Liver Flashcards
0
Q
Hypoalbuminaemia found in
A
Liver dysfunction
Hyper catabolic states - sepsis, chronic inflammation
Increased loss due to nephrotic syndrome
1
Q
Determine liver synthetic function by measuring…
A
Prothrombin time - clotting factors are synthesised in liver, increases if impaired function
Serum albumin decreases if impaired function
2
Q
Prolonged prothrombin time can be due to
A
Liver dysfunction
Vit K deficiency in biliary obstruction (iv v.K improves clotting)
3
Q
Gilbert’s disease
A
Increased bilirubin, other biochemistry normal
Due to inherited defect in bilirubin metabolism
4
Q
Isolated rise in serum bilirubin - causes
A
Gilbert’s disease
Haemolysis
Ineffective erythropoiesis (premature RBC death in bone marrow)
5
Q
Very high bilirubin levels most common in…
A
Biliary tract obstruction
6
Q
Aminotransferases are…
A
Enzymes in hepatocytes, leak if damage
7
Q
High levels aminotransferases in
A
Acute hepatitis - 20-50 times normal
8
Q
Aspartate aminotransferases (AST)
A
Found in liver, heart, skeletal muscle
Raised serum conc on hepatitis, myocardial infarct, skeletal muscle damage
9
Q
Alanine aminotransferases (ALT’s)
A
More specific to liver damage than ASTs
10
Q
Alkaline phosphatase is situated in
A
Canalicular and sinusoid all membranes of liver
11
Q
Alkaline phosphatase is increased in
A
Cholestasis - impaired bile flow from any cause
Pregnancy - as produced in placenta
Produced in bone, so growing children, bony metastases, Paget’s disease
12
Q
Gamma - GT is a..
A
Liver microsomal enzyme induced by alcohol and enzyme inducing drugs
13
Q
Gamma-GT raised in
A
Alcohol abuse
Enzyme inducing drugs eg phenytoin
In cholestasis rises in line with serum alkaline phosphatase (similar pattern of excretion)
14
Q
Predominant elevation of serum aminotransferases indicates…
A
Hepatocellular injury
15
Q
Predominant elevation of serum bilirubin and alkaline phosphatase indicates…
A
Cholestatic disorder
Eg primary biliary cirrhosis, primary sclerosing cholangitis, extra hepatic bile duct obstruction
16
Q
Isolated rise in bilirubin most likely due to…
A
Gilbert’s disease
17
Q
Use of ultrasound in hepatobiliary disease
A
Usually first imaging investigation
Useful tests for lesions in gall bladder, bile duct
18
Q
Endoscopic US (ultrasound probe at scope tip) used for…
A
Detect and stage pancreatic carcinomas
Assess bile ducts
Confirm malignancy
19
Q
MRI use…
A
Investigate focal liver disease
Allergies to iodine based contrast, so no contrast CT
20
Q
MRCP
A
Magnetic Resonance Cholangiopancreatography
High quality images pancreatic and bile ducts
Similar to ERCP - replacing its diagnostic, not therapeutic use
21
Q
ERCP
A
Endoscope to second part duodenum, image pancreatic and bile ducts with radio graphic contrast via ampulla of vater
22
Q
Percutaneous transhepatic Cholangiopancreatography (PCT)
A
Inject contrast into biliary system via intrahepatic duct
Performed if biliary dilatation if ERCP failed
If obstruction, bypass stent can be inserted
23
Q
Acute liver disease presentation
A
May be asymptomatic
Early stages - lethargy, anorexia, malaise
Later - Jaundice
24
Chronic liver disease complications
Ascites
Oesophageal varices - haematemesis, melaena
Hepatic encephalopathy - confusion, drowsiness
25
Pruritus (itching) found in
Cholestatic jaundice - any cause
| Especially - primary biliary cirrhosis
26
Signs in compensated chronic liver disease
```
Xanthelasma
Spider naevi
Gyanaecomastia
Small/large liver
Splenomegaly
Testicular atrophy
Hands - clubbing, dupuytrens contracture
```
27
Decompensated liver disease signs
```
Neurological - disorientation, drowsy, coma
Hepatic flap
Ascites
Dilated veins on abdomen (caput medusa)
Oedema
```
28
General liver signs
Jaundice
Fever
Loss of body hair
29
Bilirubin is derived predominantly from...
