2: Jaundice, Hepatitis, Hepatic Failure, Chronic Liver Disease Flashcards
(250 cards)
1
Q
Define jaundice
A
yellow discolouration of the skin and sclera
2
Q
What concentration of bilirubin results in jaundice
A
> 50
3
Q
How can the aetiology of jaundice be divided
A
Pre-Hepatic
Hepatic
Post-Hepatic
4
Q
What are the three categories of pre-hepatic jaundice
A
- Haemolytic
- Crigler-Najar
- Gilbert Syndrome
5
Q
What are the four causes of haemolytic anaemia
A
- Sickle Cell
- G6PD
- Hereditary spherocytosis
- Haemolytic disease of foetus and new-born
6
Q
Which enzyme is defective in Gilberts syndrome
A
UGT
7
Q
What is the role of the UGT enzyme
A
In hepatocytes UGT converts unconjugated bilirubin to conjugated bilirubin
8
Q
Explain Gilbert syndrome
A
There is low UGT enzyme. Meaning normally individuals are able to conjugate bilirubin. However, if haemolysis increases (illness, stress, dehydration) there will be an increase in unconjugated bilirubin as it exceeds the enzymes capacity
9
Q
What is Crigler-Najar syndrome
A
Complete absence of UGT
10
Q
What does Crigler-Najar syndrome usually lead to
A
Bilirubin encephalopathy and kernicterus
11
Q
What are 6 hepatic causes of jaundice
A
- Hepatitis
- Hepatocellular carcinoma
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Hereditary haemochromatosis
- Alcoholic liver disease
12
Q
What are 5 causes of post-hepatic jaundice
A
- Gallstones
- Cholangiocarcinoma
- Pancreatic cancer
- Abdominal mass (eg. lymphoma)
- Dubin Johnson Syndromne
13
Q
Which enzyme is deficient in Dupin-Johnson syndrome
A
Defect in MRP2
14
Q
What is the function of MRP2
A
MRP2 is responsible for transporting conjugated bilirubin to hepatic duct
15
Q
In pre-hepatic jaundice how will urine appear
A
Normal
16
Q
In pre-hepatic jaundice how will stool appear
A
Normal - Dark
17
Q
Why does urine appear normal and stool dark in pre-hepatic jaundice
A
As it is caused by an increase in physiological pathways
18
Q
In hepatic jaundice how will urine appear
A
Dark
19
Q
In hepatic jaundice how will stool appear
A
Clay
20
Q
Explain why urine is dark and stool pale in hepatic jaundice
A
As there is a problem within the liver and hence conjugating bilirubin. Reduction in conjugated bilirubin reduces amount entering stool - hence causing pale stools. Unconjugated bilirubin accumulates in the circulation and hence is excreted by the kidneys.
21
Q
How will urine appear in post-hepatic jaundice
A
Very Dark
22
Q
How will stool appear in post-hepatic jaundice
A
Pale. Clay-coloured
23
Q
Why is urine v.dark and stool pale in post-hepatic jaundice
A
Obstruction to outflow of bile. This means it cannot enter stool - giving stool a pale colour. Accumulating bilirubin backs-up the system enters the circulation causing dark urine.
24
Q
How is bilirubin formed
A
From break-down of haem in RBC
25
Explain normal processing of bilirubin
Haem is a degradation production of RBC. Haem is converted to unconjugated bilirubin. This is conjugated at hepatocytes making it water-soluble and able to be excreted via the GI tract. Two main excretion productions are stercobillin and urobilinogen.
26
Explain the pathophysiology of pre-hepatic jaundice
Increase in RBC degradation. This increases unconjugated bilirubin. It is still able to be conjugated and therefore excreted in faeces. However, unconjugated bilirubin exceeds enzymes ability to conjugate causing an accumulation in the blood-stream resulting in jaundice.
Increase billirubin in bile also increases the risk of pigment stones.
27
Explain pathophysiology of hepatic jaundice
Liver looses ability to conjugate bilirubin, leading to excess unconjugated bilirubin. If the liver becomes cirrhotic it may obstruct bile - leading to a mixed conjugated and unconjugated hyperbilirubinaemia.
