Liver Flashcards
(104 cards)
1
Q
What is the brief pathogenesis of chronic liver disease?
A
Cause of chronic liver disease –> recurrent inflammation & process of fibrosis –> cirrhosis compensated –> cirrhosis non compensated; chronic liver failure –> acute onset chronic liver failure
2
Q
How does non-alcoholic fatty liver disease show on histology?
A
Hepatocytes are larger than they should be, and there is inflammatory cell infiltrate
3
Q
What is simple steatosis?
A
An accumulation of fat in the liver, making a ‘fatty liver’. It corresponds to the accumulation of lipids (triglycerides) in the liver cells (hepatocytes) and may complicate alcoholic intoxication or metabolic disorders such as Type 2 diabetes, obesity, and dyslipemia.
- Diagnosis by ultrasound
- No liver outcomes
- Increased cardiovascular risks
- Treatment is weight loss exercise
4
Q
What is NASH?
What is the typical patient?
How is it diagnosed?
What are the associated risks?
A
Non-alcoholic steatohepatitis - increased fat in hepatocytes and inflammation
Middle aged and obese
Diagnosis is by liver biopsy
Risk of progression to cirrhosis
5
Q
Name five autoimmune lives diseases
A
- Primary Biliary Cholangitis (Cirrhosis)
- Auto-immune Hepatitis
- Primary Sclerosing Cholangitis - diseases with auto-immune features
- Alcohol related liver disease
- Drug Reactions
6
Q
What is primary biliary cholangitis (cirrhosis)? Aetiology? Typical patient? Symptoms? Associated conditions? Diagnosis? Outcome?
A
CD4+ T cell mediated chronic autoimmune granulomatous inflammation, causing progressive destruction of the SMALL bile ducts, eventually leading to cirrhosis
Female around 50
Symptoms - often asymptomatic, but may itch, jaundice, fatigue, xanthelasma
Associated with other autoimmune conditions e.g. Sjogren’s syndrome, thyroid disease and dry eyes and mouth are frequently found
Diagnosis - antimicrobial antibody (AMA), cholestatic LFTs, high ALP, serum IgM, liver biopsy
Treatment - ursodeoxycholic acid
Majority nothing major, but some develop liver failure and it’s still a common cause of liver transplant, complications are those of cirrhosis
7
Q
Auto-immune hepatitis Type 1 (most common) What is it? Who gets it? Presentation? Tests and dianosis? Biopsy?
A
Inflammatory liver disease of unknown cause whith suppressor T cell defects and autoantibodies directed at hepatocytes
Young or middle aged women
Some present with acute hepatitis and signs of autoimmune disease e.g. fever, malaise, rash, polyarthritis, while others with gradual jaundice
ANA, ASMA, elevated IgG, anaemia, low WBC and platelets
Liver biopsy - chronic hepatitis with necrosis
8
Q
Auto-immune hepatitis Type 2
Who gets it?
What do bloods show?
A
Children & teenagers
Antibodies +ve
ANA and ASMA -ve
9
Q
Primary Sclerosing Cholangitis What is it? Typical patient? Symptoms? Histology? Diagnosis? Associated with which cancers? Treatment?
A
Autoimmune destructive disease of LARGE AND MEDIUM sized bile ducts, giving progressive cholestasis and bile duct inflammation with strictures
Male, 40s, IBD - typically UC
Pruritus, fatigue, recurrent cholangitis
Histology shows scar tissue described as onion skin
Diagnosis is ERCP to differentiate between large duct and small duct disease - shows irregularities of the hepatic ducts
Bile duct, gall bladder, liver, colon
Liver transplant
Ursodeoxycholic acid may protect aganst colon cancer and improve LFT
10
Q
Hereditary Haemochromatosis What is it? What gene? Symptoms? Bloods? Imaging? Biopsy? Treatment?
A
Autosomal recessive genetic defect leading to increased intestinal iron absorption, leading to iron deposits in joints, liver, heart, pancreas and skin
HFE gene
Arthralgia, slate grey/bronze skin pigmentation, signs of chronic liver disease, hepatomegaly, diabetes
Increased LFT and serum ferritin; transferrin saturation >45%
Chondrocalcinosis; liver MRI
Liver biopsy - Perl’s stain quantifies iron loading and assesses severity
Venesection
11
Q
Wilson's disease What is it? Presentation? Tests? Treatment?
