Week 205 Addiction (Alcoholism & Hepatitis) Flashcards

0
Q

<p>What are the two MAJOR functional neuronal targets of Ethanol?</p>

A

<p>Increased efficacy of GABA receptors (More cl- into neurone for each molecule) = Net hyperpolarisation. Important for acute intoxication.

Reduces Efficacy of glutamate receptors and Ca2+ Channels. Inhibits NMDA receptor activity. May be important in acute intoxications, SPECIFICALLY associated with memory loss (blackout). </p>

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1
Q

<p>Which ion channels does alcohol affect?</p>

A

<p>GABA Receptors
NMDA Receptors
Calcium Channels
Many other molecular effects</p>

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2
Q

<p>NMDA receptors are specifically associated with what (under influence of alcohol)?</p>

A

<p>Blackouts/memory loss</p>

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3
Q

<p>Define Tolerance</p>

A

<p>Decreased response to the effects of a set drug concentration after continued use. Compensatory homeostatic mechanisms adapt to the presence of the drug. </p>

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4
Q

<p>Define Dependence</p>

A

<p>The need to take a drug to avoid withdrawal symptoms produced by compensatory homeostatic mechanisms. </p>

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5
Q

<p>Define Addiction.</p>

A

<p>NOT TOLERANCE OR DEPENDANCE.

Continued drug use despite known adverse consequences. Compulsive drug-seeking behaviour.
Can occur in the ABSENCE of tolerance and dependence. </p>

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6
Q

<p>Define Relapse.</p>

A

<p>Resumption of drug use after trying to stop taking drugs. This may occur months or years after sotpping. </p>

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7
Q

<p>What are the mechanisms underlying chronic tolerance?</p>

A

<p>Sig. increase in number and activity of enzymes that metabolize ethanol.

Long-lasting changes in the abundance and function of target areas affected by acute ethanol exposure. </p>

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8
Q

<p>What is Acute tolerance?</p>

A

<p>This occurs &quot;within a session&quot;.
Same basic mechanisms as chronic tolerance - Changes in function of GABA/NMDA receptors.
Clinically and legally important.
Specific behaviours occur at certain blood alcohol concentration.
What this means is, physiological adaptations taking place &quot; in session&quot; mean that lost or inhibited functions (AKA motor &amp; Coordination, euphoria etc) may compensate/return to normal - but at a HIGHER blood alcohol concentration than that at which they were first inhibited. This means that you might &quot;feel fine&quot; - with a much higher blood alcohol level than you realise!</p>

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9
Q

<p>What is the Himmelsbach Hypothesis?</p>

A

<p>These are related to the mechanisms of alcohol and tolerance.
Withdrawal is what happens when the adaptions that characterise tolerance are expressed without the drug on board. Crudely - symptoms of withdrawal are the opposite of the acute effects of the drug. The body has adapted for the drug - and it will take time to redress symptoms. </p>

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10
Q

<p>Full withdrawal syndrome arises from abrupt \_\_\_ after \_\_\_\_. </p>

A

<p>Cessation after chronic use. </p>

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11
Q

<p>What are symptoms of withdrawal?</p>

A

<p>Motor agitation, anxiety, insomnia, reduction in seizure threshold.
Delirium tremens
Hallucinations, tremor, hyperpyrexia, sympathetic hyperactivity, death. </p>

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12
Q

<p>Which hypothesis supports the &quot;hair of the dog&quot;?</p>

A

<p>HImmelsbach hypothesis</p>

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13
Q

<p>What is the most commonly used treatment for acute alcohol withdrawal syndome?</p>

A

<p>Benzodiazepines.</p>

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14
Q

<p>What are Naltrexone and Nalmefene?</p>

A

<p>Opiod receptor antagonists (that don't work very well) to treat alcoholism. </p>

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15
Q

<p>What is Acamprosate?</p>

A

<p>NMDA Receptor antagonist
Doesn't work very well
Treatment for alcoholism
</p>

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16
Q

<p>What three things are used to treat alcoholism?</p>

A

<p>Opioid receptor antagonists, NMDA Receptor antagonists and behaviour therapy. </p>

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17
Q

<p>Alcohol consumption causes release of \_\_\_ \_\_\_\_\_. </p>

A

<p>Endogenous opioids. </p>

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18
Q

<p>Name two Opiod receptor antagonist treatments. </p>

A

<p>Naltrexone and Nelmefene</p>

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19
Q

<p>Name an NMDA receptor antagonist treatment. </p>

A

<p>Acamprosate.</p>

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20
Q

<p>Replacement therapy of nicotine is based on which principal?</p>

A

<p>Replace a fast acting drug/prep with a slow one. </p>

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21
Q

<p>What three drug types are used in nicotine replacement therapy?</p>

A

<p>Nicotine
Opioids
Benzodiazepines
</p>

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22
Q

<p>What are the three subtypes of Opiod receptor?</p>

A

<p>Mu
Delta
Kappa</p>

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23
Q

<p>Opiods are a strong \_\_ \_\_\_\_</p>

A

<p>mu agonist.</p>

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24

Name 4 opiods.

