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Semester 4: Nutrition and Metabolism > PBL Topic 4 Case 5 > Flashcards

PBL Topic 4 Case 5 Flashcards

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
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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)
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3
Q

Identify four types of cells in the liver

A
  • Hepatocytes
  • Endothelial cells
  • Kupffer cells (reticuloendothelial cells)
  • Stellate cells
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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
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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
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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
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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
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8
Q

Under what conditions is the liver unable to restore itself following injury?

A
  • Viral infection

- Inflammation

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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

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10
Q

Outline two growth factors involved in stimulating regeneration of liver cells

A
  • Epidermal growth factor

- Tumour necrosis factor

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11
Q

Which cytokine is responsible for terminating cell division of the liver once it has returned to its original size?

A
  • TGF-Beta
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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
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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
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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.

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15
Q

What is the importance of gluconeogensis?

A
  • Formation of glucose

- Only when its concentration falls below normal

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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
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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
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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
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19
Q

What happens to the majority of cholesterol synthesised in the liver?

A
  • Converted into bile salts

- Which are secreted into bile

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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
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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
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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
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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
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24
Q

What is the keto acid precursor of alanine? What donor substance provides the amino radical to this precursor?

A
  • Pyruvic acid

- Glutamine

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25
Q

Name an enzyme type that catalyses the transamination reaction. What is it a derivative of?

A
  • Aminotransferases

- Which are derivatives of pyridoxine (Vitamin B6)

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26
Q

Outline the process of deamination

A
  • 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
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27
Q

Outline the process of urea formation by the liver

A
  • Two molecules of ammonia react with one molecule of carbon dioxide
  • To form one molecule of urea and one molecule of water
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28
Q

Why is ammonia dangerous?

A
  • Crosses blood brain barrier
  • Toxic effect on brain
  • Causing hepatic coma
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29
Q

How is urea removed from the body?

A
  • Excreted by kidneys
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30
Q

What is the importance of oxidation of deaminated amino acids

A
  • Enters citric acid cycle

- To release energy for metabolic purposes

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31
Q

What is the main vitamin stored in the liver? How long can it be stored?

A
  • Vitamin A

- 10 months

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32
Q

How long can Vitamin D and B12 be stored in the liver?

A
  • Vitamin D: 3-4 months

- Vitamin B12: 12 months

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33
Q

Describe how iron is stored and released from liver?

A
  • Hepatic cells contain apoferritin
  • Which binds with iron to form ferritin
  • Which is stored in hepatic cells until needed elsewhere
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34
Q

Identify coagulation factors formed in the lvier

A
  • Fibrinogen (1)
  • Prothrombin (2)
  • Acceletor Globulin (5)
  • Factor 7
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35
Q

Vitamin K is required for the formation of which coagulation factors?

A
  • 10
  • 9
  • 7
  • 2
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36
Q

Outline the formation of bilirubin

A
  • 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
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37
Q

Describe how free bilirubin is transported through blood and interstitial fluids

A
  • Combines with albumin

- Still considered free bilirubin

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38
Q

Outline the process of conjugation of bilirubin

A
  • 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
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39
Q

Outline how conjugated bilirubin enters the intestines

A
  • Excreted by hepatocytes into bile canaliculi by active transport
  • Then transported into intestines
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40
Q

What happens to the conjugated bilirubin in the intestines?

A
  • 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
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41
Q

Outline the oxidation of urobilinigoen

A
  • In urine it forms urobilin

- In faeces it is altered and forms stercobilin

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42
Q

What is the function of the sodium traucholate co-transporting polypeptide (NTCP)?

