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Gastroenterology > Liver > Flashcards

Liver Flashcards

1
Q

Cirrhosis is

A

Histologically the presence of bands of fibrous tissue that link central & portal areas, and form parenchymal nodules

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2
Q

Clinical jaundice at what level

A

35-50

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3
Q

Medical treatment for pruritis

A

Cholestyramine
Ursodeoxycholic acid
Opiate antagonists
Antihistamines

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4
Q

Portal hypertension defined as…

A

> 10mmHg

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5
Q

Hepatorenal syndrome
Pathophysiology

Urine features

Treatment

A

Splanchnic vasodilation
Mesenteric angiogenesis
Decreased effective blood volume
Decreased renal perfusion

Oliguria, FeNA <1%, urine sodium <10, normal urinary sediment, urine:plasma cr ratio <10

Liver transplant

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6
Q

Ascending cholangitis

  • usual micro
A

E coli
Klebsiella
Pseudomonas
Enterococcus

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7
Q

Liver functions

A

CHO metabolism

Protein metabolism

Lipid metabolism

Bio transformation eg oxidation, reduction, hydrolysis, conjugation

Bile acid synthesis and conjugation

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8
Q

Liver protein synthesis
Early fetal life
Albumin synthesis from ..
Other

A

a-fetoprotein
Alb from 7 weeks

Fibrinogen
Clotting factors (II, VII, V, IX, X)
Complement 
Caeruloplasmin
Transferrin
Lipoproteins
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9
Q

Inducers of CYP enzymes

A

Inducers of CYP enzymes

ALL- phenobarbital, phenytoin
CYP2E1 - isoniazid
CYP3A1 - spironolactone
CYP3A4 - carbamazepine, rifampin

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10
Q

Inhibitors of CYP enzymes

A 
Cimetidine
Ciprofloxacin
Erythromycin
Diltiazem
Fluconazole 
Fluoxetine 
Haloperidol 
Grapefruit juice 
Ketoconazole
Itraconazole
Omeprazole
Miconazole
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11
Q

Substrates for CYP enzymes

A 
Warfarin 
Phenytoin
Propanolol &amp; metoprolol 
Diazepam and midazolam
Amiodarone
Flecainide
Carbamazepine 
Erythromycin 
Tacrolimus
Sodium valproate
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12
Q

Important examples of drug interactions involving CYP metabolism

Antibiotic & antiepileptic

2 anti epileptics

A

Erythromycin and Clarithromycin inhibits CYP3A4
Toxic Carbamazepine levels

Phenytoin induces Valproate metabolism and increases production of a toxic metabolite

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13
Q

Rate limiting step in neonatal bilirubin excretion

A

UDPGT activity

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14
Q 
Bile acid synthesis 
From what, enzyme 
Released into
Form \_\_ with \_\_\_
Reabsorbed where
Returned to liver via
What happens to bile that reaches colon
A

From cholesterol in liver by 7a hydroxylase
Released into small bowel via gallbladder
Form micelles with cholesterol + phospholipids
Reabsorbed in terminal ileum via active transport
Returned to liver via portal circulation
Bile in colon metabolised by bacteria and reabsorbed in distal colon

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15
Q

Which transaminase is most liver specific

What ratio would make you consider extrahepatic causes

A

ALT

AST also in RBC, muscle

AST>ALT think alcohol, echovirus, metabolic disease

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16
Q

GGT/ALP

Found where
GGT inducers
ALP also found where

Which typically rises first

A

Cell membrane of bile duct canniculi

Phenytoin, morphine, alcohol

Bone, placenta

ALP then GGT

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17
Q

Vitamin K dependent factor

Which factor is a poor prognostic sign in liver failure

A

II, VII, IX, X
Affect PT or INR

FVII

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18
Q

Bilirubin
Produced by
Conjugated by - makes ___ soluble

Unconjugated hyperbili due to

Conjugated due to

A

Hemolysis or reduced conjugation (enzyme def or immaturity)

Biliary obstruction

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19
Q

What is a1AT, function
Produced by
Faecal a1AT indicates
Number of alleles

A 
Glycoprotein 
Protease inhibitor 
Acute phase protein 
Liver and macrophages 
Bowel protein loss
>20, only a few associated with disease
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20
Q