A
Autosomal recessive disease causing massive deposition of copper in liver and basal ganglia (CNS)
Children present with liver disease (hepatitis, cirrhosis, fulminant liver failure) and adults with CNS disease (tremor, dysarthia, dysohagia, random stereotyped movements, dementia)
Other presentation include change in mood, increased libido, bad memory, grey skin, blue nails, brown rim around iris
Cu in urine, increased LFTs, serum copper
Treatment is penicillamine
12
Q
Alpha-1-Anti Trypsin deficiency What is it? Associated with? Presentation? Tests? Treatment?
A
An autosomal recessive disease commonly affecting lung (emphysema) and liver (cirrhosis and hepatocellular cancer)
Associated with asthma, pancreatitis, gall stones, Wegener’s
Dyspnoea, cirrhosis, cholestatic jaundice
Serum A1AT is decreased; phenotyping, prenatal diagnosis
Supportive; liver transplant
13
Q
Budd-Chiari syndrome What is it? Causes? Presentation? Test? Treatment?
A
Hepatic vein outflow obstruction by thrombosis or tumour causing congestive ischaemia and hepatocyte damage
Caused by hypercoagulable states - pill, pregnancy, malignancy, TB, etc
Abdominal pain, hepatomegaly, ascites and increased ALT; high protein content in the ascitic fluid
USS + dopplers, CT or MRI
Anticoagulate and consider liver transplant
14
Q
Methotrexate
What is it used to treat?
What does it cause in the liver?
A
Rheumatoid arthritis and psoriasis
Causes progressive fibrosis without symptom - requires monitoring
15
Q
Name the four collateral pathways of anastomoses between the portal and systemic venous system.
What does portal hypertension do to these?
A
- Oesophageal and gastric venous plexus
- Umbilical vein from the left portal vein to the epigastric venous system
- Retroperitoneal collateral vessels
- The hemorrhoidal venous plexus
Portal hypertension causes these anastomoses to become engorged, dilated or varicosed, and subsequently rupture
16
Q
What is the normal portal vein pressure?
A
5-8 mmHg
17
Q
What are the two main classes of portal hypertension according to site?
A
- Prehepatic - blockage of the portal vein before the liver; due to portal vein thrombosis or occlusion secondary to congenital portal venous abnormalities
- Intrahepatic - due to distortion of the liver architecture, either presinusoidal (e.g. schistosomiasis, or non cirrhotic hypertension) or postsinusoidal (e.g. cirrhosis)
18
Q
Give some common signs of compensated cirrhosis and decompensated cirrhosis
A
Compensated - Spider naevi - Palmar erythema - Clubbing - Gynaecomastia Decompensated - Jaundice - Ascites - Encephalopathy - Bruising
19
Q
What are two bone related common complications of cirrhosis?
What causes this?
A
Osteoporosis and osteomalacia
Due to poor intake and absorption of calcium, vitD, malnutrition and steroid use
20
Q
What causes ascites?
What is diagnosis based on?
A
The first step is development of portal hypertension, which causes release of local vasodilators. These act on the splanchnic arteries, decreasing the arterial blood flow and pressures.
Progressive vasodilation leads to activation of vasoconstrictor mechanisms, e.g. RAAS, sympathetic, anti-diuretic.
The knock on effect is Na and H2O retention.
Diagnosis based on ultrasound
21
Q
How do you treat ascites?
A
Improve underlying liver disease No NSAIDs Reduce salt intake Diuretic plan: 1. Spironolactone first 2. Increase dose of spironolactone 3. Add a loop diuretic 4. Increase the dose Paracentesis Transplant
22
Q
Spontaneous bacterial peritonitis
What is it?
Investigation?
Treatment?
A
Translocated bacterial infection of ascites - very serious
Do a tap in ass ascites and cell count - neutrophil count >250
Antibiotics and alba; terlipressin for vascular instability, maintain renal perfusion
23
Q
Encephalopathy
What is it and what is it caused by?
