Hepatobillary Flashcards
1
Q
4 connections of the liver to the peritoneum
A
left triangular
right triangular
coronary ligament
falciform ligament (—> ligamentum teres –> round ligament connects to umbilicus)
2
Q
Blood supply of the liver
A
portal vein and the hepatic artery
3
Q
functions of the liver
A
- digestion - bile to digest fats
- metabolism (everything from the portal vein, particularly fatty acids –> ATP)
- detoxification
- storage (glycogen, vit KADE, B12, iron and copper)
- Produces: prothrombin, albumin and fibrinogen
- Immunity - produces Kuppfer cells that line the sinusoids, also produces immunoglobulins
- breaks down bilirubin
4
Q
Kuppfer cells
A
fixed macrophages part of the mononulcear phagocyte system
digests pathogens from the intestinal circulation
5
Q
What is on a LFT?
A
total bilirubin alt ast alt: ast ALP GGT albumin
6
Q
ALT
Alanine transaminase
A
raised in cell injury e.g. hepatocytosis / hepatitis
7
Q
High bilirubin in isolation
A
Gilbert’s disease
8
Q
GGT
gamma glutamyl transpepsidase
A
enzyme produced by the liver
induced by the liver
raised serum GGT in isolation –> indicates drinking
rises the same as ALP in bile duct pathology (but less specific)
9
Q
ALP
alkaline phosphatase
A
raised in bile duct pathology
also raised in bony disease - mets/ osteomalcia/ osteoporosis/ growing pains
10
Q
Other tests in liver pathology
A
Clotting Viral serology (HBV, HCV, HIV) ESR Urine MSU Ultrasound (elastography - fibroscan) Biopsy MRI ERCP (endoscopic retrograde cholangiopancreatography_
11
Q
Complications of ERCP
A
bleeding
acute pancreatitis
acute cholangitis
12
Q
Symptoms of liver pathology
A
Jaundice Bleeding (coagulopathy) RUQ pain Pain radiating to back on digesting fats Oedema/ Ascites Steatorrhoea Dark urine Increased drug toxicity Prone to infections Fatigue Malaise Itching
13
Q
Spider naevi
A
common and benign in isolation
more than 3 suggest liver disease
probable presence of oesophageal varices as well
caused by telangiectasis
14
Q
Signs of liver disease
A
Clubbing Palmar erythema Dupytrens contracture Hepatic flap Raised JVP Xanthalosmas Scleral jaundice Gynaecomastia Hepatomegaly Splenomegaly Spider naveii Acites (shifting dullness) Peripheral oedema Purpuric rash
15
Q
Sinusoid
A
- blood from hepatic artery & portal vein (mixed together)
- lined by hepatocytes and Kupffer cells
16
Q
Hepatocytes
A
line sinusoids
make bile acids, bile pigments and cholesterol
–> secreted into canaliculi
17
Q
Bile acid independent components of bile
A
produced by ductal cells that line the bile ducts
- stimulated by the hormone secretin
- makes bile alkaline
18
Q
Journey of bile
A
stored in the gall bladder
- r/l hepatic duct –> common hepatic duct –> gall bladder
–> cycstic duct –> common bile duct (joined by the pancreatic duct)
- enters the duodenum via ampulla of Vater
19
Q
Function of bile
A
- emulsifies fats
- digests fat soluble minerals and vitamins
- excretes bilirubin
- cholesterol homeostasis
- enterohepatic recirculation
20
Q
Bilirubin cycle
A
Haem –> uncongugated bilirubin (insoluble, yellow)
- -> conjugated in hepatocytes to glucuronic acid (soluble, green)
- -> biliary tree –> small intestine
–> urobilogen (by bacterial proteases ) excreted in stool (90%) and urine (10% - reabsorbed by portal circulation and is excreted by the kidneys)
21
Q
Pre-hepatic jaundice
A
increased breakdown of haemoglobin
- newborn jaundice
- malaria
- haemolytic anaemia
- sickle cell/ beta thalassemia
- polycythemia rubra vera (PCV)
22
Q
Pre-hepatic jaundice investigations
A
evidence of haemolysis - on FBC
- slightly elevated LFTs
23
Q
Hepatic jaundice (unconjugated bilirubin)
A
impaired bilirubin metabolism
- normally genetic (e.g. Gilberts syndrome)
24
Q
Hepatic jaundice (conjugated bilirubin)
A
hepatocyte damage usually with some cholestatis Causes: - Viruses - Drugs - NAFLD - AFLD - Pregnancy - Haemochromatosis - Autoimmune hepatitis
Pale stools and dark urine as excreted as urobilogen
25
Post hepatic jaundice
impaired hepatic excretion
- cholestatis --> pale stools and dark urine