28
Explain post-hepatic jaundice
Obstruction of biliary drainage leads to a conjugated hyperbillirubinaemia. Pressure in the bile-duct can cause back flow through tight junctions and enter the circulation. Bile salts and cholesterol may cause pruritus. Reduced bile excretion can cause steatorrhoea.
29
What investigation should be ordered in jaundice
LFTs
30
Why is bilirubin useful in assessing jaundice
Determine extent of hyperbillirubinaemia
31
Why is albumin useful in assessing jaundice
Determine liver function
32
Why is AST and ALT useful in assessing jaundice
Liver damage
33
Why is ALP useful in assessing jaundice
Indicates obstruction
34
Why is GGT useful in assessing jaundice
Often elevated in alcoholic liver disease
35
If the AST: ALT ratio is more than two what does it indicate
Alcoholic liver disease
36
If the AST: ALT ratio is 1 what does it indicate
Viral Hepatitis
37
In pre-hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. normal
| b. normal
38
In hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. raised
| b. normal
39
In post-hepatic jaundice how will
a. ALT/AST present
b. ALP present
a. normal
| b. raised
40
What is hepatitis
Inflammation of the liver
41
What are the two types of hepatitis
1. Autoimmune
| 2. Viral
42
What is autoimmune hepatitis
inflammation of the liver caused by T cell function and autoantibodies directed against cell-surface antigens
43
What does the type of autoimmune hepatitis depend on
antibodies present
44
What 2 antibodies are present in type I autoimmune hepatitis
ANA
| anti-SMA
45
Who does type I autoimmune hepatitis affect
adults and children
46
What antibodies are present in type 2 autoimmune hepatitis
anti-LKM1
47
Who does type II autoimmune hepatitis affect
children
48
What antibody is present in Type III autoimmune hepatitis
soluble liver and kidney antigen
49
Who does Type III autoimmune hepatitis affect
adults
50
Is autoimmune hepatitis more common in males or females
females (4:1)
51
what age-range does autoimmune hepatitis occur
10-20y and 45-70y
52
what three other conditions is autoimmune hepatitis associated with
Hashimotos thyroiditis
Coeliac disease
T1DM
53
what genes are associated with autoimmune hepatitis
HLAB8
| HLADR3
54
how do symptoms vary in autoimmune hepatitis
Can vary from asymptomatic to liver failure
55
give 5 common symptoms of autoimmune hepatitis
1. Lethargy
2. Weight Loss
3. Amenorrhoea
4. Abdominal pain
5. Jaundice
56
what will a third of patients with autoimmune liver disease develop
Acute liver failure
57
how will acute liver failure in autoimmune hepatitis present
1. Fever
2. RUQ pain
3. Jaundice
58
what investigations may be ordered in autoimmune hepatitis
1. LFTs
2. Antibodies
3. IgG
4. Liver biopsy
59
how will LFTs present in autoimmune hepatitis
Raised AST and ALT
60
what antibodies may be present in autoimmune hepatitis
Anti-nuclear antibodies
Anti-smooth muscle antibodies
61
how will IgG present in autoimmune hepatitis
May be raised - hypergammaglobulinaemia
62
when is a liver biopsy performed in autoimmune hepatitis
If autoantibodies are positive
63
what is first-line management of autoimmune hepatitis
Prednisolone.
Azathioprine may be used as steroid-sparing alternative.
64
what is the ultimate treatment for autoimmune hepatitis
Liver transplantation - if decompensated cirrhosis or failure to respond to medical therapy.
65
what is hepatitis A
Infection with hepatitis A
66
in which countries is hepatitis A common
(The A's!):
South America
Africa
67
how is hepatitis A spread and how can this be remembered
Faecal-Oral.