Heroin Morphine Oxycodone Fentanyl

25

What drugs are used in Opiod replacement therapy?

methadone or buprenorphine

26

Overdose of opioid treated with?

Naloxone

27

Pyschostimulants (i.e. amphetamines, methamphetamine, cocaine) put ____ ____ into ____ _.

Dopamine transporters into reverse.

28

What are the effects of pyschostimulants?

Pyschosis Cardiac effects Stroke Seizures

29

What is Haloperidol?

?

30

What are symptoms of withdrawal of pyschostimulants?

Ravenous apetite, exhaustion, mental depression.

31

Desoxyn is a prescribed form of _____.

Methamphetamine

32

MDMA is powder form of ___

Ecstasy

33

4-mmc is?

Mephedrone Pyschostimulant Mixed pyschostimulant and hallucinogenic properties

34

Complete this sentence. In the reward circuit, Dopamine acts as a ___ _____.

Learning signal.

35

The ____ _____ pathway is activated by drugs of abuse.

Mesolimbic Dopamine pathway.

36

The common outcome of drugs of abuse on the mesolimbic dopamine system is that ___ ______ ___ ________

More dopamine is produced.

37

Nicotine and ethanol activate neurons that release ____

Dopamine

38

Opioids inhibit those cells which inhibit dopamine release - what does this do?

Increases the abundance of dopamine

39

Pschostimulants act at dopamine transporters by doing what?

They block or reverse the action of transporters | These therefore increase the abundance of dopamine in the synapse.

40

In addiction, the self regulatory role of executive function in preventing the consumption of a drug of addiction is inhibited how?

Impaired function of the prefrontal cortex

41

Dopamine release by the VTA heads to the ____ ____.

Nucleus Accumbens

42

Which ribs overlay the spleen?

9-11

43

What are splenunculi?

"Accessory spleens" that are present in about 10% - normally near the splenic hilum, but can be found elsewhere.

44

The splenic artery is one of the main branches of the ___ axis.

Coeliac

45

The splenic artery runs along the superior border of which organ?

The pancreaas

46

Which artery from the splenic artery arise from the splenic artery?

Left gastro-epiploic arteries

47

What is the venous drainage of the spleen?

short gastric veins L and R gastro-epiploic veins Splenic veins - joins the inferios mesenteric vein, which joins to superior mesenteric to create portal vein.

48

Why is a the spleen often removed with a pancreotectomy?

Venous drainage compromised (or spleen)

49

What are the Four peritoneal reflections around the spleen?

Gastro-splenic ligament Lieno-renal (between spleen and L Kidney) Others not important ATM

50

Causes of splenomegaly?

Malaria ItP Chronic infections HAematopoetic disorders

51

The splenic notch can be found where?

RUQ (check)

52

What size is a normal adult spleen?

About the size of the fist - Not much larger than kidney.

53

The cord of billroes?

?

54

Hepatocellular diseases cause release of which liver enzymes?

ALT | AST

55

Cholestatic disease causes release of which two liver enzymes?

ALP Alpha GT

56

Acute viral Hepatitis (i.e Hepatitis A) you would expect what on LFT?

X 10 ++ ALT and AST (Hepatocellular) i.e Hep viral A or Paracetemol OD/Toxin

57

Moderate ++ ALT and AST raised in LFT may be signs of what?

Chronic liver (hepatocellular) damage. i.e. Hep b + C, Alcohol dep., autoimmune, fatty liver, or haemological disorder.

58

ALP and Alpha GT raised in LFT (Cholestatic disorder) could mean what?

Extrahepatic disorders i.e. gallstones, Cx head of pancreas, Cx Biliary tree, Stenosis, Sclerosing Cholangitis or Intrahepatic disorders i.e. Viral, alcoholic hepatitis, pregnancy, drugs, or CIRRHOSIS

59

Raised unconjugated billirubin in Lft could mean what?

Haemolysis - check FBC to see reticulocyte count - If raised, shows that bone marrow is irking hard to produce more blood cells. Or Congenital disorders. Gilbert's syndrome (Presents with jaundice)

60

Diff. Diagnosis for LFT showing raised conjugated Billirubin?