- primary biliary cirrhosis, primary sclerososing cholangitis, tumours (pancreatic), pancreatitis, ascending cholangitis, strictures
26
Fulminant liver failure
massive necrosis of liver cells --> severe impairment of liver function + hepatic encephalopathy
-acute on chronic
27
Causes of fulminant liver failure
```
Hepatocellular carcinoma
Paracetamol overdose, isoniasid, Reyes syndrome
Acute fatty liver of pregnancy
Alpha-1 antitrypsin deficiency
Autoimmune hepatitis
Wilson's disease
Viral hepatits
```
28
Hepatic encephalopathy
Causes
Protein metabolism --> alanine --> pyruvate and glutamine
glutamine + NH3 --> glutamate --> urea
Ammonia crosses BBB into astrocytes --> glutatmate --> glutamatine
Glutamine has a strong osmotic affect --> cerebral oedema
29
Hepatic encephalopathy
Jaundiced patient
Small liver
Clotting dysfunction
1. Altered mood/ behaviour, sleep distrubance (reversal of sleep pattern) and dyspraxia. No liver flap.
2. increasing drowsiness, confusion, slurred speech and liver flap, inappropriate behaviour/ personality change
3. Incoherent, restless, liver flap, stupor,
4. Coma
30
Hepatic encephalopathy investigations
```
LFT - raised ALT/AST, sky high bilirubin
derranged clotting -INR
U&E, FBC, glucose, paracetamol level, viral serology
EEG
CT head
Cultures - blood, urine, ascitic fluid
```
31
Management of hepatic encephalopathy
| Transfer to specialist liver unit
1. INR > 3
2. Presence of encephalopathy
3. Hypotension after fluid resus
4. Metabolic acidosis
5. Deterioration of prothrombin time
32
Management of hepatic encephalopathy/ fulminant liver failure
1. Assessing for transfer to specialist
- -> if paracetamol OD N-acetyl cysteine
2. Sepsis
3. Manage coagulopathy
4. Fluid status
5. Blood glucose
consider enemas/ lactulose to reduce nitrogenous producing bacteria
TRANSPLANT
33
Metabolic liver diseases
- haemachromatosis
- Wilson's disease
- alpha-1 antitryspin deficiency
34
Haemachromatosis (hereditary)
one of the most common inherited conditions in europe.
- -> increased absorption of iron, reduced function of transferrin
- accumulates in the liver (as this is where Fe is stored), heart, skin, endocrine tissue --> fibrosis --> cirrhosis
- treat with chelation and regular venesection
35
Haemachromatosis symptoms
Early --> tiredness, arthralgia
Initial skin bronzing --> slate grey skin
```
Triad of
Bronzed skin (increased melanin), massive hepatomegaly, DM, (hypogonadism, cardiomyopathy/ arrythmias, increased risk of HCC)
```
36
Haemochromatosis investigations
Fe and Ferritin
Normal LFTs
Genetic testing
Fibroscan
37
Haemochromatosis treatment
Venesection 1 unit every 1-3 weeks
Monitor HbA1C
38
Wilson's disease
Heptatolenticular degenertaion
rare, recessively inherited disorder
- decreased secretion of copper into biliary system
- reduced incorporation of copper into procaeruloplasmin (precursor of caeruloplasmin)
39
Symptoms of wilsons disease
copper accumulates in
- liver -->cirrhosis and fulminant liver failure
- basal ganglia of the brain --> parkinsonism & dementia
- cornea --> Kayser-Fleischer rings
- renal tubules
40
Diagnosis of Wilsons
low total serum copper & caeruloplasmin
increased 24 hr urinary copper excretion
increased copper in a liver biopsy specimen
41
Treatment of wilson's disease
Chelation: penicillamine or trientene
Reduce copper absorption: zinc
Liver transplant with end-stage liver disease
42
Alpha-1 anti-tripsin deficiency
reduced hepatic production of a1-AT (normally inhibits proteolytic enzyme --> neutrophil elastase
- genetic variants medium (M), slow (S) or very slow (z)
Chronic liver disease due to accumulation of abnormal protein in the liver & early onset emphysema
43
Diagnosis of Alpha-1 anti-tripsin deficiency
low serum a1-AT, genotype assessment
| histology: a1-AT containing globules in hepatocytes
44
Treatment of Alpha-1 anti-tripsin deficiency
as for chronic lung and liver disease
| smoking cessation, IV augmentation of a1-AT
45
Fatty liver disease
alcoholl
steatosis -->
hepatocytes contain macrovesicular droplets of triglycerides