Effect of abnormal a1AT synthesis

2

A

Accumulation in liver causing damage

Increased protease damage in lung

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21
Q

a1AT

Most common phenotype
Associated w lung + liver disease
Lung disease only

A

MM (90%) -normal

ZZ - deficient : 10-20% n protein. Most common abnormality
10-20% develop neonatal cholestatic hepatitis

Null/null : no accumulation, no protease inhibitor

S - slow (50% normal protein produced)

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22
Q

Skin disease associated with a1AT

A

Panniculitis

Rx dapsone (steroid)

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23
Q

Neonatal hepatitis syndrome

Ddx

A 
TORCH infection 
Metabolic 
- a1AT
- CF
- CHO metabolism: galactosaemia, GSD IV
- protein metabolism: tyrosinemia
- lipid metabolism: Wolman
- storage diseases : Gaucher, Niemann-Pick
- Cu metabolism: Wilson
- neonatal haemochromatosis
24
Q

Acute hepatitis

Ddx

A 
Hepatitis A, B, C, D, E, G
CMV/EBV
HSV/VZV
HIV
Rubella
Adenovirus 
Enterovirus 
Parvovirus B19
Arboviruses
25
Q

Chronic hepatitis

Ddx

A

Viral: hep B,C, D and CMV

Drugs: isoniazid, methyldopa, nitrofurantoin, sulfonamides, minocyline

Metabolic disease: Wilson, a1AT, CF, haemachromatosis

Autoimmune

Steatohepatitis

26
Q

Massive liver injury indicated by…

A

Falling ALT, rising bili & INR

27
Q

Autoimmune hepatitis

LFTs
FBC
Protein

Type 1
Type 2

A

3-10x transaminases
Increased SBR ( conjugated mostly)
Anaemia, thrombocytopenia, neutropenia
Low albumin, hyper gamma globulin emia

Type 1: young women, marked hypergam & lupoid features. ANA and SMA

Type 2: children. Severe hepatitis. AntiLKM Ab. Up to 20% ab neg

28
Q

Autoimmune hepatitis

Biopsy features

A

Plasmolymphocytic infiltrate expanding portal tracts, variable bile duct injury

Piece meal hepatic necrosis, bridging necrosis (spanning portal tract)

29
Q

Autoimmune hepatitis

Rx

Prognosis

A

Steroids
Azathioprine used as immunosupression
Ursodeoxycholic agent as choleretic

70% normal at 5 years
30% progress
50% relapse after steroids weaned

30
Q

Other causes of steatohepatitis

A

Steroids, MTX, pregnancy, lipid metabolic disease, HIV, IBD

31
Q

Haemochromotosis

Inheritance
Prevalence
Carrier rate
HLA associations

A

AR
1 in 200
10%

HLA A3, B7, B14

32
Q 
Neonatal haemachromatosis
Features (2)
Cause 
Antigen target
Immunohistochemical staining:
A 
Severe neonatal liver disease
Extrahepatic siderosis
Gestational alloimmune liver disease
Fetal hepatocyte specific protein 
Complement mediated 
C5b-9 complex
33
Q

Neonatal haemachromatosis
Liver biopsy

Treatment

A

Marked loss of hepatocytes
Portal tracts relatively spared
Remaining hepatocytes show siderosis, giant cell transformation, canalicular bile plugs

C5b-9 immunohistochemical staining

Exchange transfusion
IVIG
Liver transplant

34
Q

Most common cause of neonatal acute liver failure

Diagnosis rests on

Rx

Prevention

A

Neonatal haemachromatosis/ gestational alloimmune liver disease

Demonstrating extrahepatic siderosis: lip biopsy and MRI
( if both negative do biopsy with C5b-9 staining)

Rx IVIG +- exchange transfusion

IVIG in next pregnancy

35
Q

Clinical presentation of hereditary haemachromatosis

A 
Adults 
Skin bronzing 
Dilated CM
DM
HSM

Cirrhosis, arthropathy, testicular atrophy

Susceptible to
Listeria
Yersinia
Vibrio vulnificus ( seafood)

36
Q

Hereditary haemachromatosis

Lab tests

Rx

A

Increased ferritin
Low TIBC
Raised transferrin saturation ( often by adolescence)

