The Digestive System - Pancreas and Liver Flashcards
1
Q
Imaging modalities of hepatobilliary system
A
Ultrasound (trans-abdominal and endoscopic)
CT
MRI
Nuclear med e.g. PET staging
Angio e.g. tumour embolisation
Radiographs - not v useful
2
Q
Functions of liver
A
Helps manage body’s metabolism
Bile production
Detoxification
3
Q
What is the liver covered by
A
Serous membrane (visceral peritoneum) that suspends liver form Abdominal wall and diaphragm
5 peritoneal folds (ligaments)
4
Q
Ligaments of liver
A
Coronary
L triangular
R triangular
Falciform
Round
5
Q
Lobes of liver
A
R & L - seen from superior view
Also posterior caudate lobe and anterior quadrate lobe - seen from inferior view
6
Q
What is the posterior caudate and a anterior quadrate lobes of the liver separated by
A
Porta hepatitis - hepatic artery, hepaxtcic portal vein, common hepatic duct
7
Q
Role of hepatic artery
A
Carries oxygen-rich blood from heart
8
Q
Role of hepatic portal vein
A
Carries nutrient-rich blood from GI system incl pancreas
9
Q
Role of common hepatic duct
A
Drains bile from liver into gallbladder
10
Q
Functional unit of liver
A
Hepatic lobules
11
Q
Portal triad of liver
A
Hepatic artery
Portal vein
Common bile duct
Blood vessels drain into sinusoids, before scarring blood to central vein
12
Q
What do hepatocytes act as a store for
A
Vitamine A, D, E, K, B12
Minerals incl Fe and Cu
13
Q
Synthesis as a function of heptovytes
A
Proteins incl albumin and coag factors
Lipoporteins inlc VLDL and HDL
14
Q
Stellate reticuloendothelial cells
A
AKA Kupffer cells
Destroys old RBCs, WBCs, bacteria and foreign substances
15
Q
Why do we need bile
A
Digestion
Absorption of fat and fat-soluble vitamins in small intestine
Has a role in immunological defence
16
Q
Bile composition
A
Bile salts (from cholesterol)
Water
IgA
Bilirubin
17
Q
Where is bile canaliculi found
A
Between adjacent hepatocytes
Drains into bile ductules –> bile ducts
18
Q
Ducts in gallbladder
A
R and L hepatic duct combine to for common hepatic duct
Common hepatic duct combines with cystic duct to bring bile to gallbladder
19
Q
How does drug metabolism in the liver typically work
A
Process turns lipophilic molecules into hydrophilic molecules which can be excreted/ eliminated
20
Q
3 phases of drug metabolism
A
Phase 1 - modification (mainly CYP450)
Phase 2 - conjugation
Phase 3 - further modification and excretion
21
Q
Common reactions in phase 1 of drug metabolism
A
Oxidation
Sulphodixation
Dealkylation
Deamination
22
Q
Factors affecting drug metabolising enzymes
A
Pregnancy
Age
Gender
Polymorphisms
Organ transplant
Liver disease
Kidney disease
Drug-drug interaction
Infl mediators
DM
23
Q
Why are LFTs an over-simplification
A
Poor markers of synthetic function (ability to make things)
Severe liver disease can occur w/out abnormal LFTs
24
Q
What do LFTs consist of
A
Bilirubin
Albumin
Globulin
ALT
ALP
Gamma GT
NOTE - platelet count, prothrombin time (INR)
25
What may cause a high bilirubin
Over production of bilirubin or failure of excretion
26
Causes of increased bilirubin production --> hyperbilirubinaemia
Haemolysis
Ineffective erythropoiesis
Blood transfusion
Resorption of haemotomas
27
Causes of decreased hepatic uptake ---> hyperbilirubinaemia
Gilberts's syndrome (also decreased conjugation)
Drugs e.g. rifampicin
28
Where are aminotransferases found
Liver, muscle, heart, kidney, brain and pancreas
Intracellular enzymes released injured hepatocytes
29
What are aminotransferases a measure of
Necro-infl
30
Types of aminotransferases
Alanine aminotransferase (ALT) and aspartate aminotrasnbferase (AST)
ALT is more liver spp
ALT: AST ratio can be useful
31
Causes of raised aminotransferases - pathology
Alcohol
NAFLD
C/c hep B and C
CCF
32
Causes of raised aminotranferases - disorders
AI diseases
Haemachromatosis
Wilsons - excess Cu
A1AT deficiency
Coeliac
33
Meds causing raised transaminases
NSAIDs
Abx
HMG-CoA reductase inhibitors
Antiepileptic drugs
Anti-TB drugs
Illicit drugs use
34
ALP as an LFT
Sensitive test for biliary obstruction but not spp
35
Physiological causes for raised ALP
Women in 3rd trimester of pregnancy
Adolescents
Benign, familial
36
Pathological causes for raised ALP
Bile duct obstruction
PBC
PSC
Drug-induced cholestasis
Metastatic liver disease
Bone disease
37
Where is gGT present
In many organs, found particularly high in epithelial cells lining bile ducts
38
gGT as a maker of biliary obstruction
Typically associated w/ ALP
39
What is gGT inducible by
Alcohol
Phenytoin, carbamazepine, barbiturates
Sex hormones
40
Causes of raised gGT
Pancreatic disease
Alcopholism
COPD
Renal failure
DM
MI
41
Hepatitic vs cholestatic picture of LFTs
Hepatitic - Increased ALT and AST (ALT > ALP), increased alb, c/c low albumin
Cholestatic - increased gGT and ALP (ALP > ALT)
42
Haematological tests as LFTs
Prothrombin time is best marker of synthetic function - increased INR
Platelets best marker of portal HTN
Low albumin (typically seen w/ raised CRP)
43
AST: ALT ratio
ALT: AST 2:1 in alcohol related liver disease
ALT: AST in NAFLD and c/c viral hep approaches 1:1 as fibrosis progresses
44
Gilbert's syndrome
Inability to correctly conjugate bilirubin
45
Anatomy of pancreas
Soft, lobulated retroperitoneal organ
Crosses the trabnspyloric plane
Consists of head, neck, body and tail
46
Where is uncinate process of pancreas found
Behind superior mesenteric vessels
47
Where is the neck of pancreas found
In front of portal veins
48
Where is the tail of the pancreas found
Touches hilum of spleen
49
Why is the pancreas' rship to the lesser sac important
In pancreatitis, lesser sac can fill with fluid
50