- typically asymptomatic
- may be hepatomegaly
- lab tests normal (may have elevated MCV and gamma GT)
46
Alcoholic hepatitis
biopsy
ballooned hepatocytes that contain amorphous eosinophillic material --> Mallory bodies
- fibrosis and foamy degeneration of hepatocytes
47
Clincial features of AFLD
```
rapid onset jaundice
nausea
anorexia
RUQ pain
encephalopathy
fever
ascities
tender hepatomegaly
```
48
Investigations of AFLD
FBC- leucocytosis, elevated MCV, thrombocytopenia
Serum Electrolytes- hyponatraemia, elevated serum creatinine indicates hepatorenal syndrome
- LFTs- elevated AST &AKT - disproportionate rise in AST, raised, bilirubin, low serum albumin and prolonged PT
-MC&S
-USS - liver & biliary tree
- Liver biopsy
49
Management of alcoholic hepatitis
supportive treatment
adequate nutrional intake
corticosteroids (40mg/day for 4 weeks) reduce inflammatory process (CI in renal failure, infection or bleeding)
50
Alcoholic cirrhosis
- final stage of liver disease from alcohol abuse
- destruction of liver archetcture & fibrosis
regenerating nodules produce micronodular cirrhosis
Pts may be asymptomatic
51
Primary sclerosing cholangitis
chronic chloestatic liver disease
progressive obliterating fibrosis of intra & extrahepatic ducts --> cirrhosis
- Cholangiocarcinoma in 15% pts
- may be caused by cryptosporidium infection in pts with AIDS
- raised ALP
52
Symptoms of PSC (primary sclerosing cholangitis
pruritus, jaundice or cholangitis
| 60% ANCA positive
53
Diagnosis of PSCE(primary sclerosing cholangitis)
MRCP (magnetic resonance cholangiopancreatography)
Liver biopsy
54
Treatment of PSC (primary sclerosing cholangitis)
ERCP
| High dose ursodeoxycholic acid may slow disease progression
55
Budd Chiari syndrome
occlusion of hepatic vein obstructs venous outflow from the liver
- -> stasis & congestion within the liver
- -> hypoxic damage and necrosis of hepatocytes
56
Budd Chiari syndrome
aetiology
hypercoaguable state associated with:
- myeloproliferative disorders
- malignancy
- oral contraceptives
- inherited thrombophilias
57
Budd Chiari syndrome
Clinical features
depends on extent & rapidity of hepatic vein occlusion
- venous collateral circulation may have developed
- RUQ pain, hepatomegaly, jaundice & ascites
- acute may present with fulminant hepatic failure
- chronic --> cirrhosis --> portal hypertension & varices
58
Investigations of Budd Chiari syndrome
Doppler US
- abnormal flow in major hepatic vein or IVC
- thickening, tortuosity & dilatation of the walls of the hepatic veins
- Hepatosplenomgaly, ascites & caudate hypertrophy
59
Treatment of Budd Chiari syndrome
- Restore hepatic venous drainage (thrombolysis, angioplasty, stent or TIPS)
- treatment of complications of ascites/portal HTN
- detection & treatment of underlying hypercoaguable disorder
60
Gall stone formation (cholesterol)
excess of cholesterol in bile
- either relative deficiency of bile salts and phospholipids
- relative excess of cholesterol (supersaturated or lithogenic bile)
61
Gall stone formation (pigment stones)
bilirubin polymers and calcium bilirubinate
- pts with chronic haemolysis e.g. hereditary spherocytosis and sickle cell disease & cirrhosis
- may also form after cholecystectomy with duct strictures
62
Clinical presentation of Gall Stones
Biliary pain
- recurrent episodes of severe constant pain RUQ
- subsides after several hours
- may radiate to right shoulder/ right sub-scapular
- often associated with vomiting
63
Risk factors for cholesterol gallstones
```
Increasing age
female
Family history
Multiparity
Obestity ± metabolic syndrome
Rapid weight loss
Diet
Ileal disease/resection
DM
Acromegaly
Liver cirrhosis
```
64
Gall stone investigations
- History and USS
- Raised serum alkaline phosphate & bilirubin
- absence of inflammatory features (fever, WCC, local peritonism differentiates from acute cholecystitis)
65
Management of Gall Stones
- analgesia
- elective cholecystectomy
- Abnormal LFTs/ dilated common bile duct = pre-operative MRCP
66
What is acute cholecystitis?
