Liver Disease Flashcards
(233 cards)
1
Q
what are the functions of the liver?
A
metabolism of carbohydrates, lipids, proteins, ammonia, vitamins, bilirubin
storage of carbohydrate, vitamin, minerals,
Coagulation
Endocrine function
Immune and inflammatory response (kupffer cells)
2
Q
describe the role of the liver in carbohydrate metabolism?
A
Glucose homeostasis and maintenance of blood sugar
In periods of prolonged starvation ketone bodies and fatty acids are used instead
3
Q
describe the role of the liver in protein metabolism?
A
- Synthesis and storage of proteins
- amino acids from intestine and muscles.
- Controls rate of gluconeogenesis and transamination
- controls albumin levels
- Synthesises coagulation factors and complement system
- Stores vitamins
- Degradation – nitrogen excretion. Ammonia, converted to urea and exctreted by the kidneys
4
Q
describe the role of the liver in lipid metabolism?
A
Metabolising lipoproteins
• VLDL synthesis and HDL
• HDL substrate for conversion of free cholesterol to cholesterol ester
• Triglyceride removed from IDL to produce LDL
• Oxidation or de novo synthesis of FFA occurs in the liver
• Cholesterol can be dietary or produced from acetyl coa – free or esterified with FA. Occurs via LCAT enzyme which is reduced in liver disease, increasing free cholesterol to ester, altering membranestructures.
5
Q
what should you ask about in a patient with a history of liver disease?
A
- Timing and duration of symptoms and associated symptoms
- Patients concerns
- RF: blood transfusion, IV drug use, surgery, contacts – sex, chemical exposure
- Med hx: prescribed, OTC, herbal/alternative
- FH
6
Q
in general what can diseases of the liver be classified as?
A
- functional abnormalities
- pathological manifestations
7
Q
what are the functional abnormalities that can cause problems with the liver?
A
- Metabolism – protein, carb, lipid, bile acid, bilirubin, hormone and drug
- Removal of microbes/toxin
- Excretion
- Immunological function
8
Q
what are the pathological manifestations causing disease of the liver?
A
- acute hepatitis
- chronic hepatitis
- jaundice
- cirrhosis
- hepatocellular carcinoma
9
Q
describe the features of acute hepatitis (causes and consequences)?
A
Toxic Drugs – paracetamol poisoning Viruses (hep A, B, C, D, E) Alcohol Vascular damage Biliary Obstruction – gall stones, tumours Metabolic
10
Q
describe the features of chronic hepatitis (causes and consequences)?
A
Toxic, drugs – 24% alcohol related
Hep (B, C, D) – 57% Hep C
AI Disease (AI hepatitis)
Biliary Disease – primary biliary cirrhosis, sclerosing cholangitis, graft vs host disease, transplant rejection
Steatohepatitis (NASH – non-alcohol SH)
Steatosis is fatty infiltration of the liver. When inflammation is associated with fatty change, the term steatohepatitis is used.
RF: obesity, DM, hyperlipidaemia, jejunoileal bypass surgery
11
Q
what are the causes of jaundice?
A
Drugs Viruses Alcohol AI Disease (primary biliary cirrhosis, Primary sclerosis cholangitis) Biliary obstruction Sepsis
12
Q
what are the causes of crirrhosis?
A
Drugs Viruses Alcohol amyloidosis Biliary obstruction Others: haemochromatosis
13
Q
what are the most common conditions associated with elevated LFTs?
A
hep C
NAFLD
14
Q
what tests make up LFTs?
A
- Albumin
- Bilirubin (total and conjugated)
- Serum aminotransferases (AST and ALT)
- Alkaline phosphatase (APT)
- PT
15
Q
what are synthetic liver function tests?
A
- Bilirubin
- PT
- Albumin
16
Q
what is albumin?
A
– main protein synthesised by the liver and circulates in blood. Production is controlled by multiple factors including nutritional status, serum oncotic pressure, cytokines, and hormones. A serum albumin may be reflection of the synthetic function of the liver. Ability to make this and other proteins is affected in chronic liver disease.
Total protein - albumin and other in blood
17
Q
what is bilirubin and why is it important clinically?
A
bile its yellow/green colour.
Used to determine liver’s ability to clear endogenous/exogenous substances from the circulation.
18
Q
what are the types of bilirubin and when are these raised?
A
Indirect (unconjugated) bilirubin - Elevated with haemolysis, hepatic disease
Direct (conjugated) bilirubin - Elevated with biliary obstruction and hepatocellular disease.
19
Q
what level does bilirubin need to be at for jaundice to develop?
A
≥ 3 mg/dL
20
Q
what are aminotransferase enzymes?
A
Aminotransferase enzymes are intra-cellular enzymes
Also released from hepatocytes with hepatocellular injury.
examples: AST and ALT
21
Q
what is the normal AST/ALT ratio and what is it in alcoholic hepatitis?
A
normal is 0.8
In alcoholic hepatitis, is usually > 2
22
Q
what is ALT?
A
helps process proteins.
Large amounts occur in liver cells. When liver is injured or inflamed the blood level of ALT rises = hepatitis
ALT is usually considered more specifically related to liver problems than AST
23
Q
what is AST?
A
enzyme in liver cells
involved in amino acid metabolism
High levels= liver is injured – hepatic necrosis.
AST can also be released if heart, liver, kidney, pancreas or skeletal muscle is
damaged – MI, CHF.
24
Q
what is alkaline phosphatase?
A
a group of enzymes that catalyze the hydrolysis of a large number of organic phosphate esters.
In liver, believed to play an active role in down-regulating the secretory activities of the intrahepatic biliary epithelium.
25
what is gamma glutamyltranspeptidase?
induced by drugs and alcohol.
ALP normal and GGT raised = alcohol intake.
Mild GGT common with small alcohol consumption and fatty liver disease. In cholestasis ALP and GGT raised. Poor specificity. Sensitive huge.
26
what are the clotting factors that the liver synthesises?
```
Factor I (fibrinogen)
Factor II (prothrombin)
Factor V
Factor VII
Factor IX
Factor X
Factors XII and XIII
```
27
what is raised IgG suggestive off?
autoimmune hepatitis
28
what is raised IgM suggestive of?
primary billiary cirrhosis
29
what is raised IgA suggestive of?
alcoholic liver disease
30
in general what is the pattern of LFTs in patients with hepatocellular injury?