CHOLESTASIS (some congenital disorders also)

61

PTT (Prothrombin time) on Lft does what?

Shows liver function - Fast turnover, so a good monitoring progress pf disease by seeing effect on production.

62

Increased Gamma GT enzyme in LFT could be solely due to what?

Consumption of excess alcohol.

63

WHen would you do an LFT

Commencement on hepato-toxic drugs i.e. methotrexate. Anyone with suspected liver disease Ptx with known liver disease - monitoring.

64

Unconjugated billirubin is not ___ ____. This means that it must be ____ bound to be transported. In the liver, it is ___ to a water ____ compound.

water soluble. THis means that it must be protein bound. In the liver it is conjugated to a water soluble compound.

65

Too many red cells being broken down can lead to an ___ of unconjugated billirubin.

Excess

66

Pale faeces, dark urine - usually means what?

Obstructive jaundice.

67

At what level of billirubin would you expect jaundice?

This depends. Approximately when billirubin gets to about 40.

68

HIgh ALP is indicative (with regards to the liver) of a problem with the ____ _____.

Biliary tree.

69

Low Faecal elastase could indicate what?

Impaired pancreatic function. This is an enzyme produced by the pancreas, and a low count is a sign of chronic pancreatitis.

70

Drugs are in their highest concentration when they go through which organ?

The liver

71

Adverse drug reactions are responsible for what % of hospital admission?

It's varied! Different paper say different things.

72

The annual cost the NHS from adverse drug reactions is?

466 million

73

What percentage of acute liver failure is due to drugs?

Approx 50%

74

WHat are type B Drug reactions?

Bizzarre, unpredictable, tendency to be less common and more severe. They are not responsive to changes in dose - drug should be stopped.

75

What increases the risk of aDR?

```

Age - extremes ACEI Aspirin Herbal/chines meds Methotrexate Carbamazepine Cyclophosphamide Ecstasy Isniazid Leflunomide HalothNE FLUCLOXACILLIN Aspirin ``` Etc etc!

76

If adding new drugs, how do you reduce risk of aDR?

Intro one at a time MOnitoring check history - any allergies, drug history etc.

77

What is the spectrum of ALD?

