PBL Topic 4 Case 5 Flashcards
(191 cards)
1
Q
Identify five functions of the liver
A
- Filtration and storage of blood
- Metabolism of carbohydrates, proteins and fats
- Formulation of bile
- Storage of vitamins and iron
- Formation of coagulation factors
2
Q
Identify three structures located in the intralobular septa between adjacent lobules
A
- Hepatic arterioles
- Portal venules ( (to hepatic sinusoids)
- Bile ducts (from canaliculi between cellular plates)
3
Q
Identify four types of cells in the liver
A
- Hepatocytes
- Endothelial cells
- Kupffer cells (reticuloendothelial cells)
- Stellate cells
4
Q
What are spaces of Disse?
A
- Tissue spaces located beneath the endothelial cells (which contain large pores)
- Which connect with lymphatic vessels
- And drain excess fluid
5
Q
Outline the pressure changes of blood flow through the liver
A
- Pressure in portal vein is 9 mm Hg
- Pressure leading from liver to vena cava is 0 mm Hg
- Resistance to blood flow through the liver is low
6
Q
Why is the liver considered to be a blood reservoir?
A
- Blood volume is usually 450 ml
- Liver can expand and store excess of up to 1 litre of blood in hepatic veins in sinuses
- Typically occurs in cardiac failure
7
Q
Outline the pathology of ascites
A
- Blockage in portal system
- Increases pressure in hepatic veins
- Causes fluid to leak through liver
- Fluid collects in abdominal cavity
8
Q
Under what conditions is the liver unable to restore itself following injury?
A
- Viral infection
- Inflammation
9
Q
Outline an important factor in living cell division and growth, and the cell type that produces it
A
- Hepatocyte growth factor
- Mesenchymal cells in the liver
10
Q
Outline two growth factors involved in stimulating regeneration of liver cells
A
- Epidermal growth factor
- Tumour necrosis factor
11
Q
Which cytokine is responsible for terminating cell division of the liver once it has returned to its original size?
A
- TGF-Beta
12
Q
Outline the role of Kupffer cells
A
- Cleanse blood as it passes through venous sinuses
- Engulfs and digests bacteria
- Before it can enter systemic circulation
13
Q
Identify four functions of the liver in carbohydrate metabolism
A
- Glycogenesis
- Gluconeogensis
- Converts galactose and fructose to glucose
- Forms compounds from intermediate products of carbohydrate metabolism
14
Q
Outline the glucose buffer function of the lliver
A
- Storage of glycogen removes excess glucose from blood
- And returns glucose to blood when concentration falls too low.
15
Q
What is the importance of gluconeogensis?
A
- Formation of glucose
- Only when its concentration falls below normal
16
Q
Identify three functions of the liver in fat metabolism
A
- Oxidation of fatty acids to supply energy
- Synthesis of cholesterol phospholipids and lipoproteins
- Synthesis of fat from proteins and carbohydrates
17
Q
Outline how energy is derived from neutral fats?
A
- Split into glycerol and fatty acids
- Fatty acids are split into acetyl coenzyme A by beta oxidation
- Which enters the citric acid cycle and can be oxidised to liberate enetgy
18
Q
Why is acetoacetic acid formed?
A
- Liver cannot use all acetyl-CoA
- So converts two molecules of acetyl-CoA into acetoacetic acid
- Which is then transported throughout the body to other tissues
19
Q
What happens to the majority of cholesterol synthesised in the liver?
A
- Converted into bile salts
- Which are secreted into bile
20
Q
Identify four functions of the liver in protein metabolism
A
- Deamination of amino acids
- Formation of urea for removal of ammonia
- Formation of plasma proteins
- Interconversion of amino acids and synthesis of compounds from amino acids
21
Q
Identify the three plasma proteins in the blood and their function
A
- Albumin, provides colloid osmotic pressure in plasma
- Globulins, involved in natural and acquired immunity
- Fibrinogen, involved in coagulation
22
Q
What is the difference between essential and non essential amino acids? How many of each are there?