Very high AST, ALT with mild/moderately elevated alkaline phosphatase.
31
in general what is the pattern of LFTs in patients with cholestasis?
mild/moderately elevated AST/ALT with very high alkaline phosphatase
Bilirubin can be elevated with both combinations
32
What other specific blood tests can be performed in a patient with liver disease?
* Viral serology
* Blood alcohol
* Drug levels
* Liver auto antibodies
* Cu/Fe/a-1 anti-trypsin studies
* Unconjugated bilirubin, reticulocytes, hepatoglobulins/coombes test
33
what test is useful to perform for primary biliary cirrhosis?
anti-mitochondrial antibody
| raised IgM
34
what test is useful to perform for autoimmune hepatitis?
anti-nuclear, smooth muscle(actin)
liver/kidney microsomal antibody
raised IgG
35
what test is useful to perform for hepatitis A, B, C, D, E
viral markers
36
what test is useful to perform for hepatocellular carcinoma?
alpha fetoprotein
37
what test is useful to perform for hereditary haemchromatosis?
serum iron, transferrin saturation, serum ferritin
38
what test is useful to perform for wilson's disease?
serum and urinary copper
| serum caeruloplasmin
39
what test is useful to perform for cirrhosis?
alpha1 antitrypsin
40
what test is useful to perform for primary sclerosing cholangitis?
anti nuclear cytoplasmic antibodies
41
what test is useful to perform for non alcoholic fatty liver disease and hepatits C?
markers of liver fibrosis
42
what test is useful to perform for HFE gene (hereditary haemochromatosis)?
genetic analysis
43
what steps need to be taken in diagnosing a patient with acute hepatitis?
1. history and examination
2. IgM anti HAV (if positive= hep A)
3. HBsAg and IgM anti-HBc (if positive hepB then do anti HDV if risk factors)
4. anti HCV (if positive=hep C)
5. if all these are negative consider wilsons, EBV, CMV, autoimmune hepatitis, congestive heart failyre, biliary tract disease, metastases
6. consider biopsy
44
what investigations would be performed in a patient with elevated ALT?
1. history and examination
2. HBsAg->IgM anti-HBc [if +ve=acute hep B] [If -ve=chronic hep B]
3. anti-HCV->hepatitis C
4. if above -ve consider wilsons, haemochromatosis, autoimmune hepatitis, alpha 1 antitrypsin deficiency, coeliac disease
5. if all above -ve US or CT for fatty liver or biopsy
45
what investigations should be performed in a patient with mild diffuse LFT abnormalities?
1. history and examination
2. obesity, diabetes, hyperlipidaemia (non alcoholic fatty liver)
3. viral hepatitis risk factors (serological tests)
4. autoimmune features (serum globulins and auto antibodies)
5. other considerations (test for haemochromatosis, wilsons disease, alpha 1 antitrypsin deficiency, coeliac disease)
6. if all above consider US, CT, MRCP, ERCP, liver biopsy or transient elastography as suggested by results
46
what investigations should be performed in a patient with elevated alkaline phosphatase?
1. history and examination
2. GGT or isoenzymes normal ->extra hepatic source
3. elevated = hepatobiliary disesae
4. abdominal US (if normal->AMA, ACE level, serological tests for viral hepatitis, alpha fetoprotein.) gallstones, focal lesion, biliary tract abnormalities
5. if all above negative consider biopsy, transient elastography
47
when would you take a liver biopsy?
* Acute and chronic liver dysfunction
* Hepatomegaly
* Space occupying lesions
* To find cause and severity (stage of progression)
48
what action would be taken if work up is negative and AST/ALP remain elevated?
Observe:
o Patients with two-fold or less increase in AST/ALT and no hyperbilirubinemia
Liver Biopsy
o Patients with > two-fold increase in AST/ALT, or abnormalities of other liver function tests
49
what causes hepatocellular injury?
```
viral hepatitis
hepatitis due to other viruses
drug induced liver injury
toxins
metabolic
vascular events
```
50
what other viruses can cause hepatitis?
herpes viruses 1,2 and 6
adenovirus
epstein barr virus
CMV
51
what toxins can cause liver injury?
Amanita phalloides (death cap)
52
what metabolic issues can result in hepatocellular injury?
acute fatty liver of pregnancy
| reye's syndrome
53
what vascular issues can result in hepatocellular injury?
Acute circulatory failure
Budd-Chiari syndrome (occlusion of hepatic veins)
Veno-occulsive disease
Heat stroke
54
what other conditions can result in hepatocellular injury?
Wilson disease
Autoimmune hepatitis
Massive tumour infiltration
Liver transplant with primary graft dysfunction
55
describe the role of the liver in drug metabolism?
* Liver major site of drug metabolism
* between the splanchnic and systemic circulations and large amount of enzymes that are capable of transforming drugs into active compounds or degrading for elimination
* Converted from fat soluble to water soluble substances that are excreted in urine or bile
56
what is a phase I drug reaction?
oxidative and reductive processes
57
what is a phase II drug reaction?
oxidation, reduction and hydrolysis are couple with endogenous substrates such as glucuronic acid, sulfuric acid, glutathione. Render polar lipophilic compounds. Excreted in bile if molecules are large or in urine if small
58
what is a phase III drug reaction?
reactions actively transported from cell.
59
what are the 6 mechanisms that drugs can cause liver damage?
- Disruption of intracellular calcium homeostasis
- Disruption of bile canalicular transport mechanisms
- Formation of non-functioning adducts
- Present on surface of hepatocyte as new immunogens – attacked by T cells
- Induction of apoptosis -Inhibit mitochondrial function
60
describe drug induced hepatotoxicity?
* Intrinsic hepatotoxins = paracetamol
* Idiosyncratic (abnormal physical reaction to something) hepatotoxins = hypersensitivity and metabolic Can lead to hepatitis, cholestasis, fatty change and fibrosis
61
what affect can paracetamol have on the liver?
* Undergoes conjugation with glucuronide and sulphate. Remainder is metabolised by microsomal enzymes to produce toxic derivatives. Detoxified by conjugation with glutathione.
* Larger doses ingested, pathway becomes saturates and toxic derivative is produced at faster rate, binds to cell membranes. Can produce liver necrosis
62
what affect can halothane and other volatile anaesthetics have on the liver?
