Liver pathology

Question 1

What is Wilson’s disease ?

Answer 1

Rare autosomal recessive disorder.

Progressive

Excess copper stored in body tissues - especially
0 Liver
0 Brain
0 Cornea’s
of eye - Kayser - Fleischer rings ( circular brown rings around the eye )

Abnormal deposition of copper in liver.

Onset usually between 3 - 55 years - but can happen at any age.

Lead to:

Liver problems - chronic hepatitis ——-> cirrhosis

Deposition in (CNS ) brain ——-> neurological and psychiatric problems

neulogical - difficulty concentrating

• coordination
• Dysarthria - speech difficulties
• Dystonia - abnormal muscle tone.
• Deposition in basal ganglia - Parkinsonism - 3 signs - symmetrical (unlike parkistons’s - can be asymmetrical - not sure if it is always )
  0 Tremors
  0
  Bradykinesia - slowness of movement
  0 Rigidity

Psychiatric

• mild depression
• Psychosis
• can also get haemolytic anaemia , renal tubular acidosis , osteopenia.

*

Question 2

Diagnosis of Wilson’s disease ?

Answer 2

Serum caeruloplasmin

caeruloplasmin - made by liver - stores and carries copper from liber into blood to parts of the body.

low levels indicate possible Wilson’s disease.

• can also indicate

Slit lamp examination - check presence of Kayser- Fleischer rings

• Urine copper.

Liver biopsy - check liver copper content - can be used to confirm diagnosis.

0 Menkes syndrome - abnormal processing of copper - usually appear within first few months of life. Mainly affects Boys. 
    Symptoms 
       - sparse , kinky hair 
       - failure to thrive 
       - seizures 
       - hypotonia 
(occipital horn syndrome - milder form that begins in middle childhood )
0 Liver disease
0 Malnutrition
0 Malabsorption
0 Kidney disease

cannot use or eliminate copper properly.

Question 3

What can cause increased serum ceruloplasmin level ?

Answer 3

• A serious infection
• Heart disease
• Rheumatoid arthritis
• Leukemia
• Hodgkin lymphoma

non disease causes :

• pregnancy
• birth control pills

Question 4

kidney - not liver.

Answer 4

eGFR - estimated (no longer used a accurate one )

only used in chronic kidney disease.

when more than 90 - observe

below 90 have to intervene

chronic kidney disease —————> less nephron ———————-> hypertropy of teh rest of nephrons to compensate —————————-> increase in glomerular pressure / filtraryion ——————–> glomerular sclerosis.

CAUSES

third space sequestration .e,g odema
skin losses - sweating

different damage to diffrebt aspects
- vascular
- tubular necrosis
etc ———-> reduce blood supply ————–> epithelial cells start to die ——————> blockage of renal tubule —————> renal failure——————-> this can be repaired , but in some cases leads t irreversible damage.

pre - renal failure

renal failure

post renal - something is blocking secreting of urine ———–. causing back ressure on kidney causing post renal failure

rapid hypercalemia , kalemia ,, metabollic acidosis
etc - can indicate acute kidney failure

AKI 1 - observe
AKI 2- investigation of reason for failure

AKI 3-

Question 5

What is Alpha - 1 - antitripsin defiency (A1AT/)

Answer 5

Genetic disease

Not enough of this produced from liver.

FUNCTION - inactivates elastase (protease which breaks down proteins).
- elastase breaks down elastin.

IF A1AT deficiency :

elastase not inactivated so breaks down too much elastin effecting :

0 Lungs
0 Liver

Inheritance pattern :- Autosumal inheritance (not sex chromosomes ) & codominant allelle expression (e.g the expression of one allele cannot mask the expression of the other )

e. g. each mutated allele only produces 10 % of the normal 50 % of A1AT .
- 2 normal allele - 100 % produced
- 1 normal , 1 abnormal - 60 % produced (people are usually symptomatic)
- 2 abnormal - 15 -20 % produced ( A1AT DEFICIENCY) - can be asymptomatic if avoud environmental triggers e.g smoking etc.

SYMPTOMS

Lung manifestations
0 Productive cough 
0 SOB on excretion
0 wheezing
0 chest hyperinflation

Liver manifestations 
0 Hepatomegaly 
0 ascites 
0 jaundice
0 Hepatic encephalopthy - EMERGENCY 
0 Asterixis (loss of motor control of certain areas of body - resulting in flapping e.g Liver flap)

RISK FACTORS

• Family history of A1AT defiency.

Question 6

Compliactions of Alpha - 1 - antitripysin dieficieny ?

Answer 6

0 Lungs (damage walls of alveoli - lost elasticity & strength of lung tissue -----> as a result the acinus which surround the alveoli becoming enlarged causing PAN -ACINAR EMPHYSEMA (all the acinar affected) 
- Can also cause : 

o chronic bronchitis (long term inflammation & irritation of the bronchi ——> mucus build up )

o Bronchiectasis – aiways become widened causing build up of mucus - lungs vulnerable to infection.