```
Haemoglobin breakdown in spleen
Carried in blood bound to albumin
Conjugated in liver
Excreted in bile to small intestine
Terminal ileum - converted to urobilinogen and excreted, or re absorbed, excreted by kidneys
```
30
3 clinical categories of jaundice
```
Haemolytic jaundice
Congenital hylerbilirubinaemia (impaired conjugation)
Cholestatic jaundice (failure of bile excretion - abnormal LFTs)
```
31
Haemolytic jaundice
Increased breakdown RBCs, increased bilirubin
Mild
Causes = haemolytic anaemias
32
Congenital hylerbilirubinaemia
Most common Gilbert's syndrome, 5% population
Asymptomatic, often incidental finding
Reduced conjugation
Other LFTs normal
33
Two types Cholestatic jaundice
Intrahepatic cholestasis - hepatocellular swelling / abnormalities at a cellular level of bile excretion
Extrahepatic cholestasis - obstruction of bile flow distal to bile canaliculi
Both - conjugated bilirubin so pale stools, dark urine
34
Causes intrahepatic cholestatic jaundice
Viral / alcoholic hepatitis
Drugs
Cirrhosis
Pregnancy
35
Causes extrahepatic jaundice
```
Common duct stones
Carcinoma - bile duct, head of pancreas, ampulla of vater
Biliary stricture
Sclerosing cholangitis
Pancreatitis
```
36
Investigating jaundice - three things plus some
Serum liver biochemistry - confirm jaundice
US examination
Serum viral markers
Also - prothrombin time, serum autoantibodies
37
Serum biochemistry in jaundice
Confirms jaundice, larger rise AST - hepatitis, larger rise alkaline phosphatase - extra hepatic obstruction
38
Hepatitis serum viral markers
Hepatitis A and B - serum viral markers present in acute viral hepatitis
Hepatitis C - antibodies develop late, RNA detectable by 2 weeks
39
US examination shows dilated bile ducts in...
Extra hepatic cholestasis
| May identify level of cause eg gall stones, tumours
40
Acute hepatitis causes
Mostly viral
41
Acute hepatitis progression
Usually self limiting
| Occasional progression to massive cell necrosis
42
Acute hepatitis - clinical features
May be jaundiced
Enlarged, tender liver
Lab evidence of raised aminotransferases
43
Acute hepatitis assess disease severity by...
Prothrombin time
| Serum bilirubin
44
Chronic hepatitis is...
Sustained inflammation of liver >6 months
45
Most common cause chronic liver disease world wide is...
Viral hepatitis
| Causing chronic liver disease, cirrhosis, hepatocellular carcinoma
46
Hepatitis A epidemiology
```
Most common
Particularly children and young adults
Faeco-oral transmission route
Ingestion contaminated food - shellfish
Most infectious just before onset jaundice
```
47
Clinical features hepatitis A
Average incubation period 28 days
Nonspecific nausea, anorexia, distaste for cigarette
Then some jaundiced, dark urine, pale stools, prodrome improves
Moderate hepatomegally, spleen palpable 10%
Self limiting 3-6 weeks
Rare - coma and death
48
Drug causes chronic hepatitis
Methyl dopa
Nitrofurantoin
Isoniazid
Ketoconazole
49
Investigation findings Hep A
Raised ALT, then raised bilirubin
Bloods - leucopenia, lymphocytosis, high ESR
Severe cases - prothrombin time prolonged
50
Antibodies in HAV
Acute HAV - IgM anti-HAV
| Past infection - IgG anti-HAV
51
HAV prophylaxis
Active immunisation with inactivated strain given to travellers, people with chronic liver disease, occupational risk, haemophilia patients treated with clotting factors
52
HAV passive immunisation
With immunoglobulin
| Given to close contacts of confirmed HAV cases
53
HBV epidemiology
Vertical transmission most common
| Also blood, blood products, sexual intercourse
54
Acute HBV infection immune response
Penetrates hepatocyte, strong cellular immune response
Clearance of infection in 99% infected adults
Anti HBs antibodies develop
Immunity to subsequent infection
55
Fulminant liver failure
Occasional effect of HAV / HBV infection
Hepatic failure with encephalopathy in less than 2 weeks
Due to massive cell necrosis
Presents - hepatic encephalopathy, jaundice, coagulopathy
Complications - hypotension, renal failure, cerebral oedema, hypoglycaemia
56
HBsAg
Appears in blood from about 6 weeks to 3 months after an acute infection, then disappears
If chronic hepatitis, persists and indicates chronic infection / carrier state
57
HBeAg
Rises early, declines rapidly in acute disease
Chronic - persists, correlates with increases severity / infective ty
Anti HBe correlates with decreased HBeAg
58
Anti HBc
First antibody to appear, high titres suggest acute ongoing infection
59
HBV DNA
Suggests continued viral replication
60
Chronic HBV progression
Persistence of HBsAg for >6 months after acute infection = chronic
Progression depends on virulence, age, immunocompetence
61
Acquisition of HBV at / near birth
Immune tolerant phase 20-30 years, high levels replication
Normal ALT, positive HBeAg
Then immune clearance phase active hepatitis, high ALT
Ends with clearance of HBeAg, development anti-HBe
62
HBV treatment given to...