* Produces hepatitis in those having repeated exposures
| * Hypersensitivity reaction
63
what affect can steroid compounds have on the liver?
* Cholestasis caused by natural and synthetic oestrogens
| * Interfere with biliary flow
64
what affect can phenothiazines have on the liver?
* Cholestatic picture
| * Hypersensitivity reaction
65
what affect can anti TB chemo have on the liver?
• Elevated AMT
• Hepatic necrosis with jaundice
• Rifampicin produces hepatitis, pyrazinamide
produces abnormal liver tests
66
what affect can amiodarone have on the liver?
steatohepatitis?
67
describe acetaminophen overdose?
• Toxicity is likely to occur with single ingestions greater than 250 mg/kg or those greater than 12 g over a
24-hour period
• AST/ALT elevation is first sign of liver damage (usually 24-hours after ingestion)
68
what is acute hepatitis and how does it present?
* Definition: Rapid development of hepatic synthetic dysfunction
* Presentation: jaundice, bleeding, confusion, abnormal LFTs
69
what is the aetiology of acute hepatitis?
* Drugs – isoniazid – first line treatment for TB
* Halothane (general anaesthetic)
* Viruses – hepatitis A, B, C, EBV, CMV, Adenovirus, Herpes
* Alcohol
70
what is the commonest cause of liver disease worldwide?
acute viral hepatitis
71
what effective vaccines are available for acute viral hepatitis?
o Enterically transmitted: HAV, HEV
| o Blood borne: HBV, HCV, HDV, HGV
72
what are the symptoms of acute viral hepatitis?
* Asymptomatic
| * Health screen in at risk populations
73
Is hepatitis A acute or chronic?
acute
74
what part of the history are important in a patient with hepatitis A?
```
travel
recent outbreak
nausea
vomiting
jaundice
```
75
what labs are useful to diagnose hepatitis A?
hepatitis A IgM
| frequent elevated bilirubin
76
is hepatitis B acute or chronic
can be both?
77
what part of the history are important in a patient with hepatitis B?
See if patient from Asia, Subsaharan Africa; Sexual history, Drug use
78
what labs are useful to diagnose hepatitis B?
hepatitis B surface antigen
surface antibody
core antibody
79
what part of the history are important in a patient with hepatitis C?
IV drug abuse, blood transfusion prior to 1992, Sexual history, Tattoos
80
what labs are useful to diagnose hepatitis C?
Hepatitis C antibody (Hepatitis C viral load if HIV positive or immunocompromised)
81
what labs are useful to diagnose infectious mononucleosis (acute EBV)?
monospot
| EBV IgM
82
what would LFTs show in a patient with HIV?
isolated elevated aminotransferases
83
what labs are useful to diagnose HIV?
HIV antibody test
84
what part of the history are important in a patient with HIV?
sexual history
| IV drug use
85
what is the transmission of hepatitis A?
faecal oral
86
where are outbreaks of hepatitis A common?
schools
| institutions
87
what is the incubation period of hepatitis A?
28 days (between 15-50)
88
describe the onset and symptoms of hepatitis A?
```
abrupt onset
fever
malaise
anorexia
nausea
abdominal discomfort
dark urine
jaundice
```
89
how does age affect the symptoms presenting in a patient with hepatitis A?
age related
<6yrs 70% asymptomatic
>15yrs 70% icteric
90
what test is used to make a diagnosis of hepatitis A?
hep A IgM
91
what is the first sign of hepatitis A in smokers?
going of the fags
92
what is an effective way of preventing hepatitis A/
vaccination
93
describe the pre-icteric phase?
prodromal illness days to weeks
• Icteric = jaundice
• A prodromal phase from days to more than a week
• Characterised by appearance of symptoms like loss of appetite, fatigue, abdominal pain, N&V, fever,
diarrhoea, dark urine and pale stools (cholestatic phase)
• Malaise
• Anorexia
• Flu-like and GI like symptoms
• Few signs except for enlarged liver and jaundice
94
what is the icteric phase?
* Jaundice
* Pale stools and dark urine
* Improvement in symptoms
* DDx: surgical jaundice
95
what is post hepatitis syndrome?
• Malaise, depression, anorexia
• DDx: chronic hepatitis, liver biopsy after 6 months
• Fulminant hepatic failure: acute liver failure is broad that encompasses fulminant hepatic failure and
subfulminant hepatic failure = late onset. FHF describes the development of encephalopathy within 8 weeks
of the onset of symptoms in a patient with previously healthy liver.
• SHF is reserved for patients with liver disease for up to 26 weeks before the development of hepatic
encephalopathy
96
describe the hepatitis A virus?
icosahedral capsid ssRNA
97
describe the hepatitis B virus?
enveloped dsDNA
98
describe the hepatitis C virus?
enveloped ssRNA
99
describe the hepatitis D virus?
enveloped ssRNA
100
describe the hepatitis E virus?
unenveloped ssRNA
101
which hepatitis are spread via fecal-oral route?
A
| E
102
what hepatitis are spread via blood, close contact?
B
C
D
103
what is the incubation period of hepatitis A?
2-6 weeks
104
what is the incubation period of hepatitis B?
4-26weeks
105
what is the incubation period of hepatitis C?
2-26 weeks
106
what is the incubation period of hepatitis D?
4-7 weeks
107
what is the incubation period of hepatitis E?
2-8 weeks
108
which types of hepatitis are linked to hepatocellular carcinoma?
B
| C
109
which types of hepatitis become chronic?
B (5-10%)
C (.>50%)
D (coinfection-5% / superinfection-80%)
110
how is hepatitis B usually transmitted?
mother to baby
in blood
via sex
111
if contracted at birth what percentage develop chronic hepatitis B infection?
90%
112
what percentage of patients with hepatitis A get fulminant hepatitis and what is this?
20-25%
rare and fatal form of acute hpe B, radpily deteriorates with
hepatic encephalopathy, necrosis of parenchyma, renal failure and coma
113
describe the serology of hepatitis B?
* HBsAg – hallmark of infection
* Anti HBs – immunity
* Anti HBc (core) previous exposure
* HBeAg marker of viral replication
* HBV DNA – direct marker
114
how can hepatitis B be treated?
* Interferon – as hep C – unpleasant
* Lamivudine – mutation risk
* Prevention better than cure – vaccinate household contacts, vaccinate babies (active +/- passive)
115
who gets hepatitis C?