A
  • Transports bile acids across basolateral membranes of hepatocytes
  • Driven by Na+/K+-ATPase in basolateral membranes
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43
Q

What is the precursor of bile salts? Outline how bile salts are formed from this precursor

A
  • Cholesterol
  • Which is converted to cholic acid
  • Which combine with glycine or taurine
  • To form conjugated bile acids (which increases their solubility)
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44
Q

Explain how the gallbladder concentrates bile

A
  • Absorption of water and electrolytes
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45
Q

Aside from cholesterol identify three other contents of bile

A
  • Bilirubin
  • Lecithin
  • Electrolytes
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46
Q

Identify two effects of CCK on gallbladder emptying

A
  • Rhythmical contractions of the wall of the gallbladder

- Relaxation of the Sphincter of Oddi

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47
Q

Aside from CCK identify another stimulus that causes gallbladder emptying

A
  • ACh released from vagi and enteric nerve fibres
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48
Q

Most of the bile salts are reabsorbed into the blood. Where does this mostly occur?

A
  • Distal ileum
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49
Q

Outline the course of bile salts once reabsorbed into the blood

A
  • Passes through portal blood to liver
  • Passes through venous sinusoids
  • Absorbed again by hepatocytes through basolateral membrane via NTCP and OATP2 receptors
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50
Q

What is the role of secretin in bile secretion?

A
  • 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
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51
Q

Outline the pathology of gallstone formation and how it is related to diet

A
  • Cholesterol precipitates in gallbladder

- Amount of cholesterol in fat is partly determined by quantity of fat in diet

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52
Q

Identify four causes of gallstones

A
  • Too much absorption of water from bile
  • Too much absorption of bile acids from bile
  • Too much cholesterol in bile
  • Inflammation of epithelium
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53
Q

Identify the two processes in drug elimination

A
  • Metabolism

- Excretion

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54
Q

Identify the two processes of metabolism

A
  • Anabolism: build up of substances

- Catabolism: break down of substances

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55
Q

Identify the three main routes of drug elimination

A
  • Kidneys
  • Hepatobiliary system
  • Lungs
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56
Q

Identify a drug that is eliminated in faeces

A
  • Rifampicin

- Digoxin (in renal failure)

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57
Q

Identify a drug type that is eliminated in the lungs

A
  • General anaesthetics
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58
Q

What is meant by xenobiotics?

A
  • Foreign chemicals

- That can be detoxified by animals

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59
Q

What is meant by drug chirality?

A
  • More than one stereoisomer

- Which affects overall metabolism

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60
Q

Outline the process of phase 1 reactions

A
  • 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
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61
Q

Identify the role of P450 system in drug metabolism

A
  • Addition of an oxygen atom to the drug
  • To form a hydroxyl group
  • Catalysed by NADPH-P450 Reductase
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62
Q

Outline the process of phase 2 reactions

A
  • Conjugation
  • Attachment of substituent group to hydroxyl ion
  • Which is usually glucuronide
  • Which inactivates the product
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63
Q

Outline the process of glucuronide formation

A
  • Glucuronyl group is transferred to an electron rich atom on the substrate from UDPGA
  • Catalysed by UDP-glucuronyl transferase
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64
Q

What is meant by stereoselectivity? Identify two drugs that demonstrate stereoselectivity

A
  • Mixtures of stereoisomers
  • That differ in their pharmacological effects and metabolism
  • Warfarin and cyclophosphamide
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65
Q

Identify mechanisms of P450 inhibtion

A
  • Compete for active site e.g. quinidine

- Non competitive inhibitors e.g. ketoconazole

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66
Q

What is meant by first pass / presystemic metabolism

A
  • When drugs are extracted so efficiently by liver

- That the amount reaching systemic circulation is much less than that absorbed

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67
Q

Identify two problems of first pass metabolism

A
  • Much larger dose is needed when given orally compared to parenterally
  • Individual variations in first pass metabolism
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68
Q

Outline the role of bile of drug excretion

A
  • 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
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69
Q

How are bilirubin and albumin levels affected by liver disease

A
  • Bilirubin: Raised (due to reduced clearance)

- Albumin: Reduced (due to reduced synthesis)

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70
Q

How are alanine aminotransferase and aspartate aminotransferase levels affected by liver disease?

