Liver Flashcards
Cirrhosis is
Histologically the presence of bands of fibrous tissue that link central & portal areas, and form parenchymal nodules
Clinical jaundice at what level
35-50
Medical treatment for pruritis
Cholestyramine
Ursodeoxycholic acid
Opiate antagonists
Antihistamines
Portal hypertension defined as…
> 10mmHg
Hepatorenal syndrome
Pathophysiology
Urine features
Treatment
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
Ascending cholangitis
- usual micro
E coli
Klebsiella
Pseudomonas
Enterococcus
Liver functions
CHO metabolism
Protein metabolism
Lipid metabolism
Bio transformation eg oxidation, reduction, hydrolysis, conjugation
Bile acid synthesis and conjugation
Liver protein synthesis
Early fetal life
Albumin synthesis from ..
Other
a-fetoprotein
Alb from 7 weeks
Fibrinogen Clotting factors (II, VII, V, IX, X) Complement Caeruloplasmin Transferrin Lipoproteins
Inducers of CYP enzymes
Inducers of CYP enzymes
ALL- phenobarbital, phenytoin
CYP2E1 - isoniazid
CYP3A1 - spironolactone
CYP3A4 - carbamazepine, rifampin
Inhibitors of CYP enzymes
Cimetidine Ciprofloxacin Erythromycin Diltiazem Fluconazole Fluoxetine Haloperidol Grapefruit juice Ketoconazole Itraconazole Omeprazole Miconazole
Substrates for CYP enzymes
Warfarin Phenytoin Propanolol & metoprolol Diazepam and midazolam Amiodarone Flecainide Carbamazepine Erythromycin Tacrolimus Sodium valproate
Important examples of drug interactions involving CYP metabolism
Antibiotic & antiepileptic
2 anti epileptics
Erythromycin and Clarithromycin inhibits CYP3A4
Toxic Carbamazepine levels
Phenytoin induces Valproate metabolism and increases production of a toxic metabolite
Rate limiting step in neonatal bilirubin excretion
UDPGT activity
Bile acid synthesis From what, enzyme Released into Form \_\_ with \_\_\_ Reabsorbed where Returned to liver via What happens to bile that reaches colon
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
Which transaminase is most liver specific
What ratio would make you consider extrahepatic causes
ALT
AST also in RBC, muscle
AST>ALT think alcohol, echovirus, metabolic disease
GGT/ALP
Found where
GGT inducers
ALP also found where
Which typically rises first
Cell membrane of bile duct canniculi
Phenytoin, morphine, alcohol
Bone, placenta
ALP then GGT
Vitamin K dependent factor
Which factor is a poor prognostic sign in liver failure
II, VII, IX, X
Affect PT or INR
FVII
Bilirubin
Produced by
Conjugated by - makes ___ soluble
Unconjugated hyperbili due to
Conjugated due to
Hemolysis or reduced conjugation (enzyme def or immaturity)
Biliary obstruction
What is a1AT, function
Produced by
Faecal a1AT indicates
Number of alleles
Glycoprotein Protease inhibitor Acute phase protein Liver and macrophages Bowel protein loss >20, only a few associated with disease
Effect of abnormal a1AT synthesis
2
Accumulation in liver causing damage
Increased protease damage in lung
a1AT
Most common phenotype
Associated w lung + liver disease
Lung disease only
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)
Skin disease associated with a1AT
Panniculitis
Rx dapsone (steroid)
Neonatal hepatitis syndrome
Ddx
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
Acute hepatitis
Ddx
Hepatitis A, B, C, D, E, G CMV/EBV HSV/VZV HIV Rubella Adenovirus Enterovirus Parvovirus B19 Arboviruses
Chronic hepatitis
Ddx
Viral: hep B,C, D and CMV
Drugs: isoniazid, methyldopa, nitrofurantoin, sulfonamides, minocyline
Metabolic disease: Wilson, a1AT, CF, haemachromatosis
Autoimmune
Steatohepatitis
Massive liver injury indicated by…
Falling ALT, rising bili & INR
Autoimmune hepatitis
LFTs
FBC
Protein
Type 1
Type 2
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
Autoimmune hepatitis
Biopsy features
Plasmolymphocytic infiltrate expanding portal tracts, variable bile duct injury
Piece meal hepatic necrosis, bridging necrosis (spanning portal tract)
Autoimmune hepatitis
Rx
Prognosis
Steroids
Azathioprine used as immunosupression
Ursodeoxycholic agent as choleretic
70% normal at 5 years
30% progress
50% relapse after steroids weaned