2 components of pancreas as a gland
Exocrine
Endocrine
51
Which anatomical structures are anterior to the pancreas
Stomach
Lesser sac
SMA
52
Which anatomical structures are posterior to the pancreas
Aorta
IVC
R renal artery
R & L renal veins
Superior mesenteric vessels
Splenic veins
Hepatic portal vein
L kidney
L suprarenal gland
53
Which anatomical structures are superior to the pancreas
Splenic artery
54
Which anatomical structures are lateral to the pancreas
Spleen
55
Which anatomical structures are medial to the pancreas
Duodenum (descending and horizontal parts)
56
Where is the head of pancreas found
Lies in loop of D1/D2 as it exits stomach
57
Types of tissue in pancreas
Endocrine (tubular) - 90%
Endocrine (islets) - 2%
Interstitial
58
Where is exocrine tissue found in the pancreas
Surrounding interlobular ducts
59
Examples of endocrine cells in pancreas
Islets store their hormones in distant locations
Beta - insulin
Alpha - glucagon
Delta - SST
PP (pancreatic peptide) - beta cells
60
PP in disease response
Beta cells get replaced with these in 2' DM
61
Interstitial tissue of pancreas
Specialised pancreatic stellate cells involved in fibrogenesis of pancreatitis and cancer
Ca deposition in c/c pancreatitis
62
Functional unit of pancreas
Lobules
63
Structure of ducts in pancreas
Interlobular ducts come off main duct of pancreas
Interlobular ducts go INTO lobules
Intercalated ducts go into acinus (secretory epithelium)
64
Effect of autonomic nervous system on pancreas
Heavily innervated by ANS
Regulates glandular production
Regulate blood flow
65
What do pancreatic acinus cells make
Enzymes and zymogens
These are then secreted into lumen of duct
66
What are proteases produced as zymogens
Proteases are v powerful
Only activated at small bowel
67
Examples of zymogens
Trypsinogen
Chymotrypsiongen
Proelastase
68
Examples of active enzyme produced by pancreas
Alpha amylase
Lipase
RNAase
DNAase
69
Control of exocrine secretion of pancreas
Response to meal - cephalic, gastric and intestinal phase
Other important driver incl acid in small intestine, fat, proteins and bile acids
Protease levels in gut stimulate/inhibit secretion via -ve feedback
70
Pancreatic secretions
Mixture of fluid, bicarb and digestive enzymes in response to variety of n neurotransmitters and hormones
71
Activation of zymogens
Important in pathophysiology of a/c pancreatitis
Trypsinogen comes out of pancreas and is activated by enterokinase to form trypsin, which then activates all the other zymogens
72
Common pancreatic procedures
Pancreatomies but pancreatic soaring surgery
Whipple's procedure
Frey's procedure
73
Whipple's procedure
Pancreaticoduodenectomy
Complex procedure to remove head of pancreas, duodenum, gallbladder and bile duct
74
Issues w/ Whipple's procedure
Issues w/ sterility of small bowel - can cause bacteria overgrowth and small bowel should be sterile
75
When is Frey's procedure done
For benign lesions
76
Where are pancreatic ductal cells found
Just after acinus - cemntroacinar cells (carbonic hydrase)
77
Proximal vs distal intercalated pancreatic ductal cells
Proximal - low cuboidal
Distal - more cuboidal/ columnar and contain more vesicles and granules
78
Main job of pancreatic ductal cells
Make a bicarb rich fluid
79
What happens as more HCO3- is secreted in pancreatic secretion
More Cl- is reabsorbed
Link between CF and c/c pancreatitis
80
How are biliary canaliculi held together
By gap junction between two heoaocytes
Adherens junctions
Tight junctions
81
How does water enter biliary canaliculi
Water can enter via aquaporin 8 (regulated by cAMP) and aquaporin 9
Also paracellular & transcellular
82
Pathways to make bile slats
Classical
Alternative
Neural (extra-hepatic)
83
What are bile salts produced from
Cholesterol
84
What are the primary bile slats
Cholic acid
Chenodeoxycholic acid
85
Secondary bile acids
Primary bile salts that have been conjugated and then chemically modified in the intestine
86
Examples of 2' bile acids
Deoxycholic acid
Lithocholic acid
UDCA
87
What is hepatitis
A/c or c/c parenchymal liver damage
88
Dominant sx of hepatitis
Jaundice (icterus)
Detectable clinically when the serum bilirubin >50 mmol/L
89
What is hepatitis associated with in the liver
Rise fo ALT in plasma
Los of excretory and synthetic functions
90
Describe the variability of the extent if damage in hepatitis
V variable
From spotty or focal necrosis to massive hepatic necrosis
There is also infiltration of portal tracts and lobules by lymphocytes
91
Histological features of hepatitis
Hepatocytes shows degenerative changes
Hepatocytes undergo necrosis
Necrosis is maximal in zone 3
92
Degernative changes seee in hepatocytes in hepatitis
Swelling
Cytoplasmic granulation
Vacuolation
93
Necrotic changes seen in hepatocyte sinhepatitis
Become shrunken
Eosinophilic Councilman bodies
94
Causes of hepatitis
Viral infections
Drug induced (e.g. paracetomol)
Alcohol
NAFLD
AI hepatitis
95
Systemic viral infections causing hepatitis
EBV and CMV, HSV, VSV
Yellow fever
VHF
Rubella
Mumps
Coxsackie B
96
Px of hepatitis
Abdo pain
Pruritus
Muscle and joint aches
N & V
Jaundice
Fever (viral cause)
97
Features of Hep C
HCV is usually symptomless for decoded while damaging liver
Accounts for 70% cases of c/c liver disease
RNA virus spread by blood and bodily fluids
98
Signs of hepatitis
RUQ pain
Hepatomegaly
Jaundice
Pyrexia
99
Transmission of HCV
Parenteral
Permucosal - sexually
Vertical
100
Which condns are HCV associated w/
Liver disease
DM
B-cell proliferative disorders
Depression
Cognitive
101
Risk factors associated w// HCV
Tranfusion/ transplant w/ unsterilised equipment