A
  • Both are raised

- Since they leak through hepatocytes when there is hepatocyte damage

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71
Q

Which aminotransferase is more specific for liver disease?

A
  • ALT
  • Since its concentration outside liver is low
  • Compared to AST which is found in heart, brain, kidneys
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72
Q

How are alkaline phosphatase levels affected by liver disease?

A
  • Raised: Increased synthesis
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73
Q

How are gamma-glutamyl transferase levels affected by liver disease?

A
  • Raised
  • If raised on its own it suggests alcohol consumption
  • If raised with ALP suggests cholestasis
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74
Q

Identify four causes of a mild elevation of aminotransferases (<100 IU/L)

A
  • Chronic hepatitis B
  • Chronic hepatitis C
  • Haemochromatosis
  • Fatty liver disease
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75
Q

Identify four causes of a moderate elevation of aminotransferases (100-300 IU/L)

A
  • Alcoholic hepatitis
  • Non-alcoholic steatohepatiis
  • Autoimmune hepatitis
  • Wilson’s disease
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76
Q

Identify four causes of a major elevation of aminotransferases (> 300 IU/L)

A
  • Drugs (paracetamol)
  • Acute liver hepatitis
  • Ischaemic liver
  • Autoimmune liver disease
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77
Q

Mild elevation of aminotransferases, moderate elevation of GGT and a marked elevation of ALP suggests…

A
  • Biliary obstruction (causing cholestasis)
78
Q

Marked elevation of aminotransferases, and mild elevation of GGT and ALP suggests..

A
  • Hepatitis
79
Q

Normal aminotransferases and ALPs, and a moderate elevation of GGT suggests..

A
  • Alcohol/enzyme inducing drugs
80
Q

Raised mitochondrial antibody suggests, itching and raised ALP suggests

A
  • Primary biliary cirrhosis
81
Q

Raised anti-nuclear, smooth muscle, liver/kidney microsomal antibody, suggests..

A
  • Autoimmune hepatitis
82
Q

Raised serum IgG suggest..

A
  • Autoimmune hepatitis
83
Q

Raised serum IgM suggests…

A
  • Primary biliary cirrhosis
84
Q

Raised viral markers suggests…

A
  • Hepatitis A, B, C, D, E
85
Q

Raised alpha-fetoprotein suggests..

A
  • Hepatocellular carcinoma
86
Q

Raised serum iron, transferrin and ferritin, plus positive HFE gene test, and diabetes/joint pain suggest..

A
  • Haemochromatosis
87
Q

A deficiency of alpha 1 alpha trypsin suggests..

A
  • Cirrhosis

- Emphysema

88
Q

A positive anti-neutrophil cytoplasmic test, along with IBD suggest…

A
  • Primary sclerosing cholangitis
89
Q

A raised urinary copper, low serum copper and caeruloplasmin, and neurological signs suggests..

A
  • Wilson’s disease
90
Q

Raised endomysial antibody and malabsorption suggests..

A
  • Coeliac disease
91
Q

What are ultrasound scans typically used for in liver disease?

Identify one limitation of ultrasound scanning

A
  • Identification of gallstones and biliary obstruction

- Cannot identify small tumours (less than 2cm)

92
Q

What is the role of Colour Doppler ultrasound examination?

A
  • Determine blood flow in hepatic artery, portal vein and hepatic veins
93
Q

What is the role of elastography?

Identify two limitation of elastography

A
  • Increased stiffness suggests worsening liver fibrosis
  • Cannot diagnose cirrhosis or severe fibrosis
  • Cannot be used in presence of ascites and obesity
94
Q

Identify three methods of cholangiography

A
  • Magnetic resonance cholangiopancreatography (MRCP)
  • Endoscopic retrograde cholangiopancreatography (ERCP)
  • Percutaneous transhepatic cholangiography (PTC)
95
Q

Identify an advantage of MRCP over ERCP

A
  • Fewer complications
96
Q

Identify an advantage of PTC and ERCP over MRCP

A
  • Allow therapeutic interventions such as insertion of biliary stents across malignant bile strictures
97
Q

Identify four criteria for a safe liver biopsy

A
  • Cooperative patient
  • PT less than 4 seconds
  • Platelet count is greater than 80x10 ^9 / L
  • Exclusion of bile duct obstruction
98
Q

A patient has raised bilirubin only. The likely diagnosis is..