impaction of a stone in the cystic duct or neck of gall bladder
67
Clinical features of acute cholecystitis
- similar to biliary colic
- progression to severe pain localised in RUQ
- fever and tenderness with muscle guarding
- Pain worse on inspiration (Murphy's sign)
68
Complication sof acute cholycystitis
empyema
| perforation with peritonitis
69
Acute Cholecystitis Investigations
WCC- leucocytosis
Serum liver Biochem- may be mildly abnormal
Abdominal US - gall stones and distended gall bladder
70
Management of cholecystitis
conservative- NBM, IV fluids, analgesia & IV abx (cefotaxime)
Cholecystectomy within 48hrs
71
Acute cholangitis
infection of biliary tree
72
Causes of acute cholangitis
```
secondary to obstruction by gall stones
biliary strictures after surgery
chronic pancreatitis
PSC
HIV cholangiopathy
Biliary stents
```
73
Clinical features of acute cholangitis
Charcot's triad: Fever (with rigors), Jaundice, RUQ pain
74
Investigations for Acute Cholangitis
```
WCC- leucocytosis
+ Blood cultures (E. Coli)
LFTs - cholestatic pic (raised serum bilirubin & ALP)
USS - dilated CBD
MRCP
ERCP
```
75
Management of Acute Cholangitis
Resuscitation and volume replacement
Pain relief
IV Abx ((cefotaxime/ ciprofloxacin) + metronidazole)
Relief of Obstruction - ERCP ± sphincterotomy
76
Pathogenesis of Acute pancreatitis
- elevation in intracellular calcium
- leads to activation of intracellular proteases & release of pancreatic enzymes
- Acinar cell injury & necrosis --> promotes migration of inflammatory cells from microcirculation into the interstitium
- -> local inflammatory response, systemic inflammatory response, single/ multiple organ failure
77
Clinical features of acute pancreatitis
epigastric or upper abdominal pain radiating through to the back + Nausea & Vomiting
- Epigastric/ general abdo tenderness, guarding and rigidity
- Coma & Multi-organ failure
Eccymosis around the umbilicus (Cullen's sign) or flanks (Grey Turner's sign) indicate severe necrotising pancreatitis
78
Causes of Acute Pancreatitis
I: Idiopathic
G: Gall stones
E: Ethanol (alcohol)
T: Trauma
```
S: steroids
M: Mumps/ Malignancy
A: Autoimmune
S: scorpion sting/ spider bite
H: Hyperlipidaemia/ hypercalcaemia
E: ERCP
D: Drugs
```
79
Causes of Chronic Pancreatitis
```
Alcohol
Tropical diseases
Autoimmune
Idiopathic
Hereditary - trypsinogen and protein defects, cystic fibrosis
```
80
ACute Pancreatitis blood tests
LFTS- raised serum amylases/ lipase
| FBC/ CRP/ U&Es/ ABG/ plasma calcium
81
Acute Pancreatitis radiology
Erect CXR - exclude peptic ulcer
Abdominal USS
Spiral CT/ MRI
82
Management of Acute pancreatitis (mild disease)
| lasts 5-7 days
```
Medical therapy
-pain control (avoid opioids)
NBM
IV fluids (may need up to 5L / day)
?NG tube
monitor for complications
```
83
Management of Acute pancreatitis (predicted severe disease)
```
Medical therapy
Consider HDU/ ITU
Prophylactic Abx
NG/NJ feeding
ERCP
```
84
Complications of acute pancreatitis
Acute- hyperglycaemia, hypocalcaemia, renal failure, shock
85
Pathogenesis of chronic pancreatitis
inappropriate activation of enzymes leads to precipitation of protein plugs within the duct lumen
--> nidus for calcification
--> Cytokine activation --> pancreatic inflammation, irreversible morphological changes ± permanent impairment of function
86