* 60% of drug users +ve
| * >40% of prison population
116
describe chronic hepatitis C infection?
Chronic hepatitis (85%) > cirrhosis > Hepatocellular carcinoma > death or stable cirrhosis
fulminant hepatitis rare
117
what are the symptoms for hepatitis C?
* Nothing to everything
* RUQ pain
* Brain fog
* Depression
* Alcohol intolerance
118
how can hepatitis C be treated?
* PEGylated interferon and ribavirin
| * Significant SE: arthralgia, myalgia, alopecia, neutropenia, thyroid and AI disorders, rashers, pregnancy
119
what are the symptoms and signs of chronic hepatitis?
* Stigmata of CLD
* Jaundice
* Splenomegaly
* Portal hypertension late
* ALT (mild <100 mod 100-400 severe >400) Ig’s
* ALK, Phos, Bili, ALB ofte normal
120
what is seen histologically in chronic hepatitis?
* Necroinflammaotory and fibrosis score
* eAG = e antigen
* IFN = interferon
* ANA = anti-nuclear antibody
* Anti-sm = anti-smith antibody
121
what are the causes of chronic hepatitis?
drugs
viruses
Al D
wilsons D
122
describe HBV and chronic hepatitis
1. men or women more
2. age
3. making a diagnosis
4. treatment
1. men
2. any age
3. HbsAg e Ag PCR
4. IFN iamivudine
123
describe HCV and chronic hepatitis
1. men or women more
2. age
3. making a diagnosis
4. treatment
1. men=women
2. any age
3. anti-HCV and PCR
4. IFN ribavirin
124
describe autoimmune chronic hepatitis
1. men or women more
2. age
3. making a diagnosis
4. treatment
1. women
2. 10-20 and post menopause
3. ANA anti-Sm Igs
4. prednisolone
125
describe drugs causing chronic hepatitis
1. men or women more
2. age
3. making a diagnosis
4. treatment
1. women
2. middle age onwards
3. isoniazid. furantoin
4. withdrawl drugs
126
describe wilson's disease and chronic hepatitis
1. men or women more
2. age
3. making a diagnosis
4. treatment
1. Men=women. rare, haemolysis. neurological disease
2. 10-30
3. Kayser-fleischer rings. serum Cu and caeruloplasmin
4. chelation
127
what liver changes occur in alcoholic Liver disease?
• Fatty change (steatosis)
• Steatohepatitis: spotty liver cell necrosis, focal. Neutrophils, mallory’s hyaline (accumulation of eosinophilic
material in cytoplasm of damaged liver cells), perivenular fibrosis (around the vein), micronodular cirrhosis.
128
what are the symptoms of alcoholic liver disease?
* Asymptomatic to dull RUQ pain
* Mildly elevated ALT
* Hepatomegaly
* Resolves with abstinence
* 10% develop cirrhosis
129
what is the prevalence of alcohol use above recommended levels
25% men
| 18% women
130
what conditions is excess alcohol use associated with?
Directly associated with cirrhosis, epilepsy, pancreatitis, dementia and foetal abnormalities
• Contributes to chronic conditions: CAD, stroke and cancers
131
what are the acute harms associated with excess alcohol use?
RTAs
drowning
assaults
132
what is one unit of alcohol?
10G = one unit = 1/2pint = glass of wine
133
how much alcohol use leads to cirrhosis?
>80g/day for 10 years = cirrhosis
134
what are the clinical features in a patient with alcoholic liver disease?
• AST > ALT (rarely greater than 300 IU/L)
• GGT – high level is associated with heavy alcohol drinking. Involved in the break down and clear alcohol from
the body
• Hypokalaemia – alcohol is a diuretic, so will lose more potassium through kidneys
• Hyperuricaemia – high uric acid levels, alcohol increases uric acid
• Hyperlipidaemia
• Macrocytosis – near constant hb, enlarged RBC. MCV > 100femtolitres
• Dupuytren’s contracture
• Blood or urinary alcohol levels (or breath test)
• Liver biopsy – steatosis, neutrophilic infiltrate, pericellular zone 3 fibrosis
135
what are the clinical features in a patient with asymptomatic (mild hepatitis or fatty liver) alcoholic liver disease?
* Raised ALK phos/AST
| * Smooth hepatomegaly
136
what are the clinical features of acute alcoholic hepatitis?
* Pyrexia
* Tachycardia
* Shaking
* Anorexia/weight loss/malnutrition
* Nausea/ vomiting/ diarrhoea
* Tender abdomen
* Hepatomegaly
* Spider naevae
* Dupuytren’s contracture
* Icterus
137
what are the signs of liver failure or cirrhosis?
• Ascites, bleeding, encephalopathy, hypoglycaemia
138
what would laboratory tests show in a patient with alcoholic liver disease?
* LFTS: raised AST and ALK phos and bilirubin and low albumin
* FBC: Leucocytosis (raised WBC) and thrombocytopaenia (decreased levels of platelets)
* U&Es: Hypokalaemia
* Clotting profile: increase in PTT
139
what is the treatment for patients with alcoholic liver disease?
* Sedation and supportive care
* Sedation – chlormethiazole/hemineverin/chlordiazepoxide
* Prevent delirium tremens
* IV fluids 5% dextrose and KCL and antiemetics
* Vitamins (bit B and C as pabrinex, vit k)
* Calories
* Treat accompanying medical problems: GI bleeds, sepsis, ascites, encephalopathy, hepatorenal failure
* Steroids if marked coagulopathy and jaundice
* Treat addiction and complications
140
what causes Non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL)?
* DM
* Drugs
* Parenteral nutrition
* Intestinal by-pass surgery
141
1. what does exposure of drugs, DM etc to a healthy liver lead to?
2. what does severe exposure lead to?
3. once at these stages what does continued exposure lead to?
1. steatosis
2. hepatitis
3. cirrhosis
142
what damage occurs in hepatitis?
liver cell necrosis
inflammation
mallory bodies
fatty change
143
what damage occurs in cirrhosis?
```
fibrosis
hyperplastic nodules
• Micronodular cirrhosis
• Diffuse liver disease with fibrosis and nodule
• Lobular architecture is destroyed and parenchyma is converted into structurally abnormal nodules of liver cells
separated by bands of fibrosis.
