Liver,Pancreas and biliary tree clinical Flashcards
1
Q
What are the three types of true Liver function tests?
i.e actual liver function
A
- Albumin
- Bilirubin
- Prothrombin time
2
Q
what is the normal range of albumin?
A
35-50 g/L
3
Q
What are causes of hypoalbuminemia?
A
- Liver disease
- acute phase response ( sepsis,traumatic surgery)
- malabsorption
- malnutrition
4
Q
What is the normal state of bilirubin in the blood?
A
unconjugated
5
Q
What is the normal level of bilirubin?
A
<17 µmol/L
6
Q
which clotting factor is prothrombin?
A
clotting factor II
7
Q
What does the prothrombin time measure?
A
time to taken to convert prothrombin to thrombin ( i.e how long it takes for blood to clot)
8
Q
What is the difference between recording Prothrombin time and albumin?
A
Prothrombin has a shorter half life and therefore is more effective in detecting acute liver disease
9
Q
What does Vitamin K deficiency cause?
A
coagulopathy.
10
Q
How would you exclude vitamin K deficiency being a cause for a prolonged prothrombin time?
A
Give a intravenous bolus ( 10mg) of Vitamin K
If it is due to the deficiency the PT time should decrease
11
Q
What is the normal range for prothrombin time?
A
11.5-13.5s
12
Q
What are transaminases?
A
Hepatic enzymes that are usually intracellular but are released from hepatocytes due to liver cell damage.
13
Q
What are the three types of liver function tests?
i.e measure extent of liver disease
A
- serum transaminase
- Alkaline phosphatase ( ALP)
- Gamma glutamyl transpeptidase (GGT)
14
Q
What are the two transaminase used in LFT?
A
- Aspartate aminotransferase ( AST)- mitochondrial and cytosol enzyme
- Alanine aminotransferase ( ALT)- cytosol enzyme
15
Q
What are the differences between ALT and AST?
A
- AST- is found in mitochondria and cytoplasm. ALT only Cytoplasm
- ALT is more sensitive.
- AST is found in heart,muscle,kidney and brain. While ALT only in liver
16
Q
In viral hepatitis what is usual AST:ALT ratio?
ii. what is the exception?
A
- ALT is greater than AST
ii. if Cirrhosis is present AST will be greater than ALT
17
Q
In alcoholic liver disease and steatohepatitis what is the usual AST: ALT ratio?
A
AST is greater than ALT
18
Q
If the AST: ALT is greater than 1 in viral hepatitis what does this suggest?
A
cirrhosis
19
Q
If AST is greater than ALT in a patient that has liver disease without cirrhosis what is the most likely cause?
A
alcohol or obesity
20
Q
What is the role of Alkaline phophatase?
A
Catalyses the hydrolysis of organic phosphate esters.
21
Q
Where is Alkaline phosphatase present?
A
- Hepatic canalicular and sinusoidal membranes
- Bone
- Placenta
- Intestines
- Kidneys
22
Q
What causes a rise in Serum ALP?
A
- Both intrahepatic and extrahepatic cholestatic disease of any cause- PBC has highest levels
- Hepatic infiltration ( metastases)
- Cirrhosis- regardless of cholestatic jaundice
23
Q
If the GGT is abnormal and the ALP is raised where is the serum ALP presumed to come from?
A
Liver
24
Q
What is GGT?
A
enzyme involved in Glutathione metabolism and transfer of AA across cellular membranes.
25
Where is GGT found?
Present in cell membranes of Liver ( and pancreas and gallbladder), kidneys and bile ducts.
26
What drugs can cause a rise in GGT?
1. Alcohol
2. warfarin
3. phenytoin
27
What happens to GGT levels in Cholestasis?
Rises in parallel with ALP
28
What is GGT useful in diagnosing?
Liver and cholestatic diseases
29
What can cause a prolongation in Prothrombin time?
1. Drugs ( warfarin)
2. Bile malabsorption- causes relative Vitamin K deficiency
3. Consumptive coagulopathies
4. Congenital Coagulopathy
30
What would ALT/AST > ALP suggest?
Hepatocellular injury
31
What would ALP> ALT/AST suggest?
cholestasis
32
What is the normal ratio of AST: ALT?
0.8
33
What does an Alpha-1 antitrypsin deficiency suggest?
cirrhosis and or emphysema
34
What does a reappearance of high concentration of alpha fetoprotien suggest?
not pregnant:
Hepatocellular carcinoma
Can also be raised with regenerative liver tissue with:
Hepatitis
chronic liver disease
teratomas
pregnant:
Most likely fetal neural defect. As Alpha fetoprotein is normally produced in fetal liver
35
What happens to urinary copper, serum copper and caeruloplasmin levels in wilson's disease?
urinary copper increase
Serum copper decrease
Caeuloplasmin decrease
36
Which immunoglobulin has the most predominant rise in its serum levels due to PBC?
IgM
37
Which immunoglobulin has the most predominant rise in its serum levels due to Viral hepatitis?
IgG predominantly
| and IgG4
38
Which immunoglobulin has the most predominant rise in its serum levels due to pancreatitis and cholangiopathy?
IgG4
39
Anti-mitochondrial antibody is found in 95% in the serum of patients which have what?
PBC
40
Nucleic and smooth muscle antibodies are found in patients which have what ?
Autoimmune hepatitis
41
Anti-nuclear cytoplasmic antibodies are found in patients with what?
Primary sclerosing cholangitis
42
What does a positive dipstick test for bilirubinuria suggest?
Presence of conjugated bilirubin- present in patients with jaundice due to hepatobiliary disease.
43
What does a negative dipstick test for bilirubinuria suggest?
Jaundice is mainly caused by unconjugated bilirubin
44
What are benefits of ultrasound in diagnosing a malfunctioning liver, pancreas and gall bladder?
1. Detects gallstones
2. Detects extrahepatic obstruction
3. assessment of jaundiced patients ( to exclude obstruction)
4. Assessment of hepatomegaly/splenomegaly
5. identification of cirrhosis- liver edge is irregular and spleen is often enlarge in advanced cirrhosis. However normal ultrasound does not exclude cirrhosis
45
Give examples of chronic liver disease specific symptoms.
1. Right hypochondrial pain- liver distention
2. Abdominal distention due to ascites
3. ankle swelling due to fluid retention
4. Haematemesis and melaena - from GI haemorrhage
5. can be asymptomatic or non- specific symptoms ( e.g. weakness,anorexia and fatigue)
46
What is pruritus due to cholestasis an early symptom of?
PBC
47
Give examples of acute liver disease symptoms ( won't be specific).
May be asymptomatic or anicteric( without jaundice)
1. Malaise,anorexia and fever if the symptomatic disease is viral
2. Jaundice may appear as the illness progresses
48
What are common signs of acute liver disease?
1. Jaundice ( yellow discolouration of skin)
2. enlarged liver
3. In cholestatic phase- pale stools and dark urine
can have spider naevi and palmar erythema in severe acute disease
49
What are the common physical signs of chronic liver disease?
General:
1. Jaundice
2. Fever
3. Loss of body hair
Compensated:
1. Xanthelasma
2. parotid enlargement
3. Spider naevi
4. Gynaecomastia
5. Liver ( small or large)
6. Liver palms
7. clubbing
8. xanthomas
9. spenolmegaly (rare)
Decompensated
compensated symptoms as well as
1. Hepatic flap
2. Oedema
3. Ascites
4. dilated veins on abdomen
50
What is Jaundice also known as?
icterus
51
What are the most common places where jaundice is observed?
Mucous membranes, skin and sclera(white part of eyeball)
52
What is the main cause of jaundice?
plasma levels of bilirubin exceed or equal to 50µmol/L
53
What are the three types of Jaundice?
1. Prehepatic
2. hepatic (hepatocellular)
3. post hepatic (obstructive)
54
What are the two types of bilirubin?
Conjugated
Unconjugated
55
What are the difference between the two types of bilirubin?
Unconjugated is produced after the break down of RBCs
Unconjugated bilirubin then goes into liver which conjugates it.
Unconjugated is not water soluble therefore does not enter urine
56
What are the causes of prehepatic jaundice?
1. Haemolysis
| 2. malaria
57
What is the pathophysiology of haemolytic jaundice?
Increased breakdown of RBCs leads to overproduction of unconjugated bilirubin.
this overwhelms the liver to conjugate the bilirubin
58
What is the stool and urine appearance of prehepatic urine?
Normal colour for both
59
Which type of bilirubin is responsible for prehepatic jaundice?
unconjugated
60
Are the LFTs abnormal or normal in prehepatic jaundice?
Normal
61
What makes urine dark?
conjugated hyperbilirubinemia
62
What are the causes of hepatic jaundice?
Viral hepatitis
drug induced hepatitis ( e.g. paracetamol overdose or rifampicin)
Alcoholic induced hepatitis
cirrhosis
pregnancy
some congenital disorders e.g.
1. Gilbert's syndrome- mild jaundice develops asymptomatically (unconjugated)
2. Crigler- Najjar syndrome (unconjugated)
63
What does Gilbert syndrome have on the effect of hepatocellular function?