```

Alcoholic steatosis (fatty liver) thn Alcoholic Hepatitis then Chronic Hepatitis (+/- fibrosis or cirrhosis) Affected by multiple factors

```
78

What is Alcoholic steatosis?

Fatty infiltration of the liver secondary to alcohol use. Can come about in a few weeks. Can be asymptomatic, and lead to hepatomegaly.

79

What is alcoholic hepatitis?

Fever + Jaundice secondary to a background of high alcohol consumption. Decompensation Symptoms Precipitaitng event Can resolve on own, or require steroids.

80

What is chronic hepatitis?

Pericentral fibrosis leading to panlobular fibrosis MAY be reversible. On going fibrosis leads to thickened septs, lobular nodule formations, and a "knackered liver".

81

Clinical features of ALD?

Palmar erytherma Dupuytrens contracture Caput medusae (Portal hypertension) --> Causing reopening of umbilical veins Spider Naevi - 5 to be significant. Found on chest usually. NEar Sup VC. Ascites + Gynaecomastia + Unbilical hernia Jaundice

82

How many spider naevi are significant?

5 or more

83

What causes ascites?

Low albumin High pressure Sodium and fluid retention - goes to abdomen.

84

Complications of CLD? (chronic liver disease)

Portal hypertension and assoc conditions. Spontaneous bacterial peritonitis - Due to stagnant pool of fluid in ascites. Neutrophil count >200 for diagnosis. Acute decompensation - Hepatic encephalopathy and coagulopathy Hepato-Renal syndrome Hepatocellular carcinoma

85

Spontaneous bacterial peritonitis as a complication of CLD requires a diagnostic neutrophil count of what?

200

86

Hepatic (liver) flap is caused by what?

High levels of ammonia, causing hepatic encephalopathy.

87

What is hepato-renal syndrome?

The kidneys become so constricted that they don't get adequate blood supply - Usually longer term into CLD.

88

What is the child pugh score?

The score used to calculate long term survival.

89

Haemoglobin levels in CLD?

Can be low, or normal.

90

What happens to MCV in CLD?

Mean cell volume increases due to malnutrition.

91

Biochemical features of CLD?

SEE SLIDE>

92

Alcohol is a CNS _____

Depressant

93

In alcoholics, Thyamine is especially ____

Low. Supplement, also Vit B.

94

Which benzo would you typically give as meds for withdrawal?

Chlordiazepoxide

95

A lack of thiamine can cause what?

Wernicke's Encephalopathy. Triad of Encephalopathy, Occulomotor disturbance, Gait ataxia May progress to Korsakoff's syndorme. Irreversible dementia with conflabulation. Only tx is Pabrinex + Lactulose.

96

What is the cage system?

For history - Assessments of Dependency on alcohol. Not great, but it does filter some people out quickly.

97

What is the difference between hepatitis and liver failure?

In liver failure, you see all other compensation features, i.e. low albumin and encephalopathy.

98

What is the most common cause of acute liver failure?

Drug s (70-80%)

99

What % of liver failure is caused by Viral infections?

5

100

HIgh ALT compared to ALP infers what?

Hepatocytic damage

101

Which Hepatitis is associated with acute onset and diarrhoea?

A

102

What is the core antibiody of a hepatitis infection?

Anti-HBc

103

Which types of hepatitis can cause chronic liver damage?

B and C

104

What % of Hep B resolve?

90% Good chance of developing protective serum antibodies.

105

What is fulminant hepatitis?

Acute and severe, encephalopathy and jaundice developed within 7 days.

106

Is hep B carcinogenic?

YES, very if persistent (chronic)

107

How many genotypes of Hepatitis C are there and which are common in England?

6. 1 and 3

108

Which % of Hep C patients resolve?

Less than 20%! Must aim to treat ASAP after ID.

109

Glandular fever can present with ____ _______. This may cause abdo pain, URQ.

Hepato-splenomegaly. Reassure - not hepatitis!

110

Hepatitis E is a ____ disease, transferred via ____.

Zoonotic Animals Can cause acute high ALT response. Often occurs in px with co-morbidities, i.e.

111

Name a very rare cause of Hepatitis (caused by a separate infection)

Mumps Hepatitis

112

If a patient has an immunosuppressive illness or condition, which hepatitis are they susceptible to?

CMV Hepatitis (Cyclo megalo virus)

113

What virus is closesly associated with HEP B?

Hep D. You can't have Hep D without Hep B. Always check. Increased risk of Cx. Consider aggressive treatment if HEp D present.

114

SEE TABLE AT END OF LECTURE A D MAKE CARDS FOR ALL TYPES OF HEP A-E

DO IT!

115

Why is Prolonged PT a finding with liver disease?

Symptomatic of coagulopathy that occurs in liver disease.

116

Which vitamins (fat soluble) tend to be deficient in Liver diseasE?

ADKE

117

What may be RAISED with liver damage?

Alpha 1 antitrypsin and Crp are acute phase proteins. These will raise if damage occurs. B12 - because stored in liver (can sustain for a year)

118

Purposes of the spleen?

Recycling haem (blood) - Curling of the cells Storage - Blood and platelets Immune response - Spleen is involved in opsonisation of bacteria. Can also aid in blood production.

119

In splenomegaly with liver disease, you often see _________

Thrombocytopaenia.

120

Hepatitis B has three antigens. What are they.

S antigen - remains if chronic. (surface antigen) E antigen - Likely that viral load is very high. Only useful to determine treatment. Core antigen (Core IgM)

121

SVR is checked 6 months post-treatment of Hepatitis __

C

123

What is the main cause of homelessness?

Relationship breakdown

124

For ever one rough sleeper in the UK there are ___ in a hostel.

100

125

Why can some Cancer tx drugs reactivate Hepatitis B in some patients?

Immunocompromise can cause resurgence as this Genome is DNa specific - lasts much longer! Others are RNA, so not involved in genome.

126

Increased ALT is evidence of what type of damage?

Hepatocellular