• Irreversible condition = ESLF
• Formation due to regeneration
```
144
what damage occurs in steatosis?
fatty change
| perivenular fibrosis
145
what is the presentation of NASH and NAFL?
• Bland steatosis to fibrosis/cirrhosis
• 40-60% of obese individuals have NAFLD
• 80% steatosis
• 20% steatohepatitis
• 25% progress to cirrhosis over 8yrs
• Classic patient: ALT 98, aetiology screen negative, BMI 33, HT/Diabetes +/-, USS = hyperechoic liver in keeping
with fatty infiltration.
• Increase in AST/ALT are usually less than 4-fold. Ratio of AST/ALT is usually < 1
• History: Female, obesity, diabetes
• Labs:
o Labs to rule out other causes of hepatitis
o Abdominal Ultrasound: look for fatty infiltration of liver
146
what is the treatment for NASH and NAFL?
* Previously thought to be benign
* Lose weight
* Good DM control – glitazone
* Control RF
147
what are the symptoms of drug toxication?
* Varies from ALF to mild hepatitis
* Often idiosyncratic
* Isoniazid and Augmentin
* Hepatitic picture: paracetamol, methotrexate, tetracyclines
* Statins common reason for referral. Discuss and consider change in agent if 2-3X ULN ALT
148
what is the aetiology of cirrhosis?
• Alcoholic LD – 60-70%
• NAFLD
• Viral Hepatitis
• AI hepatitis
• Chronic cholestatic LD
• Metabolic: Iron and copper overload = haemochromatosis and wilson’s
• Drugs and toxins – a-1 antitrypsin deficiency, amiodarone and methotrexate
• Idiopathic
• Paediatric disease – glycogenosis (glycogen storage disease)
• Hepatic venous outflow obstruction: budd chiari syndrome (hepatic vein obstruction is a blockage of the hepatic
vein, carries blood away from the liver. This blockage > liver disease. Constrictive pericarditis – LT inflammation
of sac covering heart with thickening, scarring and muscle tightening.
• Prolonged cholestasis: hepatocellular failure, portal HT, compensated or decompensated, child-pugh
classification – assess the prognosis of CLD, mainly cirrhosis
149
what are the consequence of liver cirrhosis?
• Impaired liver function
• Hypoalbuminaemia
• Reduced coagulation factor synthesis
• Decreased metabolism of endogenous oestrogens
• Failure of detoxification – encephalopathy, hepatorenal syndrome: progressive kidney failure with cirrhosis.
• More prone to bleeding, brain disease due to increased levels of ammonia crossing BBB
• Portal HT
• Leads to sodium and water retention: pooling of blood in VD splanchnic circulation, reduced effective
circulating BV, renin release from kidney, hyperaldosteronism
• Ascites: increased transudation due to increased hydrostatic pressure in portal vein, low plasma oncotic
pressure (hypoalbuminaemia), sodium and water retention and extravasation of hepatic lymph
• Infection: kupffer cell dysfunction – macrophages, reduced synthesis of immunoregulatory proteins,
spontaneous bacterial peritonitis
• Hepatocellular carcinoma
150
what are the clinical features of cirrhosis?
* Leukonychia (white nails)
* Spider naevae
* Clubbing
* Palmar erythema
* Dupuytren’s contracture/parotid gland enlargement
* Gynaecomastia
* Testicular atrophy
* Loss of body hair
* Malnourished
* Oedema
* Ascites
* Caput medusa (engorged distended paraumbilical veins, radiate from the umbilicus across the abdomen
* Hepatosplenomegaly
151
What acute vascular changes can occur in a patient with cirrhosis?
* Hypotension
* RCHF
* Hepatic venous outflow obstruction (budd-chiari)
152
what chronic vascular changes can occur in a patient with cirrhosis?
• Right sided CF
• Venocclusive disease: condition in which some of the small veins in the liver are obstructed. Complicatons of
high dose CT and marked by weight gain due to fluid retention, increased liver size and raised bilirubin levels. (Alkaloids, Alcoholic liver disease, Blood disorders, RT, Cytotoxic drugs, Tumours, Membrane obstruction
153
what are the types of benign liver tumours?
* Focal nodular hyperplasia
* Liver cell adenoma
* Bile duct adenoma
* Haemangioma
154
what are the types of metastatic liver tumours?
* Hepatocellular carcinoma (hepatoma)
* Cholangiocarcinoma
* Angiosarcoma
155
who gets hepatocellular carcinoma?
M>F
africa and orient
frequency increasing in the west
156
what is a tumour marker of hepatocellular carcinoma?
alpha fetoprotein
157
what are the complications of hepatocellular carcinoma?
liver failure, bleeding, hypoglycaemia, mets
| poor prognosis
158
what is cholangiocarcinoma?
* Tumour of bile ducts
* Multifocal
* Associated with chronic biliary irritation: gall stones, liver fluxes, sclerosing cholangitis, cysts
* Obstructive
* Poor prognosis
159
what is hepatic angiosarcoma?
* Rare
* Multifocal haemorrhagic tumours
* Associated with: occupational exposure to vinyl chloride, arsenic, thorotrast
* Poor prognosis
160
what would labs show in a patient with hereditary hemochromatosis?
• Serum iron, TIBC
- Calculate iron saturation = serum iron/TIBC (total iron binding capacity)
- If iron saturation > 45%, check ferritin
•Ferritin
-If > 400 ng/mL in men, or > 300 ng/mL in women, then need to check liver biopsy or genetic
testing
•Liver biopsy
•Homozygous hereditary hemochromatosis if iron index > 1.9
- If under age 40, and positive genetic testing, no biopsy needed.
•Genetic Testing
161
what is autoimmune hepatitis?
Chronic, non-resolving liver disease leading to hepatocellular necrosis and cirrhosis. Sub-divided into types 1, 2 and 3
depending on associated autoantibodies & HLA type. Presentation varies – acute flares with jaundice Vs indolent disease
young to middle aged females`
162
what would labs show in a patient with autoimmune hepatitis?
o Serum protein electrophoresis (SPEP) – if polyclonal increase in gamma globulin
o Anti-nuclear antibody (ANA)
o Anti-smooth-muscle antibody (SMA)
o Liver biopsy: should be performed if the above are negative, but autoimmune hepatitis still suspected.
163
what is alpha-1-antitrypsin deficiency?