Decreases levels of UGT-1 . This is an enzymes that conjugates bilirubin with glucuronic acid. Therefore allows for unconjugated hyperbilirubinemia
64
What occurs in intrahepatic jaundice?
Hepatocellular malfunctions allowing for a rise in both forms of hyperbilirubinemia.
Either defects in secretion of bile or intrahepatic ducts
65
What are the LFT results of intrahepatic jaundice?
Concentration levels of both conjugated and unconjugated bilirubin rises
AST and ALT increases
ALP increases (cholestatic related)
GGT increases
66
What is the colour of the stool and urine if the patient has intrahepatic jaundice?
Dark urine and slightly pale stool
67
Discuss how bilirubin is produced and excreted
1. RBC's rupture and break down. During this process the haeme is broken down to eventually produce unconjugated bilirubin
2. Unconjugated bilirubin is bound to albumin in the blood and taken to the liver
3. Hepatocytes absorb unconjugated bilirubin and conjugates it with glucuronic acid into conjugated bilirubin
4. conjugated bilirubin leaves the liver via the ducts and enters small intestine
5. Conjugated bilirubin is converted either into urobilinogen by gut bacteria or reabsorbed.
6. some urobilinogen can be reabsorbed by the kidneys. Urobilinogen is oxidized to urobilin which makes urine yellow. dark as well as conjugated bilirubin urine ( bilirubinuria).
7. Urobilinogen is oxidised to stercobilin which makes the pool turn brown. If stercobilin is not present then stool is pale
68
What are the causes of posthepatic jaundice?
1. Gallstones
2. Primary biliary cholangitis (PBC)
3. Primary sclerosing cholangitis (PSC)
4. Pancreatic cancer
5. cholangiocarcinoma
6. Mirizzi syndrome- compression of common bile ducts by a gallstone in the cystic duct
69
what is the cholestasis?
failure of normal amounts of bile being secreted and reaching the intestines.
70
What are the two types of cholestasis and what are there causes?
1. Intrahepatic - Hepatic jaundice i.e hepatocellular malfunction
2. extrahepatic- obstruction jaundice i.e. obstruction in the bile ducts
71
What occurs during post hepatic jaundice?
Obstruction of biliary tract leads to back flow of conjugated bilirubin back into the liver and then into blood.
72
What are the LFT results of post hepatic jaundice?
increase in conjugated bilirubin in blood
Major increase in ALP
GGT increase
increase in AST and ALT
73
What is the stool and urine colour in post hepatic jaundice?
PALE stool
Dark urine
74
What is more likely to be the cause of jaundice in a young person?
Viral hepatitis
75
What is more likely to be the cause of jaundice in the elderly who has gross weight loss?
Carcinoma
76
What history should be taken into consideration when thinking about jaundice?
1. Any previous episodes of Jaundice/ family history or liver problems?- Gilbert syndrome
2. What medication are you taking?
3. Recent surgery on biliary tract?
4. Have they ever had carcinoma?
5. Intravenous drug use?- Increase of Hep B or C
6. Alcohol
7. Men having sex with men?- increase chance of Hep B and C
8. Traveling?- HEP E COMMON IN TRAVELERS TO SUB INDIAN CONTINENT
HEP A COMMON IN UK
9. Piercings/ tattoos?
77
What are the clinical examination with jaundice related patients?
ii. state what each implies
Exam signs for chronic liver disease:
1. Hepatomegaly- if smooth and tender = hepatitis or extrahepatic obstruction
if irregular- metastases and cirrhosis
2. splenomegaly - portal hypertension in chronic liver disease
Maybe tipped due to viral hepatitis
3. Ascites- found in cirrhosis
4. Palpable gallbladder- carcinoma of pancreas
5. General lymphadenopathy- lymphoma
6. cold sores- herpes simplex virus hepatitis
78
What investigations can be carried out for Jaundice?
Imaging:
Ultrasound of abdomen- exclude extrahepatic obstruction
Tests:
Liver:
LFTs
Urine :
dipstick test for absence of urobilinogen and presence bilirubinuria
Haematology:
FBC
Paracetamol levels
hapatoglobins-a plasma protein that binds small amounts of hemoglobin i.e. less = anaemia
79
What is acute liver disease?
rapid development of hepatic dysfunction without prior liver disease
less than 6 months duration of symptoms
80
What is chronic hepatitis?
Hepatitis lasting longer than for 6 months
81
What are the main causes of chronic hepatitis?
1. NAFLD
2. Alcohol induced liver disease
3. Viral hepatitis ( B,C and D)
4. Drugs
5. Autoimmune
6. Hereditary: Wilson's disease,haemochromatosis
82
What are the infective causes of viral hepatitis?
1. Hepatitis A
2. Hep B
3. Hep C
4. Hep D
5. Hep E
6. Cytomegalovirus
7. Herpes simplex
8. Epstein Barr virus
9. Yellow fever
83
Which Viral hepatitis are associated with acute hepatitis?
A,B,C,D,E
84
Which viral hepatitis are associated with chronic hepatitis?
B
C
D
85
What type of virus is Hepatitis A and what is its main route of transmission?
RNA virus
Faecal Oral
86
What are symptoms of Hepatitis A ?
1. Fever
2. malaise
3. Anorexia
4. nausea
5. Arthralgia
most recover however if worsens then:
This is very rare with children
1. jaundice
2. hepatomegaly
3. splenomegaly
87
Where is Hep A common?
endemic in africa and south america- i.e travellers beware
Most infections in Childhood
88
How long is the incubation for Hep A?
Short (2-3 weeks)
89
What tests confirm Hepatitis A?
Raised AST , ALT
Raised bilirubin(in icteric stage however)
Raised Anti- HAV IgM means acute infection
IgG is detectable for life
90
What is the prognosis of Hepatitis A?
HAV hepatitis never leads to chronic infection
Doesn't cause liver cancer
Very small mortality- acute hepatic necrosis
91
How do you manage Hepatitis A?
control by good hygiene
Vaccination prophylaxis
92
What type of virus is Hep B ?
DNA virus
93
What are the forms of transmission for Hep B?
1. Vertical transmission- mother to child in utero. Not through breast feeding
2. Horizontal transmission: Minor abrasions, blood to blood, sex and drug users.
94
What does getting Hep B at an older age could potentially mean?
Higher risk of acute infection
lower risk of chronic infection
95
What are the four phases of chronic Hep B infection?
1. immunotolerant- childhood no sign of infection
2. immunoactive- immune response starts ( adolescents) high level of HBeAg-positive infection
3. immunosurveillance- immune control
4. Immunoescape- reactivation of disease however negative HBeAg
96
What are the symptoms of Hep B?
Acute
Similar symptoms to HAV
however arthralgia and urticaria more common
Chronic
chronic liver disease symptoms
Can be asymptomatic
97
Where is Hep B common in?
Far east, med and africa
98
What is its incubation?
Long (1-5) months)
99
What are the test results for positive Hep B?
antigens
HBsAg- Chronic or acute infection
HBeAg- Acute infection persistence means continued infectious state and development of chronicity
Antibodies
Anti HBs- indicates immunity either from infection or vaccination
Anti HBc IgM- acute hepatitis if high titre
chronic hepatitis if low titre
Anti HBc IgG- past exposure to Hep B (HbsAg- negative)
LFT
Raised AST and ALT but can be normal
100
How do you manage Hep B?
Minimise exposure- safe sex and needle exchange, screening of pregnant women. avoid alcohol
vaccination prophylaxis
Acute
Entecavir or tenofovir for persistence of HbeAg
chronic
Antiviral agents:
Interferon(most common)- used for HbeAg- positive with active disease. Shouldn't give to those with HIV or cirrhosis
Side effects: acute-influenza like illness
Oral antiviral agents
entecavir and tenofovir - excellent for both HBeAg- positive and negative patients. Few side effects
However unlike interferon most patients require very prolonged treatment even lifelong.
101
What are the potential effects of Hep B?
Acute
acute liver failure(adult)
or can develop into chronic hepatitis
chronic
If an active carrier:
Cirrhosis
Hepatocellular carcinoma with or without cirrhosis
Fulminant hepatic failure
Inactive carrier: unlikely to develop chronic liver disease resolution of liver can occur
102
What type of virus is Hep D?
incomplete RNA particle
103
Which virus activates Hep D to cause replicate?
Hep B
104
How do you diagnose Hep D?
Acute:
IgM anti-HDV in the presence of IgM anti- HBc
HDV RNA- early sign of infection
chronic :
Anti HDV with patients who are HBsAg- positive
HDV RNA
105
What are the effects of Hep D?
acute:
Acute hepatic failure
chronic:
cirrhosis
106
How do you manage Hep D?
Prevention: Hep B vaccination prevent Hep D
treatment: pegylated interferon- alfa 2a has limited effect on Hep D
107
What type of virus is Hep C?
RNA virus
108
How is Hep C transmitted?
Blood: transfusion- high with people who have haemophilia
IV drugs
sex- limited
109
Where is Hep C found?
