, ascending cholangitis
144
What are the risk factors for biliary tract disease?
Fat, female, 40+, fertile, FHx, T2DM, NAFLD, haemolytic conditions
145
What are gallstones?
hardened deposits of bile that can form in the gallbladder. 80% are made of cholesterol (yellow-green colour), others are made of bilirubin and are called pigment gallstones (smaller, dark in colour)
146
What is the main presentation of gall stones?
RUQ biliary colic (constant severe episodes of pain 30+ minutes) - worse after fatty meal
147
What are the bloods used in diagnosis of gallstones?
ALT (high if inflammation/infection)
Bilirubin (high if blocked biliary tree)
Amylase (high if pacreatitis present)
148
What is the diagnostic investigation for gallstones?
Abdo USS
149
What are the treatment options for gallstones?
elective laparoscopic cholecystectomy (if symptomatic), mild pain = NSAIDs, severe pain = IM diclofenac (strong NSAID) + lifestyle changes (↓fatty diet)
150
What is cholecystitis?
redness and inflammation of the gallbladder caused by bile becoming trapped within the gallbladder
151
What are the symptoms of cholecystitis?
RUQ pain + fever, tender gallbladder, may have referred pain to right shoulder tip, murphy sign
152
What are the investigations for cholecystitis?
FBC = leukocytosis + neutrophilia, LFT = normal, Abdo USS (thickened gallbladder wall 3mm+)
153
What is the treatment for cholecystitis?
surgery within 1 week = laparoscopic cholecystectomy, IV fluid, analgesia, Abx if needed
154
What is ascending cholangitis?
Ascending bacterial infection of the biliary tree
155
What are the symptoms of ascending cholangitis?
RUQ pain, fever, jaundice (Charcot’s triad) - obstructive → dark urine + pale stool
156
What are the investigations for ascending cholangitis?
FBC = leukocytosis + neutrophilia, LFT = ↑conjugated hyperbilirubinemia, Abdo USS (1st line) = CBD dilation + gallstones, MRCP (GS) = diagnostic + best pre-intervention management
157
what are the treatment options for ascending cholangitis?
ERCP (bile duct clearance) then laparoscopic cholecystectomy once stable to prevent recurrence
158
What is primary biliary cholangitis?
A chronic disease of the small intrahepatic bile ducts characterised by progressive bile duct damage occurring in the context of chronic portal tract inflammation.
159
What are the risk factors for PBC?
Age 45-60 yrs
Female
FHx of PBC/autoimmune disease
Smoking
UTI
160
What is the pathophysiology of PBC?
Autoantibodies cause intralobar bile duct damage; chronic autoimmune granulomatous inflammation. This results in cholestasis which leads to fibrosis, cirrhosis, portal hypertension and infection.
161
What are the key presentations of PBC?
Often asymptomatic initially, routine tests show ↑AMA
Pruritus + fatigue (earliest Sx), then jaundice, then hepatomegaly + Xanthelesma (cholesterol deposits in skin, often on/near eyelids)
162
What are the investigations for PBC?
LFTs (↑ALP, ↑conjugated bilirubin, ↓albumin)
Serology → (5% have AMA antibodies
USS (exclude extrahepatic cholestasis)
Liver biopsy (GS)
163
What is the management for PBC?
1st line → Ursodeoxycholic acid (bile acid analogue, dampens immune response + decreases cholestasis)
For pruritus → cholestyramine
Vitamin ADEK supplements, consider osteomalacia
May ultimately need liver transplant
164
What are the potential complications of PBC?
cirrhosis, malabsorption of fats + ADEK, osteomalacia, coagulopathy
165
What is PSC?
Primary sclerosing cholangitis = autoimune destruction of intra+extralobular hepatic duct
166
What are the risk factors for PSC?
Male (atypical as autoimmune disease usually affect more women than men)
40-50 yrs
Inflammatory bowel disease
167
What are the key presentations for PSC?
Initially asymptomatic, then pruritus, fatigue,m jaundice, Charcot triad (if CBD involved), hepatosplenomegaly, IBD
168
What are the investigations for PSC?
LFTs, Serology (HBVsAg/HCVAb -ve), AMA -ve, coeliac screen anti-tTG - ve, pANCA +ve in 33-88%
MRCP (gold standard)
169
What is the management for PSC?
Conservative symptom management;
Cholestyramine for pruritus
Fat soluble ADEK
Consider liver transplant
170
What is acute pancreatitis?
Acute inflammation of exocrine pancreas
171
What are the causes of acute pancreatitis?