Diagnosis?
Treatment?
A
As the liver fails, nitrogenous waste (as ammonia) builds up in the circulation and passes into the brain, where astrocytes clear it, releasing glutamine, causing an osmotic imbalance and a shift of fluid into these cells, causing cerebral oedema
Diagnosis is based on flap confusion; any neurology; alcohol withdrawal
Small, frequent meals; think about transplant
24
Q
What two circulation changes occur in liver disease?
A
- Low albumin creates a low plasma volume the adrenal glands release more renin, which converts angiotensinogen into angiotensin I, and consequently angiotensin II, increasing blood volume and causing some type of hypertension.
- Aldosterone manufacture is impaired, causing secondary aldosteronism.
Other hormonal effects include some problems with endothelin and oestrogen, resulting in increased production of endothelin and oestrogen.
25
The middle hepatic vein separates what lobes of the liver?
Right lobe (contains caudate and quadrate lobes) and the left lobe
26
What three vessels enter the liver at the porta hepatis?
Portal vein
Hepatic artery
Bile duct
27
What is special about the blood supply to the caudate lobe?
It receives an independent blood supply from the portal vein and hepatic artery, and its hepatic vein drains directly into the IVC
28
What is the functional hepatic unit?
| What parts of the acinus are most and least susceptible to damage?
The acinus
Least susceptible = zone 1, near the portal triad
Most susceptible = zone 3, near the terminal (central) hepatic veins
29
What three vessels are contained within the portal triad?
Portal vein radicles
Hepatic arterioles
Bile ductules
30
What vessels do the right and left hepatic ducts combine with to get to the duodenum?
Right and left hepatic ducts (from right and left lobes respectively) join at the porta hepatis to form the common hepatic duct.
The cystic duct connects the gall bladder to the lower end of the common hepatic duct.
The common bile duct is formed at the junction of the cystic duct (from the gall bladder) and common hepatic duct.
This then passes through the head of the pancreas, narrowing at its lower end to pass into the duodenum.
Opens into the 2nd part of the duodenum through a common channel at the ampulla of Vater, which contains the muscular sphincter of Oddi.
31
1. What is the main protein found in plasma?
2. What are the main functions of this molecule?
3. What happens if there is reduced synthesis of this?
4. What other proteins does the liver make?
1. Albumin
2. Maintains the intra-vascular oncotic pressure; transports H2O-insoluble substances e.g. bilirubin
3. Reduced synthesis produces hypoalbuminaemia
4. Other proteins - transferring, A1AT, most factors involved in coagulation
32
How does the gall bladder concentrate bile?
The gall bladder mucosa absorbs 85% of the water and electrolytes and cholesterol
33
Describe the processes involved in bilirubin metabolism to form stercobilin
Bilirubin is produced mainly from the breakdown of RBCs by Kupffer cells (macrophages)
Hb is broken down into haem and globin
The haem is converted into biliverdin, which is converted into unconjugated bilirubin, which is transported to the liver by albumin
In the liver it is conjugated with glucuronic acid and secreted into bile
This conjugated bilirubin is water soluble and is secreted into the small intestine within bile
In the terminal ileum, enzymes convert this into stercobilin, which gives faeces (and urine) its characteristic colour
34
What immunological functions does the liver have?
Acts as a sieve for bacterial and other antigens carried to it by the portal vein from the GI tract
These antigens are phagocytosed
35
Serum albumin
What is it a marker of?
Acute or chronic liver disease?
Synthetic function of the liver
Marker of severity of chronic liver disease
May be normal in acute liver disease
36
Prothrombin time (PTT)
What is it a marker of?
Acute or chronic liver failure?
What should be excluded as a cause of increased PTT?
Synthetic function of the liver
Marker of both acute and chronic liver disease
Vitamin K deficiency should be excluded by giving an IV bolus of VitK
37
AST
What does it stand for and what is it?
High levels are seen in?
Why is it not that great?
Aspartate aminotransferase - a mitochondrial enzyme
Hepatic necrosis, MI, muscle injury
Not specific to the liver
38
ALT
What does it stand for and what is it?
What does it reflect?