UK, Africa Asia
110
Acute Hep C normally leads to chronic true or false?
true
111
What are the symptoms of Hep C?
Acute
1. Acute infections are mainly asymptomatic
2. Jaundice
Chronic:
Asymptomatic
malaise
fatigue
arthritis
112
How do you diagnose Hep C?
AST:ALT ratio less than 1 until cirrhosis
Acute
HCV RNA can be detected from 1 to 8 weeks after infection
anti HCV antibodies
Chronic
anti HCV antibodies
PCR used to detect HCV RNA in serum
113
What is the incubation for Hep C?
Long
114
How do you manage Hep C?
NO VACCINE
Antivirals
Acute:
If HCV RNA level does not decline then use peg interferon with or without ribavirin must be decided
chronic:
peg interferon alpha usually with ribavirin (and a (protease inhibitor such as telaprevir for genotype 1)
or depending on genotype can use:
Genotype 1: sofosbuvir with ( protease inhibitor) simeprevir or an NS5A inhibitor ( ledipasvir) can cure 90% of patients
more effective than interferon
genotype 2- sofosbuvir with ribavirin cure 90% of patients more effective than interferon
For genotype 3- interferon with ribavirin is prefered
side effects of telaprevir - rash and anaemia
side effects of boceprevir- anaemia
major side effects of interferon- psychosis and autoimmune (rare)
minor side effects of interferon- flu like symptoms
side effects of Ribavirin- haemolysis and pruritus(itch)- starting to be phased out at being used
HCV screening
stop drinking
115
What are the effects of Hep C?
Acute
Higher Majority of asymptomatic patients go on to have chronic liver disease than symptomatic ones.
Chronic:
Fibrosis than to cirrhosis
HCC - has to be with cirrhosis
116
What type of virus is Hep E?
RNA virus
117
How is Hep E transmitted?
contaminated water
found in 30% of dogs, pigs and rodents
118
What are the clinical symptoms of Hep E?
Very similar to Hep A
Does not cause chronic hepatitis unless patient is immunosuppressed
119
How do you diagnose Hep E?
IgG and IgM Anti-HEV
HEV RNA found in serum and stool via PCR
120
What are the potential effects of Hep E?
mortality from Fulminant hepatic failure usually very low however rises to 20% in pregnant women
121
How do you treat Hep E?
Vaccination in China
good sanitation
122
What are the symptoms of Epstein Barr virus causing Hepatitis?
Mild Jaundice
5 days of onset
causes glandular fever
123
How do you diagnose EB hepatitis?
Paul-bunnell test is positive and atypical lymphocytes are present in peripheral blood
124
What are the symptoms of Cytomegalovirus hepatitis?
Glandular fever type symptoms
125
How do you diagnose cytomegalovirus?
CMV DNA is positive
CMV igM is also positive( can have false positives)
liver biopsy shows intranuclear inclusions and giant cells
126
How do you treat herpes simplex?
aciclovir
127
What is the definition of liver failure?
liver injury with development of encephalopathy and coagulopathy( INR > 1.5) which occurs both acutely and late onset
128
How is acute liver failure defined?
1.
7 days= hyperacute
1- 4 weeks = acute
4-26 weeks= sub acute
2.
Based on development of encephalopathy after onset of any hepatic symptom
within 8 weeks= Fulminant hepatic failure
between 8-26 weeks = subfulminant
129
What is chronic liver failure associated with?
cirrhosis
130
What are the causes of acute hepatic( liver ) failure?
```
1. Viral hepatitis ( HCV is uncommon only in asia)
A
B
C
D
E
cytomegalovirus
EBV
```
2. Drugs - paracetamol overdose common cause in UK
antibiotics
NSAIDs
3. Toxins
Amanita phalloides- mushroom toxin
4. Hepatic failure in pregnancy- mainly acute fatty liver of pregnancy
5. Vascular causes
ischaemic hepatitis
Budd-Chiari syndrome
131
what are the clinical features of acute hepatic failure?
1. Jaundice
2. hepatic encephalopathy
3. Fetor Hepaticus ( smells like pear drops)
4. fever, vomiting ,hypotension and hypoglycemia
5. mental state varies from slight drowsiness to coma
6. ascites and splenomegaly are rare
132
What tests should be carried out for suspected AHF?
1. hyperbilirubinemia
2. high level AST and ALT levels and INR/PT (LFT)
3. paracetamol level
4. FBC
5. U&E
Imaging
abdominal ultrasound will define liver size
EEG for encephalopathy
doppler flow studies of the portal vein (and hepatic veins if Budd-chiari syndrome suspected)
133
How do you manage AHF?
No main treatment but treat cause if possible
1. Important patients put in specialised unit for treatment
2. Tilt head 20 degrees to deal with encephalopathy
3. check FBC, U&E, LFT and INR daily
Treat complications
Cerebral oedema- 20% mannitol iV
Ascites- restrict fluid
Coagulopathy: Vitamin K IV 10mg, platelets and blood or fresh frozen plasma
prophylaxis against bacterial and fungal infection
potentially a liver transplant based on severity
134
What is the prognosis of AHF?
1. cerebral oedema forms in 80% of patients however less common in subacute- 25% of deaths
2. Bacterial and viral infections lead to death
3. GI bleeding
4. respiratory arrest
5. kidney injury ( hepatorenal syndrome)
1. Grade 1-2 encephalopathy( Altered mood- increasing drowsiness) -2/3 of patients survive
2. grade 3-4 ( incoherent, stupor- coma) and drug induced liver failure have a worse prognosis
135
What are the causes of Autoimmune hepatitis?
Unknown however it is defined by abnormal of T cell function and antibodies attacking liver cell surface antigens
136
What are the symptoms of Autoimmune hepatitis?
1. can be asymptomatic
2. jaundice( fever, rash,malaise, urticaria and arthralgia). stool colour and urine change too
3. some can have Autoimmune disease
4. some can have acute hepatitis ( type II Autoimmune Hep)
137
How do you diagnose autoimmune hepatitis?
ALT and AST high levels
ALP high
IgG is very high ( double value)
PT often high
Autoantibodies
Type 1: anti nuclear (ANA) and Anti- actin (AMSA) both very high
Type 2: anti-liver/kidney also very high (anti-LKM1)
138
How do you treat autoimmune hepatitis?
immunosuppressant therapy: prednisolone 30 mg 2-4 weeks then lower to maintenance dose of 5-15 mg
for steroid-sparing agent then azathioprine main one used- sole long-term therapy and used for maintenance
liver transplantation if failed to respond or decompensated cirrhosis
139
what are the two types of autoimmune hepatitis?
Based on autoantibodies present
Type I- typical patient (80%) usually found in women younger than 40. ANA and AMSA is positive but respond well to immunosuppressants. 25% present with cirrhosis
Type II- more often older children and young adults. More common cirrhosis Anti-LKM1 positive. worse
140
what is the prognosis of autoimmune hepatitis?
80% of patients induce remission due to immunosuppression
HCC less frequent than viral-induced cirrhosis
can cause cirrhosis
141
What are the risk factors for Non -alcoholic fatty liver disease (NAFLD)?
1. Obesity
2. Hypertension
3. type 2 diabetes
4. old age ( progression)
142
What are the symptoms of NAFLD?
1. Most asymptomatic
2. Hepatomegaly may be seen
3. inflammation of liver due to fat deposition
4. jaundice
5. cirrhosis
143
What are the causes of NAFLD?
1. deposition of fat causing inflammation of the liver causing Non alcoholic steatohepatitis( NASH)
2. Fibrosis of liver due to normal steatosis (fatty liver)
144
How do you diagnose NAFLD?
Ultrasound detects steatosis if not drinking
Liver biopsy stages of disease of steatosis
elastography can be used to detect degree of fibrosis
145
What is the staging of NAFLD?
1. Steatosis (fat deposition of liver causing fatty liver)
2. advanced fibrosis
3. cirrhosis
Hepatitis of fatty liver ( NASH)- severe form of NAFLD
146
How do you manage NAFLD?
Lifestyle advice ( no alcohol, lose weight)
vitamin E - antioxidant that improves steatohepatitis. increase risk of Prostate cancer and stroke and mortality ( if above 400 IU/day)
pioglitazone also used against NASH only improves like vitamin E no cure
Bariatric surgery- not to be used if advanced cirrhosis or portal hypertension present
orlistat- causes malabsorption of dietary fat- fat soluble vitamin deficiency may occur
NASH indication for liver transplant ( 3rd highest in U.S)
147
What is the prognosis of NAFLD?
HCC is caused by NASH
cirrhosis
Risk factors of NAFLD are causes for many issues not just hepatic related:
obesity is cause for many malignancies
Type II diabetes
148
What is cirrhosis?
Scarring of liver from chronic liver disease
condition where liver responds to hepatocellular injury/necrosis and replaces damaged tissue with interlacing strands of fibrous tissue which separates regenerating nodules of functioning liver.
149
What is the shape of the liver in cirrhosis?
tawny coloured
small shrunken
hard
150
What are the two types of clinical cirrhosis?