(THESE COLLECTIVELY ARE KNOWN AS COPD )

SYMPTOMS

• SOB
• Wheezing
• mucus production
• chronic cough

0 Liver - Cirrhosis (scar tissue in liver )

Cirrhosis can cause :

• Jaundice
• Inability to make coagulation factors
• build up of waste products (impaired detoxifcation) —————–> hepatic encephalopathy
• Portal hypertension —————–> osephageal varices
• Higher risk of hepatocellular carcinoma

(Those who have the gene that codes for absent A1AT - usually dont have liver symptoms vs those which encode for misfolded A1A1. )

Question 7

Diagnosis of A1AT deficiency ?

Answer 7

0 Plasma A1AT (AAT)

0 PFTs - pulmonary

0 CXR
0 Chest CT

0 Liver function tests

Question 8

Treatment of AAT ? (A1AT)

Answer 8

1ST LINE - lifestyle advice
(Smoking cessation , pollution avoidance )

ADJUNCT -Hepatitis vaccination (A , B protect against hepatic manifestations )

PULOMONARY MANIFESTATIONS PRESENT :

PLUS - COPD treatment (if present )
(e.g. bronchodilators , inhaled corticosteriods , antibiotics , oxygen , & oral cortiosteriods.

if end - stage lung disease present - LUNG TRANSPLANT
(< 25% or there are signs of chronic CO2 retention)

HEPATIC MANIFESTATIONS PRESENT:

• Standard liver disease treatment (for presenting complaint)
  e.g. LFT monitoring
  diuretics - ascities
• liver transplant
• oesophagogastroduodenoscopy - to dectect & manage varices.

PLUS - alchohol avoidance.

Question 9

What is Alcoholic fatty liver disease?

Answer 9

3 stages :

1. fatty liver
   (alcohol breaks down & overall increase the amount of fatty acid produced —-> steatosis (build-up of fat in liver )) - ASYMPTOMATIC - fatty , heavy, enlarged liver.
   (TO TREAT STOP DRINKING ALCOHOL)
2. alcoholic hepatitis (inflammation & necrosis of liver )

(Alcohol when broken down release reactive oxygen species reacting with molecules in cells e,g . protein
& damaging cells also breakdwon products of alcohol combine with cell components - immune system recognises it as foreign and destroys cells ———-> CAUSES IRRITATION.
(Mallory bodies - can be seen on histology)
(HEPATOMEGALY , neutrophilic leukocytosis - may be happening at this point)

(damage to liver causes ALT , AST To leak out )

3. alcoholic liver cirrhosis - (damage done - cause scarring ———–> can cause liver failure )

CAUSES :
Chronic heavy alcohol ingestion.

SIGNS / SYMPTOMS

0 RUQ pain
0 Hepatomegaly (alcoholic hepatits, fatty liver stage)
0 ascities - cirrhosis complication
0 weight loss , anorexia- associated with high TNF - alpha and inflammatory response
0 weight gain - bcc of ascities / oedema
0 Fatigue

Uncommon

• Haematemesis
• melaena
• Venous collaterals
• splenomegaly
  hepatic mass
• jaundice
• palmar erythema
• cutaneous telangiectasia
• asterixis.
• pruritis (itch - bcc Bilirubin deposition in skin)
• leg swelling
• finger clubbing .
• nausea & vomiting
• Confusion - HEPATIC ENCEPHALOPATHY

Question 10

Investigation of alcoholic liver disease ?

Answer 10

Serum AST , ALT
(AST/ALT > 2 - suggestive of alcholic liver disease)

0 ASP , GGT

0 serum Bilirubin

0 serum albumin

0 FBC

0 Serum electrolytes

• hyponatraemia - common in ALD
• Hypokal/phosphataemia - common causes of muscle weakness in ALD.
• Hypomagnesaemia - can cause persistent hypokalemia and can pre-dispose patients to seizures during alcohol withdrawal.

0 serum U & Creatinine

0 Serum PT , INR

0 hepatic ultrasound.

Can consider others if alternative causes suspected or need to be ruled out e.g. viral hepatitis serology , ceruloplasmin , urine copper , alpha 1 antitryspin , folate etc.

Question 11

Treatment of ALD ?

Answer 11

1ST LINE

• Alcohol abstinence + alcohol withdrawal management
  ( AA meetings - rehabilitation services etc)
• Benzodiapines e.g diazepam , oxazepam - 1st , lorapam - 2nd. ( Used to help control alcohol withdrawal syndrome.

PLUS - weight loss (for overweight patient - slows down ALD) + Smoking cessation

PLUS - Immunisation (Hepatitis A, B, influenza , pneumococcal)

PLUS - Nutritional supplementation + multivitamins

PLUS - sodium restrcition +/- diuretics - if ascities / oedema
(furosemide & Spirolactone)

2ND LINE - Liver transplant + alcohol abstinence etc.