Idiopathic
Gallstones
Ethanol
Trauma
Steroids
Mumps
Autoimmune
Scorpion sting/spider bite
Hypercalcaemia/hyperlipidaemia
ERCP
Drugs (azathioprine)
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What is the pathophysiology of acute pancreatitis?
Gallstones obstruct the pancreatic secretions which leads to accumulation of digestive enzymes in the pancreas.
Host defences (A1AT, pancreatic secretory transport inhibition) soon overwhelmed => autodigestion --> inflammation and leakage of enzymes into blood
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What are the key presentations of acute pancreatitis?
sudden severe epigastric pain radiating to back + jaundice, pyrexic, steatorrhoea, Grey Turner sign (flank bleeding), Cullen sign (periumbilical bleeding)
174
What are the investigations for acute pancreatitis?
Bloods = ↑serum amylase/lipase
Erect CXR to exclude gastroduodenal perforation
GS: Abdo USS
CT/MRI assesses extent of damage
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What is the management for acute emergency pancreatitis?
Nil by mouth
IV fluid
Analgesia e.g. IV morphine
Catheterise
Antibiotic prophylaxis
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What is Glasgow score for pancreatitis?
Scoring system for the severity of pancreatitis which gives a numerical score based on how many criteria are present
0 or 1 - mild pancreatitis
2 - moderate pancreatitis
3+ severe pancreatitis
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What are the criteria for the Glasgow Score?
P – Pa02 < 8 KPa
A – Age > 55
N – Neutrophils (WBC > 15)
C – Calcium < 2
R – uRea >16
E – Enzymes (LDH > 600 or AST/ALT >200)
A – Albumin < 32
S – Sugar (Glucose >10)
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What is chronic pancreatitis?
3 month Hx of pancreatic deterioration; irreversible pancreatic inflammation + fibrosis
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what are the causes of chronic pancreatitis?
alcohol (>75%)
CKD
trauma
recurrent acute pancreatitis
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What are the risk factors for chronic pancreatitis?
alcohol
smoking
FHx
coeliac disease
181
What are the key presentations of chronic pancreatitis?
epigastric pain exacerbated by alcohol
steatorrhoea
jaundice
weight loss + malnutrition
N+V
182
What are the investigations for chronic pancreatitis?
bloods - lipase, amylase
faecal elastase
abdo USS + CT (GS)
183
What is the management for chronic pancreatitis?
alcohol cessation
NSAIDs for pain
pancreatic supplements
184
what is portal hypertension?
pathologically increased pressure in portal vein
185
What are the causes of portal hypertension?
pre-hepatic: portal vein thrombosis
intra-hepatic: cirrhosis, schistosomiasis
post-hepatic: Budd Chiari, RHS heart failure, constrictive pericarditis
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What is the normal pressure in the portal vein?
5-8mmHg
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What is the pathophysiology of portal hypertension?
Cirrhosis increases resistance to flow in portal vein → splanchnic dilation and compensatory increase in cardiac output → fluid overload in portal vein (pressure >10 - bad, >12 = very bad)
Results in collateral blood shunting to gastrooesophageal veins (typically small → become oesophageal varices)
188
What are the key presentations of portal hypertension?
Mostly asymptomatic
present when oesophageal varices rupture
189
What are the investigations for portal hypertension?
Duplex Doppler USS
Pressure measurement studies
190
What is the management for portal hypertension?
BBs, otcreotide
Endoscopy to treat varices
Liver transplant
191
What are oesophageal varices?
Dilated collateral blood vessels that develop as a complication of portal hypertension, usually in the setting of cirrhosis
192
What are ascites?
accumulation of free fluid in abdominal cavity, complication of cirrhosis
193
What is the staging for ascites severity?
Stage 1: detectable only after careful examination/USS (mild)
Stage 2: easily detectable but of relatively small volume
Stage 3: obvious, but not tense ascites
Stage 4: tense ascites
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What are the causes of ascites?
local inflammation: peritonitis, TB, abdo cancer (ovarian especially)
low protein: nephrotic syndrome, hypoalbuminaemia (liver failure)
flow stasis (build up causes leakage): cirrhosis, Budd Chiari, congestive heart failure, constrictive pericarditis
195
what are the risk factors for ascites?
IV drug abuse
obesity
high cholesterol
T2DM
kidney disease
ovarian lesions
severe malnutrition
pancreatic, liver, or endometrial cancer
196
what is the pathophysiology of ascites?
- increased pressure in the portal system causes fluid leakage out of the capillaries in the liver and bowel and into the peritoneal cavity
- a drop in the circulating volume caused by loss into the peritoneal space causes a reduction in blood pressure entering the kidneys
- renin is release by the kidneys in response to the low pressure --> aldosterone secretion via RAAS and reabsorption of fluid and sodium into the kidneys
- cirrhosis causes a transudative (low protein content) ascites
197
what is the pathophysiology of ascites?
