Liver conditions Flashcards
Describe the architecture of a liver lobule
Histologically, the liver is composed of hepatocytes, bile canaliculi, and hepatic sinusoids:
- Hepatocytes are arranged in chords, with blood flowing inbetween in sinusoids from the portal triads → central vein
- Endothelial cells form space of Disse between hepatocytes and sinusoids
Describe the roles of the several vessels entering or leaving the liver
- Portal vein bringing food-rich blood from the gut.
- Hepatic artery bringing oxygenated arterial blood. Liver has dual blood supply.
- Heptic veins taking away processed blood into the vena cava.
- Lymphatics taking away some lymph and some by-products.
- Hepatic ducts removing bile to the gallbladder & gut (biliary system).
Describe the general anatomical features of the liver
- Large, lobated exocrine/blood-processing gland, with vessels/ducts entering/leaving at the porta
- Enclosed by a thin collagen tissue capsule, mostly covered by mesothelium.
- Collagen tissue of the branching vascular system provides gross support.
- Parenchymal cells are supported by fine reticular fibres.
Describe the hepatic lobular flow
Blood flows:
- From branches of the portal vein and hepatic artery; from the periphery towards the centre;
- in the sinusoids, between the cell plates (blood flows slowly from portal triad to central vein, allowing exchange of nutrients for the enrichment of blood)
- Blood collected in central veins → sublobular veins → collecting veins → hepatic veins leaving the liver.
Describe the liver acinus
The territory of an acinus (as its axis) has one final branch
of the portal vein, and is subdivided into:
- Periportal zone – roughly spheroid, isolated from periportal zones of adjacent acini
- Intermediate zone
- Perivenous zones – near the central vein
What does this slide show?
Normal liver
No fatty infiltration
No inflammation
No fibrosis or cell plate thickening
What types of cells are found within the sinusoids of the liver?
Kuppfer (stellate) cells- resident liver macrophages
Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections
Roughly speaking, what do the 3 main LFTs measure?
LFTs measure liver enzymes which can leak from damaged liver cells- so they reflect liver injury
- ALT + AST = liver parenchymal damage (hepatocellular)
- ALP = obstructive cause (cholecystatic)
Gamma-GT = mirrors ALP (unlike ALP, only produced by liver so good way of discerning hepatic pathology)
State the sources of ALT, AST, ALP
ALT = hepatocytes ONLY
AST = liver, heart, skeletal muscle, kidneys, pancreas
ALP = biliary ducts, bone, placenta, small intestine, kidneys
What is the correct way of assessing ALT and AST levels? Explain which pathologies would affect assessment of AST:ALT
must look at AST:ALT ratio
High AST:ALT >2.5 = alcoholic damage/cirrhosis, metastases
Low AST:ALT <1 = paracetamol OD (toxin-induced hepatitis), viral hepatitis (hep A/B/E, EBV, CMV), hepatic obstruction
SALT
Compare the likely diagnoses for a:
- Marked
- Moderate
- Mild
increase in ALT
Marked increase (1000s):
- Toxin/drug induced hepatitis e.g. paracetamol
- Acute viral hepatitis e.g. hep A/B/E, EBV, CMV
Moderate increase (300-500):
- chronic/alcoholic/autoimmune hepatitis
- biliary obstruction
MIld increase (<300):
- Cirrhosis
- Haemachromotosis
- hepatocellular carcinoma
- Wilson’s
- NASH
State some non-hepatic causes for raised ALP
- placenta: pregnancy
- small intestine: fatty meals
- kidney: CKD
- bone: paget’s, bony metastases, fractures, osteomalacia, renal bone disease
Which marker can be measured to determine whether ALP is hepatic in origin?
Gamma-glutamyl transferase (Gamma-GT)
Mirrors ALP but specific to liver
And isolated rise in Gamma-GT is suggestive of what?
alcoholic liver disease
What is a high ALP with high gamma-GT suggestive of?
bile duct disease
liver metastases
Summarise the production of bilirubin
reticuloendothelial cells metabolise Hb into haem and globin
haem → iron and bilviderin
bilviderin → unconjugated bilirubin (binds to albumin and travels to liver)
conjugated bilirubin excreted into bile
in colon: conjugated bilirubin → urobiligen (20% absorbed via enterophepatic circulation)
80% urobiligen → stercobilin
How can jaundice be categorised? For each, state the underlying cause and the type of bilirubin that is in excess
Pre-hepatic = increased haemolysis = ^UNCONJUGATED
Heptic =liver impairment = ^UNCONJUGATED+CONJUGATED
Post-hepatic = biliary tree obstruction = ^CONJUGATED
EXPLAIN the causes of pre hepatic jaundice
Caused by increased haemolysis.