Clinical features of chronic pancreatitis
-Epigastric abdominal pain (intermittent or constant)
radiating to the back
- Severe weight loss (due to anorexia)
- DM & steatorrhoea (due to endocrine (insulin) and exocrine (lipase) insufficiency)
- Jaundice due to CBD obstruction
87
Investigations for chronic pancreatitis
Abdo X-ray / US / CT- pancreatic calcification
MRCP / endoscopic US
Functional assessment - feacal elastase (reduced)
88
Treatment of chronic pancreatitis
- stop drinking alcohol
- opiates for pain relief
- surgical resection with drainage of pancreatic duct into small bowel
- ERCP for small stones or strictures
- pancreatic enzyme supplication
89
Epidemiology of pancreatic Ca
5th most common causes of cancer death in the western world
men more than women
incidence increases with age (most >60)
Adenocarcinomas of ductal origin
90
Aetiologyy of pancreatic Ca
Hereditary
environmental - smoking & obesity
Chronic pancreatitis is pre-malignant
91
Clinical features of pancreatic Ca
head of pancreas/ ampulla of vater
painless jaundice (obstruction of CBD) with classic scratch marks and palpable gall ladder (Coursoisier's law)
weight loss
Central Abdominal mass
92
Clinical features of pancreatic Ca
Body or tail
```
abdominal pain
weight loss
anorexia
DM
increased risk of thrombophlebitis
```
93
Incestigation sof pancreatic Ca
Diagnosis made by USS/ contrast CT
MRI & endoscopic US for staging
ERCP for palliation
94
Management of pancreatic ca
surgical resection
Chemo-radiotherapy
endoscopic stenting for palliation
95
Prognosis of pancreatic ca
```
vey poor (30-40% 3 yr survival)
locally advanced disease 8-12 months
metastatic disease 3-6 months
```
96
Cancer of the bile ducts
epidemiology
disease of the elderly with poor prognosis
| common in primary sclerosing cholangitis, congenital bile duct abnormalities & infection with liver flukes
97
Cancer of the bile ducts presentation
jaundice secondary to bile duct obstruction of metastatic disease
imaging shows bile duct stricture, hilar mass or multiple mets
98
Gilbert's syndrome
common congenital hyperbilirubinaemia
asymptomatic - often found as incidental finding
mutation of UDP-glucuronyl transferase = reduced enzyme activity and reduced conjugation of bilirubin with glucuronic acid
99
Diagnosis of Gilbert's syndrome
uncongugated hyperbilirubinaemia
normal lFTS
normal FBC/ smear and reticulocyte count
Abscence of signs of liver disease
100
Autoimmune hepatitis
aetiology
Immunological abnormalities
- hypergammaglobulinaemia with high IgG
- presence of circulating autoantibodies
- interface hepatitis with portal plasma cell infiltration on liver histology
101
Autoimmune hepatitis
clinical features
```
Anorexia
Malaise
Nausea
Fatigue
25% acute
75% chronic with signs of liver disease
```
102
Autoimmune hepatitis
Investigations
Circulating antibodies
(anti-nuclear, smooth muscle, soluble liver antigen, liver/kidney microsomal antibodies)
Hypergammaglobulinaemia
Elevated serum bilirubin and aminotransferases
103
NAFLD
Associations
Obesity
T2DM
HTN
Hyperlipidaemia
104
Clinical features of NAFLD
- asymptomatic
- elevated aminotransferases on LFTs
- hepatomegaly on examination
105
Investigations of NAFLD
USS - hyperechoic texture due to diffuse fatty infiltration
106
Management of NAFLD
Management of risk factors
107
What is Cirrhosis?