A
- Essential: Cannot be synthesised in body
- Non essential: Can be synthesised in body
- Ten of each
23
Q
Outline the process of synthesis of non-essential amino acids
A
- Formation of alpha keto acid, the precursor of amino acids
- Amino radical is transferred from donor to alpha keto acid ‘transamination’
- Oxygen is transferred to donor from the keto acid
24
Q
What is the keto acid precursor of alanine? What donor substance provides the amino radical to this precursor?
A
- Pyruvic acid
- Glutamine
25
Name an enzyme type that catalyses the transamination reaction. What is it a derivative of?
- Aminotransferases
| - Which are derivatives of pyridoxine (Vitamin B6)
26
Outline the process of deamination
- Removal of amino group from amino acids
- By transamination, where amino group is transferred to alpha-ketoglutaric acid
- Which then becomes glutamic acid
- Glutamic acid transfers its amino group to other substances to form ammonia
27
Outline the process of urea formation by the liver
- Two molecules of ammonia react with one molecule of carbon dioxide
- To form one molecule of urea and one molecule of water
28
Why is ammonia dangerous?
- Crosses blood brain barrier
- Toxic effect on brain
- Causing hepatic coma
29
How is urea removed from the body?
- Excreted by kidneys
30
What is the importance of oxidation of deaminated amino acids
- Enters citric acid cycle
| - To release energy for metabolic purposes
31
What is the main vitamin stored in the liver? How long can it be stored?
- Vitamin A
| - 10 months
32
How long can Vitamin D and B12 be stored in the liver?
- Vitamin D: 3-4 months
| - Vitamin B12: 12 months
33
Describe how iron is stored and released from liver?
- Hepatic cells contain apoferritin
- Which binds with iron to form ferritin
- Which is stored in hepatic cells until needed elsewhere
34
Identify coagulation factors formed in the lvier
- Fibrinogen (1)
- Prothrombin (2)
- Acceletor Globulin (5)
- Factor 7
35
Vitamin K is required for the formation of which coagulation factors?
- 10
- 9
- 7
- 2
36
Outline the formation of bilirubin
- Erythrocytes die after 120 days
- Cell membrane ruptures and haemoglobin
- Haemoglobin is phagocytosed by Kupffer cells into globulin and haem
- Haem is broken down into transferrin and four pyrrole nuclei
- Pyrrole nuclei forms biliverdin
- Which forms free bilirubin
37
Describe how free bilirubin is transported through blood and interstitial fluids
- Combines with albumin
| - Still considered free bilirubin
38
Outline the process of conjugation of bilirubin
- Free bilirubin is absorbed by hepatic cells
- Released form albumin
- 80% conjugated with glucuronic acid to form bilirubin glucuronide
- 10% conjugated with sulfate to bilirubin sulfate
39
Outline how conjugated bilirubin enters the intestines
- Excreted by hepatocytes into bile canaliculi by active transport
- Then transported into intestines
40
What happens to the conjugated bilirubin in the intestines?
- Converted by bacteria into urobilinogen
- Which is soluble and reabsorbed through intestinal mucosa back into blood
- Most of which is re-excreted by kidneys into urine
41
Outline the oxidation of urobilinigoen
- In urine it forms urobilin
| - In faeces it is altered and forms stercobilin
42
What is the function of the sodium traucholate co-transporting polypeptide (NTCP)?
- Transports bile acids across basolateral membranes of hepatocytes
- Driven by Na+/K+-ATPase in basolateral membranes
43
What is the precursor of bile salts? Outline how bile salts are formed from this precursor
- Cholesterol
- Which is converted to cholic acid
- Which combine with glycine or taurine
- To form conjugated bile acids (which increases their solubility)
44
Explain how the gallbladder concentrates bile
- Absorption of water and electrolytes
45
Aside from cholesterol identify three other contents of bile
- Bilirubin
- Lecithin
- Electrolytes
46
Identify two effects of CCK on gallbladder emptying
- Rhythmical contractions of the wall of the gallbladder
| - Relaxation of the Sphincter of Oddi
47
Aside from CCK identify another stimulus that causes gallbladder emptying
- ACh released from vagi and enteric nerve fibres
48
Most of the bile salts are reabsorbed into the blood. Where does this mostly occur?