Compensated
Decompensated
151
What are differences between the two types of clinical cirrhosis?
compensated - clinically normal but histologically have cirrhosis. mildly abnormal blood tests can have portal hypertension.
decompensated- histologically have cirrhosis and have acute on chronic liver failure( infection causing insult- able to be treated and liver can be fixed) or end stage liver disease ( chronic liver failure)- not able to be fixed as to far down.
152
What are the causes of cirrhosis?
1. Alcohol
2. Hep B(D) and C
3. NAFLD ( particulary NASH)
4. Wilson's disease
5. Budd-Chiari
6. PBC
7. secondary biliary cirrhosis
153
What are the symptoms of cirrhosis?
Compensated:
1. Xanthelasma
2. parotid enlargement
3. Spider naevi
4. Gynaecomastia
5. hepatomegaly or small liver if late disease
6. Liver palms
7. clubbing
8. xanthomas
9. spenolmegaly (rare)
Decompensated
all compensated symptoms and
1. Hepatic flap
2. Oedema
3. Ascites
4. dilated veins on abdomen
154
What are the potential complications of Cirrhosis?
1. Coagulopathy
2. encephalopathy
3. oedema
4. Portal hypertension
5. ascites
6. splenomegaly
7. Variceal bleeding
8. HCC - 2-5% third commonest death in tumours worldwide
9. portosystemic shunt
10. caput medusae- enlarged superficial periumbilical veins
155
why in liver cirrhosis does ascites occur mainly in the abdomen?
because of the low albumin and very higher pressure from portal system
(large hydrostatic pressure of capillaries [Pc], low osmatic drive of capillaries [pieC])
156
What tests should you carry out to diagnose cirrhosis?
ii. what are the results?
LFT: Increase in AST ALP and GGT- can be normal however
Albumin and PT are the best indicators. Albumin levels decrease while PT increases.
Low serum sodium - indicates severe liver disease due to a defect in free water clearance or excess diuretic therapy
Creatine- elevated concentration
Also test for suspected causes e.g. autoantibodies and alpha trypsin
Imaging:
Ultrasound and duplex- show hepatomegaly,splenomegaly,small liver, focal liver lesions and Ascites
MRI- useful in detecting tumours and caudate lobe sizes as well as presence of the right posterior hepatic notch
Liver biopsy- confirms diagnosis
157
What is present in alcoholic cirrhosis rather than viral induced cirrhosis?
right posterior hepatic notch
158
How do you manage cirrhosis?
Treat underlying cause and complication- overall arrest or reversal of compensated cirrhosis will occur
Good nutrition: 35-40 kcal/Kg and a protein intake of 1.2-1.5 g/Kg are recommended
small Frequent meals and snacks
Avoid alcohol- vitamin B supplementation thiamine mandatory in excess alcohol intake
Avoid NSAIDs,sedatives and opiates- may precipitate GI bleeding or renal impairment
Ultrasound screening every six months
For ascites: Aim to reduce sodium and to increase sodium excretion
Diuretics; Spironolactone first. If no response then add furosemide
check U&E regularly- especially after dose change or paranceentosos
TIPPs- if paracentesis is too regularly used
Paracentesis may be required- if too large to drain and kidneys cant take it. Give albumin regularly to avoid hypovolaemia and encephalopathy
Spontaneous bacterial peritonitis- use prophylaxis for high risk patients
encephalopathy- prophylactic lactulose and rifaximin
159
What is the prognosis of cirrhosis?
extremely variable 5-year survival rate is 50%
Child's grading A B C grades cirrhosis. A being best
Measures ascites, encephalopathy, bilirubin ,albumin and PT ( seconds over normal)
160
What is the prognosis of acute on chronic liver failure?
High short term mortality
different to traditional decompensated cirrhosis
why?
based not only on the presence of organ fialure and high mortality but more likely with younger age, higher alcohol use and bacterial infection, higher level of systemic inflammation
161
Portal hypertension is caused only by cirrhosis true or false?
false
162
What are the two subgroups of cirrhosis?
micronodular- mainly caused by alcohol or biliary tract disease. Nodules usually less than 3 mm
macronodular- mainly chronic hepatitis nodules are of variable sizes
163
What types of portal hypertension are there?
Prehepatic- blockage of portal vein before the liver
Intrahepatic- due to distortion of the liver architecture can be split into either presinusoidal or postsinusoidal
Post hepatic- venous blockage outside the liver (rare)
164
What causes prehepatic portal hypertenstion?
Portal vein thrombosis or occlusion secondary to congenital portal venous abnormalities.
congenitial examples: neonatal sepsis of the umbilical vein or inherited prothrombotic conditions
165
How do prehepatic patients present?
GI bleeding often at young age. They have normal liver function
166
What does the portal vein consist of?
1. Superior mesenteric vein
2. Splenic vein
3. Gastric vein
4. Inferior mesenteric vein
167
What happens if portal hypertension occurs?
The four collateral pathways of the portal system in the systemic system dilate.
This leads to them becoming engorged and dilated or varicose leading to rupture
Gastro-oesophageal junction is the main place where rupture occurs due to portal hypertension as it is superficial. It forms varices which then rupture.
other areas of the collateral pathways rarely rupture or have symptoms
168
What are the causes of intrahepatic portal hypertension?
Presinusoidal: Schistosomiasis,sarcoidosis, PBC
post-sinusoidal: cirrhosis , alcoholic hepatitis
169
What are the causes of post-hepatic portal hypertension?
Budd Chiari and veno occlusive disease
right heart failure is rare
170
What are the symptoms of portal hypertension?
often asymptomatic
main clinical feature is splenomegaly and ascites
however other chronic liver disease features may be present
171
why can chronic liver disease cause haematemesis?
ruptured oeophageal varices due to portal hypertension
172
Where are normally varicies found ?
Gastro-oesophageal junction
and other portosystemic collateral sites
ectopic sites too
173
what are the differences between rectal varices and haemorrhoids?
anorectal varices= dilation of portal-systemic anastomosis due to portal hypertension
haemorrhoids = prolapse of rectal venous plexus (not due to portal hypertension)
174
How do you identify portal vein blockage?
Ultrasound with doppler imaging
175
How do you manage variceal bleeding?
1. Acute initial management ( i.e Variceal bleeding has occurred)
Main is rescustitation(control bleeding): Access patient, Restore blood volume, carry out ascitic tap, monitor for alcohol withdrawal( give IV thiamine) then start prophylactic antibiotics
Vasoconstrictor therapy: Restrict portal inflow by splanchnic arterial constriction
1. Terlipressin- only vasoconstrictor proven to reduce mortality ( 2mg 6-hourly after 48 hours then 1 mg-4 hourly if still required). Don't give to patients with ischaemic heart disease.
2. Somatostatin - used for contraindications for terlipressin
Endoscopy- confirm diagnosis and to exclude bleeding from other site.
With endoscopy variceal banding can occur- Bands oesophageal varice which sucks varix to end of the scope.
Can't control pulse and pressure and bleeding from endoscopic therapy then use Balloon tamponade:
Inflates balloon in stomach and pulls it so it is close to apposition to the gastro-oesophageal junction.
Complication: Aspiration pneumonia( as blood may go up oesophagus and into trachea), esophageal rupture and mucosal ulceration
Balloon tamponade is only temporary allows for preparation of TIPS or Banding
TIPS
2. Acute Rebleed:
Transjugular intrahepatic portocaval shunt( TIPS)- used for rebleed or acute management. Creates total shunt decreasing both sinusoidal and portal vein pressures.
Far more effective at reducing rebleeding rates then endoscopic techniques
complication: Increase risk of encephalopathy
3. Primary prophylaxis ( patients with diagnosed cirrhosis and have varices that have not bled)
Endoscope to diagnose varices
Non selective beta blockers ( Propranolol and carvedilol)
If patients are tolerant or unreliable with beta blockers then use variceal band ligation.
4. Secondary Prophaylaxis ( survived variceal bleed)
Variceal banding ligation and Non selective beta blockers are both used at the same time not like primary which is a choice between the two.
Poor liver function: Liver transplant
176
What might be seen in a patient with oesophageal varices?
Red signs in the oesophagus
177
what is 'caput medusae'?
when the umbilical vein (ligamentum hepes) becomes back in use because of portal hypertension
178
Patients with cirrhosis have a high risk of what?
bleeding as well as clotting easily
Therefore high risk of thrombosis and haemorrhage
179
why should NSAIDs be avoided if possible in patients in dehydrated states (such as alcoholism/cirrhotic livers)?
NSAIDs inhibit vasodilator prostaglandins so will worsen kidney impairment due to vasoconstriction
(due to the high concentration of vasoconstrictors produced because of the dehydration)
180
if you are prescribing a NSAID for a patient with cirrhotic liver what must be co-prescibred?
a proton pump inhibitor
181
why can chronic liver disease cause oedema?
reduced albumin synthesis resulting in hypoalbuminaemia
182
What is ascites?
Fluid within the peritoneal cavity
183
What types of ascitic fluid are there?
ii. what are the main causes?