IVDU
Haemodialysis (duration of treatment)
Multiple sex partners
102
Natural hx of HCV
Most pts (80%) fail go clear virus and develop c/c hepatitis (>6/12) ---> cirrhosis, HCC
103
Features of c/c HCV infection
C/c persistent hepatitis
Cirrhosis
HCC
Extrahepatic disease - mixed essential cryoglobulinaemia, Glomerulonephritis, sporadic porphyria cutanea tarda
104
Mx of HCV
Directly acting antiviral - used in combination (given for 8/52 to 12/52)
Protease inhibitors - telaprevir, simeprevir
NS5 A/B inhibitors - Elbasavir, Velpatasivir
hCBV is totally curable
105
Hep D virus
Defective RNA virus requiring hep B for replicate
106
Types of infection of HDV
Coinfection - HBV and HDV at same time
Superinfection - development of HDV in pt w/ pre-existing HBV
107
Decompensated cirrhosis
Inability of liver to carry out normal functions
108
Features of decompensated cirrhosis
Development of ascites
Encephalopathy
Jaundice
Coagulopathy
GI bleeding
109
HDV clinical progression
Most severe form of viral hep
C/c infection --> cirrhosis --> HCC
110
Mx of HDV
Only treatment for c/c HDV
Pegylated IFNa
111
Testing for HCV
Hep C antibody screen
Hep C RNA confirms dx, csalulate viral load, assess genotype
112
Features of HEV
RNA virus transmitted by faecal oral route
Normally produces only mild illness, except in immunocompromised and pregnant
No vaccination
113
Characteristics of a/c liver failure
Confusion (i.e. encephalopathy)
Jaundice
Asterixis
GI bleeding
Ascites
Bruising (high INR)
114
What is cirrhosis
Severe, irreversible fibrosis of liver
115
Which complications are cirrhosis associated w/
HCC
GI bleeding
Spontaneous bacterial peritonitis
116
What is c/c liver disease characterised by
Caput medusae
Splenomegaly
Palmar erythema
Dupuytren's
Leuconychia
Gynaecomastia
Spider naevi
117
Features of HBV
2nd most important carcinogen
DNA virus
Causes 1 million deaths/ yrs
100x more contagious than HIV
118
modes of transmission of HBV
Sexual
Parenteral - HCWs at increased risk
Perinatal
Transfusion
119
Nature of HBV infection
Most people recover within 2/12
Only 10% are symptomatic
10% become c/c HBV carriers
120
Viral markers of HBV
HBsAg
HBeAg
HbcAg
HbsAb
HBV DNA
121
HBsAg for HBV
Surface antigen
Used as general marker of active infection
122
HBeAg for HBV
E antigen
Marker of viral load and implies high infectivity
123
HBcAg for HBV
Core antibodies
Implies past or current infection
124
HBsAb for HBV
Surface antibody
Implies vaccination or past or current infection
125
HBV DNA for HBV
Direct count of viral load
126
Vaccination for HBV
Involves injecting Hep B surface antigen - 3 doses
Vaccinated pts are tested to confirm response to vaccine
127
Prevention of HBV infection
UK antenatal screening
Exposure-prone procedure for HBV infected HCW
Global eradication programme (immunisation)
Prophylaxis
128
Prophylaxis for HBV
Pre exposure is active immunisation
Post-exposure is accelerated active immunisation
129
Approach to c/c HBV infection therapy
Treat when they enter the immune elimination phase and develop active hepatitis
(ALT elevation and bx evidence of c/c hepatitis and fibrosis)
130
Treatment for c/c HBV infection
Immunomodulators - pegylated IFNa
Nucleoside analogues - lamivudine
Nucleotide analogues - adefovir, tenofovir
Given for 48/52
131
Features of HAV
Most common viral hep
RNA virus transmitted by faecal-oral route
Rarely, fulminant hep ensues but never c/c liver disease
132
HAV transmission
Close personal contact (e.g. household contact, sexual contact)
Homeless person - poor hygiene
Drug use
Contaminated food
Blood exposure
133
Px of HAV
Nausea
Vomiting
Anorexia
Jaundice
Can cause cholestasis
134
Mx and vaccination for HAV
Resolves without mx - 1-3 months
Mx is usually basic analgesia
Vaccination is available to reduce chance of developing infection
135
Types of autoimmune hepatitis
Type 1
Type 2
136
Type 1 AI hepatitis
Occurs in women in late 40s/50s
Presents around menopause w/ fatigue and features of liver disease on examination
Less a/c course that Type 2
137
Type 2 AI hepatitis
Occurs in pts in their teenage/ early twenties w/ a/c hepatitis
High transmianases and jaundice
138
Ix for AI hepatitis
Raised transaminases
IgG levels
Associated w/ many autoantibodies
139
Autoantibodies for Type 1 AI hepatitis
ANA
Anti-actin
Anti-soluble liver antigen (anti-SLA/LP)
140
Autoantibodies for Type 2 AI hepatitis
anti-LKM1
anti-LC1
141
Dx for AI hep
Confimed w/ liver bx
142
Mx for AI hepatitis
High dose steroids e.g. pred, that are tapered over time as immunosuppressants are introduced e.g. azathioprine
Liver transplant may be required end stage however can recur n transplanted liver
143
What is liver cirrhosis
Result of c/c infl and damage to hepatocyte - permannaet architectural change
144
Main causes of crrhosis
HCV
Alcohol
NAFLD
Hep B
145
Rarer cases of cirrhosis
AI hepatitis
PSC
PBS
Wilson's disease
Haemochromatosis
Cytogenic
Drug induced
A1AT deficiency
146
Relevance of hepatic stellate cels in fibrosis
Can cause wither progression or regression of liver fibrosis
147
What is portal HTN
Increased resistance in the blood bessie leading INTO the liver cause by fibrosis
148
Different approaches to treating liver fibrosis
Control or curve primary disease
Target receptor-ligand interactions
Inhibit fibrpgenesis
Promote resolution of fibrosis
149
Why does portal HTN cause a lot of morbidlity vs mortality
Poor synthetic function
150
Fixed and dynamic component of portal HTN
Fixed - localised HTN in portal system due yo architectural change bin liver
Dynamic - triggered by infl, toxin, causes a/c rise in pHTN and vascular issues
151