Hepatitis A and E are the vowels - they are spread by the bowels
68
what food is hepatitis A particularly associated with
Shell-Fish
69
what is risk factor for catching hepatitis A
Travelling
70
what is the incubation period of hepatitis A
1-2W
71
how does hepatitis A initially present
Pro-drome
72
what is a KEY feature of hepatitis A prodrome
RUQ pain and tender hepatomegaly
73
what are 4 features of hepatitis A pro-dromal phase
1. Fever
2. Anorexia
3. N+V
4. RUQ - tender hepatomegaly
74
what are 2 symptoms of icteral phase of hepatitis A
Jaundice
Dark Stool, Pale Urine
Pruritus
75
How will LFTs present in hepatitis A
Raised AST + ALT
76
What is the AST to ALT ratio in hepatitis A
AST:ALT = 1
77
What is another investigation for hepatitis A
anti- HepA IgM and IgG
78
what does a raised anti-hep A IgM indicate
Current Infection
79
what does a raised anti-hep A IgG indicate
Previous Infection
80
how is hepatitis A managed
Self-resolving
81
is there a vaccine for hepatitis A
Yes
82
how many vaccinations of hep A does a person need
initial vaccine, followed by a booster 6-12m later
83
who is given Hep A vaccines
- Travellers
- MSM, IVDU, HIV
- Chronic liver disease
- Occupational risk
84
does hep A cause chronic disease
No
85
What is hepatitis B
Infection with hepatitis b virus
86
In which countries is HBV more common
- Far East
- Africa
- Mediterranean
87
What are the three methods of HBV transmission
Vertical
Parental
Sexual
88
What are 5 risk factors of HBV
- MSM
- IVDU
- HIV
- Baby of HbSAg +ve mother
- Prison staff
- Haemodialysis patients
89
What is the incubation period of HBV
6m
90
In acute infection what % will be symptomatic
30%
91
What are some symptoms of acute-hepatitis B
- Fever
- Lethargy
- Arthralgia
- Jaundice
- RUQ pain
92
What defines acute-hepatitis B infection
Manifests within 6m of infection
93
What defines chronic hepatitis B infection
Manifests beyond 6m of infection, or longer with positive HbSAg
94
How do individuals with chronic Hep B present
Often asymptomatic carriers
95
If individual has re-activation of chronic hep B how may it present
Liver Failure
96
Explain pathophysiology of acute Hepatitis B
HBV infects hepatocytes, which then express it's antigen on their surface. Lymphocytes respond to HBV antigen and are activated - causing destruction of hepatocytes and subsequent inflammation.
97
Explain pathophysiology of chronic hepatitis B infection
Chronic inflammation leads to necrosis resulting in cirrhosis. Also causes cell dysplasia which is a risk factor for hepatocellular carcinoma
98
What two investigations should be ordered for HBV patients
HBV serology
| LFTs
99
What is the first-marker of HBV infection to appear
HbsAg
100
If HbsAg is present more than 6-months what does it indicate
Chronic Infection
101
What does HbsAg trigger
anti-HBS
102
If anti-HBS is present on its own what does it indicate
individual has been vaccinated against HBV
103
What is HbcAg
HBV core-antigen
104
What does anti-HBC IgM imply
current infection
105
What does anti-HBC IgG imply
previous infection
106
What does presence of HbeAg indicate
highly infectious strain of HBV
107
What else is included in HBV serology
anti-HBV DNA
108
If individual has anti-HBS only what does it indicate
previously vaccinated against HBV
109
If individual has
anti-HBS
anti-HBC IgG
what does it indicate
previous infection with HBV
110
If individual has
HbsAg
anti-HBC IgG
What does it indicate
They are a carrier of chronic HBV
111
If individual has
HbsAg
HbeAg
What does it indicate
Severe Infection
112
If individual has
HbsAg
anti-HBC IgM
HBV DNA
What does it indicate
Current Infection with HBV
113
How will LFTs present in HBV infection
Raised AST and ALT
114
What is the AST: ALT ratio in HBV infection
<1
115
What is first-line in managing HBV infection
Pegylated Interferon Alpha
116
What is second-line in managing HBV infection
Tenofovir and Entecavir
117
Is there a vaccine for HBV
Yes
118
When is the HBV vaccine given
As part of routine immunisation schedule at:
| 2, 3 and 4 months
119
When is testing for anti- HBs only recommended