- Distal ileum
49
Outline the course of bile salts once reabsorbed into the blood
- Passes through portal blood to liver
- Passes through venous sinusoids
- Absorbed again by hepatocytes through basolateral membrane via NTCP and OATP2 receptors
50
What is the role of secretin in bile secretion?
- Secretes a sodium-bicarbonate rich watery solution
- From epithelial cells of bile ductules
- To wash the bile salts through the bile ducts into the small intestine
- Where the bicarbonate neutralises HCl from stomach
51
Outline the pathology of gallstone formation and how it is related to diet
- Cholesterol precipitates in gallbladder
| - Amount of cholesterol in fat is partly determined by quantity of fat in diet
52
Identify four causes of gallstones
- Too much absorption of water from bile
- Too much absorption of bile acids from bile
- Too much cholesterol in bile
- Inflammation of epithelium
53
Identify the two processes in drug elimination
- Metabolism
| - Excretion
54
Identify the two processes of metabolism
- Anabolism: build up of substances
| - Catabolism: break down of substances
55
Identify the three main routes of drug elimination
- Kidneys
- Hepatobiliary system
- Lungs
56
Identify a drug that is eliminated in faeces
- Rifampicin
| - Digoxin (in renal failure)
57
Identify a drug type that is eliminated in the lungs
- General anaesthetics
58
What is meant by xenobiotics?
- Foreign chemicals
| - That can be detoxified by animals
59
What is meant by drug chirality?
- More than one stereoisomer
| - Which affects overall metabolism
60
Outline the process of phase 1 reactions
- Catabolic reactions e.g. oxidation, reduction or hydrolysis
- Which introduces a reactive group such as a hydroxyl group (functionalisation)
- Allowing a conjugating system (e.g. glucuronide) to attach
61
Identify the role of P450 system in drug metabolism
- Addition of an oxygen atom to the drug
- To form a hydroxyl group
- Catalysed by NADPH-P450 Reductase
62
Outline the process of phase 2 reactions
- Conjugation
- Attachment of substituent group to hydroxyl ion
- Which is usually glucuronide
- Which inactivates the product
63
Outline the process of glucuronide formation
- Glucuronyl group is transferred to an electron rich atom on the substrate from UDPGA
- Catalysed by UDP-glucuronyl transferase
64
What is meant by stereoselectivity? Identify two drugs that demonstrate stereoselectivity
- Mixtures of stereoisomers
- That differ in their pharmacological effects and metabolism
- Warfarin and cyclophosphamide
65
Identify mechanisms of P450 inhibtion
- Compete for active site e.g. quinidine
| - Non competitive inhibitors e.g. ketoconazole
66
What is meant by first pass / presystemic metabolism
- When drugs are extracted so efficiently by liver
| - That the amount reaching systemic circulation is much less than that absorbed
67
Identify two problems of first pass metabolism
- Much larger dose is needed when given orally compared to parenterally
- Individual variations in first pass metabolism
68
Outline the role of bile of drug excretion
- Drug conjugates are concentrated in bile
- And delivered to intestine
- Where the glucuronide is hydrolysed and drug is released
- Allowing the drug to be reabsorbed to repeat cycle
69
How are bilirubin and albumin levels affected by liver disease
- Bilirubin: Raised (due to reduced clearance)
| - Albumin: Reduced (due to reduced synthesis)
70
How are alanine aminotransferase and aspartate aminotransferase levels affected by liver disease?
- Both are raised
| - Since they leak through hepatocytes when there is hepatocyte damage
71
Which aminotransferase is more specific for liver disease?
- ALT
- Since its concentration outside liver is low
- Compared to AST which is found in heart, brain, kidneys
72
How are alkaline phosphatase levels affected by liver disease?
- Raised: Increased synthesis
73
How are gamma-glutamyl transferase levels affected by liver disease?