127

With hepatocellular damage, what tends to be the main problem. and what effect will this have on bilirubin?

Stasis, with primarily conjugated hyperbilirubinaemia. Explanation: With hepatocellular damage there is a small increase in unconjugated bilirubin due to a functional reduction in the livers ability to conjugate bilirubin. The MAIN PROBLEM HOWEVER, tends to be STASIS, resulting in REDUCED EXCRETION of CONJUGATED Bilirubin - Thus the patient will have primarily a conjugated hyperbilirubinaemia.

128

What are the diffrerential diagnoses for a well 21YO male Px with greatly raised ALT and mildly raised Bilirubin?

Acute Viral infection (HEP-A-E, EBV, infection etc) Alcohol as AAH Drug reactions Toxins/Chemicals Herbal Remedies Recent travel - STD or CMV Hepatitis?

129

A fluctuating serum Bilirubin level (with otherwise normal LFTs), rising especially on fasting, and in the absence of haemolytic disease, and a history of no medication suggests what?

Gilbert's disease. This is a common autosomal dominant condition affecting up to 7% of the population. There is reduced conjugation and bilirubin transport in the liver. The prognosis is excellent, and there seems no clinical consequence.

130

What can Spherocytosis cause - and what IS it?

It means spherical red cells with increased Haemolysis (red cell damage/death). It can cause Haemolytic anaemia, with substantial shortening of red cell life.

131

what is obstructive jaundice otherwise known as?

Cholestatic jaundice.

132

Phase 1 reactions are catalysed by which family of closely related haemoproteins?

Cytochrome P450

133

The P-450 genes are distributed among different ___

Chromosomes

134

Ethanol is _____highly ______soluble and absorbed by all parts of the gastrointestinal tract. Rapid increase in concentration in _____diffuses ____across all ____ _________.

Ethanol is uncharged highly lipid soluble and absorbed by all parts of the gastrointestinal tract. Rapid increase in concentration in blood diffuses quickly across all cell membranes.

135

When ethanol concentration is _____it is mostly dealt with by ___________ ______ _________ ___________.

When ethanol concentration is low it is mostly dealt with by first past hepatic metabolism.

136

How does the metabolism of ethanol change at higher concentrations?

At higher concentrations, the fraction removed on first-pass decreases, it is therefore removed by second pass metabolism.

137

Which enzyme in the liver breaks down alcohol at low concentrations?

Alcohol dehydrogenase.

138

Where is alcohol dehydrogenase found?

The cytoplasm.

139

Alcohol elimination is carried out at a rate that is largely independent of__________

Alcohol elimination is carried out at a rate that is largely independent of plasma alcohol concentration.

140

What is activated in the secondary pathway of alcohol metabolism in the liver?

The microsomal ethanol oxidising system. This system is also used to metabolise many drugs this explains the interaction between alcohol and certain drugs.

141

Describe the equations for first-pass metabolism of ethanol in the liver

Ethanol is oxidised by alcohol dehydrogenase to form acetaldehyde, NAD+ is reduced to NADH. Acetaldehyde is oxidised to form acetate by acetaldehyde dehydrogenase. Acetate transforms to carbon dioxide and water.

142

In the first reaction of first-pass metabolism of ethanol in the liver what is the name of the enzyme that oxidises to form acetaldehyde?

Alcohol dehydrogenase.

143

At the end of alcohol metabolism, acetate is bound to coenzyme A. In a nutrient replete individual, what will this lead to the synthesis of?

The synthesis of fatty acids.

144

What happens to the equilibrium of the lactate dehydrogenase reaction when a large amount of alcohol is metabolised by the liver? What effect may this have on a patient, if they are experiencing a period in which blood glucose is already falling?

If a large amount of alcohol is metabolised by the liver, the ratio of NADH and NAD+ pushes the equilibria of lactate dehydrogenase reaction towards lactate production. This means that pyruvate will be unavailable for gluconeogenesis. If this coincides with the period when blood glucose is falling, this will lead to hypoglycaemia. The parts of the brain most vulnerable to hypoglycaemia are affected, i.e. those that control body temperature. As a result the patients may experience hyperthermia.

145

What percentage of ingested alcohol is excreted and or exhaled?

About 5%. The remaining 95% is metabolised to carbon dioxide and water.

146

What is the main pharmacological effect of ethanol?

The main effect is on the central nervous system, a depressant action ( at the cellular level ) that is similar to volatile anaesthetics.

147

What specific effects on the central nervous system does alcohol have?

The action of alcohol involves the inhibition of calcium entry through voltage gated calcium channels, the enhancement of GABA mediated synaptic inhibition, antagonism of excitatory amino acids, and inhibition of neurotransmitter release. Ethanol also inhibits NMDA receptor activation. this may lead to depression and memory loss.

148

What are the signs and symptoms of acute ethanol intoxication?

Slurred speech, motor incoordination, increased self-confidence and euphoria. The effect on mood varies. Some people become louder, some become more morose and withdrawn. At higher levels of intoxication the mood is highly variable, swinging from euphoria to melancholy, aggression to submission within seconds.

149
What does gamma GT stand for?
Gamma-Glutamyl transpeptidase
150

At approximately which plasma alcohol concentration in milligram per hundred mil would you expect death from respiratory failure as a result of alcohol intoxication?

400-500

151

What are the functions of the liver?