This results in the increased presence of unconjugated bilirubin in the blood as the liver is unable to conjugate it all at the same rate.
This is caused by:
- Tropical disease, e.g. malaria, yellow fever
- Genetic disorders, e.g. sickle-cell anaemia, Gilbert’s syndrome
- Haemolytic anaemias
EXPLAIN the causes of hepatic jaundice
Hepatic jaundice is caused by liver impairment.
This causes the decreased ability of the liver to conjugate bilirubin, resulting in the presence of conjugated and unconjugated bilirubin in the blood. Liver damage can result from:
- Viral hepatitis
- Hepatotoxic drugs, e.g. paracetamol overdose, alcohol abuse
EXPLAIN the causes of post hepatic jaundice
Post-hepatic jaundice is caused by the blockage of bile ducts.
This results in backflow of conjugated bilirubin into the blood as it cannot move past the obstruction.
Bile duct obstruction can be caused by:
- Gallstones
- Hepatic tumours
- Pancreatic tumours
What is the key liver protein and what is a specific outcome of not having enough
Albumin
When albumin is low, there is reduced oncotic pressure so water leaks out of cells contributing to ascites.
May be low due to low production or increased loss (nephrotic syndrome)
State some pathologies that cause:
- Low albumin + low protein
- Low albumin + normal protein
- Low albumin + high protein
-
Low albumin + low protein =
- advanced cirrhosis
- protein malnutrition
- chronic inflammation
-
Low albumin + normal protein =
- infection
-
Low albumin + high protein =
- myeloma
State some causes of raised INR
- liver disease with impaired function
- vit K deficiency
- consumptive coagulopathy (DIC)
- overdose of oral anticoagulants (VKAs)
- Coagulation factors deficiency (fibrinogen and factors II, V, VII, or X, or a combined deficiency) in the extrinsic pathway
Define Liver Abscess and Liver Cyst
Localised infection in the liver parenchyma that may be bacterial, fungal, or parasitic in origin…
resulting in a walled off collection of …
- abscess = pus
- cyst = cystic fluid
State the common causative oganisms for liver abscesses and cysts
Pyogenic (producing pus)
- E. coli
- K. pneumoniae
- S. constellatus
- Klebsiella species
- Streptococcus
Anaerobes:
- Bacteroides fragilis
- Fusobacterium necrophorum
Amoebic abscess
- Following infection by Entamoeba histolytica
Which antimicrobial agent would be a good choice in treating an amoebic liver abscess?
metronidazole
What is the optimal management of a non-amoebic liver abscess?
drainage + antibiotic therapy
Liver abscesses form by spread of infection from which sources?
- Biliary tree
- Portal vein
- Hepatic vein
- Penetrating trauma
- Extension of contiguous infection
What is the most common identifiable source of pyogenic liver abscess?
The biliary tract
cholecystitis, colangitis, strictures, congenital cysts
State the most common causes of liver abscess
40% of cases = idiopathic
Infective abscesses:
- Cholecystitis, cholangitis
- caused by pyelophlebitis:
- appendicitis
- diverticulitis
- IBD
- pancreatitis
- Immunocompromise
- diabetes mellitus
Malignant/parenchymal abscesses:
- Primary hepatocellular cancer + liver mets
- Cirrhosis
Iatrogenic abscesses
- Post-transplant
- chemoembolisation or percutaneous ablation of hepatic neoplasms
- Biliary sphincterotomy
- hepatic cryotherapy
Summarise the epidemiology of liver abscesses and cysts
Uncommon- annual incidence is approximately 3.6/100,000
Pyogenic = most common in the industrialised world
Amoebic liver abscess - most common WORLDWIDE
Hydatid cysts - common in sheep-rearing countries
What are the presenting symptoms of liver abscess?
Acute onset in amoebic abscess, insidious in pyogenic:
- Fevers and chills
- RUQ pain/tenderness
- weight loss, anorexia
- N+V
- fatigue
-
chest symptoms: cough, SOB, pleuritic chest pain
- due to diaphragmatic inflammation
- may see reactive pleural effusion in right lower lobe
Why is it important to ask about travel when taking a history for suspected liver abscess?