Classification of aetiologies of PHTN
Pre-hepatic
Intra-hepatic
Post-hepatic
152
Pre-hepatic aetiologies of PHTN
Budd-Chiari syndrome
Cardiac causes
153
Intra-hepatic causes of PHTN
Pre-sinusoidal - schistomaniasis
Sinusoidal - cirrhosis, alcohol hepatitis
Post-sinusidal - venoocclusive syndrome
154
Signs of cirrhosis
Jaundice
Hepatosplenomegaly
Spider naevi
Palmar erythema
Gynaecomastia
Bruising
Ascites
Caput medusae
Asterixis
155
Hepatosplenomegaly in cirrhosis
However liver may shrink as it becomes more cirrhotic
Splenomegaly due to PHTN
156
Spider naevi
Telangiectasia with a central arteriole and small vessels radiating away
157
Palmar erythema in cirrhosis
Red discolouration on palm, typically hypothenar eminence
Caused by hyper dynamic circulation
158
Why do we see gynaecomastia and testicular atrophy in cirrhosis
Endocrine dysfunction
159
Caput medusae
Distended paraumbilical veins due to PHTN
160
Asterxixis in cirrhosis
Flapping tremor as a result of toxic metabolic encephalopathy - decompensated cirrhosis
161
Bloods for liver cirrhosis
LFT - usually normal unless decompensated (deranged)
Low albumin and increased PT (INR)
Hyponatreamia
Deranged U&Es
Enhanced liver fibrosis test - 1st line for NAFLD
162
Ix for liver cirrhosis
Bloods
Ultrasound
Fibroscan - transient electrography
Endoscopy
CT/ MRI
Liver bx
163
What might you see on an ultrasound for liver cirrhosis
Nodularity on surface of liver
'Corkscrew' appearance of arteries
Enlarged portal vein
Ascites
164
Endocsopy for cirrhosis
Assess for and treat oesophageal varices when PHTN is suspected
165
CT/MRI for liver cirrhosis
Useful when looking for:
HCC
Hepatosplenomegaly
Ascites
166
Liver bx for cirrhosis
Used to conform dx
167
Gading of cirrhosis
Child-Pugh score
From 5 - 15
Takes into account: bilirubin, albumin, INR, ascites, encephalopathy
Provides estimated one-year survival
168
MELD score
Used every 6/12 for pts w/ compensated cirrhosis
Represents 3/12 mortality in %
169
General mx of cirrhosis
Screening for HCC every 6/12
Endoscopy every 3 years
High protein, low sodium diet
Mx of complications
HAV and HBV imunistaion to prent viral superinfection
170
Screening for HCC in cirrhosis pts
Ultrasound
Alpha-fetoportein - tumour marker for HCC
171
Complications of cirrhosis
Malnutrition
PHTN, variceal bleeding
Ascites*
HCC
Hepatic encephalopathy
Hepatorenal syndrome
172
How does cirrhosis cause malnutrition
Increased use of muscle tissue as food
Affected metabolism of proteins in liver and reduced production of proteins
Disrupted ability to store and release glycogen
173
How does PHTN cause varices
Back pressure from portal system causes vessels at the sites where the portal system anastomoses w/ systemic venous system to become swollen and tortuous
174
Where can varices occur
GOJ
Ileocaecal junction
Rectum
Anterior abdominal wall (caput medusae)
175
Treatment of stable varices
Non-selective beta blocker e.g. propanolol
Elastic band ligation
Sclerotherpay - less effective
TIPS if all else fails
176
TIPS for varices
Transjugular Intra-hepatic portosystemic shunt
Stent placed in connection made between hepatic and portal vein
Allows blood to flow from portal vein into hepatic and relieve pressure
177
Treatment for bleeding oesophageal varices
Resusc
Endoscopy - injection of sclerosant, elastic band ligation
Sengstaken Blakemore tube
178
Resus for bleeding varices
Vasopressin analogue e..g terlipressin
Corect coagulopathy w/ vit K and FFP
Prophylactic BSAbx
Consider ITU as pts may exsanguinate
179
Sengstaken Blakemore tube for bleeding varices
Inflatable tube inserted into oesphagus to tamponade bleeding varices
Used when endoscopy fails
180
When are pts typically listed for a liver transplant
MELD > 15
Point at which survival w/ transplant is higher than w/out
181
What is ascites
Excess fluid in peritoneal cavity
182
Pathophys of ascites in c/c liver disease
Increased portal venous pressure --> increased vasodilators --> fluid leaks out of capillaries and bowel --> decreased blood pressure entering kidneys, activates RAAS --> Na+ and fluid retention
Low albumin also decreases oncotic pressure
183
Causes of ascites
Portal HTN
HCC
Infection or infl - TB, pancreatitis
Decreased albumin - nephrotic syndrome, IBD (protein losing enteropathy)
Myxoedema
184
Ix for ascites
Diagnostic paracentesis
RBC and WBC count
Culture - SBP suspected
Glucose
LDH
Amylase - increased in pancreatitis
185
Diagnostic paracentesis for ascites
Allows calculation of serum-ascites albumin gradien
SAAG = serum albumin - ascites albumin
High gradient (>11) = transudate: portal HTN
Low gradient (<11) = exudative: HCC, pancreatitis, TB
186
Mx of ascites
Low sodium diet
Diuretics - spiro, furosemide
Paracentesis
Prophylactic abx for SBP
Consider TIPS and liver transplant in refractory ascites
187
SBP
Spontaneous Bacterial Peritonitis
Infection developing in ascitic fluid and peritoneal lining w/out any clear cause
188
Px of SBP
May be asymptomatic - have low threshold fro ascitic fluid culture
Fever
Abdo pain
Vomiting
189
Dx of SBP
Neutrophils >250 per micro litre
190
Common causative organisms for SBP
E. coli
Klebs penumoniae
Gram +ve cocci
191
Mx for SBP
Abx - co-amoxi, cephalosporins
192
What is hepatorenal syndrome
Kidney failure w/out known cause in presence of severe liver disease
Dx of exclusion
193
Pathophys of hepatorenal syndrome
RAAS seen in portal HTN leads to regional vasoconstriction --> renal hypoperfusion
Tjis causes rapid deterioration of kidney function, may be fatal
194
Mx of hepatorenal syndmrome
Terlipressin
Refer for liver transplant
195
Hepatic encephalopathy (a/c decompensated liver disease) px