Patients most likely to develop progressive liver disease - high HBV DNA,
63
HBV / HIV co-infection
10-20%
| Test all chronic HBV for HIV
64
Hepatitis C epidemiology
UK - iv drug use
| Worldwide - blood products, poorly sterilised instruments
65
Clinical features HCV
Acute often mild, jaundice rare, most progress to chronic liver disease
Present with elevated aminotransferases or signs/symptoms CLD
66
Px with cirrhosis secondary to HCV are at increased risk of...
Hepatocellular carcinoma
67
Diagnosis of HCV
HCV antibody in serum
8 weeks to appear after acute infection
Positive HCV RNA suggests active disease
68
HCV treatment
Aims for viral clearance
Depends on genotype (2&3 more responsive so even treat mild)
1&4 less responsive so treat moderate/ severe
IFN-Alfa and ribavirin
69
Autoimmune hepatitis what, who
Progressive liver disease
Often associated with autoimmune eg pernicious anaemia, thyroiditis
Most common in young-middle aged women
70
Autoimmune hepatitis aetiology
Unknown
Disease characterised by hypergammaglobulinaemia
High IgG, circulating autoantibodies
71
Clinical features autoimmune hepatitis
Insidious onset, anorexia, malaise, nausea, fatigue
| 25% present acute hepatitis - rapid progressive liver disease
72
Treatment autoimmune hepatitis
Prednisolone 2-3 weeks
| Maintenance dose may be required, and azathiopene as steroid sparing agent
73
Autoimmune hepatitis prognosis
Steroid and azathiopene induce remission in over 80% cases
| Liver transplant may be necessary
74
Non-alcoholic fatty liver disease
Liver biopsy finds changes indistinguishable from alcohol excess
But no heavy drinking
75
Non alcoholic fatty liver disease is associated with..
Obesity, T2DM, hypertension, hyperlipidaemia
| Considered the liver component of 'metabolic syndrome'
76
NAFLD pathogenesis
Not entirely known
Thought that insulin resistance is key, then 'second hit' oxidative injury, progresses to inflammatory component - steatohepatitis (NASH)
77
Clinical features non-alcoholic fatty liver disease
Most asymptomatic
Mild elevation aminotransferases picked up
Hepatomegaly common
78
Management non alcoholic fatty liver disease
No proven effective therapy
Treat risk factors
Transplant may be needed for end stage disease
79
Cirrhosis
Results from necrosis of liver cells
Then fibrosis, nodule formation
Therefore impairment of liver cell function, gross distortion anatomy, portal hypertension
80
Aetiology cirrhosis
Alcohol, viral hepatitis
81
Histologically two types cirrhosis
Micronodular - small, uniform, ongoing alcohol/ biliary tract disease
Macronodular - variable size, normal acini in larger nodules, chronic viral hepatitis
Some is mixed.
82
Clinical features hepatitis
Secondary to portal hypertension / liver cell failure
83
Decompensated cirrhosis has...