Necrosis of liver cells followed by fibrosis and nodule formation
impairment of liver cell function & gross distortion of the liver architecture--> portal hypertension
108
Pathology of cirrhosis
| - micronodular
uniform small nodules of up to 3mm in diameter
| - caused by ongoing alcohol damage or biliary tract disease
109
Pathology of cirrhosis
| - macronodular
variable nodule size and normal acini with large nodules
| - seen after chronic viral hepatitis
110
Clinical features of cirrhosis
Secondary to portal hypertension & liver cell failure
| Decompensated cirrhosis - encephalopathy, ascites, variceal haemorrhage
111
Investigations of cirrhosis
LFTs, FBC, Serum electrolytes, liver biochem, serum alpha-fetoprotein
112
aetiology of cirrhosis
response to chronic liver injury
113
Further investigations of cirrhosis
Endoscopy - oesophageal varices
USS - Hepatocellular carcinoma
DEXA for osteoporosis
114
Management of cirrhosis
irreversible & frequently progresses to HCC
| Management of complications as they arise
115
Pre-hepatic causes of portal hypertension
portal vein thrombosis
116
INtra-hepatic causes of portal hypertension
```
Cirrhosis
Alcoholic hepatitis
Idiopathic non-cirrhotic portal hypertension
Schistosomiasis
Veno-occlusive disease
```
117
Post-hepatic causes of portal hypertension
Budd-Chiari syndrome
Right heart failure
Constrictive pericarditis
IVC obstruction
118
What is the portal vein?
Union of the supermesenteric and splenic veins
75% of hepatic blood flow
enters the liver through the hilum (porta hepatis)
blood passes into hepatic sinusoids via portal tracts
119
Clincial features of portal hypertension
- GI bleeding from oesophageal or gastric varices
- Ascites
- Hepatic encephalopathy
120
Aetiology of Ascites
peripheral arterial vasodilation reduces effective blood volume
--> activation of sympathetic nervous system and renin-angiotensin system
--> renal salt and water retention
Formation of oedema encouraged by hypoalbuminaemia
localises in abdominal cavity as a result of portal HTN
121
Clinical features of ascites
Fullness in flanks
Shifting dullness
Tense ascites is uncomfortable - produces respiratory distress
Pleural effusion and peripheral oedema may also be present
122
Investigation of ascites
```
Aspiration
Serum albumin
FBC
gram stain and culture/ cytology
Amylase to exclude pancreatic ascites
```
123
Transudate causes of ascites
low protein content
low specific gravity
```
portal HTN
Hepatic outflow obstruction
Budd-Chiari
Hepatic veno-occlusive disease
cardiac failure
tricuspid regurgitation
constrictive pericarditis
Meig's syndrome
```
124
Exudate causes of ascites
```
Peritoneal carcinomatosis
Peritoneal TB
Pancreatitis
Nephrotic syndrome
Lymphatic obstruction (chylous ascites)
```
125
Management of Ascites
Diuretics (furosemide)
Paracentesis
Transjugular intrahepatic portsystemic shunt (TIPS)
126
Complications of Ascites
- Spontaneous bacterial peritonitis (e.coli- IV cefotaxime)
127
Primary biliary cirrhosis
Chronic disorder with progressive destruction of intrahepatic bile ducts causing cholestatis --> cirrhosis
128
Epidemiology of primary biliary cirrhosis
women 40-50
129
Aetiology of Primary biliary cirrhoiss
inherited abnormality of immunoregulation - leads to T-lymphocyte mediated attack of bile duct epithelial cells
Possible environmental trigger
AMA antibodies
130
Clinical features of primary biliary cirrhosis
```
Pruritis ± jaundice
hepatosplenomegaly
xanthelasma
raised serum ALP & autoantibodies
Steatorrhoea
```
131
Primary biliary cirrhosis investigations
Raised serum ALP
Serum AMA (antimitochondrial antibodies)
Raised Serum IgM
Liver biopsy --> loss of bile ducts, lymphocyte infiltration at portal tracts, granuloma formation --> fibrosis --> cirrhosis
132
Management of primary biliary cirrhosis
lifelong ursodeoxycholic acid
colestyramine for pruritus
Supplementation of fat soluble vitamins
Liver transplant in severe disease