A
  • Gilbert’s syndrome
99
Q

A slate-grey skin suggetsts.

A
  • Haemochromatosis
100
Q

Xanthomas suggests..

A
  • Primary biliary cirrhosis
101
Q

Splenomegaly suggests

A
  • Portal hypertension
102
Q

Palmar erythema suggests

A
  • Hyper dynamic circulation
  • Pregnancy
  • Thyrotoxicosis
  • Rheumatoid arthritis
103
Q

What is jaundice and when is it detectable?

A
  • Yellowish tint to skin
  • Best seen in conjunctivae and sclerae
  • When serum bilirubin exceeds 50 micromoles per litre
104
Q

Identify three types of jaundice

A
  • Haemolytic jaundice
  • Congenital hyperbilirubinaemia
  • Cholestatic jaundice
105
Q

Outline the pathology of haemolytic jaundice

A
  • 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
Q

Outline the pathology of cholestatic jaundice

A
  • 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
Q

Identify the early clinical features of cholestatic jaundice

A
  • Jaundice
  • Pale stools
  • Dark urine
  • Pruritus
108
Q

Outline Courvoisier’s Law

A
  • 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
Q

Identify the clinical features of cholangitis

A
  • Charcot’s triad (jaundice, right upper quadrant pain, fever)
  • Raised ALP and GGT
110
Q

Why is urobilin not present in urine in obstructive jaundice

A
  • Bilirubin cannot reach intestines intestines to be converted into urobilinogen
111
Q

Why are stools clay coloured in obstructive jaundice?

A
  • No bilirubin can reach intestines to be converted into stercobilin which gives faeces its colour
112
Q

Why do significant quantities of conjugated bilirubin appear in the urine in obstructive jaundice?

A
  • 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
Q

Outline the pathology of Gilbert’s syndrome

A
  • 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
Q

Outline the pathology of Crigler Najjar syndrome

A
  • 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
Q

Outline the pathology of Dubin Johnson syndrome

A
  • Autosomal recessively inherited condition
  • Defects in canalicular excretion of bilirubin
  • Due to mutations in MRP2 transporter genes
116
Q

Outline the pathology of Rotor syndrome

A
  • Autosomal recessively inherited condition

- Decrease in bilirubin uptake and reduction in intrahepatic binding

117
Q

A history of jaundice with weight loss in older patients suggests that the cause of jaundice is ..

A
  • Malignancy
118
Q

An outbreak of jaundice in the community suggests that the cause of jaundice is…

A
  • Hepatitis A
119
Q

Jaundice following consumption of shellfish suggests that the cause of jaundice is..

A
  • Hepatitis A
120
Q

Intravenous drug use suggests that the cause of jaundice is..

A
  • Hepatitis B

- Hepatitis C

121
Q

Jaundice in men who have sex with men or female sex workers suggests..

A
  • Hepatitis B
122
Q

A family history of jaundice suggests..

A
  • Gilbert’s disease
123
Q

Those living in rural areas, work on a farm or sewage workers, suggests that the cause of jaundice is..

A
  • Hepatitis E
124
Q

Jaundice accompanies by fever and rigors suggests…

A
  • Cholangitis
125
Q

Outline the epidemiology of Hepatitis A

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
Q

Describe the structure and incubation of the Hepatitis A virus

A
  • Picornavirus, 27 nm
  • Consists of four polypeptide chains which form a capsid around RNA
  • Fast incubation (2-3 weeks)
127
Q

Outline the clinical features of Hepatitis A virus

A
  • Initially: Nausea, anorexia and distate for cigarettes
  • Following 2 week: Jaundice, dark urine pale stools (intrahepatic cholestasis)
  • Recovery after 3-6 weeks
128
Q

Outline the complications of Hepatitis A virus

A
  • Inflammation: arthritis, vasculitis, myocarditis
  • Severe fulminant hepatitis, causing liver coma and death
  • Both of which are rare
129
Q

Outline the investigations in Hepatitis A

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
Q

Why is the Anti-HAV of the IgG type of no diagnostic value in HAV?