- Raised
- If raised on its own it suggests alcohol consumption
- If raised with ALP suggests cholestasis
74
Identify four causes of a mild elevation of aminotransferases (<100 IU/L)
- Chronic hepatitis B
- Chronic hepatitis C
- Haemochromatosis
- Fatty liver disease
75
Identify four causes of a moderate elevation of aminotransferases (100-300 IU/L)
- Alcoholic hepatitis
- Non-alcoholic steatohepatiis
- Autoimmune hepatitis
- Wilson's disease
76
Identify four causes of a major elevation of aminotransferases (> 300 IU/L)
- Drugs (paracetamol)
- Acute liver hepatitis
- Ischaemic liver
- Autoimmune liver disease
77
Mild elevation of aminotransferases, moderate elevation of GGT and a marked elevation of ALP suggests...
- Biliary obstruction (causing cholestasis)
78
Marked elevation of aminotransferases, and mild elevation of GGT and ALP suggests..
- Hepatitis
79
Normal aminotransferases and ALPs, and a moderate elevation of GGT suggests..
- Alcohol/enzyme inducing drugs
80
Raised mitochondrial antibody suggests, itching and raised ALP suggests
- Primary biliary cirrhosis
81
Raised anti-nuclear, smooth muscle, liver/kidney microsomal antibody, suggests..
- Autoimmune hepatitis
82
Raised serum IgG suggest..
- Autoimmune hepatitis
83
Raised serum IgM suggests...
- Primary biliary cirrhosis
84
Raised viral markers suggests...
- Hepatitis A, B, C, D, E
85
Raised alpha-fetoprotein suggests..
- Hepatocellular carcinoma
86
Raised serum iron, transferrin and ferritin, plus positive HFE gene test, and diabetes/joint pain suggest..
- Haemochromatosis
87
A deficiency of alpha 1 alpha trypsin suggests..
- Cirrhosis
| - Emphysema
88
A positive anti-neutrophil cytoplasmic test, along with IBD suggest...
- Primary sclerosing cholangitis
89
A raised urinary copper, low serum copper and caeruloplasmin, and neurological signs suggests..
- Wilson's disease
90
Raised endomysial antibody and malabsorption suggests..
- Coeliac disease
91
What are ultrasound scans typically used for in liver disease?
Identify one limitation of ultrasound scanning
- Identification of gallstones and biliary obstruction
| - Cannot identify small tumours (less than 2cm)
92
What is the role of Colour Doppler ultrasound examination?
- Determine blood flow in hepatic artery, portal vein and hepatic veins
93
What is the role of elastography?
Identify two limitation of elastography
- Increased stiffness suggests worsening liver fibrosis
- Cannot diagnose cirrhosis or severe fibrosis
- Cannot be used in presence of ascites and obesity
94
Identify three methods of cholangiography
- Magnetic resonance cholangiopancreatography (MRCP)
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Percutaneous transhepatic cholangiography (PTC)
95
Identify an advantage of MRCP over ERCP
- Fewer complications
96
Identify an advantage of PTC and ERCP over MRCP
- Allow therapeutic interventions such as insertion of biliary stents across malignant bile strictures
97
Identify four criteria for a safe liver biopsy
- Cooperative patient
- PT less than 4 seconds
- Platelet count is greater than 80x10 ^9 / L
- Exclusion of bile duct obstruction
98
A patient has raised bilirubin only. The likely diagnosis is..
- Gilbert's syndrome
99
A slate-grey skin suggetsts.
- Haemochromatosis
100
Xanthomas suggests..
- Primary biliary cirrhosis
101
Splenomegaly suggests
- Portal hypertension
102
Palmar erythema suggests
- Hyper dynamic circulation
- Pregnancy
- Thyrotoxicosis
- Rheumatoid arthritis
103
What is jaundice and when is it detectable?