Why is it better than AST?
Alanine aminotransferase - a cytosol enzyme
Reflects hepatocellular damage
Specific to the liver
39
ALP
What does it stand for and what is it?
If gamma-GT is also raised, what does it indicate?
Alkaline phosphatase - an enzyme
| Raised in both intrahepatic and extrahepatic cholestatic disease of any kind
40
gamma-Glutamyl transpeptidase
| What induces its intake?
Drugs and alcohol
| If ALP is normal can be a useful guide to alcohol intake
41
What serum immunoglobulin is increased in:
(i) Primary biliary cirrhosis
(ii) Autoimmune hepatitis
(i) PBC --> IgM
| (ii) Autoimmune hepatitis --> IgG
42
What serum antibodies are increased in:
(i) Primary biliary cirrhosis
(ii) Autoimmune hepatitis
(iii) Primary sclerosing cholangitis
(i) AMA
(ii) Nucleic, SM, liver/kidney antibodies
(iii) ANCA
43
```
ERCP
What does it stand for and what is it?
Diagnostic or therapeutic?
Uses?
Complication?
```
Endoscopic retrograde cholangiopancreatography
Outlines the pancreatic and biliary ducts - involves the passage of an endoscope into the second part of the duodenum and cannulation of the ampulla
Common bile duct stones can be removed
Biliary system can be drained
Pancreatitis - look for raised serum amylase
44
What are some common symptoms and signs of chronic liver disease?
Right hypochondrial pain due to liver distension
Abdominal distension due to ascites
Ankle swelling due to fluid retention
Haematemesis and melaena due to GI haemorrhage
Pruritus due to cholestasis - often an early symptom of PBC
Breast and testicle swelling
Slate-grey skin caused by haemochromatosis
Spider naevi
Palmar erythema - hyperdynamic circulation
45
What are the three types of jaundice?
Haemolytic jaundice - increased bilirubin load for the liver cells
Congenital hyperbilirubinaemias - defects in conjugation
Cholestatic (acquired) jaundice - includes hepatocellular liver disease and large duct obstruction
46
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Haemolytic Jaundice
What is it caused by?
Mild/moderate/severe jaundice?
Urinary urobilinogen?
Causes?
Clinical features?
Investigations?
```
Increased breakdown of RBCs leads to an increase in production of bilirubin
Mild - normal liver function can easily handle the increased bilirubin
Urinary urobilinogen is increased
Caused by those of haemolytic anaemia e.g.
Clinical features depend on the cause - may be anaemia, splenomegaly, gall stones, leg ulcers
Unconjugated bilirubin is increased
Serum ALP, AST, and ALT are normal
47
Give two causes of unconjugated congenital hyperbilirubinaemia
Briefly describe each
1. Gilbert's syndrome - most common. Is asymptomatic and usually incidental finding of slightly increased albumin. All other liver biochemistry is normal and there are no signs of liver disease. FHx of jaundice in some patients. Raised unconjugated bilirubin is diagnostic and rises on fasting and mild illness
2. Crigler-Najjar syndrome - very serious, requires transplantation
48
Give four causes of conjugated hyperbilirubinaemia
| Describe each
1. Dubin-Johnson syndrome
2. Rotor syndromes
3. Benign recurrent intrahepatic cholestasis - rare and presents early in adulthood; recurrent attacks of acute cholestasis occur without progression to chronic liver disease
4. Progressive familial intrahepatic cholestasis (PFIC) syndromes - defective secretion of bile acids; autosomal recessive; type 1 - cholestasis in the first few weeks of life
49
Give two types of cholestatic (acquired) jaundice
Briefly explain each and give some examples of causes
What do they both commonly present with?
1. Extrahepatic cholestasis - due to large duct obstruction of bile flow at any point in the biliary tract distal to the bile cannaliculi e.g. common duct stones; carcinoma, biliary stricture; sclerosing cholangitis
2. Intrahepatic cholestasis - occurs owing to failure of bile secretion, e.g. viral hepatitis; drugs; alcoholic; cirrhosis; pregnancy
50
What questions should always be asked in a jaundice history?