Strongly associated risk factor for amoebic liver abscess:
origin in or having visited endemic areas for amoebiasis.
What are the signs of liver abscesses and cysts on physical examination?
-
Fever - continuous or spiking
- Pyogenic abscess should be considered in all patients presenting with pyrexia of unknown origin associated with associated abdominal pain or bloating
- Tender hepatomegaly (right lobe affected more than left)
-
Signs of reactive pleural effusion:
- Dullness to percussion (RHS)
- Reduced breath sounds (RHS)
- If the abscess ruptures (a rare complication), then patients may present with signs of shock.
Identify appropriate investigations for liver abscesses and cysts
-
Bloods
- FBC- leukocytosis
- LFTs- raised ALP, ALT and bilirubin
- Blood and fluid cultures
- PTT + APTT - prior to aspiration, check for deranged clotting factors
-
Liver USS (80-90% sensitive)
- poor-defined lesions with hypo- and hyper-echoic areas
- guide aspiration
-
CT abdo contrast (>95% sensitive)
- lesion seen with surrounding oedema
- gas within lesion highly sugestive of pyogenic abscess
- Gram stain and culture of aspirated abscess fluid
Describe the stages of ALD
Alcoholic liver disease (ALD) has 3 stages of liver damage:
- fatty liver (steatosis)
- alcoholic hepatitis (inflammation and necrosis)
- alcoholic liver cirrhosis
All are caused by chronic heavy alcohol ingestion
What are the defining and associated histopathological features of alcoholic hepatitis?
defining histological features:
- hepatocyte degeneration and necrosis
- inflammation
- fibrosis
associated histological features:
- fatty change- steatosis
- megamitochondria
- Mallory-hyaline inclusions (eosinophilic intracytoplasmic aggregates of cytokeratin intermediate filaments)
What does the following slide show?
Histochemical liver stain- collagen staining blue
Shows a fatty liver with scarring, inflammation and damage
Swollen balloon cells, inflammatory cells
Mallory hyaline bodies
What does the following slide show?
Disorganised- hepatocytes are not arranged in a trabecular fashion- this is a sign of liver damage
clear spaces = steatosis = fatty cells
arrows pointing at mallory hyaline = hepatocyte damage
What is another cause of fatty buildup in the liver apart from alcoholic liver disease?
Nonalcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat in the liver.
- Newly emerging issue
- Patients with insulin resistance
- Due to obesity epidemic
What is the name of the condition in ALD where bile cannot flow from the liver to the duodenum?
cholestasis
red is bile
inflammation/obstruction disturbs bile flow
Summarise the epidemiology of alcoholic hepatitis
In the UK, 24-28% of adults drink in a harmful way.
alcoholic hepatitis occurs in 10-35% of heavy drinkers
What are the presenting signs and symptoms of chronic liver disease?
A long history of heavy drinking is required for ALD development (15-20yrs)
Key features:
- RUQ abdominal pain
- Hepatomegaly
Other features:
- Haematemesis/melaena- from oesophageal/gastric varices + coagulopathy
- caput medusae
- splenomegaly
- ascites /abdo distention
- asterixis
- Testicular atrophy
- spider naeviae- cutaneous telaniectasia
- jaundice
- palmar erythema
- gynaecomastia
State the 5 primary causes of liver disease
- Alcohol
- Autoimmune
- Drugs
- Viral
- Biliary disease
What are the symptoms of acute liver disease?
There may be triggering events (e.g. aspiration pneumonia, trauma)
- Malaise
- Anorexia / N+V
- Fever
- Jaundice
What are the signs of encaphalopathy, such as that caused by ALD? What is this caused by ?
Signs:
- asterixis
- drowsiness
- disorientation
Cause:
- Build up of ammonia in the blood - inadequate hepatic clearance
- This crosses the BBB
Explain the blood results in alcoholic hepatitis
FBC:
- Low Hb- iron / folate deficiency, GI bleeding, haemolysis, hypersplenism
- High MCV
- Leukocytosis- alcoholic hepatitis-related leukaemoid reaction or associated infection.
- Thrombocytopenia- 2/2 alcohol-induced bone marrow suppression, folate deficiency, or hypersplenism.