- Yellowish tint to skin
- Best seen in conjunctivae and sclerae
- When serum bilirubin exceeds 50 micromoles per litre
104
Identify three types of jaundice
- Haemolytic jaundice
- Congenital hyperbilirubinaemia
- Cholestatic jaundice
105
Outline the pathology of haemolytic jaundice
- Rapid haemolysis of red cells (e.g. haemolytic anaemia)
- Hepatocytes cannot excrete bilirubin as quickly as it is formed
- Plasma concentration of bilirubin (and hence urobilinogen) rises above normal
106
Outline the pathology of cholestatic jaundice
- Caused by either damage to hepatocytes (hepatitis) or obstruction of bile duct (gallstone or tumour)
- Bilirubin enters hepatocytes and becomes conjugated
- Returned to blood by rupture of a congested bile canaliculi
107
Identify the early clinical features of cholestatic jaundice
- Jaundice
- Pale stools
- Dark urine
- Pruritus
108
Outline Courvoisier's Law
- If gallbladder is palpable, biliary obstruction due to gallstones is unlikely
- Because an inflamed gall bladder containing stones cannot readily dilate
- Jaundice is likely due to biliary obstruction e.g. pancreatic cancer
109
Identify the clinical features of cholangitis
- Charcot's triad (jaundice, right upper quadrant pain, fever)
- Raised ALP and GGT
110
Why is urobilin not present in urine in obstructive jaundice
- Bilirubin cannot reach intestines intestines to be converted into urobilinogen
111
Why are stools clay coloured in obstructive jaundice?
- No bilirubin can reach intestines to be converted into stercobilin which gives faeces its colour
112
Why do significant quantities of conjugated bilirubin appear in the urine in obstructive jaundice?
- In haemolytic jaundice the bilirubin is in free form
- In obstructive jaundice the bilirubin is in conjugated form
- Kidneys can excrete conjugated bilirubin but not the free form
113
Outline the pathology of Gilbert's syndrome
- Reduction in UDP-GT
- Which conjugated bilirubin with glucuronic acid
- Due to mutations in HUG-Br1 gene
- Reduced excretion of bilirubin
- As kidneys can only excrete conjugated bilirubin
114
Outline the pathology of Crigler Najjar syndrome
- Autosomal recessively inherited condition
- Type 1 causes absent glucuronyl transferase, resulting in neonatal death due to kernicterus (bilirubin accumulates in brain)
- Type 2 causes reduced glucuronyl transferase and is treated using liver transplant
115
Outline the pathology of Dubin Johnson syndrome
- Autosomal recessively inherited condition
- Defects in canalicular excretion of bilirubin
- Due to mutations in MRP2 transporter genes
116
Outline the pathology of Rotor syndrome
- Autosomal recessively inherited condition
| - Decrease in bilirubin uptake and reduction in intrahepatic binding
117
A history of jaundice with weight loss in older patients suggests that the cause of jaundice is ..
- Malignancy
118
An outbreak of jaundice in the community suggests that the cause of jaundice is...
- Hepatitis A
119
Jaundice following consumption of shellfish suggests that the cause of jaundice is..
- Hepatitis A
120
Intravenous drug use suggests that the cause of jaundice is..
- Hepatitis B
| - Hepatitis C
121
Jaundice in men who have sex with men or female sex workers suggests..
- Hepatitis B
122
A family history of jaundice suggests..
- Gilbert's disease
123
Those living in rural areas, work on a farm or sewage workers, suggests that the cause of jaundice is..
- Hepatitis E
124
Jaundice accompanies by fever and rigors suggests...
- Cholangitis
125
Outline the epidemiology of Hepatitis A
- Most common type, often in epidemics
- Spread by faeco-oral route (contaminated food/water e.g. shellfish)
- Mainly affects children and young adults
- No carrier state
- Notifiable disease
126
Describe the structure and incubation of the Hepatitis A virus
- Picornavirus, 27 nm
- Consists of four polypeptide chains which form a capsid around RNA
- Fast incubation (2-3 weeks)
127
Outline the clinical features of Hepatitis A virus
- Initially: Nausea, anorexia and distate for cigarettes
- Following 2 week: Jaundice, dark urine pale stools (intrahepatic cholestasis)
- Recovery after 3-6 weeks
128
Outline the complications of Hepatitis A virus
- Inflammation: arthritis, vasculitis, myocarditis
- Severe fulminant hepatitis, causing liver coma and death
- Both of which are rare
129
Outline the investigations in Hepatitis A
- Prodromal state: Raised AST and ALT
- Icteric state: Raised bilirubin
- Anti-HAV of the IgM type (diagnostic)
- Haematological tests: leucopenia, lymphocytosis, prolonged PT
130
Why is the Anti-HAV of the IgG type of no diagnostic value in HAV?