Other causes of steatohepatitis
Steroids, MTX, pregnancy, lipid metabolic disease, HIV, IBD
Haemochromotosis
Inheritance
Prevalence
Carrier rate
HLA associations
AR
1 in 200
10%
HLA A3, B7, B14
Neonatal haemachromatosis Features (2) Cause Antigen target Immunohistochemical staining:
Severe neonatal liver disease Extrahepatic siderosis Gestational alloimmune liver disease Fetal hepatocyte specific protein Complement mediated C5b-9 complex
Neonatal haemachromatosis
Liver biopsy
Treatment
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
Most common cause of neonatal acute liver failure
Diagnosis rests on
Rx
Prevention
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
Clinical presentation of hereditary haemachromatosis
Adults Skin bronzing Dilated CM DM HSM
Cirrhosis, arthropathy, testicular atrophy
Susceptible to
Listeria
Yersinia
Vibrio vulnificus ( seafood)
Hereditary haemachromatosis
Lab tests
Rx
Increased ferritin
Low TIBC
Raised transferrin saturation ( often by adolescence)
Gene test : HFE gene
Phlebotomy
Vaccine hep B and A
Screen relatives
Hepatomegaly
Ddx
Infection Inflammation Infiltration Storage Congestion Metabolic Bile duct drainage problems Endocrine (thyroid + pituitary)
Reye syndrome
What is
Aetiology
Pathology
Acute encephalopathy without jaundice
? Influenza or varicella with aspirin administration
Liver grossly fatty: foaminess of liver cytoplasm
Mitochondrial injury- loss of FA & carnitine metabolism
Reye syndrome
Clinical features
Labs
Viral URTI with recovery
5-6d later: intractable vomiting, confusion, agitation, reduced LOC
Mild liver enlargement,
deranged LFTs
Elevated PT
Ammonia
Hypoglycaemia
Metabolic causes of ‘reye like ‘ syndrome
Fatty acid oxidation Carnitine deficiency MCAD LCAD - manifest as recurrent hypoglycaemia, hypoketotic encephalopathy
Urea cycle defects (OTC)
Organic acidurias
Respiratory chain defects
CHO defects
Hepatitis C
Virus family
Genotypes common
Incubation period
Flaviviridae
6 total; 1>3>2
6-7 weeks
Hep C transplacental transfer
LCSC?
Breastfeeding?
Test when, what
5-10%
No evidence for section
Advise to BF
12 mo
Hep C ab, HCV RNA, LFTs
Hep C virus
Risk cirrhosis by 20
HCC
20%
Males
Alcohol
Longer duration infection
1-4% HCC by 20 if not cirrhotic
Hep C
Extrahepatic manifestations
Cutaneous vasculitis
Porphyria cutaneous tarda
Type II cryoglobulinemia
Cerebritis, peripheral neuropathy
Renal- membranous GN
Hep C
New therapy for genotype 1
For genotype 2,3
Genotype 4-6
What age
Harvoni ( ledipasvir, sofosbuvir )
For genotypes 1-3
Sovaldi (ribavir, sofosbuvir) 4-6
12 years plus
Interferon side effects
Pyrexia Headache GI Weight loss, poor growth Retinopathy, uveitis BM supression Neuropsychiatric
Ribavirin side effects
Contraindications
Effect
Hemolytic anaemia
Teratogenic
Decompensated liver failure
No effect alone, combined sustained response
How to diagnose osmotic diarrhoea
Suggestive of secretory diarrhoea
2x [(Na) + (K)] + 50 < faecal osm (~290)
> 70mmol/L Na+
Hep D
When to consider
Outer protein
Acute liver failure
HBsAg
Caroli disease
What
Complication
Association (renal)
Saccular dilatation of intrahepatic bile ducts
Ascending cholangitis
ARPKD
PFIC
Gene for PFIC1
Low GGT in…
High in…
Diarrhoea post transplant in…
Malignancy risk in…
Late onset of jaundice in…
ATPB1
PFIC1 + 2
High in PFIC3
PFIC1 diarrhoea, pancreatitis, hearing
Malignancy pfic2
Pfic3 can present later, the others in infants
Treatment for Wilson’s disease
Low copper diet
Zinc: competes with Cu absorption
Penicillamine
Trientine
Cu chelation
Chronic hep B infection
Serology
Lfts
HBsAg + HBeAg positive
LFTs normal- no immune mediated liver disease
Hep B infection
Replicant phase
Serology
Viral load
Deranged LFTs
HBsAg + HBeAg positive
High viral load
Deranged LFTs
Presence of HBsAg beyond 6 months indicates
Chronic infection
Treatment for Hep B infection
Which phase
Drugs (2)
Chronic infection
Immune active or reactivation phase
Interferon
Lamivudine
Entecavir
Wilson’s
Organs affected
Liver
Descemets membrane of cornea
Brain (BG or cerebrum)
Hemolytic anaemia