```
Country of origin - HepB virus
Duration of illness - carcinoma
Recent consumption of shellfish - HepA
IV drug use/tattoos - HebB, HepC
Gay bum sex - HepB
Female prostitute - HepB
Blood transfusion - HepB, HepC
Alcohol consumption
Drugs (prescribed)
Travel
Recent anaesthetic
FHx - e.g. Gilbert's
Recent surgery on biliary tract or carcinoma
```
51
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Hepatitis A Virus - the most common type
Who commonly gets it?
How is it spread?
Clinical features?
Inestigations & biochemistry?
Antibodies?
Treatment and prognosis?
```
Children & young adults
Faecal oral & saliva - eating contaminated food e.g. shellfish
Viraemia - nausea, anorexia, generally unwell, distaste for cigarettes
As jaundice deepens, stool becomes pale and urine dark owing to intrahepatic cholestasis
Early stage - bilirubin normal; bilirubinuria; raised serum AST or ALT
Late stage - serum bilirubin; raised AST or ALT
IgG antibodies are common, but IgM means acute infection
No treatment, great prognosis!!
52
Acute Hep B infection
How is it transmitted?
Clinical features
Treatment and prognosis?
Blood/blood; vertical; saliva; sexual
Vertical transmission - from mother to child in utero, or shortly after birth
Horizontal transmittion - particularly in children
Features generally the same as HepA, however in many it is sub clinical
Additional symptoms may occur e.g. rash, urticaria, polyarthritis
Most patients recover completely but some go on to develop chronic hepatitis or hepatocellular cancer
53
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Chronic Hep B infection
Who gets it?
Clinical features?
Investigations?
Histology?
Treatment?
Prognosis?
```
Following and acute Hep B infection, around 5% of patients will not clear the virus and develop chronic Hep B infection
Often not preceeded by an acute attack; may be asymptomatic or slowly progressive; 50% present with chronic liver disease
Tests show a moderate rise in aminotransferases; serum bilirubin is normal; HBV DNA is in serum
Histology can show a full sprectrum of changes
Entecavir is very effective and reduces HBV DNA rapidly
Tenofovir is used in HIV patients with HBV
Established cirrhosis is associated with poor prognosis
Hepatocellular carcinoma is also a complication
54
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Hepatitis D
Aka?
How is it activated?
Who typically gets it?
What two ways can infection occur?
Diagnosis?
```
HDV or delta virus
It is unable to replicate on its own but is activated by the presence of HBV
IV drug users - it is a parasite of a parasite
1. Co-infection of HDV and HBV - clinically indistinguishable from HBV infection, but a biphasic rise of ALT/AST may be seen
2. Superinfection which results in an acute flare up of previously unknown chronic Hep B infection
Diagnosis is based on presence of serum IgM anti-HDV in the presence of IgM anti-HBc; or finding HDV RNA
55
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Acute Hepatitis C Infection
How is it transmitted?
Who typically gets it?
Clinical features?
Treatment?
Course?
```
Blood/blood
IV drug users, MSM, sex workers
Most acute infections are aymptomatic, whith about 10% having mild flu-like illness and jaundice
Most patients will not be diagnosed until years later when they have chronic hep C infection
Treatment is interferon
Most asymptomatic patients develop chronic liver disease; only half of symptomatic develop this
Course is adversely affected by HIV and alcohol
56
Chronic Hep C infection
Clinical features?
Diagnosis?
Treatment?
Usually asymptomatic - only discovered following a routine biochemical test
Diagnosis is made by finding HCV antibody in the serum --> should be genotyped if intending to treat
Treatment is Ribavirin and pegylated interferon (Peg)
57
Hep E virus
How is it transmitted?
Presentation?
Mortality?
Faeco-oral e.g. contaminated water
More common in tropics
Source of infection in the UK is pigs, deer, rabbits
Presents similarly to Hep A
Mortality is 1-2%; but 20% in pregnant women
Doesn't progress to chronic liver disease
58
Infective mononucleosis
What virus causes this?
What test leads to diagnosis?
Epstein-Barr (EB) virus
Monospot test
Treatment is symptomatic
59
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Fulminant Hepatic Failure
What is it?
What causes it?