- Hepatitis A is common and the antibody persists in the body for years after infection
131
Outline the management of Hepatitis A
- Reduced overcrowding
- Improved sanitation
- Hepatitis A Vaccine
132
Outline the epidemiology of Hepatitis B
- Carrier state is much higher in Africa, Middle and Far East
- Vertical transmission
- Also spread through intravenous route, sexual intercourse and saliva
- Incubation is 4-20 weeks
133
Outline the structure of the Hepatitis B Virus
- dsDNA Hepadna Virus (42 nm)
- Nucleocapsid formed of core protein (HBcAg)
- Surface coat formed of surface protein (HBsAg)
- One DNA strand is a complete circle codes for structural proteins
- Other strand is variable and is involved in viral replication
134
Why are there multiple genotypes of Hepatitis B?
- HBsAg contains a 'a' determinant as well as several subtypes which vary
135
Outline the pathogenesis of Hepatitis B
- S1 and S2 regions of HBsAg bind to receptor on hepatocyte
- Virus enters cell, loses its coat and it transported into nucleus
- Viral DNA is converted into a closed circular form
- Which is transcribed into viral mRNA
- Translation of viral proteins which are exported out of cell
136
Outline the immune response to a Hepatitis B infection
- CD8 T cells recognise viral antigen via HLA Class I on infected hepatocytes
- Th1 response (IL-2, IFN-Y) are involved in viral clearance
- Th2 response (IL4,5,6,10,13) responses are involved in chronic infection and severity
137
Outline the two stages of chronic HBV infection
- Replicative phase: Viral replication with hepatic inflammation
- Integrated phase: Viral genome integrated into host DNA
138
What is the role of X protein of Hepatitis B virus?
- Involved in transcriptional activity
139
Outline the clinical features of acute hepatitis B infection
- Same as HAV
| - Immunological syndrome may occur (urticaria and maculopapular rash and polyarthritis)
140
Outline the investigations in acute Hepatitis B infection
- Anti-HBcAg IgM is diagnostic
| - HBV DNA
141
Outline the management of acute Hepatitis B infection
- Entecavir or tenofovir if HbeAg is present after 12 weeks
- Hepatitis B vaccination high risk individuals
- Combined with immunoglobulin
- Prevention includes avoiding sharing needles and safe sex
142
What percentage of patients with acute Hepatitis B infection develop a chronic infection? Which age group is this most likely in?
- 10%
| - Neonatal and childhood infection
143
Outline the clinical features of Chronic hepatitis B infection
- Typically asymptomatic
| - Develop complications such as cirrhosis or hepatocellular carcinoma after many years
144
Outline the investigations in chronic Hepatitis B infection
- Moderate rise in aminotransferases
- Mild rise in ALP
- HBsAg (ground glass appearance in cytoplasm) in serum
- HBV DNA in serum
145
Outline the treatment for Chronic Hepatitis B infection
- Aim is seroconversion of HBeAg when present to anti-HBe and reduction of HBV DNA (<400 IU/L) and normalised aminotransferases and ALP
- Interferon
- Entecavir
- Tenofovir
146
Outline the structure of the Hepatitis D virus
- Incomplete Flavi RNA Virus (27 nm)
- Enclosed in a shell of HBsAg
- Requires HBV for replication
- Where it can super infect those who have HBV
147
Outline the epidemiology of Hepatitis D
- Endemic in Mediterranean, Africa and South America
- Same sources and mode of spread as HBV
- In non-endemic areas main cause of spread is parenteral drug misuse
148
Outline the investigations in Hepatitis D
- Anti-HDV of IgM type
| - Superinfection with chronic HBV produces anti-HDV of IgG type
149
Outline the management of Hepatitis D
- Effective management of hepatitis B
| - Pegylated alpha-2a interferon and adefovir for 12 months
150
Outline the epidemiology of Hepatitis C
- Mainly transmitted in blood
| - High incidence in IV drug users
151
Describe the structure of Hepatitis C virus
- Single stranded RNA Flavivirus (34 nm)
- Six common genotypes
- With 1a and 1b most common in Europe and USA
152
What is the importance of antigens from the nucleocapsid regions of the Hepatitis C virus?