Jaundice
Coagulopathy
Ascites
Confusion/ Asterixis
GI bleeding
196
Grading for hepatic encephalopathy
0 - 4
0 is minimal HE - no clinical manifestation
1 is mild - alteration in behaviour, mild confusion
2 is moderate - lethargy, moderate confusion
3 - severe - stupor, incoherent speech
4 - coma
197
Pathophys of hepatic encephalopathy
Build up toxins affecting brain
Ammonia is produced by intestinal bacteria when breaking down protein, usually absorbed
Liver cannot metabolise ammonia and collateral vessels allow ammonia to pass directly into systemic system
198
Ppting factors for HE
Constipation*
Infection
Medications
High protein diet
199
Mx of hepatic encephalopathy
Laxatives e.g. lactulose
Long-term bx e.g. rifaxim
Supportive - basic airway support, NG feeding, stop bleeding into gut
Liver transplant
200
Why are laxative given in the mx of hepatic encephalopathy
Promotes excretion of ammonia
Alters gut pH favouring bacteria that produce less urea
201
Prognosis of hepatic encephalopathy
1 yr if not given liver transplant
202
Px of Budd-Chiari syndrome
Triad of hepatomegaly, abdominal pain and ascites due to hepatic venous obstruction
203
Stages in alcoholic and fatty liver disease
Steathosis - fatty liver
Steatohepatitis - fatty liver plus progressive infl, characterised by Mallory bodies
Cirrhosis
HCC
Similar pattern seen in A1AD and drug-induced
204
Clinical states of cirrhosis
Compensated - pts are asymptomatic and small amount of residual function remains
Decompensated - liver no longer has capacity to carry out normal function. If insult is removed, liver may 'recompensate'
205
What is PBC
Primary biliary cirrhosis - AI cholestatic liver disease that can lead to cirrhosis
206
Pathophys of PBC
AI destruction of small, INTRAhepatic bile ducts --> cholestasis ---> progressive fibrosis ---> cirrhosis
207
Epidemiology of PBC
Seen in older women, 40+
F: M is 10:1
Increased incidnecr of other AI disorder e.g. thyroid, coeliac
208
Auto-antibodies for PBC
Anti-mitochondrial - hallmark
ANA
Anti-gp210 and anti-sp100
209
Blood results for PBC
Raised ESR
Raised IgM
210
Sx of PBC
Most pts are asymptomatic at dx
Fatigue
Pruritus
RUQ pain
211
Dx of PBC
AMA +ve in 95%
Cholestatic picture on LFTs
Imaging - liver USS and MRCP
212
When should PBC be considered
In any pt that has unexplained rise in ALP
213
Mx of PBC
Urseodeoxycholic acid - helps flow of bile
Asses response after 12/12
2nd line is oecticholic acid
Liver transplant
Treat pruritus
214
Drugs to treat pruritus in PBC
Sertraline
Gabapentin
Rifampicin
215
Complications of PBC
Mainly due to cirrhosis and cholestasis
Hypercholesterolaemia
Malabsorption of fat-soluble vits
Malabsorption
Osteoporosis
216
PSC
Primary sclerosing cholangitis
Immune-mediated disease charcterised by cholestasis, bile duct structures and hepatic fibrosis
217
Pathophys of PSC
Progressive infl, fibrosis and destruction of BOTH intra- and extra-hepatic bile ducts
218
Intra vs extra-hepatic bole ducts
Intra - small ducts proximal to R and L hepatic duct
Extra - large bile ducts starting at R and L hepatic ducts
219
Types of sclerosing cholangitis
Primary - referes to PSC
Secondary - any condn causing bile duct damage and biliary obstruction
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Secondary causes of sclerosing cholangitis
Infl - Ig4-sclerosng cholangitis, pancreatitis
Malignancy - cholangiocarcinoma
Infection
Choledocholithiasis
Drugs
Papillary stenosis
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Epidemiology of PSC
More commonly seen in men
Avg age is 40
IBD is seen in 80% of pts w/ PSC but only 4% of pts with IBD have PSC
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Sx of PSC
Fatigue
Pruritus
Features of cholangitis
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Signs of PSC
Hepatomegaly
Splenomegaly
Excoriation
Stigmata of c/c liver disease
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Dx of PSC
Liver biochem - cholestatic pattern
MRCP - biliary stricturing or dilatation
ERCP
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When is ERCP used in dx of PSC
Pts who also need therapeutic interventions (e.g. treat duct stricture) or who cannot undergo MRI
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Tumour marker for cholangiocarcinoma
CA19.9
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Mx for PSC
Only effective treatment is liver transplant
Lifestyle and preventative
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Complications
Cholangitis
Cholangiocarcinoma (10%)
Osteoporosis
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Surveillance for PSC
Annual colonoscopy for colorectal cancer
Annual USS of gallbladder for biliary malignancy
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Pathophys of autoimmune hepatitis (AIH)
AI hepatocyte damage
Minority of cases triggered by drugs e.g. minocycline
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Clinical features of AIH
Asymptomatic
A/c or c/c presentation
PMH or Fhx of AI disease
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Ix for AIH
Bloods - increased ANA, ASMA and IgG
LFTs - hepatitic picture
Bx is always needed
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1st line treatment for AIH
Pred +/- azathioprine
Continue mx until LFTs normlaise then maintain on reduced dose
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Prognosis of AIH
Excellent on treatment - 95% survival in 10 yrs
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Px pf alcholic hepatitis
Jaundice
Fever
Tender hepatomegaly
Worsening of underlying cirrhosis if present