LFTs:
- Low albumin
- Prolonged PT (longer = more damage)
- High AST + ALT- found in hepatocytes
- High bilirubin
- elevated GGT- more sensitive than ALT/ALP, less specific
U&Es:
- Normal or low sodium, potassium, magnesium, phosphorus
- elevated urea- suggests active GI bleeding when paired with normal creatinine
What does the AST:ALT ratio tell us about the cause of hepatitis?
Raised AST= AST>ALT (ratio >2) = alcoholic cause
Raised ALT= ALT>AST (ratio <1)= viral, non-alcoholic fatty liver
In what conditions is AST raised?
present in heart, muscle, kidney and brain
raised in:
- MI
- hepatic necrosis
- muscle injury
- congestive cardiac failure
- ALD
In what conditions are ALT and AST raised?
(very raised → mildly raised)
Indicate hepatocellular injury
+++ = viral, toxic or alcoholic hepatitis (<50x), ALT>AST
++ = cirrhosis and other chronic liver diseases (<5x) AST>ALT
+ = obstructive jaundice (<3x)
State some non-bedside investigations for alcoholic hepatitis
- Ultrasound - used to screen for HCC every 6-12 months in ALD patients with cirrhosis.
- Upper GI Endoscopy - investigate varices
- Liver Biopsy - diagnostic of ALD and/or alcoholic cirrhosis
- EEG - slow-wave activity indicates encephalopathy
How would you manage acute hepatitis?
- Thiamine
- Vitamin C and other multivitamins (Pabrinex)
- Monitor and correct K+, Mg2+ and glucose
- Ensure adequate urine output
- Steroid therapy for prevention of short-term mortality- prednisolone
- Glypressin and N-acetylcysteine for hepatorenal syndrome
How would you provide nutrition to those with acute alcoholic hepatitis?
Via oral or NG feeding is important
Protein restriction if encephalopathic
Parenteral nutritional supplementation (B group, thiamine and folic acid)
How would you treat ascites and encephalopathy caused by ALD?
Encephalopathy:
- oral lactulose or phosphate enemas
- decrease ammonia generation by bacteria
Ascites:
- diuretics (spironolactone with/without furosemide)
- therapeutic paracentesis
What management should be taken to slow the progression of ALD?
-
alcohol abstinence +/- withdrawal management
- lond-acting benzodiazepines- oxazepam/diazepam for seizure prevention.
- May worsen encephalopathy
- weight reduction and smoking cessation
Explain 2 syndromes arising from live failure caused by activation of RAAS
portal hypertension
→ splanchnic vasodilation (increased NO)
→ reduced blood volume detected in JGA
→ activation of RAAS
2 outcomes:
- vasoconstriction of renal vessels ⇒ HEPATORENAL SYNDROME
- Renin stimualtes reabsorption of salt + water ⇒ ASCITES
Identify the possible complications of alcoholic hepatitis
- hepatic encephalopathy
- portal hypertension
- hepatorenal syndrome
- GI bleeding 2/2 gastro-oesophageal varices, haemorrhoids, and portal hypertensive gastropathy + coagulopathy
- hepatocellular carcinoma
- sepsis
Summarise the prognosis for patients with alcoholic hepatitis
Mortality:
- First month = 10%
- First year = 40%
If alcohol intake continues, most will progress to cirrhosis within 1-3 years
To calculate prognostic score can use Maddrey’s discriminant function or Glasgow alcoholic hepatitis score
Define autoimmune hepatitis
Chronic inflammatory disease of the liver of unknown aetiology.
Characterised by:
- presence of circulating auto-antibodies with a high serum globulin concentration
- inflammatory changes on liver histology
- favourable response to immunosuppressive treatment
What are the risk factors for autoimmune hepatitis?
- female gender
-
genetic pre-disposition
- HLA- different for types 1+2
-
immune dysregulation
- other autoimmune condtions
- Viruses:
- measles virus
- cytomegalovirus
- Epstein-Barr virus
- hepatitis viruses A, C, and D
- certain drugs
Explain the aetiology of autoimmune hepatitis
- Genetic predisposition + environmental factor
- hepatocyte production of HLA antigens → T-cell-mediated autoimmune attack
- Chronic inflammatory changes- lymphoid infiltration of the portal tracts
- hepatocyte necrosis → fibrosis → cirrhosis
Summarise the epidemiology of autoimmune hepatitis
Type 1 (commonest): occurs in ALL age groups (but mainly young women)
Type 2: generally occurs in girls and young women
What are the presenting symptoms of autoimmune hepatitis
May be asymptomatic and discovered incidentally through abnormal LFT
non-acute:
- fatigue/malaise
- abdominal discomfort
- nausea
- arthralgia involving small joints
- anorexia
- spider angiomata
- pruritus
acute(25):
- fever
- jaundice
- N+V, diarrhoea
- Some may present with serum sickness (e.g. arthralgia, polyarthritis, maculopapular rash)
What are the signs of autoimmune hepatitis on physical examination?