Only if occupational exposure to HBV - test 4m following vaccine
120
What does infection with HBV predispose to
HDV Infection
121
What are three other complications of HBV infection
Chronic hepatitis
Fulminant hepatitis
Hepatocellular carcinoma
122
What is acute hepatitis C infection
infection with hepatitis C in the past 6-months
123
What is chronic hepatitis C infection
infection with hepatitis C more than 6-months ago
124
What are the three methods of transmitting hepatitis C
1. Sexual
2. Parental
3. Vertical
125
What are three risk factors for hepatitis C
- IVDU
- Recipients of blood transfusions before 1992
- Prisoners
126
What is the incubation period of hepatitis C
6-9W
127
what proportion of acute hepatitis C infections are asymptomatic
80%^
128
what are 4 possible symptoms of hepatitis C infection
- Malaise
- RUQ pain
- Jaundice
- Tender hepatomegaly
129
what % of hepatitis C patients develop silent chronic infection
85%
130
what % of hepatitis C patients will develop cirrhosis
25%
131
what % of hepatitis C patients will develop hepatocellular carcinoma
4%
132
What are possible haematological complications of chronic cirrhosis
Cryoglobulinaemia
133
What are possible rheumatological complications of chronic cirrhosis
Arthalgia
| Arthritis
134
What are possible ophthalmological complications of chronic cirrhosis
Sjogren's
135
What are possible dermatological complications of chronic cirrhosis
Percutaneous Cutanea Tarda
136
what are liver complications of chronic hepatitis C
Cirrhosis
| Hepatocellular carcinoma
137
what are renal complications of HCV
Membroproliferative glomerulonephritis
138
what is first-line investigation of HCV
ELISA
139
how will LFTs present in HCV
Raised AST and ALT
140
what will be seen on ELISA in hepatitis C
anti-HCV antibodies
141
what diagnostic tests are ordered for HCV
PCR for HCV RNA
142
if HCV RNA is positive what does it indicate
Current Infection
143
If anti-HCV antibodies are positive, but HCV RNA negative what does it indicate
previous infection
144
if HCV RNA positive what should be performed
Non-invasive elastography
145
What is used to manage HCV
Protease inhibitor w/wo ribavirin
146
Name two combination protease inhibitors
Daclatasvir and Sofosbuvir
Sofosbuvir and simeprevir
147
What is the aim of treatment in HCV
sustained virological response: undetectable HCV RNA at 6-months
148
Is there a vaccine for HCV
No
149
What % will develop chronic HCV
50-80%
150
What are three complications of HCV
- Cirrhosis
- Hepatocellular carcinoma
- Fulminant hepatitis
151
What does hepatitis D require for infection
Hepatitis B
152
What is hepatitis D co-infection
When Hep B and Hep D infect at the same time
153
What is hepatitis D super-infection
When a HbsAg positive individual is infected with Hep D
154
Explain pathophysiology of hepatitis D
Hepatitis D is a single-stranded RNA virus. It requires HbsAg to complete its replication cycle.
155
What is first-line investigation for HDV
ELISA:
| anti-HDV antibody
156
When should anti-HDV antibody only be requested
If HbsAg positive
157
What is second line investigation for HDV
rtPCR for HDV RNA
158
What is first-line management for HDV
pegylated interferon-alpha
159
What is ultimate management for HDV
liver transplantation
160
How can HDV infection be prevented
vaccination with hepatitis B at 2,3 and 4 months
161
What are three risks of super-infection HDV
- Chronic hepatitis
- Fulminant hepatitis
- Cirrhosis
162
What is hepatitis E
Infection with RNA virus hepatitis E
163
Which countries is hepatitis E infection more common
India
| China
164
Which countries is hepatitis A infection more common
Africa
| South America
165
How is hepatitis E transmitted
Faecal-Oral Route
166
What food in particular is associated with hepatitis E
Pork
167
What is the incubation period of hep E
2-8W
168
How does hep E initially present
Pro-drome 1-2W
169
What is are features of pro-drome in Hep E
- RUQ pain
- Tender hepatomegaly
- Fever
- Malaise
- N+V
170
What are 3 symptoms of icteral hepatitis E phase
Jaundice
Pale stools, Dark Urine
Pruritus
171
What is first line investigation for Hep E
ELISA for anti-HEV antibodies