Straw coloured- malignancy ,cirrhosis and infection ( e.g. TB or any bacteria found in intra abdominal perforation)
Chylous(milky)- obstruction of main lymphatic duct or cirrhosis
Haemorrhagic (bloody)- Malignancy, ruptured ectopic pregnancy ,abdominal trauma or acute pancreatitis
184
What factors lead to the formation of ascitic fluid?
1. Sodium and water retention: Peripheral arterial vasodilation occurs which reduces effective blood volume. This in turn promotes salt and water retention
2. Portal hypertension- increases local hydrostatic pressure
3. Low serum albumin- reduces oncotic pressure
With patient who have ascites , urine sodium excretion rarely exceeds 5mmol in 24 hours
185
What are the clinical features of asictes?
Abdominal swelling develops
Mild abdominal pain and discomfort are common
If worse than SBP might be present
Precipitating factors include HCC and high-sodium intake.
186
How do you diagnose and investigate ascites?
Shifting dullness
ultrasound- darkness is the fluid surrounding nodule of liver
cell count- neutrophil count >250 cells/mm3 usually indicator of bacterial peritonitis
gram stain and culture
Protein measurement- high serum albumin= portal hypertension cause. Low= non liver related
cytology
187
How do you manage ascites?
1. check eGFR every two days
2. bed rest
3. dietary sodium restriction
4. Avoid NSAIDS as they are sodium retaining
5. Diuretics- main choice is spironolactone
6. Paracentesis
7. if too much paracentesis then use TIPS
188
Discuss the differing usage of diuretics for ascites.
If new ascites escalates use spironolactone
chronic use causes gynaecomastia
in recurrent ascites use both spironolactone and loop diuretic(e.g. furosemide or butenamide).
Stop using diuretics temporarily if: rise in serum creatinine= over diuresis and hypovolaemia. Or if there is hyperkalemia. or if sodium falls below 128 mmol/l
189
What is paracentesis?
ii what are the risks?
Drain in the abdomen which removes ascites
Used if there is a large volume or kidneys do react well to diuretics
ii. hypovolemia, risk of infection and encephalopathy are risks
190
How do you manage risk of paracentesis?
Patients with normal renal function can have albumin given regularly
191
When is TIPS used for ascites?
If ascites is regularly occurring and no spontaneous portosystemic encephalopathy
creates artificial pathway between hepatic vein in liver and portal vein in the liver via a stent.
60% have no ascites after and don't require diuretics
192
What is SBP?
When patients have ascites and the bacteria translocate into the peritoneum due to ascites
193
How do you diagnose SBP?
Raised neutrophil count (250 cells /mm3)
Ascitic tap
194
What is SBP exclusively associated with?
portal hypertension
195
Which bacteria are the most common causes for SBP?
1. E Coli
2. Klebsiella
3. enterococci
196
How do you manage SBP?
Antibiotics with infusion of albumin
Vascular instability? then use terlipressin
Maintain renal perfusion
197
What are the signs of SBP?
patient with ascites has quickly deteriorated
abdominal pain and pyrexia
198
How does encephalopathy occur?
1. Ammonia generated in the intestine by colonic flora and glutaminase bypass the liver due to portal hypertension as well as porto systemic shunts
2. This impairs brain function by inducing several disturbances in astrocytes; these may impair mitochondrial and the glutamate-glutamine trafficking between the neurons and astrocytes.
199
What are the factors leading to portosystemic encephalopathy?
1. high dietary protein
2. Gi haemorrhage
3. constipation
4. infection including SBP
5. TIPS and paracentesis
200
What are the symptoms of encephalopathy?
1. Altered mood
2. increased drowsiness and confusion, apraxia slow liver flap.
3. coma if very late
signs
4. fetor hepaticus ( sweet smell from breath)
5. a coarse flapping tremor- when arm outstretched
6. Loss of mental function
General: nausea,vomiting and weakness. Hyperreflexia and higher tone
201
How do you test for apraxia?
Ask to draw a five pointed star
202
How do you diagnose Encephalopathy?
clinical ( looking for signs)
203
How do you manage encephalopathy?
Treat cause (look for infection, drug, liver failure)
Give lactulose-osmotic purgative reduces the colonic pH and reduce transmit time
Rifaxamin- antibiotic
Stop or reduce diuretic therapy
small frequent meal - maintain nutrition
if spontaneous consider transplantation
204
Prognosis of encephalopathy?
Acute encephalopathy in acute hepatic failure has a very poor prognosis
in cirrhosis chronic PSE adversely affects prognosis but the course is very variable
205
What is hepatorenal syndrome?
cirrhosis + Ascites + renal failure
Urine output is low with a low urinary sodium concentration
206
what precipitating factors are the cause HRS ?
over vigorous diuretic therapy
NSAIDs usage
diarrhoea
paracentesis
SBP
207
How do you treat HRS?
Terlipressin and albumin help with renal function
Liver transplantation best option
208
What Is primary biliary cirrhosis/cholestasis?
Interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation causing cholestasis.
209
Which group of people have the highest likelihood of getting PBC?
Middle aged women
210
What are the clinical features of PBC?
asymptomatic mainly
usually diagnosed due to high ALP
Jaundice and itch and
hepatosplenomegaly are common
xanthelasma may be seen
211
What results would you get from diagnosing PBC?
immunoglobulin increase ( especially IgM)
antimitochondrial antibodies (AMA) are the hallmark of PBC
High ALP and GGT and bilirubin
serum cholesterol high
imaging
ultrasound excludes extrahepatic cholestasis
Biopsy shows granulomas and cirrhosis
212
What are the associate disorders of PBC?
Autoimmune disorders ( thyroid disease,sjogren's syndrome and scleroderma)
dry eyes and mouth seen in 70% of patients
213
How do you manage PBC?
1. Ursodeoxycholic acid - improves bilirubin and aminotransferase levels. MUST be given in asymptomatic stage
2. Vitamin A,D and K given due to malabsorption
3. steroids- improve - do cause osteoporosis
4. For pruritus - use cholestyramine. Rifampicin and naloxone is also useful
no response? liver transplant
214
What is PSC?
primary sclerosing cholangitis.
Autoimmune fibrosis and stricturing of the large and medium sized bile ducts.
The fibrosis is described as onion skinning
215
what is the epidemiology of PSC?
more common with men and those with UC
216
What are the signs and symptoms of PSC?
Asymptomatic
Fluctuating pruritus, jaundice and cholangitis sometimes fatigue (lethargy)
hepatic failure
217
How would you test for PSC?
High ALP and Bilirubin
Might have increase in IgM , ANA, SMA and ANCA but not AMA
Imaging
MRCP or ERCP
218
What can PSC lead to?
cirrhosis
cancers in the Bile duct, gallbladder and colon
Hepatocellular carcinoma
219
How do you manage PSC?
Liver transplant main way
ursodeoxycholic might help with LFT but high dosage can be harmful
if dominant lesion is sited in the extrahepatic ducts (rare) then endoscopic biliary intervention can occur
220
What are the causes for secondary biliary cirrhosis?
bile duct strictures
Gallstones
sclerosing cholangitis
221
why is hyoglycaemia a very serious clinical sign of acute liver disease?
because the liver usually makes glucose until the very end
222
What is hereditary haemochromatosis?
Inherited disorder ( autosomal recessive) of iron metabolism in which increase of intestinal iron absorption leads to iron deposition in joints, liver and pancreas.
223
Hereditary haemochromatosis occurs more in men than women true or false?
true
224
What is the difference between primary and secondary haemochromatosis?
primary : an autosomal recessive condition which causes excess iron within the liver due increased absorption of iron from food
secondary:excess iron within the liver caused by iron overload from diet, transfusions or iron therapy
225
What are the symptoms of hereditary haemochromatis?
early: asymptomatic or and arthralgia
late: slate grey skin, hepatomegaly and cirrhosis.
cardiac manifestations: heart failure and arrhythmias ( very common in younger patients)
Endocrinopathies: Bronze skin pigmentation ( due to melanin deposition) and diabetes - occurs late on
226
how do you diagnose hereditary haemochromatosis?
testing:
LFT increase not always
serum iron is increased ( sometimes normal in heterozygotes)
serum ferritin is increased ( sometimes normal in heterozygotes)
Liver biopsy: Perl's stain quantifies iron loading and shows degree of tissue damage
MRI: liver and pancreas signal intensity is dramatically reduced due to paramagnetic effect of ferritin
227
How do you manage HH?
Venesection(phlebotomy)- will be needed for life to make sure iron does not rise again. This prolongs life and may reverse tissue damage. Doesn't remove risk of malignancy
over the counter drugs- ensure vitamin preparations contain no iron
Screening all first degree family members
228
What are the risks of HH?
Primary hepatocellular carcinoma
cirrhosis and fibrosis
229
What is wilson's disease?
rare congenital disease ( autosomal recessive) of copper deposition in various organs including the liver, basal ganglia of the brain and the cornea.