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Blood for alcoholic hepatitis
Neutrophilia
Increased AST/ALT
AST:ALT ratio >2
Increased bilirubin
Increased PT/ INR
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Layers of GB
Mucosa
Muscularis propria
Lamina propria
Serosa
No mucosa
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Physiology of GB emptying
Bile stored and concentrated up to 15x in GB
Vagal stimulation causes weak contraction of GB
Bile acids via blood stimulate parenchymal secretion
Secretin via blood stream stimulates liver ductal secretion
CCK in blood stream
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Effects of CCK on GB
Gallbladder contraction
Relaxation of Sphincter of Oddi
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Types of gallstones (cholelithiasis)
Cholesterol stones
Pigment stones
Mixed stones
Stones w/ Ca content
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Types of pigment stones
Black - cirrhosis risk factor
Brown
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Cause of black pigment gallstones
C/c haemolysis
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Where do brown pigment stones typically dvelop
In obstructed and infected bile ducts
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Factors associated w/ cholelithiasis formation
Impaired GB function - emptying, absorbing
Superstaurated bile - age, diet
Absorption/ enterohepatic circulation of bile acids
Cholesterol nucleating factors
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Where can gallstones cause complicatiosn
In GB
In bile ducts
In intetsine
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Complications of gallstones in GB
Biliary colic
A/c or c/c cholecystitis
Empyema of GB
Mucocele
Perforation
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Complications of gallstones in bile ducts
Biliary obstruction
A/c cholangitis
A/c pancreatitis
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Complication of gallstones in intestine
Intestinal obstruction - gallstone ileus
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Risk factors for gallstones
Fat
Forties
Female
Fair
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Biliary colic pain
Intermietent - occurs in waves
Seen in RUQ
Typically squeezing pain, pt unable to get comfortable
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Pathophys of biliary colci
Biliary obstruction w/ OUT infection, causing pain as GB contracts against it
Due to stone impaction in GB neck or cystic duct
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Structures in GB
Neck Body
Fundus
Cystic duct
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Signs and sx of biliary colic
Continuous RUQ/ epigastric pain - may radiate to back (below scapular), worse after fatty meal
N & V
Usually resolves 20mins - 6 hrs
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Important -ve findings in biliary colic
No fever
No peritonism
Normal WBC
Murphy's sign -ve
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Ix for biliary colic
Abdo US - looking for stone and duct dilation
LFTs
Consider MRCP if duct dilation and/or abnormal LFTs
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Conservative mx for biliary colic
Analgesia
Avoid triggering foods i.e. low fat diet
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Surgical mx for biliary colic
Laporoscopic cholecystectomy
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A/c cholecystitis
A/c infl of GB, typically caused by cholelithiasis impaction
Usually sterile chemical infl but becomes infective in 1/3
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Clinical features of a/c cholecystitis
Continuous RUQ pain, may raidate
Fever and local peritonism - pts lying still (not writhing)
+ve Murphy's sign
Vomiting
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Murphy's sign
Ask pt to deep breath and use 2 fingers to press on RUQ
Pain/ arrest of inspiration but NO pain in LUQ
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Bloods for a/c cholecystitis
Icreased WBC
Increased CRP
Deranged LFTs in 1/3
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US for a/c cholecystitis
4hrs NBM as this will distend GB
May show stones, thick-walled GB and normal bile ducts
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Extra options of imaging in a/c cholecytsitis
HIDA cholescintigraphy (nuclear med) - cystic duct obstruction
CT abdo for ddx or complications
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Mx for a/c cholecystitis
Conservative - fluids, anagelsia, IV abx (ITU if perforation)
Surgical - lap chole (done before abx if v a/c)
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Complications of a/c cholecystitis
Perforation (presnsts as shock)
GB empyema
C/c cholecystitis - leads to fibrosed and shrunken GB
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Mirrizzi syndrome
Syndrome where impacted stone in cystic duct or neck of GB causes extrinsic compression of CBD
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GB mucocele
Overdistended GB filled with mucous
Usually non-infl
Caused by impaction of stone in cystic duct or neck of GB
Px is same as cholecystitis
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Empyema of GB
Most severe complication of a/c cholecystitis
Results from progression of a/c cholecystitis and in background of bile stasis and cystic duct obstruction
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Mx of GB empyema
Surgical emergency
Prompt treatment w/ IV abx and surgical removal or aspiration (cholecystotomy)