A failure of release from hepatocytes, rather than production
• Low serum levels of AAT
• No alveolar protection from elastases
• Build-up within hepatocytes results in damage
Emphysema and cirrhosis are the end result
• History: Family history, emphysema, young age
164
what labs should be done to diagnose a patient with alpha 1 antitrypsin deficiency
alpha 1 antitrypsin level/phenotype
165
what is the treatment for alpha 1 antitrypsin deficiency?
Intravenous alpha-1 antiprotease helps with lung disease, but liver transplant is ultimately only
treatment for liver disease.
166
what is Wilson's disease?
genetic disorder of biliary copper excretion
167
what investigations would be performed in a patient with Wilson's disease?
• History: Age (usually age 5 – 25, but up to age 40), family history of liver disease; neuropsychiatric disease
• Evaluation:
o Serum ceruloplasmin: Low
o Ophthalmologist: Exam for Kayser-Fleisher rings
o 24-hour urine copper
o Liver biopsy: Evaluate liver copper levels
168
what is the treatment for Wilson's disease?
o Copper chelating agents
o Zinc
o In some cases, ultimately liver transplant
169
what is the aetiology of shock liver (ischaemic hepatits?
shock
| severe hypotension
170
what would lab results show in a patient with shock liver?
Severely elevated AST/ALT (50 times normal)
171
what is the treatment for shock liver?
re-establish good blood pressure/perfusion
172
what is the prognosis for shock liver?
Usually patients recover, but can progress to fulminant liver failure requiring transplant.
173
what non-hepatic causes can cause mild increase in AST/ALT?
```
• Muscle disorders
•Hypothyroidism/Hyperthyroidism
• Celiac Disease
• Adrenal Insufficiency
• Anorexia nervosa
• Drugs:
o Anabolic steroids, contraceptives, antibiotics
• Total parenteral nutrition (TPN)
• Cirrhosis:
o Viral hepatitis (Hepatitis B, C)
o Alcohol hepatitis
```
174
what is jaundice?
yellow discolouration of the skin and mucous membranes caused by an increase in bilirubin
concentration in the body fluid
175
what is the normal level of bilirubin?
3-17micromol/l
176
what level does jaundice become detectable?
40micromol/l
177
what tissues concentrate bilirubin best?
high content of elastic tissue – skin, sclera and blood vessels
178
what causes raised bilirubin?
Obstructive liver disease – ALP and GGT usually raised too
Mechanical obstructive >50% of bilirubin is conjugated
Isolated levels: defect in conjugation – Gilberts disease, there is an increase in unconjugated bilirubin,
including haemolysis
179
describe the physiology of bilirubin?
• Bile pigment produced by breakdown of haem and reduction of
biliverdin
o Unconjugated is insoluble > transported bound to albumin
o Normally 95% is unconjugated
• The hepatic sinusoids are large so that bilirubin-albumin complex can
diffuse to the plasma membrane of the hepatocyte. Made water
soluble in the liver cells by attaching sugar molecule to it =
conjugated. Passed into bile duct. Here, unconjugated bilirubin
dissociates from albumin and enters cytosol via facilitated transport
• In cytosol, conjugated by enzyme bilirubin UDP-glucuronyl
transferase > bilirubin diglucuronide
• Raised level of conjugated occurs in liver and bile duct conditions.
High if flow of bile is blocked. Gallstones or tumour in pancreas.
Also raised with hepatitis, liver injury or LT alcohol abuse.
• Enters gut via biliary tree, bilirubin glucoronides are degraded and
converted > urobilinogen and stercobilinogen. Urobilinogen
excreted into faeces > urobilin = brown
180
what are the causes of jaundice?
• Pre-hepatic
• Hepatic
• Post-hepatic
Divided into unconjugated and conjugated bilirubin
181
what are the prehepatic causes of jaundice?
haemolysis
182
what are the intrahepatic causes of jaundice?
```
viral hepatitis
drugs
alcoholic hepatitis
cirrhosis
pregnancy
recurrent idiopathic cholestasis
some congenital disorders
```
183
what are the extrahepatic causes of jaundice?
```
common duct stones
carcinoma
biliary stricture
sclerosing cholangitis
pancreatic pseudocyst
```
184
what do you ask for in a patient with jaundice?
• Age: younger = viral hepatitis, older = gallstones/malignancy
• Onset: slow with pruritus = cholestasis, rapid with nausea and anorexia = viral, episodic = gilberts
• Gender: F = AI disease, M = alcohol induced
• Other symptoms: pale stool/dark urine/itching = cholestasis. Pain = gallstones. Fever/rigors = cholangitis
(infection of common bile duct carriers bile from liver to GB and intestines)
• Drugs: prescribed, OTC, illicit/IV
• PMH: previous jaundice, ops, gallstones, carcinoma
• FH: jaundice, liver disease, haemolytic anaemia
• Social: high alcohol exposure, industrial exposure (vinyl chloride), food – shellfish, sexual contacts, travel
history/vaccinations.
185
what do you check for on examination in a patient with jaundice?
```
• Stigmata of LD
• Clubbing
• Palmer Erythema
• Dupuytren’s contracture
• Spider naevi
• Hepato-splenomegaly
• Ascites (fluid that accumulates in the abdominal (peritoneal) cavity. Complication of cirrhosis and appears as
an abdominal bulge)
```
186
describe pre-hepatic jaundice?
* Inability of liver to handle increase in bilirubin (haemolysis)
* Limiting factor = enzyme glucuronyl transferase
* Serum bilirubin increased, is unconjugated
* NO urinary bilirubin as not water soluble
* Other indicators are within normal range
187
what is the aetiology of pre-hepatic jaundice?
• Physiological neonatal jaundice – most common
• Haemolysis (abnormality of RBC: sickle cell, spherocytosis),
-Leads to excessive breakdown of RBC with excessive bilirubin production> unconjugated
hyperbilirubinaemia (rare exceeds capacity of the liver to excrete bilirubin)
• Haematoma
• Ineffective erythropoiesis e.g. pernicious anaemia
• Severe rhabdomyolysis with release of myoglobin
• Bleeding into tissues e.g. in sports injuries
188
describe hepatic causes of jaundice?
* Inherited conditions of the liver which give a conjugated hyperbilirubinaemia
* GILBERTs SYNDROME
* AS dominant inherited.