- increased pressure in the portal system causes fluid leakage out of the capillaries in the liver and bowel and into the peritoneal cavity
- a drop in the circulating volume caused by loss into the peritoneal space causes a reduction in blood pressure entering the kidneys
- renin is release by the kidneys in response to the low pressure --> aldosterone secretion via RAAS and reabsorption of fluid and sodium into the kidneys
- cirrhosis causes a transudative (low protein content) ascites
198
What are the key presentations of ascites?
Abdominal distension
shifting dullness
abdominal discomfort
weight gain
early fullness
SOB
with bacterial peritonitis, fever, tenderness in abdomen, confusion
199
What are the investigations for ascites?
bloods
USS
laparoscopy
200
What is the management for ascites?
low sodium diet
anti-aldosterone diuretics (spironolactone)
paracentesis
prophylactic antibiotics against bacterial peritonitis
201
what is SAAG?
the difference between the concurrently obtained serum albumin concentration and the albumin concentration of the ascitic fluid obtained during paracentesis
202
What is spontaneous bacterial peritonitis?
an infection of ascitic fluid that cannot be attributed to any intra-abdominal, ongoing inflammatory, or surgical correctable condition
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what is the aetiology of SBP?
infection of the ascitic fluid most commonly cause by E. coli, Klebsiella pneumoniae, gram +ve cocci (e.g. staphylococcus, enterococcus)
204
What are the risk factors for SBP?
decompensated hepatitis state (usually cirrhosis)
low ascitic protein/complement
GI bleeding
endoscopic sclerotherapy for oesophageal varices
205
What is the pathophysiology SBP?
develops through the haematogenous spread of bacteria with subsequent colonisation of the ascitic fluid
bacterial source is either intestinal or non-intestinal
206
What are the key presentations of SBP?
can be asymptomatic
fever abdominal pain
hypotension
ascites
GI bleeding
nausea/vomiting
diarrhoea
207
What are the investigations for SBP?
FBC, serum creatinine, ascitic fluid culture, blood cultures, ascitic fluid culture
208
What is the management for SBP?
piperacillin/tazobactam
cephalosporins
levofloxacin + metronidazole (alternative for penicillin allergy)
209
What is Wilson's disease?
excessive accumulation of copper in the body and tissues
210
What is the aetiology of Wilson's disease?
caused by a mutation in the WIlson disease protein (ATP7B copper-binding protein) on chromosome 13
211
What is the pathophysiology of Wilson's disease?
Impaired biliary copper excretion + normal transport bound to ceruloplasmin, ↑↑ copper accumulation in the liver and CNS (basal ganglia)
copper deposition in the liver leads to chronic hepatitis and eventually liver cirrhosis
212
What are the key presentations of Wilson's disease?
hepatic: liver disease e.g. jaundice
neurological: parkinsonian, memory issues
psychological: mild depression, psychosis
Kayser-fleischer rings (Cu deposits in cornea, greenish brown ringer appearance)
213
What are the investigations for Wilson's disease?
copper chelation using penicillamine, trientene
214
What is A1 antitrypsin deficiency?
An autosomal recessive genetic disorder which results in ineffective activity of A-1 antitrypsin, the enzyme responsible for neutralising neutrophil elastase (protease which digests connective tissues).
215
What are the risk factors for A1-antitrypsin deficiency?
32-41 yr old male
smoking history
exposure to gas, fumes and /or dust
FHx
216
What is the pathophysiology of A1 antitrypsin deficiency?
A1 antitrypsin is usually created in the liver but in the deficiency an abnormal "mutant" version of this protein is produced which gets trapped in the liver, builds up and causes liver damage --> cirrhosis and hepatocellular carcinoma (over time)
217
What are the key presentations of A1 antitrypsin deficiency?
COPD-like symptoms: productive cough, SOB exertion, barrel chest
Hepatomegaly
Ascites
Confusion
218
What are the investigations for A1 antitrypsin deficiency?
Serum A1 antitrypsin, barrel chest on exam
CXR shows hyperinflated lungs, CT = panacinar emphysema, LFT = spirometry show obstruction (FEV:FVC <0.7)
genetic test = +ve Serpina-1 gene mutation
219
What are the treatments for A1-antitrypsin deficiency?
no curative treatment
stop smoking
manage emphysema e.g. inhalers (SABAs, LABAs)
consider hepatic decompensation patients for liver transplants
220
What is haemochromatosis?
iron storage disorder that results in excessive total body iron and the deposition of iron in tissues
221
What is the aetiology of haemochromatosis?
autosomal recessive mutation of the human haemochromatosis protein (HFE) located on chromosome 6 --> most cases of haemochromatosis
other genes can also cause the condition
222
What are the risk factors for haemochromatosis?