172
What does anti-HEV IgM indicate
Current Infection
173
What does anti-HEV IgG indicate
Previous Infection
174
How is HEV managed
Supportive
175
Is there a vaccine for hep E
No
176
What is a good way to remember there is no vaccines for hep C and E
vaCcinEs
C
E
= have no vaccines
177
in which population is hepatitis E a great risk
pregnant women
178
why is hepatitis E a risk to pregnant women
20% risk fulminant hepatitis
179
Define hepatic failure
Deterioration of liver function resulting in coagulopathy and encephalopathy
180
What defines coagulopathy
INR > 1.5
181
What is acute-liver failure
Development of encephalopathy or coagulopathy in a previously healthy liver
182
what time-frame defines hyper-acute liver failure
<7d
183
what time-frame defines acute liver failure
8-21d
184
what time frame defines sub-acute liver failure
4-26W
185
what is chronic liver failure
when liver failure develops on a background of previous liver disease
186
what is fulminant hepatic failure
syndrome where there is massive necrosis of liver cells causing impairment of liver function
187
what are the 4 etiological categories of liver failure
- Medications
- Infections
- Vascular
- Other
188
what infections can cause liver failure
Hepatitis
Yellow Fever
Leptospirosis
189
what drugs may cause liver failure
Paracetamol over-dose
| Isoniazid
190
what vascular disease can cause liver failure
Budd-Chiari
191
what are other causes of liver failure
- Alcohol
- Fatty Liver Disease
- Wilson's
- Haemochromatosis
- Autoimmune hepatitis
192
What are 5 symptoms of hepatic failure
- Jaundice
- Hepatic encephaloapthy
- Constructional apraxia
- Asterixis
- Fetor hepaticus
193
Why does hepatic encephalopathy occur
As the liver fails, ammonia accumulates in the brain.
This is cleared by astrocytes, which produce glutamine.
Glutamine causes a shift in the osmotic balance - drawing fluid into cells
194
what is constructional apraxia
Unable to construct a 5-point star
195
what is fetor hepaticus
Breath smells like pear drops
196
what are the four features of grade I hepatic encephalopathy
1. Constructional apraxia
2. Mood disturbance
3. Sleep disturbance
4. Poor arithmetic
197
what are the 5 features of grade 2 hepatic encephalopathy
1. Drowsy
2. Confused
3. Slurred speech
4. Liver Flap
5. Inappropriate behaviour
198
what are the 4 features of grade 3 hepatic encephalopathy
Incoherent
Restlessness
Liver Flap
Stupor
199
what is grade 4 hepatic encephalopathy
coma
200
what diagnostic system is used for liver failure
Kings-College Criteria in Acute Liver Failure
201
According to kings college criteria in acute liver failure, if paracetamol-induced liver failure what arterial pH is required for diagnosis
pH <7.3
202
According to kings college criteria in acute liver failure, if individual does not have pH <7.3 what 3 other criteria must be met to make a diagnosis
1. PT > 100
2. Creatinine > 300
3. Grade III or IV encephalopathy
203
According to kings college criteria in acute liver failure, if non-paracetamol acute liver failure what criteria should be met for diagnosis
Prothrombin time > 100s
204
According to kings college criteria in acute liver failure, if non-paracetamol acute liver failure and PT <100s what criteria should be met for diagnosis
Requires 3 out-of the following 5:
1. <10 or >40-years
2. Medication induced liver failure
3. >1W between jaundice and onset encephalopathy
4. PT > 50s
5. Bilirubin > 300
205
What investigations are ordered for liver failure
1. LFTs
2. Coagulation studies
3. FBC
4. Virology studies
5. Ascitic tap
206
How may prothrombin time and INR present
- Prothrombin time = prolonged
| - INR = >1.5
207
How may LFTs present in liver failure
- Raised billirubin
- Raised AST and ALT
- Raised/Normal ALP
208
How may FBC present in chronic liver failure
Chronic liver disease is associated with IDA
209
Why are viral serologies ordered
Check for hepatitis
210
If an ascitic tap is ordered and has neutrophils >250 what does this indicate
Spontaneous bacterial peritonitis (SBP)
211
How is liver failure treated
- Intubate if required
- NG tube
- Catheter