Stigmata of chronic disease:
- spider naevi
- palmar erythema
- jaundice
- hair loss
- leuconychia
- asterixis
Ascites, oedema and hepatic encephalopathy are late features
Explain the aetiology of hepatitis A + E
Small non-enveloped single-stranded RNA viruses
- Transmission = faecal-oral route
- Viruses replicate within hepatocytes and are secreted into bile
- Infected hepatocytes are targeted by CD8+ T cells and NK cells → necrosis + liver inflammation
What are the 3 phases of hepatitis A+ E? For each phase, state the symptoms
Prodromal phase- abrupt onset pre-jaundice (1 week)
- Anorexia
- Fever
- N+V
- Malaise, fatigue
- Distaste for cigarettes in smokers
- Headache
Icteric phase (1-4 weeks)
- Jaundice
- Tender hepatomegaly
- RUQ pain
-
Pale stools + dark urine
- acholic stools = clay coloured
- Pruritis
Recovery/convalescence phase
- 1-2 weeks after jaundice
- Full recovery takes 4-6 weeks
note the ABSENCE of stigmata of chronic liver disease (although some spider naevi may appear transiently)
Identify appropriate investigations for viral hepatitis
-
LFTs
- high AST, ALT and bilirubin
- ALP mildly raised
- low albumin
-
FBC, coagulation profile, U+Es
- microcytic anaemia, thrombocytopaenia
- due to cirrhosis-induced portal hypertension
- other signs of cirrhosis- high PTT, high urea, hyponatraemia
- microcytic anaemia, thrombocytopaenia
-
Viral serology
- IgM HAV / IgM HEV - shows current infection (IgG shows past)
- Hepatitis B surface antigen -HBsAg (HB antibody shows past)
- HCV antibody test
- HEV in stool
-
Urinalysis
- Positive for bilirubin
- Raised urobilinogen
What are the possible complications of viral hepatitis A+E?
- Fulminant hepatic failure (in a very small proportion of patients but is more common in pregnant women)
- Cholestatic hepatitis with prolonged jaundice and pruritus can develop after HAV infection
- Post-hepatitis syndrome: continued malaise for weeks to months
State the risk factors for hepatitis B and C
- perinatal exposure in an infant born to an HBV-infected mother
- high-risk sexual behaviours
-
unsafe medical practices
- most common worldwide cause is unsafe injection practices
- unscreened blood transfusion
- IV/intranasal drug use
-
family history of HBV, hepatocellular carcinoma, and/or chronic liver disease
- genetic factors are associated with varying rates of viral clearance
younger individuals (particularly babies) are more likely to become chronic carriers
incarceration increases risk of the above risk factors
How is hepatitis B and C managed?
Immunisation
- active = recombinant HBsAg (at risk individuals, neonates with HBV+ mothers)
- passive = HB immunoglobulin/antibodies (post-exposure)
Symptomatic Tx
- acutely eg antipyretics, antiemetics and cholestyramine
Antiviral therapy
- entecavir, TDF, TAF, interferon-alpha
- see algorithm for indications
- usually life-long
- Nucleoside/nucleotide analogues. entecavir is a cytokine
What are the risk factors for HCC?
Chronic liver damage
- cirrhosis
- chronic hepatitis B and C
- chronic heavy alcohol use >80 g/day for more than 10 years
- Diabetes and obesity- insulin resistance
- FHx
- Aflatoxin
- Haemachromotosis (iron overload in liver)
What other investigations other than bloods would you do for HCC?
-
Abdo USS- initial staging test + cirrhosis screening every 6 months
- sensitive but not specific
- see irregular echos and poorly defined margins
-
CT/MRI abdo w/contrast
- more specific than USS
- used if AFP raised/abnormal USS
-
Liver biopsy
- not required in majority- radiological diagnosis
- see central necrosis, multinucleated giant cells, poorly differentiatd hepatocytes
What are the risk factors for NASH?