Clinical features?
Treatment?
```
Defined as severe hepatic faiure in which encephalopathy develops in under 2 weeks in a patient with a previously normal liver
Most causes are due to viral hepatitis, some are due to paracetamol poisoning
Examination shows a jaundiced patient with a small liver and signs of hepatic encephalopathy - mental state varies from drowsy to convulsions
There is no specific treatment, but patients should be monitored in HDU
60
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Autoimmune hepatitis
Pathogenesis?
Clinical features?
Biochemistry?
Treatment?
```
In a genetically predisposed person, an environmental agent (e.g. a virus) causes a sequence of T cell mediated events against liver antigens, producing a progressive necroinflammatory process which results in fibrosis and cirrhosis
In post menppausal women, presentation may be asymptomatic or just with fatigue
In teens and early 20s, presents as acute hepatitis with jaundice and very high AST/ALT which do not lower over time
Budesonide is preferred to prednisolone
61
Drug induced hepatitis
How does it present?
Which drugs?
Clinically is very similar to autoimmune hepatitis
| Isoniazid, amiodarone, methotrexate
62
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Non-Alcoholic Fatty Liver Disease (NAFLD)
Pathophysiology?
Risk factors?
Clinical features?
Diagnosis?
Management
```
Oxidative stress injury leads to lipid oxidation in the presence of fatty infiltration and inflammation results.
Fibrosis may then occur, which enhanced by insulin resistance
RF - obesity, hypertension, type II diabetes. hyperlipidaemia
Most patients are asymptomatic; hepatomegaly may be present
Diagnosis is by demonstration of a fatty liver, usually on USS
Management is weight loss, exercise etc
63
Cirrhosis
Cause?
Pathogenesis?
What two types are seen on pathology?
Alcohol; viral infection
Chronic liver injury results in inflammation, necrosis and eventually fibrosis
Fibrosis is initiated by stellate cells
In the space of Disse, the normal matrix is replaced by collagen
1. Micronodular cirrhosis - regenerating nodules are
64
Cirrhosis
What is seen on bloods?
Management?
Serum albumin and PTT are the best indicators of liver function
Low Na indicates severe liver disease
Serum copper and a-1-a should always be measured in young cirrhotics
Patients should have 6 monthly USS to detect early development of hepatocellular cancer
65
Give some common indications for liver transplantation
```
Primary biliary cirrhosis - serum bilirubin persistently >100
Chronic Hep B is HBV DNA negative
Chronic hep C - most common cause
Autoimmune hepatitis
Alcoholic liver disease
Primary metabolic disorders
```
66
Portal hypertension
What causes it?
How can the cause be classified?
Clinical presentation?
The portal vein is formed by the union of the superior mesenteric and splenic veins
The pressure within it is 5-8 mmHg
Can be classified according to site of obstruction:
1. Prehepatic - due to blockage of the portal vein before the liver e.g. portal vein thrombosis
2. Intrahepatic - due to distortion of the liver architecture e.g. Budd-Chiari, PBC etc
3. Post-hepatic - due to venous blockage outside the liver e.g. right heart failure, constrictive pericarditis
Usually asymptomatic, only clinical evidence is splenomegaly
67
Variceal Haemorrhage
| Management - acute and long term
Acute
- Resiscitate
- Urgent endoscopy
- Variceal banding or injection scleropathy
- While waiting for endoscopy, can give Terlipressin (a vasoconstrictor)
- Balloon tamponade can be used if initial attempts don't control bleeding
Acute Rebleed or bleeding cannot be stopped
- Transjugular intrahepatic portocaval shunt (TIPS) - reduces portal vein pressure
Prophylactic measures
- Long term cardioselectibe beta blockers e.g. propranolol to decrease portal pressure
68
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Ascites
Cause?
Clinical features?
What can aspirated protein count tell you?
Management?
```
Secondary to renal Na and H2O retention
Mild generalized abdominal pain and discomfort are common
Resp distress accompanies tense ascites
Many patients have peripheral oedema
Pleural effusion may occur from congenital diaphragmatic defects
A high serum ascites albumin (>11g/L) suggests portal hypertension
A low serum ascites albumin
69
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Portosystemic Encephalopathy
What is it?