```

Storing glycogen Production of clotting factors Processing medicines Toxin Removal Production of Bile

```
152

The liver is located in what part of the circulation?

Between the splanchnic and systemic circulations, in the upper right abdomen.

153

Most orally administered drugs are ___ soluble.

FAT

154

Which protein is most common in the liver?

Albumin

155
Serum and urinary copper, and serum caeruloplasm are signs of what disease?
Wilsons. A rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if not recognized and treated when symptomatic.
156
What are Xanthomas, and when may they be seen (in the context of liver disease)
These are cholesterol deposits seen in the palmar creases or above the eyes in primary billiary cirrhosis.
157

Name some of the contributing factors to fatty liver as a result of chronic alcohol consumption.

Contributing factors: Increased release of fatty acids from adipose tissue Reduced triacylglycerol secretion from the liver Reduced rates of fatty acid oxidation due to metabolic load of ethanol Increased rates of lipid biosynthesis

158

If a patient that has identified fatty liver continues to abuse alcohol, what would you expect to happen to the disease?

With continued abuse, fatty liver progresses to hepatitis (inflammation) this can cause irreversible necrosis and fibrosis of the liver.

159

What is fatty liver?

Fatty liver is the earliest and most common manifestation of alcoholic liver disease. It occurs in all persons consuming alcohol in excess of 60 g per day, and can resolve within 2 to 4 weeks of cessation of alcohol consumption.

160

What symptoms characterise the classic syndrome of alcoholic hepatitis?

Anorexia, malaise, fever, jaundice and hepatomegaly characterise the classic syndrome of alcoholic hepatitis.

161

What percentage of patients for the clinical diagnosis of alcoholic hepatitis already have a liver cirrhosis on biopsy?

50%.

162

What a liver function tests used for?

Liver function tests are used to help diagnose liver disorders, especially following suggestive symptoms (such as jaundice or general illness associated with high alcohol consumption). To monitor the progress and severity of liver disorders. As a routine precaution after starting certain medicines to check that they are not causing damage as a side effect.

163

Which liver enzyme is found in high levels in liver cells and is found to be raised in the blood if the liver is injured or inflamed (as in hepatitis)?

Alanine transaminase.

164
Which forms of hepatitis can be passed by sexual contact?
ABC
165

Which liver enzyme is found mainly in liver cells | Bile ducts, and in bone? It's blood level is raised in some types of liver and bone disease.

Alkaline phosphatase.

166

What is the name to the main protein made by the liver which circulating the bloodstream? The ability of the liver to make this protein is affected in some types of liver disorder. A low level of this protein occurs in some liver disorders.

Albumin.

167

What is the result of a higher level of bilirubin in the blood?

Jaundice.

168

Which type of bilirubin would you expect to be high in haemolytic anaemia?

You would expect a breeze level of unconjugated bilirubin, because this occurs when there is excessive breakdown of red blood cells, e.g. in haemolytic anaemia.

169
What are the transfer criteria for ITU for patients with an acute liver injury?
``` INR >3.0 Presence of Hep Encephalopathy Hypotension post fluid resuscitation Metabolic acidosis Prothrombin time (seconds) > interval (hours) from overdose (paracetemol cases) ```
170

What is gamma-glutamyltransferase?

This is an enzyme associated with clearance of alcohol. High-level is particularly associated with high alcohol consumption.

171

Which antibodies are associated with primary biliary Cirrhosis ?

Anti mitochondrial antibodies

172

Which type of antibody is associated with autoimmune hepatitis?

Smooth muscle Ab.

173

Which type of antibody is associated with primary sclerosing cholangitis?

Antinuclear cytoplasmic antibodies

174

Which protein is reduced in Wilsons disease?

Ceruloplasmin

175

Lack of which protein is an uncommon cause of liver cirrhosis?

1 antitrypsin

176

A high-level of ferritin is a marker of what?

Haemochromatosis

177

name the three major causes of chronic liver disease.

Alcoholic liver disease Chronic viral hepatitis C Obesity

178

When taking a history from patient with suspected with the disease, what should you ask about specific?

```

Personal contacts Institutionalisation Occupation Foreign travel Male homosexuality Illicit parenteral drug use

```
179

Which forms of hepatitis transmitted through the oral faecal route?

Hepatitis A and hepatitis E

180

Which forms of hepatitis are transmitted through the parenteral route?

Hepatitis B and hepatitis C | Hepatitis D in the presence of active hepatitis B

181

Describe a typically presenting patient with acute onset hepatitis.

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Doc you're in the Pale stall soon follows Jaundice Abdominal pain Itch (pruritus) Arthralgia and skin rash

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182

What are you differential diagnosis for a patient presenting with suspected hepatitis?

Acute drug induced liver injury (e.g. paracetamol, ecstasy) Acute HIV infection Drug induced hypersensitivity reaction

183

In a patient with hepatitis, what would you expect to find upon examination?