- obesity
- insulin resistance or diabetes
- hyperlipidaemia
- hypertension
- metabolic syndrome
- history of rapid weight loss
- hepatotoxic medications- oestrogens (tamoxifen), corticosteroids, methotrexate
- total parenteral nutrition
- increasing age
What investigations are undertaken for NASH?
LFTs-
- mildly elevated ALT/AST 1-4x normal
- AST:ALT ratio = <1 (in acute alcoholic, usually >2)
- mildly elevted/normal bilirubin, ALP, GGT
FBC-
- anaemia, thrombocytopaenia in advanced disease (due to hypersplenism)
Metabolic panel
- hyperglycaemia- due to insulin resistance
- hyperlipidaemia in lipid panel
Liver Ultrasound
- specific and sensitive
- diffuse hyperechoic echotexture (bright liver)
Liver Biopsy
- ultimately required for diagnosis
Abdo MRI/CT
- Show decreased liver attenuation and increased fat content
What are the presenting signs and symptoms of cirrhosis?
-
abdominal distension w/shifting dullness-
- from ascites due to portal hypertension
-
Haematemesis + meleana -
- from GO varices
- skin features:
- jaundice and pruritus
- impaired hepatic secretion of conjugated bilirubin and bile
- hand and nail features:
- leukonychia, palmar erythema, spider naevi, dupuytrens contracture
- facial features:
- telangiectasia, jaundiced sclera
- abdominal features:
- collateral circulation (caput medusae), hepatosplenomegaly, hair loss
- peripheral features:
- sarcopenia
- peripheral oedema
Explain 2 grading systems to estimate the prognosis in cirrhosis
Child-Pugh score + end stage liver disease :
Stage 1
- without GO varicies or ascites
- 1% mortality p/a
Stage 2
- GO varices but no bleeding + no ascites
- 4% mortality p/a
Stage 3
- ascites +/- GO varices but no bleeding
- 20% mortality p/a
Stage 4
- GI bleeding due to portal hypertension +/- ascites
- 57% mortality p/a
Define portal hypertension
Abnormally high pressure within the hepatic portal vein.
Clinically significant portal hypertension is defined as a hepatic venous pressure gradient > 10 mmHg
Explain the aetiology/pathophysiology of portal hypertension due to cirrhosis
Pressure within portal venous system is dependent on:
-
input from blood flow in the portal vein
- sodium retention + vasoactive NO increase (buildup of toxic metabolites)
- → increased plasma volume + splanchnic vasodilation
-
hepatic resistance to outflow
- Vascular channels go smooth → tortuous + irregular (collagen depositions and fibrosis)
- → increased resistance to flow
- → increased pressure → varices and dilations
State the pre-hepatic cuases of portal hypertension
- Splenic/ portal vein thrombosis (sepsis, trauma)
- Congenital stenosis
- Extrinsic compression eg by tumour
State the hepatic causes of portal hypertension
- CIRRHOSIS
- Schistomiasis
- Sarcoidosis + hepatic granulomas
- Myeloproliferative disease (CML/polycythaemia vera/essential thrombocytaemia)
State some post-hepatic causes of portal hypertension
Anything causing HEPATIC VENOUS OUTFLOW OBSTRUCITON
- Budd-Chiari syndrome (obstructing lesions of the hepatic veins and IVC)
- Constrictive pericarditis
- Tricuspid regurgitation
- Right heart failure (congestive cardiac)
What are the presenting symptoms of portal hypertension?
- splenomegaly, hepatomegaly
- ascites
- jaundice
- stigmata- spider naevi, caput medusae, umbilical hernia
- peripheral oedema
- gynaemcomastia
- GI varices - malaena, haemetemesis (may present with this)
- Encephalopathy- lethargy, irritability, disturbed sleep
How is portal hypertension managed?
Aimed at prevention of complications by decreasing portal pressures.
Pharmacotherapy
-
Beta-blockers eg propanolol
- reduce risk of variceal bleeding- only use if present
-
Somatostatin + vasopressin/terlipressin
- acute bleeding of varices
- vasoconstrictors of splanchnic beds
- Prophylactic antibiotics
Treating varices/GI haemorrhage
- Sclerotherapy
- Oesophageal band ligation
- Balloon Tamponade
Transjugular Intrahepatic Portosystemic Shunt (TIPSS)
Indicated in patients who have had recurrent bleeding despite medical or endoscopic management
Main side effect is hepatic encephalopathy + thrombosis
Liver transplant
Only effective treatment for end-stage liver disease.