* Abnormality of glucuronidase activity
* Jaundice is mild, worse with fasting and drinking alcohol or intercurrent illness
189
what changes would you expect to see in a patient with hepatic jaundice?
Serum / blood:
• bilirubin (micormoles/l) 50-150; normal range 3-17
• Liver enzymes normal: AST, ALP, GGT, Albumin, PTT
• reticulocytes(%) 10-30; normal range <1
Urinary changes:
• bilirubin: absent
• urobilinogen: increased or normal
Faecal changes:
• stercobilinogen: normal
190
descibe conjugated bilirubin?
* Bilirubin taken up into hepatocytes from blood
* Bound intracellularly
* UDP glucuronic acid reacts with bilirubin to form mainly bilirubin diglucuronide
* Glucuronide conjugated form of bilirubin is water soluble and excreted into bile
* Disorders of bilirubin take up or conjugation can lead to hepatic jaundice
191
describe hepatic jaundice?
* Failure in function of hepatocytes to take up, metabolise or excrete bilirubin (secretion of bile)
* Jaundice is rapid
* Fatigue and malaise are common
* Serum transaminases increased
* Albumin reduced in chronic disease
* PTT prolonged
192
what are the most common aetiologies of hepatic jaundice?
• Hepato-cellular disease (viral hepatitis (hep A/B/C/E), alcoholic hepatitis, drugs, AI, cirrhosis)
• Cholestatic D (bile ducts – bile can’t flow from liver to the duodenum)
(Drugs, Mets, Cirrhosis, Sepsis, AI)
193
what changes would you expect to see in hepatic jaundice?
* serum / blood:
* bilirubin (micromoles/l) 50-250; normal range 3-17
* AST I.U. 300-3000; normal range <35
* ALP I.U. <250-700; normal range <250
* gamma GT I.U. 15-200; normal range 15-40
* albumin g/l 20-50; normal range 40-50
* reticulocytes (%) <1; normal range <1
* prothrombin time (secs) 15-45; normal range 13-15
* ( " + parenteral vit. K) 15-45
* urinary changes:
* bilirubin: normal or increased
* urobilinogen: normal or reduced
* faecal changes:
* stercobilinogen: normal or reduced
194
describe post-hepatic jaundice?
• Converted to di- monoglucuronide before secretion into biliary canaliculi
• Degraded to urobilinogen
• Can be reabsorbed by gut and to the liver
• Converted to urobilin that colours faeces or reabsorbed and excreted by kidneys
• Or conjugated bilirubin can be acted upon by bacterial enzymes within the gut to form bile pigment
stercobilinogen
• Can be recycled in the liver or excreted by the kidney
• Or oxidised to stercobilin – is bile pigment, appears brown in faeces
• Failure of bilirubin to reach gut results in reduction in pigment within the stool = pale stools
195
what are the causes of post hepatic jaundice?
• Biliary tract causes (CBD)
- Gallstones
- Stricture
- Carcinoma
- Extrinsic pressure
•Pancreatic Causes (head)
- Carcinoma
- Chronic pancreatitis
• Extrahepatic cholestasis results from mechanical obstruction to large bile ducts outside liver
* Liver enlarged and intra hepatic bile ducts widely dilated
* Bile ducts proliferate in portal zones
* Infection of bile leads to cholangitis
* Pale stool – no bilirubin reaching GI tract for conversion to stercobilin
* Dark orange urine – conjugated bilirubin into blood, excreted in urine
* Icterus
* Pruritus
196
what is courvoisiers law?
* Jaundice and palpable gall bladder = unlikely to be due to gallstones more likely to be pancreatic cancer
* Bastardisation: progressive painless jaundice = carcinoma
197
what is Murphy's sign used for and describe it?
• sign for gallstones/cholecystitis
•During abdo exam
• Breathe out and place hand below costal margin on the R side at the mid-clavicular line
• Patient then instructed to inspire (breathe in)
• During inspiration, abdo contents are pushed down as the diaphragm moves down. If patient stops breathing
in (as the GB is tender and moving down, comes in contact with examiners fingers)
• Winces with a catch in breath
• Test considered positive
• Same manoeuvre must not elicit pain when performed on the L side.
• Tender in RUQ on inspiration but not in LUQ
198
what is charcot's triad?
triad for ascending cholangitis-infection of common bile duct
• Fever
• Jaundice
• RUQ pain
199
what is the aetiology of obstruction in the bile ducts?
```
The cause of obstruction of any hollow organ may be divided into luminal, mural and extramural causes:
Obstruction of the lumen of the bile ducts:
• Gall stones – common
• Tumours
• Parasites:
o Hydatid disease
o Liver fluke
o Round worms
• Iatrogenic:
o Post-T-tube cholangiography
```
200
what is mural obstruction?
* congenital atresia
* traumatic stricture e.g. ampullary stricture
* sclerosing cholangitis
* cholangiocarcinoma
201
what is extramural obstruction?
* carcinoma of the head of pancreas - common
* carcinoma of the ampulla of Vater
* pancreatitis
* porta hepatis tumours (often secondary deposits)
* chronic duodenal ulceration
202
what changes occur when there is obstruction of bile ducts?
* serum / blood:
* bilirubin (micromoles/l) 100-500; normal range 3-17
* AST I.U. 35-400; normal range <35
* ALP I.U. >500; normal range <250
* gamma GT I.U. 30-50; normal range 15-40
* albumin g/l 30-50; normal range 40-50
* reticulocytes(%) <1; normal range <1
* prothrombin time (secs) 15-45; normal range 13-15
* ( " + parenteral vitamin K) falls
* urinary changes:
* bilirubin: increased
* urobilinogen: reduced or absent
* faecal changes:
* stercobilinogen: reduced or absent
203
What is cholestasis?
failure of normal amounts of bile to reach duodenum
o Source may reside in the main bile ducts = extrahepatic cholestasis 70% -
o Or in the liver = intrahepatic cholestasis 30%
204
what is chronic cholestatic disease?
• Decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or
extrahepatic bile ducts.
• Clinical definition of cholestasis is any condition in which substances normally excreted into bile are retained.
205
what is primary biliary cirrhosis?