230
What is copper normally bound to when carried to the liver?
ii. what is it later synthesised to?
albumin
ii. it is then synthesised to caeruloplasmin
rest of copper is excreted
231
What are the symptoms and signs of wilsons disease?
More likely to be found in young adults and kids
Children: present with liver disease ( Hepatitis, cirrhosis, fulminant liver failure)
Young adults present with CNS signs ( tremor, dysarthria, dementia, parkinsonism)
cornea: kayser fleischer ring - greenish brown pigment ( use slit lamp for exam) maybe absent in young kids
mood: depression, personality change.
Cognition: memory; slow to solve problems decrease in IQ
Blue nails , arthritis and grey skin and haemolysis are common
232
How do you diagnose Wilson's disease?
serum copper and caeruloplasmin levels are low
urinary copper is increased
Slit lamp exam for KF rings
Genetic testing
Liver biopsy- weigh amount of copper in liver
imaging: copper deposition in CNS can be viewed with MRI
233
How do you manage Wilson's?
Diet: avoid food with high copper content
penciliamine- lifetime treatment is effective in chelating copper
asymptomatic screening of siblings
if acute hepatic failure or decompensated cirrhosis then transplant
234
What are the risk of wilson's?
fatal events include liver failure, bleeding or infection
235
What is alpha antrypsin deficiency?
Autosomal recessive condition which causes a deficiency of alpha 1 antitrypsin enzymes leading to liver and lung problems
236
What is the main role alpha 1 antryspin?
Inhibit the proteolytic enzyme neutrophil elastase
237
What are the signs and symptoms of Alpha 1 deficiency?
Symptomatic patients are homozygotes with piZZ phenotype
associated diseases: emphysema, cirrhosis and HCC
symptoms: dyspnoea from emphysema,cholestatic jaundice
238
How do you diagnose alpha 1 antitrypsin deficiency?
serum alpha 1 is usually decreased
Lung biopsy; Periodic acid Schiff ( staining method) is positive. Cirrhosis and fibrosis can be observed
239
How do you manage alpha 1 deficiency?
Stop smoking!
Liver transplantation if decompensated cirrhosis
240
What is the prognosis of alpha 1 antitrypsin deficiency?
Some are asymptomatic and live a healthy long term life
most die from emphysema
worse in males
241
why does being a long term alcoholic increase risk of overdosing when taking too many paracetamol tablets?
as a long term alcoholic your body has more receptors and so the paracetamol will be metabolised much quicker and acetyl-p-benzoquinomine is formed at a much faster rate
242
What are the three main liver diseases caused by alcohol?
1. Fatty liver- liver cells becoming swollen with fat ( steatosis). Can sometimes progress to cirrhosis without hepatitis. improves after drink cessation
2. alcoholic hepatitis- mallory bodies sometimes can be seen in hepatocytes along with large mitochondrias. Continue drinking leads to cirrhosis. Steatohepatitis occurs.
3. cirrhosis- mainly micronodular type. Hepatitis may also be present sometimes
243
What are the signs and symptoms of alcoholic liver disease?
fatty liver- often asymptomatic
symptoms: nausea, vomiting and diarrhoea hepatomegaly
alcoholic hepatitis: jaundice, chronic liver disease symptoms. Look for fever, hepatomegaly, hepatic bruit and leukocytosis mainly.
cirrhosis: chronic liver disease symptoms. alcoholic dependency. portal hypertension symptoms ( caput medusa).
244
What are the general symptoms of alcoholism in the body?
CNS:
Acute: Violence and accidents
chronic:Neuropathies, cerebellar degeneration, dementia and wernicke-Korsakoff's syndrome (psychosis and encephalopathy)
GI:
Acute: oesophagitis, ulceration, acute pancreatitis,
chronic: obesity, cancers, chronic pancreatitis
Cardiovascular:
Chronic: Arrhythmias, hypertension, stroke and MIs and cardiomyopathies
Resp:
Acute: overdose and aspiration
Reproduction:
chronic: testicular atrophy, decrease in testosterone and progesterone. Increase in oestrogen
Fetal alcohol syndrome
245
What is fetal alcohol syndrome?
collection of conditions in children due to overuse of alcohol in parents
Conditions: Low IQ, growth deficiency, small eyes, behavioural problems, microcephaly, small chin, no distinct philtrum
246
How do you diagnose alcoholic liver disease?
Fatty liver: increase Mean cell volume . Increase in GGT sign of alcoholism
Imaging: ultrasound will show fatty infiltration. Elastography will show degree of fibrosis
Alcoholic hepatitis: Increase in bilirubin, AST and ALT and ALP and prolonged PT. Low albumin may also be found.
Prolonged PT means that Liver biopsy has to be throw transjugular route
cirrhosis: see how to diagnose cirrhosis. Cba as it took me fucking ages before. I could copy and paste but nah im even to lazy for that.
247
How do you manage alcoholic liver disease
Stop drinking alcohol!- alcohol free beers maybe?
1. For withdrawal symptoms- diazepam
2. for prevention of wernicke korsakoff syndrome- IV thiamine
3. Bed rest. Limit proteins diet due to encephalopathy
Fatty liver- stop drinking should be enough
alcoholic hepatitis- see discriminant function for steroid therapy
vitamin supplementation
Liver transplant- if proven they will give it up after and continue to not drink. for cirrhosis and hepatitis
treat chronic liver disease symptoms
Hypophosphataemia is common in alcoholic withdrawal due to malnutrition
248
What is delirium tremens?
a withdrawal symptom
249
What is discriminant function?
Suggests which patients with alcoholic hepatitis may have a poor prognosis and benefit from steroid administration.
>32 correlates 45% mortality at day 28
But there is a concern over accuracy
250
What is the prognosis?
severe cases mortality can be at least 50%
encephalopathy and acute kidney failure= 90% risk
need transplant as soon as possible with acute hepatitis and cirrhosis.
risk of HCC with men in particular
251
What is Budd chiari syndrome?
condition of the obstruction of the venous outflow of the liver owing to occlusion of the hepatic vein.
252
What are the causes of budd chiari syndrome?
1/3 of patients it is unknown
other 2/3s
1. Hypercoagulability states
2. thrombophilia
3. contraceptive pill
4. pregnancy
5. leukaemia
6. abdominal wall sarcoma
7. renal or adrenal tumours
8. HCC.
9. infections of the liver
253
What are the symptoms of Budd chiari syndrome?
acute: abdominal pain, nausea, vomiting , hepatomegaly and ascites. Fulminant form of budd chiari very common in pregnant women.
chronic: Hepatosplenomegaly, jaundice, ascites, negative hepatojugular reflux and portal hypertension
254
How do you diagnose Budd Chiari syndrome?
High protein content in ascitic fluid
LFT: High ALT
ultrasound with doppler flow show hepatic vein occlusion and abnormality of flow in the hepatic vein.
thrombophilia screening required
coagulation defects present
255
How do you manage Budd chiari syndrome?
Thrombolytic therapy can be given
treat underlying cause
TIPS is treatment of choice
liver transplantation for chronic budd chiari
anticoagulation required after transplantation or TIPS
256
what is the most common benign liver lesion?
ii. which is it more common in male or female?
Haemangioma
ii female
257
Describe the clinical features of haemangioma?
usually asymptomatic.
normally small and single can be large and multiple however
Well demarcated capsule
258
How do you diagnose and treat haemangioma?
Ultrasound: echogenic spot
CT: for venous enhancement
MRI: for high intensity area
Treatment: none required
259
What is a hepatic adenoma?
ii. what are they associated with?
benign liver tumor composed of hepatocytes with no portal tract,central veins or bile ducts
ii. contraceptive pills and androgenic steroids
260
What are the symptoms of Hepatic adenomas?
Asymptomatic
can present with Abdominal pain or intraperitoneal bleeding
261
How do you treat hepatic adenomas?
Resection only required for symptomatic patients and with tumours >5cm in diameter
stop taking contraceptive pills!
262
what are the 4 main benign focal nodules?
hemangioma
focal nodular hyperplasia
adenoma
liver cysts
263
What are the clinical features of Focal nodular hyperplasia?
1. benign nodule formation of normal liver tissue.
2. classically has a central scar containing a large artery which radiates branches to the periphery
3. form due to abnormal arterial flow
4. SInusoids, bile ductules and kupffer cells present on histology
5. more common in women ( young to middle aged)
6. usually asymptomatic
264
How do you diagnose and treat FNH?
Ultrasound and CT or MRI
FNA normal hepatocytes and kupffer cells with central core
treatment: none required
265
what does hyperintense mean on MRI?
brighter than surrounding tissue
266
what does hypointense mean on MRI?
darker than surrounding tissue
267
what does isointense mean on MRI?
same colour as surrounding tissue
268
what can be the complications of a hepatic adenoma?
rupture
haemorrhage
malignant transformation
Very rare
269
Malignant transformation of hepatic adenomas are higher in men or women?
Men
270
Which lobe is hepatic adenoma usually found in?
right lobe
271
What is adenomatosis?
ii. what is it associated with?
condition with Multiple adenomas
ii. Glycogen storage disease
272
How do you diagnose Hepatic adenoma?