Explain how varices develop
Varices develop when portal blood is rerouted to the systemic circulation, through collateral vessels
Due to increased resistance to blood flow to/through the liver.
The pressure within these irregular vessels is great and they have the potential to rupture.
What are the complications of portal hypertension?
- Variceal bleeding
- Ascites
-
Hepatopulmonary syndrome
- hepatic dysfunction
- hypoxaemia
- extreme intrapulmonary vasodilation
-
Hepatic hydrothorax
- pleural effusion for hepatic reasons (i.e. no cardiac, pulmonary, or pleural disease)
-
Hepatorenal syndrome
- rapid decline in kidney function (see diagram)
- Complications of liver failure- encephalopathy,
What are some causes of ascites?
Define liver failure (both acute and acute-chronic)
Rapid decline in hepatic function characterised by:
- jaundice
- coagulopathy (INR >1.5)
- hepatic encephalopathy
- acute/fulminant* = patients with no prior liver disease
- acute-on-chronic* = acute decompensation of chronic liver disease
Explain the pathogenesis of hepatic encephalopathy
- Ammonia is absorbed in the gut and enters the enterohepatic circulation
- Impaired liver function leads to impaired ammonia clearance + cirrhosis leads to portosystemic shunting → absorbed into blood
- Hyperammonaemia causes brain dysfunction as NH3 crosses the BBB and acts as a neurotoxin
- NH3 converted to glutamine in astrocytes causing swelling and oedema
What are the presenting symptoms of ALF?
- RUQ pain
- N+V
-
jaundice
- defining feature of ALF
- malaise
- signs of hepatic encephalopathy + cerebral oedema
- defining feature of ALF
- hepatomegaly but NO splenomegaly
- NO stigmata of chronic liver disease
- NO ascites
How is ALF managed?
-
Monitoring-
- blood glucose, electrolytes, cultures
- coagulopathy - IV vitamin K, FFP, platelet infusions
-
neurological status for encephalopathy
- manage = lactulose and phosphate enemas
- decrease ICP with mannitol
- blood glucose, electrolytes, cultures
-
Treat cause-
- acetylcysteine- paracetamol overdose
- autoimmune heptitis- methylprednisolone
- HBV- nucleoside/tide analogue- TDF, entecavir
- Budd Chiarri- anticoagulation (LMWH) + TIPSS
- Liver transplant
Wilson’s disease
An autosomal recessive disorder characterised by reduced biliary excretion of copper and accumulation of copper in the liver and brain, especially in the basal ganglia.
Also known as hepatolenticular degeneration.
What is the aetiology of Wilson’s disease?
Mutation in the ATP7B gene, which is part of the biliary excretion of copper by hepatocytes
Interference with the transport of copper by ATPases into hepatocyte compartments
Therefore no incorporation into caeruloplasmin or bile excretion
Excess copper damages the hepatocyte mitochondria → necrosis and copper release into plasma
Recognise the presenting symptoms of Wilson’s disease
May present with hepatitis, liver failure, cirrhosis (and associated symptoms- jaundice, ascites, oedema)
- Kayser-Fleischer Rings – visible to naked eye in late stages, early stages seen by slit lamp
-
behavioural abnormalities
- delusions, loss of emotional control, memory loss, depression
-
dysarthria, dystonia
- speech may be slow/slurred
-
incoordination, dysdiadochokinesis, tremor
- sloppy or small handwriting
- can’t alternate hands from prone to supine
-
abnormal extraocular movements
- saccadic movements, esotropia, diplopia
Identify appropriate investigations for Wilson’s disease
- LFTs: high AST, ALT, ALP
- FBC- thrombocytopaenia, low WCC
-
Low serum caeruloplasmin
- acute phase protein- may give false-negatives in inflammation/chronic liver disease/pregnancy
- Serum copper
- 24 hour urinary copper - high
- Slit-lamp exam- KF rings
- Liver biopsy - increased copper content
- Genetic analysis - ATP7B mutations
- MRI head – degeneration in basal ganglia, fronto-temporal, cerebellar and brainstem