• AI disease of liver. Slow progressive destruction of the small bile ducts of the liver with the intralobular ducts
(canals of Hering) affected early on.
o Predominately in women, usually ages 35-65
o May have history of other autoimmune disease
• When these ducts are damaged, bile builds up in the liver = cholestasis and damages tissue. This can lead to
scarring, fibrosis and cirrhosis
206
what are anti-mitochondrial antibodies?
autoantibodies formed against mitochondria in the cells of the liver.
Presence of AMAs in the blood or serum is indicative of AI diseases – present in 95% of cases of primary billiary cirrhosis
207
what are the symptoms of primary billiary cirrhosis?
Prurutis, fatigue, hyperpigmentation, musculoskeletal complaints
208
what investigations should be done in patients with primary biliary cirrhosis?
RUQ Ultrasound
Anti-mitochondrial antibody
Liver biopsy to verify diagnosis
209
what is primary sclerosing cholangitis?
• Disease of the bile ducts that cause inflammation and
subsequent obstruction of bile ducts both at intrahepatic and
extrahepatic level. Impedes the flow of bile to the gut, lead to
cirrhosis of the liver, LF and Liver cancer.
• Chronic progressive disorder of unknown etiology that is
characterized by inflammation, fibrosis, and stricturing of
medium size and large ducts in the intrahepatic and
extrahepatic biliary tree.
• Underlying cause – AI
• More than 80% of those with PSC have UC
• Treat with liver transplant
210
what are the clinical features of primary sclerosing cholangitis?
• Pruritus
• Icterus (jaundice)
• Xanthomas: palmar creases, below the breast, on the neck.
They indicate raised serum cholesterol of several months.
Xanthomas on the tendon sheaths are uncommonly
associated with cholestasis.
• Xanthelasma on the eyelids
• scratch marks: excoriation
• finger clubbing
• loose, pale, bulky, offensive stools – steatorrhoea leading to ADEK malabsorption
• bruising/bleeding (vitamin K deficiency)
• Vitamin D bone disease
• dark orange urine
211
how does extrahepatic cholestasis present?
* pain, due to gallbladder disease, malignancy, or stretching of the liver capsule
* fever, due to ascending cholangitis
* palpable and / or tender gallbladder
* enlarged liver, usually smooth
212
what are the initial investigations for jaundice?
* Cause always sought as not a diagnosis itself
* 2 most useful tests: viral markers for HAV, HBV, HCV with an US
* liver biochemistry confirms
* US for extrahepatic obstruction – dilated bile ducts, level of obstruction and cause
213
describe liver biochemistry in jaundice?
* In hepatitis, serum AST, ALT high early in disease
* Extrahepatic obstruction, ALP high
* PT prolonged in longstanding disease, serum albumin low
214
what would haematological tests show in jaundice?
* Bilirubin raised other is normal
* Raised WCC indicate infection – cholangitis
* Leucopenia in viral hepatitis
* Mononuclear cells = infectious mononucleosis
215
what are the common findings in a patient with cholestatic jaundice?
* Dark urine (conjugated bilirubin)
* Pale stools
* Pruritus
* Little in the way of pain
* Oedema, ascites, bruising, spider naevi
* Complications: GI bleeding (varices)
216
what are the common findings in a patient with primary biliary cirrhosis?
* AI condition intrahepatic biliary tree
* Female:male 10:1
* Antimitochondrial antibody
* Liver biopsy
* Supportive treatment, ursodeoxycholic acid, liver transplant
217
what are the common clinical features of hepatomegaly?
* Hepatomegaly: smooth generalised enlargement, with or without jaundice
* Hepatomegaly: knobbly generalised enlargement with or without jaundice
* HM: localised swellings
* HM: mild, moderate, massive
218
what causes massive hepatomegaly?
* Secondary carcinoma
* Alcoholic liver disease with fatty infiltration
* RHF
* Myeloproliferative disease
219
what causes moderate hepatomegaly?
* Haemochromatosis
* Haematological disease
* Fatty liver secondary to diabetes
220
what causes mild hepatomegaly?
* Hepatitis
| * Biliary obstruction
221
what causes smooth, generalised hepatomegaly with jaundice?
* Infective causes: viral hepatitis, bacterial, protozoal, parasitic
* Extra-hepatic biliary tract obstruction
* Cholangitis
222
what causes smooth generalised hepatomegaly without jaundice?
* Congestive cardiac failure
* Liver cirrhosis
* Hepatic vein obstruction
* Amyloidosis
223
what causes knobbly hepatomegaly with jaundice?
* Extensive secondary carcinoma
| * Liver Cirrhosis
224
what causes knobbly hepatomegaly without jaundice?
Secondary carcinoma
• Cirrhosis
• Polycystic disease
225
what causes localised swelling on the liver?
* Secondary carcinoma
* Liver abscess
* Cysts
226
what investigations are done in a patient with hepatomegaly?
* Bloods: FBC, U&Es, LFT, clotting, inflammatory markers
* Full lover screen
* US abdomen.
227
describe chronic Al hepatitis (lupoid hepatitis), plasma cell hepatitis?
* W more commonly than M
* Associated with other AI disorders
* Often presents with lethargy and rash/sub clinical and asymptomatic
* Acute, fulminant onset
* Chronic active hepatitis
* Anti-antibody positive ANA/ASMA LKM1 antibodies
* Aetiology screen and liver biopsy
* Anti-nuclear AB associated with SLE, scleroderma, AI hepatitis
* Liver kidney microsomal type 1 AB associated with AI hepatitis
228
what is haemochromatosis?
* AS Recessive – common
* 75% present with abnormal LFTs
* W present later than M
* High ferritin
* Multiple associations
229
how does haemochromatosis present?
LFT – 75%
• Weakness and lethargy 74%
• Skin hyperpigmentation 70%
• Diabetes Mellitus – 48%
230
what is the treatment of haemochromatosis?
* Venesection – twice weekly until ferritin falls then infrequent
* Cirrhosis can reverse
231
describe alcoholic hepatitis?
* Excess alcohol for a long time – without ill effect 40-70units/week
* Suddenly become ill
* Hepatomegaly, jaundice, pyrexia, anorexia
* 50% die, 50% > cirrhosis
232
Where is alkaline phosphatase found?
Found in liver, bone, intestine, first trimester placenta and kidney.
233
When are alkaline phosphatase levels raised?
Raised in liver and bone disease.
If raised with GGT = liver.
Raised in cholestasis and biliary obstruction