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Caustaive organism for a/c cholecystitis
E. coli
Klebsiella
Clostridia
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What is ascending cholangitis
Infection of CBD secondary to choledocholithiasis
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Risk factors for ascending cholangitis
Biliary malignancy
Post ERCP
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Px of ascending cholangitis
Charcot's triad - fever, RUQ pain, jaundice
Raynuad's pentad - add confusion, hypotension (sepsis)
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Ix for ascending cholangitis
Deranged LFTs (typically indication for MRCP)
Raised WBC/ CRP
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Imaging for a/c cholangitis
USS - stones, dilation and thickening bile ducts
MRCP
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Mx of ascending cholangitis
IV abx and fluid
ERCP once stable - sphincterotomy and stone clearance
Consider stone exploration as an alternative
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How is a lap chole performed
Using 4 ports w/ 2 ports at least 10mm in size and 2 ports at least 5mm in size
Must see critical view of safety - identified cystic duct and artery
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Complications of lap chole
Bleeding - bleeding disorders are CI
CBD injury
Missed CBD stones
Bowel injury
Potetnial seeding of tumour if GB cancer is present (CI)
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ERCP
Endoscopic retrograde cholangiopancreatography
Upper GI endoscopy w/ injection of contrast in biliary tree and pancreas, can then proceed to sphincterotomy, stone clearance and stenting
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Infl complications of ERCP
A/c pancreatitis
Cholangitis
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Traumatic complications of ERCP
Bleeding
GI perforation
Bile duct injury
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What is gallstone ileus
Gallstone eroded through GB and duodenum (fistula formed)
Typically impact in terminal ileum (narrowest part of small intestine) to cause SBO
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Imaging for gallstone ileus
Air in biliary system (pneumobiliary) - Mercedes Benz sign
Dilated loops of bowel
Both seen on AXR
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Sx of gallstone ileus
Nausea and vomiting
Biliary colic
Absolute contipation
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What type of jaundice is caused by choledocholithiasis
Obstructive
Unconjugated bilirubin unable to GIT - backing up in system, then kidneys
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At which size do we operate on GB polyps
>10mm - 8% chance of cancer
Can be dismissed if <6mm
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Types of adenomas (GB polyps)
Pyloric gland type
Intestinal type
Foveolar papillary type
Tubopapillary type
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When are adenomas in the GB significant
PSC
Any size maters as there's a higher risk of cancer
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Cholangiocarcinoma
Cancer of bile ducts
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Epidemiology of GB cancer
2.5:1 F:M
Presents in older age, 70 yrs
Normally adenocarcinoma
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Lifestyle risk factors for GB cancer
DM
DMI
Sweetened beverages
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Environmental risk factors for GB cancer
C/c bacterial infections
Arsenic
Aflatoxins
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Genetic risk factors for GB cancer
Female sex
Age
PSC
Anomalous pancreaticobiliary ductal junction
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Associated diseases with GB cancer
GB polyps
Crohn's disease
Sjorgrens syndrome (decreased risk)
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GB cancer px
Presents at late stage
Invading liver mass
Obstructive jaundice
Wt loss/ anorexia/ RUQ pain
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Biliary atresia
Condn in infants where bile ducts inside and outside liver are scarred so bile cannot ENTER intestine
Bile builds up in liver and damages it --> cirrhosis
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Px of biliary atresia
Jaundice in children 3-6 weeks old
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Mx of biliary atresia
Kasai procedure - intestine attaches to liver to allow bile to drain
Eventually liver transplant
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Choledochal cyts
Congenital dilation of bile ducts
Can be classified in 5 types - Type 1 is most common
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Natural hx of choledochal cysts
Choledochal cysts are infl in nature
Can lead to cholangitis or pancreatitis
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Key difference in pathology - IgG4 sclerosing cholangitis vs PSC
Lymphoplasmacytic infiktration
Storiform firbosis
Obliterative fibrosis
Lymphoplasmacytic-type psuedotumors in hilar bile duct
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Tropical infections affecting biliary system
Clonirchis sinesis
Opisthorcis viverrini
Opisthorchis felineus
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Risk factors for cholangiocarcinoma
Cholestatic liver disease - PSC, choledochal cysts
Liver cirrhosis
Biliary stone disease
Infections
Infl disorders
Toxins - alcohol, drugs
Metabolic condn
Genetic disorder - Lynch syndrome
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Infections as risk factors for cholangiocarcinoma