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Hepatomegaly Jaundice Fever with temperatures of up to 40°C Features of chronic liver disease Evidence of decompensation

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184

How many viral? hepatitis are there?

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Hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E. Adenovirus EBV. (Epstein-Barr virus) CMV ( cytomegalovirus) Herpes simplex virus NANE ``` And others

185

What would you give as postexposure prophylaxis for hepatitis B?

Hepatitis B immunoglobulin

186

What do you know about hepatitis E virus?

It's an enterically transmitted non-a non-B hepatitis. It is spherical, non-envelope, single-stranded RNA virus. It is in the genus of HPV-like viruses (unassigned genus). Located worldwide approximately around the Tropic of Cancer.

187

What is the incubation period of hepatitis E?

On average 40 days. It can range from 15 to 60 days.

188

What is the case fatality rate of hepatitis E?

Overall, 1%-3% | Pregnant woman, 15%-25%

189

Which factors increase the severity of hepatitis E?

Increased age | Coexisting liver disease

190

Most outbreaks of hepatitis E are associated with what?

Faecally contaminated drinking water.

191

How many people worldwide have been infected with hepatitis B?

Approximately 2 billion people have been infected worldwide. 400 million people are chronically infected. 10-30,000,000 will become infected each year. An estimated 1 million people die each year for hepatitis B and its complications.

192

What is the prevalence of hepatitis B in the UK?

0.3%

193

What factors are we trying to achieve in hepatitis B virus therapy?

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Loss of viral replication. Normalisation of transaminases. Improvement in liver histology. Loss of E antigen. Loss of surface antigen.

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194

Name of the drugs used to treat hepatitis B viral infection.

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Peg interferon Entecavir Tenofovir Lamivudine Adefovir Telbivudine

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195

In which country do you find 22% of the global hepatitis C infections?

Egypt.

196

Which other two groups and most at risk of contracting hepatitis C?

Recipients of clotting factors before 1987 Injection drug users

197

What drugs do you use to treat hepatitis C infection

PEG-interferon alpha 2a or 2b + ribavirin Also direct acting antivirals.

198

What are the adverse affects of interferon medication?

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Flulike symptoms Injection site reactions Muscle and joint pain Neuropsychiatric Bone marrow suppression Thyroid dysfunction Exacerbation of autoimmune diseases

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199

What are the adverse affects of ribavirin?

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This drug is teratogenic Haemolytic anaemia Skin rash Cough Insomnia

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200

What are the adverse affects of Telaprevir?

Rash in 50% of patients Anal irritation Per rectal bleeding

201

Hepatitis B and see both formal chronic infections. Is this true?

Yes, if left untreated.

202

Which two forms of hepatitis can be transmitted sexually?

Hepatitis B and hepatitis D.

203

For which forms of viral hepatitis are there a vaccine?

A B E

204

In histology, what structure of the spleen is enclosed by the mantle?

The germinal centre.

205

In histology? The outside of the spleen is covered by what?

The Sure. | The Sure in encapsulates the red pulp of the spleen.

206

What is the function of the red pulp of the spleen?

Removal of old red blood cells after 120 days | Recycling of iron and haeme pigments

207

What is the white pulp of the spleen? What is its purpose?

The white pulp is lymphoid tissue. | Function: immune defence against septicaemia

208

Name the causes of splenomegaly.

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Infection Congestion (cirrhosis with portal hypertension, right-sided heart failure) Haemolytic anaemia Autoimmune i.e. rheumatoid arthritis Haematological malignancy i.e. leukaemia Amyloid Rare storage disorders

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209

How would you conduct prophylaxis for splenectomy?

Vaccinated against encapsulated organisms: Haemophilus Pneumococcus Meningococcaemia's Prophylactic penicillin the 250 mg twice daily for life Carrie alert card and bracelet

210

Jason is refusing to have any further doses of salbutamol as the tremor is so unpleasant. What type of reaction is this?

This is a type a (augmented) reaction

211

Chelsea, who recently started taking lamotrigine reports a worsening rash to her GP. What type of drug reaction is this?

This is a type a drug reaction

212

Alex is found semiconscious by her neighbour. It is established that her GP increase the dose of gliclazide yesterday. What type of drug reactions this?

This is a type a drug reaction.

213

Harry, he currently takes a drug, asks to be swapped to an alternative due to the headache it causes him.what type of drug reaction is this?

This is a type two (bizarre drug reaction) drug reaction

214

Holly has developed a hepatitis after receiving the anaesthetic. What type of drug direction is this?

Type 2

215

Robbie is taken to accident and emergency with difficulty breathing and swollen lips which she developed after taking the second Dose of the course of flucloxacillin. What type of drug reaction is this?