Encephalopathy, ascites, varicella haemorrhage
84
Compensated cirrhosis has NO
Ascites, encephalopathy, varicella haemorrhage
85
Liver biochemistry in cirrhosis
May be normal
| Often some increase serum alkaline phosphatase and aminotransferases
86
FBC in cirrhosis
Thrombocytopenia at most diagnoses
| Leukopenia, anaemia develop later
87
Measure liver function in cirrhosis with
Prothrombin time and serum albumin
88
Serum electrolytes in cirrhosis
Low sodium - severe liver disease secondary to impaired free water clearance / excess diuretic therapy
Elevated serum creatinine associated with worse prognosis
89
Serum alpha-fetoprotein (AFT) in cirrhosis
Usually undetectable post partum
May be raised in chronic liver disease
High level suggests hepatocellular carcinoma
90
Aetiology of cirrhosis
Response to any chronic liver injury
| Liver biopsy to confirm severity, type
91
Further investigations in cirrhosis
Seek and treat oesophageal varices - endoscopy
| US for HCC and assess patency portal and hepatic veins
92
Cirrhosis management
```
Manage complications
Underlying problems - halt progress
Screen for HCC
End stage consider transplant
Flu vaccine
```
93
Portal vein formed from union of
```
Superior mesenteric (gut)
Splenic vein (spleen)
```
94
Portal vein carries blood to
Liver
| Accounts for 75% hepatic vascular inflow
95
Blood vessel passage in liver
enter liver via hilum (porta hepatis)
Passes into hepatic sinusoids via portal tracts
Leaves liver through hepatic veins to join IVC
96
Normal portal pressure
5-8mmHg
97
Three types blockage hepatic blood flow
Prehepatic - due to blockage portal vein before liver
Intrahepatic - from distortion of liver architecture
Post hepatic - venous blockage outside liver - rare
98
Most common cause portal hypertension
Cirrhosis
99
1cause prehepatic portal hypertension
Portal vein thrombosis
100
3 causes intrahepatic portal hypertension
Cirrhosis
Alcoholic hepatitis
Schistosomiasis
101
Two causes post hepatic portal hypertension
Right heart failure
| Constrictive pericarditis
102
Common signs portal hypertension
Splenomegaly
GI bleeding
Ascites
Hepatic encephalopathy
103
Management bleeding oesophageal varices
Endoscopic therapy - eg band ligation
Pharmacological - emergency control bleeding
Balloon tamponade if endoscopy fails - inflate gastric balloon, pull back to block blood G-O junction !aspiration pneumonia, oesophageal rupture!
104
Ascites is
Presence of fluid in peritoneal cavity
105
Commonest cause ascites is
Cirrhosis
106
Pleural effusion in ascites
Usually right sided
107
Causes ascites - transudate
Portal hypertension
Hepatic outflow obstruction
Cardiac failure
108
Causes ascites - exudate
Peritoneal carcinomatosis
Peritoneal TB
Pancreatitis
Nephrotic syndrome
109
Cirrhotic ascites and high neutrophil count (>250)
Bacterial peritonitis
110
Management ascites - cirrhotic
Dietary sodium restriction, plus spironolactone
Frusemide added if poor response
Maybe paracentesis, plus albumin infusion
111
Aim of ascites treatment
Lose 0.5kg weight/day
| Too rapid diuresis - intravascular depletion, encephalopathy
112
Rising creatinine / hyponatraemia in management ascites...
Inadequate renal perfusion
| So temporary cessation diuretic therapy
113
Spontaneous bacterial peritonitis in cirrhotic ascites patients
Occurs in 8%
Mortality rate 10-15%
Mostly E-Coli
Perform diagnostic aspiration and empiric antibiotics
114
Portosystemic (hepatic) encephalopathy
Occurs in advanced chronic/acute hepatocellular disease
Also following TIPS shunts
Failure of toxin breakdown
115
Clinical features hepatic encephalopathy
Drowsy, comatose
Increased tone, hyperreflexia
Chronically - irritable, slurred speech, reversed sleep
116
Signs hepatic encephalopathy
Fetor hepaticus - sweet smelling breath
Asterixis
Constructional apraxia
117
Hepatic encephalopathy investigations
EEG
| Arterial blood ammonia
118
Factors precipitating hepatic encephalopathy
High dietary protein
GI haemorrhage
Constipation
Infection...