2 copies of altered HFE gene
FHx
Ethnicity (white ancestry)
Male
223
What are the key presentations of haemochromatosis?
Chronic tiredness
Joint pain (iron deposits)
Bronze discoloration of skin
Hair loss
Erectile dysfunction
Amenorrhoea
Memory and mood disturbance
224
What are the investigations for haemochromatosis?
serum ferritin, transferrin saturation
genetic testin
CT abdomen
MRI scan
225
What is the management for haemochromatosis?
venesection (removes blood + therefore iron)
monitor serum ferritin
treat complications
226
what are the complications of haemochromatosis?
T1DM, liver damage, cirrhosis, pituitary/gonadal/thyroid iron deposition
227
What is the definition of a paracetamol overdose?
Ingestion of >75mg/kg paracetamol
228
What are the risk factors for paracetamol overdose?
Hx of self harm or overdose
drug/alcohol abuse
depression
unstable mental state
bipolar disorder
229
What is the pathophysiology of paracetamol overdose?
Normally 90% paracetamol metabolism is via the pathway of phase II conjugation (glucuronidation) → excretion
10% is metabolised via phase I conjugation which produces NAPQ1 (toxic) and this is metabolised by glutathione in phase II conjugation and then excreted.
In a paracetamol overdose the normal pathway is overrun leading to increased amounts being metabolised by the secondary pathway and there is insufficient glutathione to breakdown the drug causing a buildup of NAPQ1 in the liver → acute liver injury
230
What are the key presentations of paracetamol overdose?
acute severe RUQ pain, severe nausea + vomiting
asterixis, bruising, jaundice, oliguria/anuria, tachycardia/hypotension, coma
anorexia, malaise, altered mental state, confusion
231
what is the treatment for paracetamol overdose?
activated charcoal (within 1hr of overdose)
N-acetyl-cystene
232
What is Gilbert's syndrome?
Mild, non-haemolytic, unconjugated hyperbilirubinaemia, defined by bilirubin levels of <102micromol/L
233
What are the risk factors for Gilbert's syndrome?
male
T1DM
FHx
Post-pubertal age
234
What is the pathophysiology Gilbert's syndrome?
deficient or abnormal UGT --> ↑unconjugated hyperbilirubinaemia
235
What are the key presentations of Gilbert's syndrome?
30% = asymptomatic
painless jaundice
236
What are the investigations for Gilbert's syndrome?
unconjugated bilirubin, liver aminotransferase
FBC
genetic testing
237
What is a hernia?
protrusion of an organ through a defect in its containing cavity (most commonly the bowel)
238
What are 6 types of hernia?
- hiatal
- femoral
- inguinal
- umbilical
- incisional
- epigastric
239
What is a hiatal hernia?
stomach hernia through diaphragm aperture
240
What is the meaning of rolling and sliding hiatus hernias?
Rolling (20%) = left oesophageal sphincter stay in abdomen, part of fundus rolls into thorax
Sliding (80%) = left oesophageal slide into abdomen
241
What are the symptoms of hiatal hernia?
GORD, dysphagia
242
What are the investigations for hiatal hernia?
CXR, barium swallow (GS), oesophagogastroduodenoscopy
243
What is a femoral hernia?
Protrusion of the bowel through the femoral canal
244
What is the key presentation of femoral hernia?
swelling in the upper thigh (pointing down)
245
What are the investigations for femoral hernia?
USS abdo/pelvis if unsure but usually clinical diagnosis
246
What is an inguinal hernia?
Herniation of the spermatic cord through the inguinal canal
247
What are the risk factors for inguinal hernias?
male
Hx of heavy lifting/abdo pressure
248
What are the symptoms of inguinal hernias?
Painful swelling in the groin, points along the groin margin +/- reducible
249
What is an umbilical hernia?
loop of umbilical protruding through umbilicus
250
What are the symptoms of abdominal hernias?
abdo pain + tenderness, constipation, fever, full + round abdomen, vomiting
251
What is an incisional hernia?
protrusion of an organ through a surgical incision following surgery
252
What are the symptoms of incisional hernia?
constipation, nausea, vomiting, fever, tachycardia
253
What is an epigastric hernia?
protrusion of fat through a weak spot in the abdominal wall above the belly button and below the sternum of the rib cage
254
What are the symptoms of epigastric hernia?
tenderness and pain but often symptomless