Pathogenesis?
Clinical features?
Management?
```
A chronic neuropsychiatric syndrome secondary to cirrhosis
In cirrhosis, portal blood bypasses the liver via the collaterals and the 'toxic' metabolites pass directly to the brain
It is a clinical disorder of personality
May have a sweet smell to breath
Coarse flapping tremor
Management - identify and remove possible precipitating cause; give purgation and enemas to empty the bowels; maintain nutrition with adequate calories, give antibiotics e.g. Rifaximin
70
Hepatorenal syndrome (Renal Failure due to liver disease)
What conditions does the patient usually have?
How is the urine output affected?
What is the pathogenesis?
Typically the patient has advanced cirrhosis, portal hypertension with jaundice and ascites
Urine output is reduced with a low Na concentration
Pathogenesis is similar to ascites
The initiating factor is extreme peripheral vasodilation (possibly due to NO), leading to a decrease in circulating blood volume, activating homeostatic mechanisms which constrict the renal vasculature
71
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Alcoholic liver disease
Pathophysiology?
What three main features on pathology?
Clinical features?
Investigations?
Management?
What scores are used to predict prognosis?
```
Ethanol is metabolized in the liver by two pathways, resulting in an increase in the number of free radicals
This impairs protein and CHO metabolism, causing necrosis
1. Fatty change - produces fat in zone 3
2. Alcoholic hepatitis - infiltration of neutrophils
3. Alcoholic cirrhosis
Clinical features range from asymptomatic to full blown cirrhosis
Investigations range, but MCV often indicates heavy drinking
Patients should stop drinking alcohol; diazepam can be given for withdrawal
Glasgow alcoholic hepatitis score (>9 = poor prognosis)
72
Hepatic Sinusoidal Syndrome
What is it and what does it present similarly to?
What causes it?
Due to injury of the hepatic veins and presents clinically similar to Budd-Chiari
Can be be caused by some Jamaican tea, chemo, total body irradiation
73
What is the most common solid liver tumour in non-cirrhotic patients?
Haemangioma (a benign mass)
74
Name four common benign focal lesions in the liver
Haemangioma
Focal nodular hyperplasia
Adenoma
Liver cysts
75
Haemangioma
Clinical features?
How does it appear on imaging?
Treatment?
THIS IS THE MOST COMMON BENIGN TUMOUR OF THE LIVER
Usually asymptomatic
Hypervascular tumour; usually single and small; well marked capsule
No need for treatment
76
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Focal Nodular Hyperplasia
How does it form?
Who typically gets it?
Symptoms?
How does it show on imaging?
```
Hyperplastic response to increased blood flow; classically central scar containing a large artery, radiating branches to periphery
Young and middle aged women
Usually asymptomatic, sometimes vague abdo pain
Imaging shows nodule with varying echogenicity
77
Hepatic adenoma
What type of tumour?
Caused by?
Symptoms?
Benign neoplasm composed of normal hepatocytes; no portal tract, central veins, or bile duct
Mainly solitary fat containing lesions, incidence is increasing
Caused by contraceptive hormones
Symptoms are pain and bleeding on rupture
78
What two drugs may be used for relief of biliary spasm?
Atropine
| GTN
79
What is the aim of drug metabolism in the liver?
To convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney, facilitating excretion
80
Describe the two phases of drug metabolism in the liver
Phase I - involves chemical conversions, e.g. oxidation, reduction, hydrolysis, to make the drug more polar by adding a chemically reactive group, permitting conjugation
Phase II - adds an endogenous compound, increasing the polarity, e.g. with sulphate, methyl
81
The Cytochrome P450 Family of Monooxygenases
| What are these?
Haem proteins located in the endoplasmic reticulum of liver hepatocytes (and elsewhere) mediating oxidation reactions (phase 1) of many lipid soluble drugs
P450 is responsible for metabolism of at least 50% of all prescribed drugs
82
What are the basic events of the Monooxygenase P450 cycle?