119
Management hepatic encephalopathy
Laxatives - lactulose, limits ammonia absorption
Antibiotics decrease bowel flora therefore ammonia production
Initially restrict protein
120
Hepatorenal syndrome
Development AKI if advanced liver disease
Due to peripheral vasodilatiation, hypovolaemia
Decreased renal perfusion
Diagnosis - oliguria, rising serum creatinine, low urine sodium
121
Hepatopulmonary syndrome
Inteapulmonary vascular dilatation in chronic liver disease, hypoxaemia, can be breathless on standing
Diagnose by echo, improve with liver transplant
122
Liver transplantation
```
Liver failure, any cause
Psychological assessment
Education
Few over 65 years
6 month abstinence if alcohol related
```
123
Primary biliary cirrhosis
Type of chronic liver disease
Destruction of bile ducts, cholestasis, cirrhosis
Predominantly women middle age
Abnormal immuneregulation inherited anti-mitochondrial antibodies often present
124
Primary biliary cirrhosis features
```
Pruritus, sometimes jaundice
Advanced - hepatosplenomegaly, xanthelasma
Raised serum alkaline phosphatase
Autoantibodies
Steatorrhoea
```
125
Primary billiard cirrhosis investigations
Raised alkaline phosphatase, IgM
Often anti mitochondrial antibodies, antinuclear factor
Liver biopsy - loss of bile ducts, later cirrhosis (staging)
126
Primary biliary cirrhosis prognosis
Asymptomatic - near normal
| Jaundiced - poor, death in 5 years without transplant
127
Secondary biliary cirrhosis
Cirrhosis due to prolonged large duct biliary obstruction
| Eg bile duct strictures, CBD stones, sclerosing cholangitis
128
Hereditary haemochromatosis
Autosomal recessive, 1in400 prevalence (Caucasian)
Approx 10% population carriers
Excess iron deposition - fibrosis - organ failure
129
Aetiology haemochromatosis
Increased iron absorption from small intestine
HFE gene mutation
Few cases due to defects in metabolism
130
Clinical features haemochromatosis
Often incidental finding increased iron / ferritin or screening
Less overt disease in women do to iron loss
Symptoms due to iron deposition
131
Symptoms of iron deposition in organs
```
Liver - hepatomegally, lethargy
Pancreas - diabetes
Myocardium - cardiomegally, heart failure, conduction disturbances
Pituitary - loss of libido, impotence
Joints - arthralgia
Skin - hyperpigmentation
```
132
Investigations hereditary haemochromatosis
Serum liver biochemistry often normal
Serum iron increased, iron binding capacity reduced
Serum ferritin elevated
Genotyping - mutation HFE gene
Non invasive assessment fibrosis/cirrhosis
133
Management haemochromatosis
Venesection - 500ml blood removed twice weekly till normal
Then three or four venue sections / year maintenance
If cirrhosis, surveillance for HCC required
Screen relatives HFE mutations
134
Prognosis haemochromatosis
Major complication development HCC if cirrhosis
| Life expectation fairly normal
135
Wilson's disease (hepatolenticular degeneration)
Rare, recessive inheritance, mutations ATP7B gene
Decreased secretion of copper into biliary system
Copper accumulates in liver - fulminant hepatic failure, cirrhosis
Basal ganglia - Parkinsonism, dementia
Cornea - Keyser-Fleischer rings
Renal tubules
136
Diagnosis Wilson's disease
Demonstrate low serum copper and caeruloplasmin
Increased urinary copper excretion
Increased copper in liver specimen
137
Alpha-1 anti trypsin deficiency
Rare cause of cirrhosis
Abnormal protein accumulates in liver
Treat for chronic lung and liver disease - stop smoking!
138
Alcohol and liver...
Most common cause liver disease western world
Alcohol is hepatotoxic
Only 15% excessive drinkers develop cirrhosis
3 major findings - fatty change, alcoholic hepatitis, alcoholic cirrhosis
139
Three major clinical illnesses associated with excessive alcohol intake
Fatty change
Alcoholic hepatitis
Alcoholic cirrhosis
140
Fatty liver change
Most common biopsy finding in alcoholics
Can be caused by just a few weeks - macro vascular lipid in hepatocytes
Symptoms often absent, may be hepatomegally
Often normal lab tests
Increased MCV may suggest heavy drinking
Gamma GT usually elevated
REVERSIBLE
141
Alcoholic hepatitis
Years of heavy drinking
May coexist with cirrhosis
Swollen hepatocytes contain Mallory bodies, surrounded by neutrophils.