Liver flukes
Hep B/C
Typhoid
Recurrent pyogenic cholangitis
HIV
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Infl disorders as risk factors for cholangiocarcinoma
IBD
C/c pancreatitis
Gout
Thyrotoxicosis
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Prognosis of cholangiocarcinoma
5 yesr survival is 5%
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Where is cholangiocarcinoma endemic in
Thailand
Vietnam
Cambodia
Laos
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Choledocholithiasis
Gallstones within billiary tree
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Biliary tree
Ductal system that transmits bile produced by hepatocytes to 2nd part of duodenum (via ampulla of Vater and sphincter of Oddi)
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Biliary tree anatomy
R & L hepatic ducts converge to form the common hepatic duct
GB is drained by cystic duct
Cystic duct and common hepatic duct converge to form CBD
Pancreatic duct also joins common bile duct, proximal to ampulla of Vater
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How can gallstones cause a/c pancreatitis
Stones get impacted distally in biliiopancreatic duct causing disruption to flow of pancreatic enzymes
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What is post cholecystectomy syndrome attributed to
Changes in bile flow after removal
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Sx of post cholecystectomy syndrome
Diarrhoea
Indigestion
Epigastric or RUQ pain and discomfort
Nausea
Intolerance of fatty foods
Flatulence
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Types of contrast in MRI for liver lesions
Gadovist stays in vascular sytsem
Primovist gets taken up liver cell and excreted in biliary system
If there's a lesion and it takes up primovist, means there are functioning hepatocytes. If the lesion is metastatic, it WONT take up primovist dye
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Haemangiomas in liver
Non-cancerous mass in liver made up of blood vessels
Most common benign liver lesion
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Haemangioma features on MRI
Appears hyperchoic (looks white compared to greyness of liver)
Lights up to T2 image, lightbulb sign
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Giant haemangioma in liver
Can trap platelets and cause thrombocytopenia
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Giant haemangioma features on MRI
Seen on T1
Sharply marginates, hypointense mass
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Focal nodular hyperplasia
2nd most common benign liver tumour
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Focal nodular hyperplasia features on MRI
Hypoechoic mass
Arterially enhancing lesion, if given primovist
Results of increased hepatocyte numbers caused by hypo perfusion or hyperperfusion from anomalous arteries within the hepatic lobule
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What can adenomas turn into
Adenomas can bleed and turn into HCCs
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What does the type of adenoma its classified as, depended on
What protein is mutated: beta catenin and HNF 1 alpha
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Who are adenomas most common in
Males who use anabolic steroids
Can also be driven by oestrogen
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Histopathology of HCC
Takes most of its supply from hepatic artery
Often fat calcification, may have necrosis and multiple masses of variable attenuation
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HCC features on MRI
Hypointense compared to surrounding iver
Rapid washout - supply to HCC is predominantly from hepatic artery rather than portal veins
Diffusion restriction/ rim enhancement on post-contrast images causing a capsule
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Px of HCC
Constitutional sx
Jaundice
Portal HTN
Hepatomegaly
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Mx of HCC
If lesion is small, resect
If not, liver transplant
Trans arterial chemo embolism (TACE) and trans arterial radioembolism, thermal/ cryo ablation can be used
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LI-RAD classoifictaion
Used to score liver lesions
LR1-2 : benign
LR 3-4: proability for HCC
LR5: 100% HCC
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Risk factors for HCC
HBV and HCV infection
Alcoholism
Biliary cholangitis
Food toxins
Congenital biliary atresia
Wilson disease, A1AT deficiency
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How does uncojugated bilirubin enter the circulation
RBCs enter senescence after 120 days
Macrophages in spleen and bone marrow engulf and degrade RBC and Hb into heme and globin
Globin is broken down into iron and unconjugated bilirubin
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How do we go from unconjugated bilirubin to conjugated
Glucuronic acids are added
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How is conjugated bilirubin excreted
By the liver in bile through CBD
Conjugated bilirubin is water soluble
Conjugated bilirubin travels through terminal ileum and start of large intestine
Bacteria converts conjugated bilirubin into urobilinogen by removing gluronic acid
Urobilinogen is lipid soluble
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How is conjugated bilirubin distributed
15% re absorbed by blood bound to albumin
80% oxidised by intestinal bacteria to stercobilinogen - excreted in the faeces
5% to kidney - converted to urobilinogen - gives urine its yellow colour