- 10% dextrose
- Treat cause
- Use phenytoin to treat any seizures
212
If individual with liver failure has ascites how is this managed
- Fluid restriction
- Low salt diet
- Diuretics
- Daily weight
213
If individual with liver failure is bleeding what is given
Vitamin K
FFP
Platelets
214
When is hypoglycaemia treatment in liver failure
<2
215
What two medications may be given to treat encephalopathy in liver-failure
Lactulose
| Rifaximin
216
What is the role of lactulose
Lactulose is catabolised by gut flora where it decreases pH trapping ammonia
217
What is rifaximin
Non-absobable antibiotic that reduces concentration of ammonia-producing bacteria
218
What is cirrhosis
chronic liver damage
219
In which gender is cirrhosis more common
males (2:1)
220
What are the 3 broad etiological categories for cirrhosis
- Hepatotoxic
- Inflammation
- Metabolic
221
What hepatotoxic substances may cause cirrhosis
Alcohol
Medications:
- Amiodarone
- Methotrexate
222
What are 6 inflammatory causes of cirrhosis
- Hep B
- Hep C
- Hep D
- Primary sclerosing cholangitis
- Primary biliary cholangitis
- Autoimmune hepatitis
223
What are 4 metabolic causes of cirrhosis
- Wilson's
- Haemachromatosis
- Budd-Chiari
- Non-alcoholic fatty liver disease
- a1 alpha trypsin deficiency
224
What is the most common cause of liver cirrhosis
Hep C
225
What is the second most common cause of liver cirrhosis
Alcohol
226
What 3 nail signs may be present in cirrhosis
- Clubbing
- Leuconychia
- Terry's sign = telangiectasia of outer 1/3 of nail
227
What 2 signs on the palm may present present in cirrhosis
Dupuytrens contracture
| Palmar erythema
228
What does enlargement of the parotid gland in cirrhosis indicate
Alcohol
229
Explain pathophysiology of cirrhosis
Recurrent inflammation of hepatocytes heals by fibrosis and scarring which results in decrease in function.
Cytokines also activate stellate cells to produce collagen reducing liver function
Loss of liver function leads to:
- Reduced clotting factor production = coagulopathy
- Increase ammonia = hepatic encephalopathy
- Decrease albumin = ascites
- Decrease bile acids = malabsorption fat-soluble vitamins
230
What 4 blood tests are ordered in cirrhosis
1. LFT
2. Coagulation profile
3. FBC
4. Viral serology
231
How will LFTs present in cirrhosis
Raised ALT, AST
Raised ALP
Raised GGT
232
How will coagulation studies present in cirrhosis
Raised INR
233
why may an individual with cirrhosis have a microcytic anaemia
If caused by alcoholic liver disease - may have vitamin B12 deficiency.
234
what is first-line imaging for cirrhosis
Fibroscan
235
what is a fibroscan also called
Transient elastography and acoustic radiation force impulse imaging
236
what should all individuals with a new diagnosis of cirrhosis be offered and why
Upper GI endoscopy to check for oeseophageal varices
237
How should liver cirrhosis be managed
- Good nutrition
- Alcohol abstinence
- Cholestyramine for tiching
- Ursodeoxycholic acid for hepatitis
238
How is ascites managed
- Fluid restriction <1.5L
- Low-salt
- Spirinolactone
239
What is the only definitive treatment for liver cirrhosis
Liver transplant
240
If individual has liver cirrhosis how often should they receive an US scan and AFP to check for hepatocellular carcinoma
Every 6-months
241
What scoring system is used to predict prognosis in liver cirrhosis
Child-Pugh
242
What is the child-pugh score based on
Ascites
Albumin
Bilirubin
PT
Encephalopathy
243
What are two complications of liver cirrhosis
Acute liver failure
| Portal HTN
244
How may portal hypertension manifest
- Caput medusa
- Oesophageal varices
- Splenomegaly
- Ascites
245
What is spontaneous bacterial peritonitis
Type of peritonitis seen in those with ascites secondary to liver failure
246
how will SBP present
- Fever
- Abdominal pain
- Ascites
247
what is used to investigate SBP
Paracentesis
248
what is seen on paracentesis in SBP
Neutrophils > 250
249
what is used to managed SBP
IV Cefotaxime
250
Who is prophylactic cirpofloxacin against SBP given to
1. One episode of SBP
2. Serum protein <15 and one of:
- Child-pugh 9
- hepatorenal syndrome