A
  • Hepatitis A is common and the antibody persists in the body for years after infection
131
Q

Outline the management of Hepatitis A

A
  • Reduced overcrowding
  • Improved sanitation
  • Hepatitis A Vaccine
132
Q

Outline the epidemiology of Hepatitis B

A
  • 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
Q

Outline the structure of the Hepatitis B Virus

A
  • 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
Q

Why are there multiple genotypes of Hepatitis B?

A
  • HBsAg contains a ‘a’ determinant as well as several subtypes which vary
135
Q

Outline the pathogenesis of Hepatitis B

A
  • 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
Q

Outline the immune response to a Hepatitis B infection

A
  • 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
Q

Outline the two stages of chronic HBV infection

A
  • Replicative phase: Viral replication with hepatic inflammation
  • Integrated phase: Viral genome integrated into host DNA
138
Q

What is the role of X protein of Hepatitis B virus?

A
  • Involved in transcriptional activity
139
Q

Outline the clinical features of acute hepatitis B infection

A
  • Same as HAV

- Immunological syndrome may occur (urticaria and maculopapular rash and polyarthritis)

140
Q

Outline the investigations in acute Hepatitis B infection

A
  • Anti-HBcAg IgM is diagnostic

- HBV DNA

141
Q

Outline the management of acute Hepatitis B infection

A
  • 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
Q

What percentage of patients with acute Hepatitis B infection develop a chronic infection? Which age group is this most likely in?

A
  • 10%

- Neonatal and childhood infection

143
Q

Outline the clinical features of Chronic hepatitis B infection

A
  • Typically asymptomatic

- Develop complications such as cirrhosis or hepatocellular carcinoma after many years

144
Q

Outline the investigations in chronic Hepatitis B infection

A
  • Moderate rise in aminotransferases
  • Mild rise in ALP
  • HBsAg (ground glass appearance in cytoplasm) in serum
  • HBV DNA in serum
145
Q

Outline the treatment for Chronic Hepatitis B infection

A
  • 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
Q

Outline the structure of the Hepatitis D virus

A
  • 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
Q

Outline the epidemiology of Hepatitis D

A
  • 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
Q

Outline the investigations in Hepatitis D

A
  • Anti-HDV of IgM type

- Superinfection with chronic HBV produces anti-HDV of IgG type

149
Q

Outline the management of Hepatitis D

A
  • Effective management of hepatitis B

- Pegylated alpha-2a interferon and adefovir for 12 months

150
Q

Outline the epidemiology of Hepatitis C

A
  • Mainly transmitted in blood

- High incidence in IV drug users

151
Q

Describe the structure of Hepatitis C virus

A
  • Single stranded RNA Flavivirus (34 nm)
  • Six common genotypes
  • With 1a and 1b most common in Europe and USA
152
Q

What is the importance of antigens from the nucleocapsid regions of the Hepatitis C virus?

A
  • From NS3, NS4 and NS5 regions

- Development of ELISA-3

153
Q

Outline the clinical features of an acute hepatitis C infection

A
  • Asymptomatic maybe mild flu like symptoms
  • Jaundice
  • Arthritis, cyroglobilinaemia, glomerulonephritis, porphyria cutanea tada
154
Q