Ultrasound: filling defect
CT: diffuse arterial enhancement
MRI: Hypo or hyper intense lesion
FNA: May be needed
273
what are the main differences between adenomas and focal nodular hyperplasia?
adenoma is purely a hepatocyte tumour which FNH contains all liver ultrastructure
adenomas can bleed and become malignant while FNH can't do either
all FNH has central scar adenomas vary
274
What are the main similarities between adenomas and FNH?
Both hypervascular
both can cause pain
275
What are the five types of cystic lesions?
1. simple-liquid collection lined by an epithelium
2. hydatid-a multilobular cyst
(ie contains many irregular cavities)
3. atypical
4. polycystic lesion- embryonic ductal plate malformation of the intrahepatic biliary tree. Numerous cysts throughout liver parenchyma
5. Pyogenic or amoebic abscess
276
What are the symptoms of simple cysts?
Usually asymptomatic
symptoms can be :
Intracystic haemorrhage
infection
rupture
compression
277
There is no biliary tree communication with simple cysts true or false?
true
278
How do you manage simple liver cysts?
No follow up if in doubt image every 3-6 months
279
Which bacteria causes hydatid cysts?
Echinococcus garanulosus
280
How do patients present with Hydatid cyst?
usually from endemic regions of eastern europe, central america, south america, middle east or north africa
disseminated disease or erosion of cysts into IVC
281
How do you diagnose Hydatid cysts?
anti echinococcus antibodies are present
282
How do you manage Hydatid cysts?
Drugs: albendazole
surgery: Open cystectomy or pericystectomy ( for complete curative action)
surgery Risks: anaphylaxis and dissemination of infection
Can do percutaneous drainage-The PAIR (puncture-aspiration-injection-reaspiration; sometimes percutaneous aspiration-injection-reaspiration) procedure is a noninvasive treatment option to remove hydatid cysts. PAIR is considered an alternative treatment for cystic echinococcosis (hydatid disease) and is often indicated for patients who do not respond to surgery or benzimidazoles
283
What three types of polycystic liver disease is there?
1. Von meyenburg complexes ( VMC)
2. Polycystic liver disease
3. Autosomal dominant polycystic kidney disease (ADPKC)
284
What is Von meyenburg complexes?
Benign cystic nodules throughout the liver.
cystic bile duct malformations originate from the peripheral biliary tree
285
What is Autosomal dominant polycystic kidney disease?
Renal failure due to Polycystic kidneys and non renal extra hepatic features
286
What are the symptoms of polycystic liver disease?
usually asymptomatic
Abdominal pain and distention
oesophageal varices very rare
287
How do you treat PCLD?
pharmacological: somatostatin
Invasive procedures such as aspiration or liver transplants are very rarely used. Only used in advance PCLD
288
What are liver abscesses?
Mass filled with pus inside the liver
289
what two main types of liver abscesses are there?
Pyogenic
Amoebic
290
What is the most common type of organism which causes pyogenic liver abcesses?
E.coli
Streptococcus milleri and bacteroides are also commonly seen
291
What are the signs and symptoms of a pyogenic abscess?
acutely ill Patients:
Malaise
High Fever
rigors, anorexia, vomiting, weight loss and abdominal pain
gram negative septicaemia with shock can occur
liver is tender and enlarged with potential PE
292
How do you diagnose Pyogenic abscess?
Bilirubin increase can occur
Raised ALP
vitamine B12 very high
ESR and CRP are often raised
Imaging;
ultrasound is useful
CT can be used if there are multiple lesions
293
How do you manage pyogenic abcess?
1. Aspiration with Ultrasound control
2. Antibiotics
3. Further drainage via a large-bore needle if resolution is slow
294
What is the most common cause of the amoebic abscess?
Entamoeba histolytica- causes portal hypertension
295
What are the signs and symptoms of Amoebic abscess?
Fever, anorexia weight loss and malaise
hepatomegaly
sign of PE
Jaundice unusual
296
Where is pain from liver tumours most likely to be felt at?
RUQ
297
How do you diagnose Amoebic abscess?
Test for amoeba - haemagglutination
diagnostic aspiration of fluid: looks like anchovy sauce
298
How do you manage amoebic abscess?
Metronidazole
if fail to respond then aspiration especially if with multiple lesions
299
what are the 6 primary liver cancer?
```
hepatocellular carcinoma
cholangiocarcinoma
fibrolamellar carcinoma
hepatoblastoma
angiosarcoma
haemangioendothelioma
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300
What is the most important risk factor of HCC?
cirrhosis
301
What are the signs and symptoms of HCC?
1. Asymptomatic- if patients have cirrhosis
weight loss
Chronic liver disease signs which are pre existing
anorexia
fever
Pain in RUQ
ascites
hard enlarged mass of RUQ
liver bruit (rare)
302
Where does Liver metastasise go to?
1. rest of liver
2. portal vein
3. lymph nodes
4. Lung
5. Bone
6. Brain
303
Histologically what do HCC cells look like?
Cells resembling hepatocytes
304
How do you diagnose HCC?
Serum alpha fetoprotein is raised. This is HCC tumour marker
ultrasound shows filling defects in 90% of cases
Tumour biopsy- less used now
305
How do you manage HCC?
Resecting solitary tumours- as long as no jaundice or portal hypertension
liver transplant- best choice
Percutaneous ablation- temporary measure
Tumor embolization ( TACE)- inject chemotherapy selectively in to the hepatic artery then inject embolic agent. Only in patients with early cirrhosis
Sorafenib- can be used for advanced HCC but Side effects are common
306
What are the causes of cholangiocarcinoma?
PSC
Biliary cysts
caroli's disease
HBV HCV
307
What is the main type of cholangiocarcinoma?
Extrahepatic
308
What are the signs and symptoms of Cholangiocarcinoma?
Fever, abdominal pain malaise
jaundice frequent with hilar tumours
weight loss , anorexia , lethargy
cholangitis
309
How do you diagnose cholangiocarcinoma?
Increase in bilirubin and high increase in ALP
duplex ultrasound
310
How do you treat cholangiocarcinoma
Praying- 70% of patients when diagnosed are inoperable
Liver transplantation rarely possible
resection rarely possible
normally major hepatectomy and extrahepatic bile excision with caudate lobe resection.
loads of complication: Liver failure, bile leak and GI bleeding
311
Fibro-lamellar carcinoma is related to cirrhosis true or false?
false
312
What age group is fibro-lamellar carcinoma usually related to?
young age (5-35)
313
What are the two main types of gallstones?
mainly mixed
1. Cholesterol stones-imbalance between the ratio of cholesterol to bile salts
2. pigment stones- predominantly composed of calcium bilirubinate or polymer-like complexes and some cholesterol. less frequent then cholesterol stones
314
What three factors ensure the formation of cholesterol gallstones via crystallization from gallbladder bile?
1. cholesterol supersaturation of bile
2. Crystallization-promoting factors within bile
3. motility of the gallbladder- gallbladder stasis leads to cholesterol crystallisation mediated by hypersecretion of mucin
315
How are statins effective in treating hypercholesterolaemia?
competitively inhibiting HMG-CoA reductase
also reduce cholesterol secretion
316
What is leptin?
a hormone
317
What is Leptin's effect on cholesterol?
increase cholesterol secretion into bile.
elevated levels of leptin during weight loss may account for increased incidence of gallstones.
318
What are the two main types of bile pigment stones?
Black and Brown
319
What are black pigment gallstones made of?
calcium bilirubinate and a network of mucin glycoproteins that interlace with salts
320
what are black pigment gallstones associated with?
ii. why is this?
All major haemolytic anaemias (due to sickle cell and thalassemia)
subclinical haemolysis ( due to malaria)
Hypersplenism ( due to hepatic cirrhosis)
high prevalence in gilbert syndrome
ii. Hyperbilirubinbilia is a major risk factor for these conditions
321
What are brown pigment stones composed of?
calcium salts of fatty acids
Calcium bilirubinate
322
Where are brown stones found?
anywhere in the biliary tree secondary to chronic stasis and anaerobic bacterial infection
Always found in the presence of bile stasis or biliary infection
323
What are the main risk factors for cholesterol gallstones?
1. increasing age
2. being a woman
3. genetics
4. obesity
5. rapid weight loss
6. diabetes
7. ileal disease - causes loss of bile salt into the colon which promotes reabsorption of bilirubin which leads to more enterohepatic circulation causing more biliary secretion- gallstones.