1. Drug enters cycle as drug substrate, DH
2. Molecular oxygen (O2) provides two atoms of oxygen
3. One atom of oxygen is added to the drug to yield the hydroxyl product, ROH, which leaves the cycle, the second oxygen combines with protons to form H20 (4 in diagram)
83
What deficiency do babies born with jaundice have?
Glucose-6-phosphatase deficiency and so bilirubin is not conjugated, so is not effectively excreted, so builds up in fatty tissues giving a yellow appearance
84
Antibody for Primary Biliary Cirrhosis
Anti mitochondrial antibodies
85
How does primary sclerosing cholangitis show on ERCP?
"Beading" of the intra and extrahepatic ducts
86
One of the main functions of the liver is to produce plasma proteins,
What are the main functions of plasma proteins?
```
Maintenance of oncotic pressure
Transport of hydrophobic substances, e.g. steroids, free fatty acids
pH buffering
Enzymatic, e.g. blood clotting
Immunity - as immunoglobulins
```
87
What is the most common cause of acute viral hepatitis locally?
Hep E
88
What is the most commonly diagnosed viral hepatitis infection?
Hep B
89
Is spontaneous cure found in Hep B or Hep C infection?
Hep B - spontaneous cure not uncommon, even after many years of infection
Hep C - once chronic infection is established, spontaneous cure is not seen
90
What is the treatment criteria relating to serology for viral hepatitis?
HCV RNA present and genotype known
| HBsAg and Hep B DNA present
91
How does the level of chronic HBV relate to risk of cancer?
The higher a chronic HBV patient’s starting HBV DNA load the greater their risk of cancer on follow up.
92
What generally are ALT and AST and where should they reside?
Intracellular chemicals that should remain inside the hepatocytes
93
What compound do you need to remember in paracetamol poisoning?
NAPQI
94
What is fulminant hepatic faiure?
Jaundice and encephalopathy in a patient with a previously normal liver
95
What causes pre-hepatic jaundice?
Too much haemoglobin to break down
- Haemolysis of all causes
- Haemolytic anaemias
- Unconjugated bilirubin
96
What causes intra-hepatic jaundice?
Injured or dead liver cells
- Acute liver failure e.g. virus, drugs, alcohol
- Alcoholic hepatitis
- Cirrhosis
- Bile duct loss
- Pregnancy
97
What causes post hepatic jaundice?
Bile cannot escape into bowel
- Congenital biliary atresia
- Gall stones blocking CBD
- Strictures of CBD
- Tumours e.g. CA head of pancreas
98
Is alcoholic cirrhosis micronodular or macronodular?
Micronodular
99
Simple Liver Cyst
Clinical Features?
Symptoms can be caused by what?
Management?
```
Liquid collection lined by an epithelium with no biliary tree communication - it is solitary and uniloculated
Most of the time asymptomatic
Symptoms can be related to
- Intracystic haemorrhage
- Infection
- Rupture
- Compression
No follow up necessary; if in doubt monitoring 3-6 months
```
100
```
Hydatid Cyst
What causes it?
Clinical features?
Diagnosis?
Management?
```
Eating eggs of the dog parasite Echinococcus granulosus - endemic in developing countries
Hepatomegaly, obstructive jaundice, cholangitis
Serologic detection of anti-Echinococcus antibodies
Surgical
101
Polycystic liver disease
What is it caused by?
What are the three types?
Embryonic ductal plate malformation of the intrahepatic biliary tree
1. Von Meyenburg complexes (VMC)
2. Polycystic liver disease
3. Autosomal dominant polycystic kidney disease
102
Von Meyenburg Complexes (microhamartomas)
What are they?
Clinical features?
Benign cystic nodules throughout the liver
| Remain silent during life - incidentally found
103
```
Hepatocellular liver cancer
Incidence?
Risk factors?
Clinical features?
HCC tumour marker?
```
Most common primary liver cancer, more common in men
Cirrhosis from any cause, e.g. hepatitis, alcohol
Weight loss, RUQ pain, acute liver failure, asymptomatic
AFR - alfa fetoprotein
104
Fibro-Lamellar Carcinoma
Who gets it?
AFP?
Treatment?
Young patients (5-35)
Not related to cirrhosis?
AFP normal
Resection, if not possible then TACE