May be fibrosis, degeneration of hepatocytes
142
Alcoholic hepatitis clinical features
Rapid onset jaundice
Also nausea, annorexia, RUQ pain
Fever, ascites, encephalopathy, tender hepatomegally
143
Full blood results in alcoholic hepatitis
Leukocytosis
Raised MCV
Often thrombocytopenia
144
Liver biochemistry in alcoholic hepatitis
Elevated AST, ALT, disproportionate rise AST, but <500
Bilirubin may be markedly elevated
Serum albumin low
Prothrombin time prolonged
145
Management severe alcoholic hepatitis
Nutritional input, support
Corticosteroids for inflammation
Steroids contraindicated in renal failure, infection, bleeding
146
Alcoholic cirrhosis
Final stage liver disease form alcohol abuse
Fibrosis, destruction liver architecture
May be symptomatic, or cirrhotic presentation
147
Primary sclerosing cholangitis
Chronic liver disease, progressive fibrosis of intra and extra hepatic ducts, -> cirrhosis
Unknown cause, link ulcerative colitis
Often diagnosed while asymptomatic but with IBD
Raised alkaline phosphatase
Symptomatic - pruritus, jaundice, cholangitis
148
Budd-Chiari syndrome
Occlusion hepatic vein- stasis and liver congestion - hypoxia, necrotic damage hepatocytes
Often due to hypercoagulable state - myeloproliferative disorders, thrombocytopenia, OCP, malignancy, inherited thrombophillias
149
Clinical features Budd-Chiari syndrome
RUQ pain, hepatomegally, jaundice, ascites
Acute - may -> fulminant hepatic failure
Chronic - cirrhosis, portal hypotension etc
Differentials ! Right heart failure, IVC obstruction, constrictive pericarditis!
150
Budd-Chiari investigations
Doppler US - abnormal flow, IVC thickening
Plus non specific signs hepatomegally etc
Biopsy not often necessary
151
Treatment Budd-Chiari syndrome
Three aims:
Restore venous drainage, if acute - thrombolysis, stent, angioplasty
Treat portal hypertension ascites complications
Detect underlying hypercoagulable disorder, treat
152
Causes liver abscesses
Biliary sepsis, portal pyaema from intra-abdominal sepsis
Trauma, bacteraemia, peri euphoric access
Most common is E Coli
Also strep milleri and anaerobes - bacteriodes
153
Amoebic liver abscess
Spread of entamoeba histolytica from bowel to liver via portal vein
Serological tests eg compliment / ELISA
Often recent travel endemic country
Single access right lobe liver
154
Clinical features liver abcess
Fever, lethargy, weight loss, abdominal pain
Liver - enlarged, tender,
Right side chest - consolidation/effusion
155
Investigations in liver abcess
Non specific infection signs inc low albumin
Raised alkaline phosphatase
US lesions, CT - non enhancing cavities with surrounding rim inflammation
156
Pyogenic liver abcess management
Aspirate under radiological control
Pigtail catheter for further drainage
Initial empirical antibiotics, then check
157
Liver tumours
Most are metastatic - GI tract, breast, bronchus
| Can be confused with cysts
158
Hepatocellular carcinoma
5th most common tumour worldwide
Most due to hepB, hepC, pathogens
In patients with CLD / cirrhosis
159
Clinical features HCC
Weight loss, abdo pain, anorexia, fevers ascites - rapid development suggests HCC
Focal lesion in cirrhotic liver very likely HCC
160
Hepatocellular carcinoma investigations
Serum AFP can be raised (alpha fetoprotein)
US / CT show large filling defects
Biopsy / MRI if diagnostic doubt
161
Management hepatocellular carcinoma
Sometimes resection or transplant possible
Percutaneous ablative therapies - high frequency US or ethanol injection can produce tumour necrosis
Transarterial chemoembolisation in large tumours
Iv chemo not much use
162
Prognosis hepatocellular carcinoma
Median survival 6-20 months
163
Most common benign liver tumours
Haemangiomas - incidental finding
| Hepatic adenomas - resect if symptomatic