- From NS3, NS4 and NS5 regions
| - Development of ELISA-3
153
Outline the clinical features of an acute hepatitis C infection
- Asymptomatic maybe mild flu like symptoms
- Jaundice
- Arthritis, cyroglobilinaemia, glomerulonephritis, porphyria cutanea tada
154
Outline the diagnosis of an acute Hepatitis C infection
- Anti-HCV 8 weeks following infection
| - HCV RNA can be detected from 1 week after infection
155
Outline the management of an acute Hepatitis C infectoin
- Interferon to prevent chronic disease
156
Outline the pathogenesis of Chronic hepatitis C infection
- Th2 phenotypes are pro-fibrosis and lead to development of chronic infection
- Dominant CD4 Th2 and a weak CD8 IFN-Y response may lead to rapid fibrosis
- Other factors include male gender, high alcohol intake, fatty liver and diabetes
157
Outline the clinical features of Chronic Hepatitis C infection
- Asymptomatic
| - Cirrhosis in severe disease
158
Outline the diagnosis of Chronic Hepatitis C infection
- HCV antibody using third generation ELISA-3
- HCV RNA
- Histological scoring systems such as METAVIR and Ishak evaluate inflammation and therapy to guide therapy
159
Outline the management of Chronic Hepatitis C infection
- Pegylated interferon gamma alpha 2a with ribavirin
- Daclatasvir
- Asunaprevir
160
Outline the mechanism of action of Daclatasvir
- HCV NS5A replication complex inhibitor
161
Outline the mechanism of action of Asunaprevir
- HCV NS3 protease inhibitor
162
Outline the structure of the Hepatitis E virus
- Single stranded RNA Herpesvirus (27 nm)
163
Outline the epidemiology of Hepatitis E
- Transmitted by contaminated water
- 30% of dogs, pigs and rodents carry the virus
- Epidemics in developing countries
- High mortality in pregnant women (up to 20%, ten times greater than that in non pregnant women)
164
Outline the investigations of Hepatitis E virus
- Elisa for anti-HEV IgG and IgM
- HEV RNA in serum or stools by PCR
- Vaccine
165
Outline the mechanism of action of entecavir
- Nucleoside reverse transcriptase inhibitor
- Enters cell and is phosphorylated to give 5'-triphosphate derivative
- Which competes with host cellular trisphosphate substrate for DNA synthesis by reverse transcriptase
- Which causes chain termination with little viral resistance
166
Outline the side effects of entecavir
- GI disturbances: Nausea, and vomiting and abdominal pain)
- CNS effects (insomnia, dizziness, headaches)
- Blood disorders (anaemia or neutropenia)
- MSK and dermatological effects
- Metabolic effects (pancreatitis, lactic acidosis, lipodystrophy)
167
What is the duration of entecavir treatment?
- Currently lifelong
168
Identify two other nucleoside reverse transcriptase inhibitors
- Tenofovir
| - Lamivudine
169
What is immunoglobulin therapy, when and how should it be given?
- Contains antibodies against various viruses
- Often hyperimmune meaning they are specific against a particular virus (e.g. Hepatitis B)
- Should be given 24 hours after exposure
- Often with vaccine (active-passive immunisation)
170
Outline the mechanism of action of interferon
- Bind to ganglioside receptors on host cell membrane
- Induce ribosomal production of enzymes that inhibit translation of viral mrNA into viral proteins
- Thus halting viral replication
171
Identify two types of interferon and which type of hepatitis infection each is used to treat
- IFN-alpha-2a is used to treat hepatitis B
| - IFN-alpha-2b in a pegylated form is used to treat hepatitis C along with ribavirin (a guanosine analogue)
172
What is the treatment duration of IFN-a-2b?