Gene test : HFE gene

Phlebotomy
Vaccine hep B and A
Screen relatives

37
Q

Hepatomegaly

Ddx

A 
Infection 
Inflammation 
Infiltration
Storage 
Congestion 
Metabolic 
Bile duct drainage problems 
Endocrine (thyroid + pituitary)
38
Q

Reye syndrome

What is

Aetiology

Pathology

A

Acute encephalopathy without jaundice

? Influenza or varicella with aspirin administration

Liver grossly fatty: foaminess of liver cytoplasm
Mitochondrial injury- loss of FA & carnitine metabolism

39
Q

Reye syndrome

Clinical features

Labs

A

Viral URTI with recovery

5-6d later: intractable vomiting, confusion, agitation, reduced LOC
Mild liver enlargement,

deranged LFTs

Elevated PT
Ammonia
Hypoglycaemia

40
Q

Metabolic causes of ‘reye like ‘ syndrome

A 
Fatty acid oxidation 
Carnitine deficiency 
MCAD
LCAD
- manifest as recurrent hypoglycaemia, hypoketotic encephalopathy

Urea cycle defects (OTC)
Organic acidurias
Respiratory chain defects
CHO defects

41
Q

Hepatitis C

Virus family
Genotypes common
Incubation period

A

Flaviviridae
6 total; 1>3>2

6-7 weeks

42
Q

Hep C transplacental transfer

LCSC?

Breastfeeding?

Test when, what

A

5-10%

No evidence for section

Advise to BF

12 mo
Hep C ab, HCV RNA, LFTs

43
Q

Hep C virus

Risk cirrhosis by 20

HCC

A

20%

Males
Alcohol
Longer duration infection

1-4% HCC by 20 if not cirrhotic

44
Q

Hep C

Extrahepatic manifestations

A

Cutaneous vasculitis
Porphyria cutaneous tarda
Type II cryoglobulinemia

Cerebritis, peripheral neuropathy

Renal- membranous GN

45
Q

Hep C

New therapy for genotype 1

For genotype 2,3

Genotype 4-6

What age

A

Harvoni ( ledipasvir, sofosbuvir )
For genotypes 1-3

Sovaldi (ribavir, sofosbuvir) 4-6

12 years plus

46
Q

Interferon side effects

A 
Pyrexia
Headache 
GI
Weight loss, poor growth 
Retinopathy, uveitis 
BM supression
Neuropsychiatric
47
Q

Ribavirin side effects

Contraindications

Effect

A

Hemolytic anaemia

Teratogenic

Decompensated liver failure

No effect alone, combined sustained response

48
Q

How to diagnose osmotic diarrhoea

Suggestive of secretory diarrhoea

A

2x [(Na) + (K)] + 50 < faecal osm (~290)

> 70mmol/L Na+

49
Q

Hep D

When to consider

Outer protein

A

Acute liver failure

HBsAg

50
Q

Caroli disease

What

Complication

Association (renal)

A

Saccular dilatation of intrahepatic bile ducts

Ascending cholangitis

ARPKD

51
Q

PFIC

Gene for PFIC1
Low GGT in…
High in…

Diarrhoea post transplant in…
Malignancy risk in…

Late onset of jaundice in…

A

ATPB1

PFIC1 + 2

High in PFIC3

PFIC1 diarrhoea, pancreatitis, hearing

Malignancy pfic2

Pfic3 can present later, the others in infants

52
Q

Treatment for Wilson’s disease

A

Low copper diet

Zinc: competes with Cu absorption

Penicillamine
Trientine

Cu chelation

53
Q

Chronic hep B infection

Serology
Lfts

A

HBsAg + HBeAg positive

LFTs normal- no immune mediated liver disease

54
Q

Hep B infection

Replicant phase

Serology
Viral load
Deranged LFTs

A

HBsAg + HBeAg positive

High viral load

Deranged LFTs

55
Q

Presence of HBsAg beyond 6 months indicates

A

Chronic infection

56
Q

Treatment for Hep B infection

Which phase

Drugs (2)

A

Chronic infection

Immune active or reactivation phase

Interferon
Lamivudine
Entecavir

57
Q

Wilson’s

Organs affected

A

Liver
Descemets membrane of cornea
Brain (BG or cerebrum)
Hemolytic anaemia

Gastroenterology (7 decks)

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