Outline the diagnosis of an acute Hepatitis C infection

A
  • Anti-HCV 8 weeks following infection

- HCV RNA can be detected from 1 week after infection

155
Q

Outline the management of an acute Hepatitis C infectoin

A
  • Interferon to prevent chronic disease
156
Q

Outline the pathogenesis of Chronic hepatitis C infection

A
  • 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
Q

Outline the clinical features of Chronic Hepatitis C infection

A
  • Asymptomatic

- Cirrhosis in severe disease

158
Q

Outline the diagnosis of Chronic Hepatitis C infection

A
  • 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
Q

Outline the management of Chronic Hepatitis C infection

A
  • Pegylated interferon gamma alpha 2a with ribavirin
  • Daclatasvir
  • Asunaprevir
160
Q

Outline the mechanism of action of Daclatasvir

A
  • HCV NS5A replication complex inhibitor
161
Q

Outline the mechanism of action of Asunaprevir

A
  • HCV NS3 protease inhibitor
162
Q

Outline the structure of the Hepatitis E virus

A
  • Single stranded RNA Herpesvirus (27 nm)
163
Q

Outline the epidemiology of Hepatitis E

A
  • 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
Q

Outline the investigations of Hepatitis E virus

A
  • Elisa for anti-HEV IgG and IgM
  • HEV RNA in serum or stools by PCR
  • Vaccine
165
Q

Outline the mechanism of action of entecavir

A
  • 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
Q

Outline the side effects of entecavir

A
  • 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
Q

What is the duration of entecavir treatment?

A
  • Currently lifelong
168
Q

Identify two other nucleoside reverse transcriptase inhibitors

A
  • Tenofovir

- Lamivudine

169
Q

What is immunoglobulin therapy, when and how should it be given?

A
  • 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
Q

Outline the mechanism of action of interferon

A
  • 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
Q

Identify two types of interferon and which type of hepatitis infection each is used to treat

A
  • 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
Q

What is the treatment duration of IFN-a-2b?

A
  • 4 months in genotype 1
  • 6 months in genotypes 2 or 3
  • 12 months in genotypes 4 and 6
173
Q

Identify unwanted effects of interferon

A
  • Fever
  • Lassitude
  • Headache
  • Myalgia
174
Q

What is the main side effect of ribavirin?

A
  • Haemolytic anaemia
175
Q

What is cirrhosis?

A
  • End stage of all progressive liver disease
  • Development of fibrous septa in the liver
  • That subdivide the parenchyma into nodules
176
Q

Outline the epidemiology of cirrhosis

A
  • Alcohol is most common cause in West

- Viral infection is most common cause worldwide

177
Q

Outline the pathogenesis of cirrhosis

A
  • 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
Q

Identify the morphological classifications of cirrhosis

A
  • 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
Q

Outline the clinical features of cirrhosis

A
  • 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

-

180
Q

Outline the investigations used in Cirrhosis

A
  • 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
Q

Outline the treatment options for cirrhosis

A
  • Reduces salt intake
  • Avoidance of NSAIDs
  • Avoidance of alcohol
  • Liver transplantation
182
Q

Identify three complications of cirrhosis

A
  • Liver failure
  • Portal hypertension
  • Liver cell carcinoma
183
Q

Outline the four characteristics of liver failure

A
  • 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
Q

Outline the three causes of portal hypertension

A
  • Increased portal blood flow
  • Increased hepatic vascular resistance
  • Intrahepatic arteriovenous shunting
185
Q

Outline a complication of portal hypertension

A
  • Varices due to thin walled dilated vessels which are prone to rupture
  • Resulting in fatal haematemesis
186
Q

What is caput medusae

A
  • Another manifestation of portal hypertension

- Radiating distended subcutaneous veins around the umbilicus following recanalisation of the umbilical vein

187
Q

Outline the pathophysiology of alcoholic liver disease

A
  • 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
Q

Outline the three clinical features of alcoholic liver disease

A
  • 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
Q

Outline the investigations used in alcoholic liver disease

A
  • 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
Q

Outline the management of alcoholic liver disease

A
  • 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
Q

Identify 2 functions of stellate cells

A
  • Vitamin A storage

- Production of extracellular matrix and collagen

Semester 4: Nutrition and Metabolism (17 decks)

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