- 4 months in genotype 1
- 6 months in genotypes 2 or 3
- 12 months in genotypes 4 and 6
173
Identify unwanted effects of interferon
- Fever
- Lassitude
- Headache
- Myalgia
174
What is the main side effect of ribavirin?
- Haemolytic anaemia
175
What is cirrhosis?
- End stage of all progressive liver disease
- Development of fibrous septa in the liver
- That subdivide the parenchyma into nodules
176
Outline the epidemiology of cirrhosis
- Alcohol is most common cause in West
| - Viral infection is most common cause worldwide
177
Outline the pathogenesis of cirrhosis
- Stellate cells are activated by cytokines
- With upregulation of fibrogenic cytokines such as PDGF and TGFB1
- Normal matrix is replaced by collagens 1,3 and fibronectin
- Collagenases are inhibited by TIMPS
- Increasing fibrosis cause bridging between portal triads
178
Identify the morphological classifications of cirrhosis
- Micronodular: Nodules are less than 3mm and are caused by alcoholic damage and biliary tract disease
- Macronodular: Greater than 3mm and often follow viral hepatitis
- A mixed picture with both types may be seen
179
Outline the clinical features of cirrhosis
- Hepatomegaly, jaundice, ascites
- Clubbing and Dupuytren's contracture
- Circulatory changes e.g. spider naevi and palmar erythema
- Endocrine changes e.g. hair loss, gynaecomastia, testicular atrophy, impotence, breast atrophy and amenorrhoea
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180
Outline the investigations used in Cirrhosis
- LFTs: Reduced albumin and prolonged platelet time
- Elevation of ALP and aminotransferases
- Ultrasound and elastography demonstrate changes in size and shape of liver
- MRI useful in diagnosis of tumours and haemangiomas
- Biopsy used to confirm type and severity of disease
181
Outline the treatment options for cirrhosis
- Reduces salt intake
- Avoidance of NSAIDs
- Avoidance of alcohol
- Liver transplantation
182
Identify three complications of cirrhosis
- Liver failure
- Portal hypertension
- Liver cell carcinoma
183
Outline the four characteristics of liver failure
- Hypoalbuminaemia, causing oedema due to reduced plasma oncotic (colloid) pressure
- Clotting factor deficiencies, causing bruising
- Ascites, due to low albumin, portal hypertension and disturbances in aldosterone metabolism
- Encephalopathy, due to failure of liver to eliminate toxic nitrogenous products of gut bacteria which mimic the effects of neurotransmitters
184
Outline the three causes of portal hypertension
- Increased portal blood flow
- Increased hepatic vascular resistance
- Intrahepatic arteriovenous shunting
185
Outline a complication of portal hypertension
- Varices due to thin walled dilated vessels which are prone to rupture
- Resulting in fatal haematemesis
186
What is caput medusae
- Another manifestation of portal hypertension
| - Radiating distended subcutaneous veins around the umbilicus following recanalisation of the umbilical vein
187
Outline the pathophysiology of alcoholic liver disease
- Metabolism of ethanol to acetaldehyde which adducts with cellular proteins and activates the immune system
- CYP2E1 releases free radicals, leading to lipid peroxidation which induces mitochondrial damage
- Increased gut permeability causes endotoxin into blood which causes release of cytokines form Kupffer cells
188
Outline the three clinical features of alcoholic liver disease
- Enlarged liver and presence of peripheral stigmata
- Alcoholic fatty liver disease: elevated transaminases
- Alcoholic hepatitis: jaundice with hepatomegaly and portal hypertension
- Alcoholic cirrhosis: variceal haemorrhage or ascites
189
Outline the investigations used in alcoholic liver disease
- Discriminatory function (Maddrey score) from PT and bilirubin to assess prognosis
- Glasgow score uses age, white cell count, renal function, PT and bilirubin to assess prognosis (cut off is 9)
190
Outline the management of alcoholic liver disease
- Cessation of alcohol consumption
- Good nutrition
- Nasogastric feeding may be needed
- Corticosteroids in patients with severe alcoholic hepatitis
- Pentoxifylline has a weak anti-TNF action
191
Identify 2 functions of stellate cells
- Vitamin A storage
| - Production of extracellular matrix and collagen