324
What are the signs and symptoms of gallstones?
usually asymptomatic
if complications arise then symptoms become recurring
325
what can gallstone obstruction lead to?
gallstones in gallbladder- asymptomatic
gallstones in cystic duct- acute cholecystitis
gallstone in common bile duct- biliary obstruction
gallstone in pancreatic duct- pancreatitis
326
What is biliary(gallstone) colic?
term used to describe pain associated with temporary obstruction of the cystic or common bile duct by a stone ( usually gallstone)
327
What are characteristics of Biliary colic?
usually sudden onset
commonly felt in the mid-evening until early hours of the morning
mainly epigastrium but can be also RUQ
pain may radiate to right shoulder and right subcapsular region
nausea and vomiting accompany pain usually
associated with indigestion too
328
How do you treat biliary colic?
can end spontaneously
or give opiate analgesia
rehydrate
Observe in 3-6 months
If the patient is getting recurrent episodes of pain consider elective cholecystectomy
If patient unfit, try to dissolve gallstones with ursodeoxycholic acid
329
what does protracted pain of biliary colic with fevers and rigors imply?
secondary complications (cholecystitis, cholangitis or gallstone-related pancreatitis)
330
what is the usual pathogenesis of acute cholecystitis?
gallstones obstructing outflow of bile
this becomes infected and may cause empyema (gallbladder become distended with pus) rupture and peritonitis (rare)
intense adhesions are formed
331
what are the signs and symptoms of acute cholecystitis?
similar to biliary colic
RUQ pain is more localised and continuous
vomiting, fever,local peritonism
gallbladder mass present
murphy's sign is present- pain on taking a deep breath when the examiners fingers are on the gallbladder
if stone moves to cystic biliary duct then obstructive jaundice and cholangitis can occur
332
How do gallstones form?
1. abnormal bile composition
2. bile stasis
3. infection
4. excess cholesterol and bilirubin
333
What is the difference between acute cholecystitis and biliary colic?
Inflammatory reaction occurs in cholecystitis ( local peritonism and fever) unlike in biliary colic which doesn't
334
How do you test and diagnose for Acute cholecystitis
increase in White cell count (leukocytosis)
raised inflammatory markers ( CRP)
Ultrasound - shows a thick-walled shrunken gallbladder
shows dilated CBD
335
How do you treat acute cholecystitis?
Pain relief( opiate analgesia)
iv fluids and antibiotics e.g. co-amoxiclav
laparoscopic cholecystectomy is the main choice due to being incredibly safe. Needs to be urgent tho
336
What are the signs and symptoms of chronic cholecystitis?
same as acute and flatulent dyspepsia
337
What are the complications of cholecystectomy ?
biliary leak- from cystic duct or gallbladder bed
injury to the bile duct itself is very very rare.
338
What are three main symptoms of acute cholangitis?
RUQ pain, jaundice and rigors
339
How do you diagnose acute cholangitis?
elevated neutrophil count and raised inflammatory markers are common
bilirubin rise is mild
LFT rise in proportion to hyperbilirubinemia
imaging
US
CT
ERCP
340
How do you manage acute cholangitis?
urgent bile duct drainage- via ERC
antibiotics- e.g. piperacillin
Laparoscopic cholecystectomy
341
What is Gallstone ileus?
Stone enters through the Gallbladder into duodenum via a cholecysto-enteric fistula
Then obstructs the distal ileum.
342
How do you diagnose Gallstone ileus?
X Ray- shows air in the cystic bile duct (pneumobilia)
Small bowel obstruction
stone found in small bowel (US)
343
How do you treat Gallstone ileus?
Urgent laparotomy - In Small bowel enterotomy is used to remove stone
interval cholecystectomy in 3 months
344
What is the most common cancer in the gall bladder?
adenocarcinoma- still only makes 1% of all cancers
345
How do you detect adenocarcinoma?
MRCP
accidentally
346
How do you treat adenocarcinoma of the gallbladder?
radical surgery with negative resection margins offers the only potential cure
if spread to lymph- curative resection
palliative chemo can be given
very few respond to radiotherapy
347
what is the difference between cholangitis and cholecystitis?
cholangitis- inflammation and secondary infection of the bile duct due to biliary obstruction and stasis. gallstones or tumours block bile duct.
cholecystitis- inflammation of the gallbladder. mainly
due to gallstones obstructing the cystic duct
348
What is acute pancreatitis
syndrome of inflammation of the pancreatic gland initiated by any acute injury.
349
What are the causes of acute pancreatitis?
Remember GET SMASHED
gallstones
ethanol (alcohol)
Trauma
steroids
mumps
autoimmune
scorpion venom
hyperlipdaemia,hypothermia and hypercalcaemia
ERCP
Drugs (ace inhibitors ,antibiotics, oestrogens)
350
How does gallstone pancreatitis occur?
gallstones cause obstruction to pancreatic drainage at the ampulla by a stone or associated oedema. intracellular calcium rises leading to extensive damage to acinar cells.
351
What are the signs and symptoms of acute pancreatitis?
Epigastric pain is prominent accompanied with nausea and vomiting
pain can radiate to back- can be relieved if sitting forward
fever, jaundice,shock and rigid abdomen may be present
Main two signs are cullens and Grey turner's
Cullen's- periumbilical bruising
Grey Turner's- flank bruising
352
How do you diagnose acute pancreatitis?
serum amylase - dramatic increase- main test as it is very sensitive
urinary amylase- may be elevated
serum lipase levels also elevated
Chest X Ray- excludes gastro duodenal perforation- can also raise amylase
US- screening test to see if Gallstones are cause of pancreatitis
CT is the standard choice of imaging to assess severity and for complications
353
what are the 6 main complications of acute pancreatitis?
```
death
shock
pseudocyst formation
abscess formation
hypocalcaemia
hyperglycaemia
```
354
how do you manage acute pancreatitis?
must assess severity of condition
1. don't feed by mouth - consider nasojejunal tube
2. Give analgesia (pethidine or morphine). Note morphine may cause sphincter of oddi to contract
3. may have to take to ITU give O2 . Give parenteral nutrition and laparotomy if pancreatic necrosis is suspected
4. ERCP for gallstone removal may be needed if gallstone caused
GIve fluids
give antibiotics
355
What are the causes of chronic pancreatitis?
Alcohol
chronic kidney disease
cystic fibrosis (rare)
Obstructive(rare)
trauma
Autoimmune
Recurrent acute pancreatitis
356
What are the symptoms and signs of chronic pancreatitis?
Epigastric and often radiates through into the back
Can be episodic pain
Anorexia and weight loss can be common
Diabetes occurs late
Jaundice
357
How do you diagnose chronic pancreatitis?
Serum Amylase and lipase may be elevated- however may not be depending on number of acinar cells still remaining
Serum IgG may be elevated for autoimmune pancreatitis
Faecal elastase- abnormal in majority of patients
US and CT - pancreatic calcification confirms diagnosis
358
which is the diagnostic tool- MRCP or ERCP?
MRCP
359
what is the function of an ERCP?
an interventional tool to treat common biliary duct stones causing
obstruction
(shouldnt be used for diagnostits)
360
what blood gases state is usually present with acute pancreatitis?
metabolic acidosis
361
why can pancreatitis cause a splenic pseudoaneurysm and haemorrhage?
the pancreatic digestive enzymes start digesting the blood vessel
362
How do you manage Chronic pancreatitis?
give analgesia
lipase and fat soluble vitamins
No alcohol
low fat diet
Autoimmune- glucocorticoid therapy
diabetes- insulin and low fat diet
malabsorption- steatorrhoea associated with pancreatitis. pancreatic enzyme supplements and acid suppressor.
Duct drainage procedure if unremitting pain occurs
363
What are the complications of chronic pancreatitis?
pseudocysts
diabetes
biliary obstruction
local arterial aneurysm
splenic vein thrombosis
gastric varices
pancreatic carcinoma
Ascites and PE
364
what is the main type of exocrine pancreatic cancer?
adenocarcinoma
365
What are the signs and symptoms of Adenocarcinoma of the pancreas?
>70 years old
smokes
drinks alcohol
2/3s of pancreatic cancers are found in the head of the pancreas
Abdominal pain weight loss anorexia
pain radiates to back
jaundice- dark urine and pale stools and pruritus
diabetes is present in 50% of patients
unusual: polyarthritis, thromboembolic phenomena and skin nodules
Gallbladder may be palpable
hepatomegaly
splenomegaly
epigastric masses
366
how do you diagnose for Pancreatic carcinoma?
cA19-9 increase- tumor marker but does have high false positive rate
Ultrasound ( most sensitive) or CT show pancreatic mass and dilated biliary tree
367
How do you treat pancreatic carcinoma?
surgery:
Resection
whipple's procedure
pain: analgesics or radiotherapy
chemotherapy after surgery
368
what is the prognosis of pancreatic carcinoma?
pretty Shit start praying boi
unless: tumour is less than 3 cm and no nodes are involved
369
what are the 3 main type of endocrine pancreatic cancers?
gastrinoma
insulinoma
glucagonoma
370
what are the consequences of a gastrinoma?
produces gastrin causing increased stomach acid causing gastric/duodenal ulcers
371
what are the consequences of an inulinoma?
produces insulin causing increased glucose uptake from the blood- hypoglycaemia
372
what are the consequences of a glucagonoma?
produces glucagon to increase blood sugar levels- hyperglcaemia
373
what is the most common cause of nodular hepatomegaly?
Liver metastases
374
what is charcot's triad?
ii. what is it associated with?
Jaundice
fever
RUQ
ii. ascending cholangitis