This is a bizarre drug reaction Type II.

216

Name some of the common health problems associated with homeless people.

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Schizophrenia Depression that Psychosis Bipolar disorder Anxiety Panic attacks Personality disorders Sprains and strains Head injury Open wound Foot trauma

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217

Point out the Red Pulp, Arteriole, Germinal centre and Mantle. From which organ is this tissue?

This is from the SPLEEN.

218
219
Which artery supplies 25% of Hepatic blood flow?
The hepatic artery. | This autoregulates flow to ensure a constant total blood flow.
220
From where does 75% of hepatic blood flow come?
The portal vein. The normal portal pressure is 5-8mm Hg. This pressure increases slightly after meals.
221
What is the name of the functional hepatic unit?
The Acinus. This consists of parenchyma supplied by the smallest portal tracts containing portal vein radicles, hepatic arterioles and bile ductules.
222
Which is more resistant to damage: Hepatocytes near Acinus hilum(s) or those closer to the terminal hepatic (central) veins?
Those nearest the central veins.
223
How is ammonia produced in the liver?
Amino acids are degraded by transamination and oxidative deamination to produce ammonia.
224
Approximately how many g of glycogen does the liver store?
approx 80g
225
Where is cholecystokinin secreted from, and what are its effects?
/secreted from cells of the Duodenal mucosa, and stimulates contraction of thre gall bladder and relaxation of the sphincter of Oddi, allowing bile to enter the duodenum.
226
Which cells in the liver break down mature red cells ?
Kupffer cells
227
Which compound is formed from haem, and reduced to form billirubin?
Billverdin
228
What does AST stand for?
Serum aspartate
229
What does ALT stand for?
Aminotransferase (this level reflects hepatocellular damage)
230
What does ALP stand for?
Serum alkaline phosphatase - This is raised in cholestasis
231
What does gamma GT stand for?
Gamma-Glutamyl transpeptidase
232
What are serum albumin and PT markers of?
Synthetic function. A dropping albumin level is a worrying sign. Cause of low PT make be Vit K, so be sure to give a course before test.
233
What disease is raised Anti-mitochondiral antibody a sign of?
Primary Billiary cirrhosis
234
What is A-Fetoprotein a sign of?
Hepatocellular carcinoma
235
Raised serum iron, transferring and ferritin is a sign of what?
Hereditary Haemochromatosis.
236
Anti-Nuclear cytoplasmic antibodies (raised) are a sign of what?
Primary sclerosing cholangitis
237
Serum and urinary copper, and serum caeruloplasm are signs of what disease?
Wilsons. A rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if not recognized and treated when symptomatic.
238
What are Xanthomas, and when may they be seen (in the context of liver disease)
These are cholesterol deposits seen in the palmar creases or above the eyes in primary billiary cirrhosis.
239
Name a congenital hyperbilirubinaemia.
Gilbert's syndrome.
240
What is the difference between extrahepatic and intrahepatic cholestatic jaundice?
Extra: Due to large obstruction of bile flow at any point distal to the bile canaliculi. Intrahepatic is failure of bile secretion.
241
Which form of hepatitis virus is most dangerous to pregnant women?
Hep E
242
Hep A is usually which age group?
YOUNG
243
Which hepatitis virus has DNA
Hep B
244
Which hepatitis viruses can be passed vertical (parent to offspring)?
Hep B, and C (C is rare)
245
Which forms of hepatitis can be passed by saliva?
ABC
246
Which forms of hepatitis can be passed by sexual contact?
ABC
247
The current HEp B vaccine is based on which HBV protein?
Surface (HBsAg) - The envelope protein of HBV.
248
Of Serum ALT, IgM HAV and IgG HAV, which would you expect to raise first in HAV, and which would you expect to raise/remain last?
SERUM ALT first | IgG HAV would raise last and remain high for some time post infection.
249
In HBV infection, HBV DNA levels can be a marker for what?
The response to treatment.
250
/What is yellow fever?
A Viral infection spread by them osquito Aedes aegypti, which can cause acute hepatic necrosis. There is no specific treatment.
251
What are the transfer criteria for ITU for patients with an acute liver injury?
``` INR >3.0 Presence of Hep Encephalopathy Hypotension post fluid resuscitation Metabolic acidosis Prothrombin time (seconds) > interval (hours) from overdose (paracetemol cases) ```
252
What is the most common intrahepatic cause of portal hypertension?
Cirrhosis
253
What is Budd-Chiari syndrome?
There is obstruction to the venous outflow of the liver owing to occlusion of the hepatic vein.