liver Flashcards
Describe the drug metabolism of aspirin
Phase I:
- Hydrolysis reaction:
Aspirin + H2O —> Salcylic acid + Ethanoic acid
Phase II:
- Conjugated with glycine or glucuronic acid
- Forms a range of ionised products which can be excreted
What is the metabolism reaction of alcohol
ADH = alcohol dehydrogenase
ALDH = aldehyde dehydrogenase
Ethanol—ADH—> acetaldehyde—ALDH—> Acetate —> CO2 + H20
Functions of the liver
(ADMIReS)
Albumin
Detoxification
Metabolism of carbs and billirubin
Immunity (Kuppfer cells)
Regulation of oestrogen levels
e
Storage (vitamins ADEK, Fe, Cu, fat)
Liver function tests (LFTs) - markers of liver function
- Bilirubin (mainly unconjugated)
- Albumin
- Prothrombin time (PT/INR)
Direct markers of liver damage
- Highun conjugated bilirubin
- Low albumin
- High PT/INR
Enzymes that show liver damage is likely
- AST and ALT
- AST:ALT usually around 1
If your AST levels are too high, it might be a sign of an injury affecting tissues other than the liver. High ALT levels may mean you have a liver injury.
Bilirubin metabolism
1 – Creation of Bilirubin
Reticuloendothelial cells are macrophages which are responsible for the maintenance of the blood, through the destruction of old or abnormal cells. They take up red blood cells and metabolise the haemoglobin present into its individual components; haem and globin. Globin is further broken down into amino acids which are subsequently recycled into new rbcs.
Meanwhile, haem is broken down into iron and biliverdin, a process which is catalysed by haem oxygenase. The iron gets recycled to rbcs, while biliverdin is rapidly reduced (bilverdin reductase) to create unconjugated bilirubin.
2 – Bilirubin Conjugation
In the bloodstream, unconjugated bilirubin binds to albumin to facilitate its transport to the liver. Once in the liver, glucuronic acid is added to unconjugated bilirubin by the enzyme glucuronyl transferase. This forms conjugated bilirubin, which is more soluble. This allows conjugated bilirubin to be excreted into the duodenum in bile.
3 – Bilirubin Excretion
Once in the colon, colonic bacteria deconjugate bilirubin and convert it into urobilinogen. Around 80% of this urobilinogen is further oxidised by intestinal bacteria and converted to stercobilin and then excreted through faeces. It is stercobilin which gives faeces their brown colour.
Around 20% of the urobilinogen is reabsorbed into the bloodstream as part of the enterohepatic circulation. It is carried to the liver where some is recycled for bile production, while a small percentage reaches the kidneys. Here, it is oxidised further into urobilin and then excreted into the urine.
What is the name of the cells responsible for fibrosis?
Stellate
Functions of the peritoneum
In health:
- Visceral lubrication
- Fluid and particulate absorption
In disease:
- Pain perception
- Inflammatory and immune response
- Fibrinolytic activity
Risk factors for biliary tract disease
- Female
- Fat (BMI 30+)
- Forty (+)
- Fertile (pregnant or many children)
- Fair
also:
- Family history
- Fatty liver disease (non-alcoholic)
- T2DM
- Haemolytic conditions
Symptoms of ascending cholangitis
Charcot’s triad:
- RUQ pain
- High fever
- Jaundice
Reynold’s pentad:
- Charcot’s triad + altered mental state + hypotension
Diagnosis of ascending cholangitis
- FBC: leukocytosis
- LFT: high conjugated hyperbilirubinaemia
- Abdo ultrasound for CBD dilation and gallstones
- MRCP: diagnostic
Treatment of ascending cholangitis
- ERCP (bile duct clearance)
- Laproscopic cholecystectomy once stable to prevent recurrence
- Consider risk of sepsis
- Empiricle while waiting Abx - co-amoxiclav
MRCP and ERCP
MRCP = Magnetic resonance cholangio-pancreatography
ERCP = Endoscopic retrogade cholangio-pancreatography
Murphy sign
- RUQ tenderness, ask patient to take a breath in while pressing RUQ
- Will wince or stop inspiring normally in cholecystitis
Symptoms of cholecystitis
- RUQ pain
- Fever
- Tender gallbladder
- Referred pain to tip of right shoulder (phrenic)
- Murphy sign positive
Diagnosis of cholesystitis
- FBC: leukocytosis + neutrophilia
- LFT: normal
- Abdo ultrasound shows thickened gallbladder wall 3mm≤
and stones/sludge in and fluid around gallbladder
Treatment for cholecystitis
- Surgery within 1 week, typically done within 72 hours
- via laproscopic cholecystectomy
- Until then: IV fluids, analgesia, antibiotics if necessary, nothing by mouth
Complications of cholecystitis
- Sepsis
- Gallbladder empyema
- Gangrenous gallbladder
- Perforation
What are gall stones made from?
- Cholestrol (80%)
- Pigment
- Or mixed
Symptoms of gallstones
- Colicky or sharp pain
- Fever
- Jaundice
- Dietary upset
Worse after a fatty meal, may come in episodes
Diagnosis of gall stones
Bloods:
- Alanine transaminase
- Bilirubin
- Amylase
Then:
First line: Abdominal ultrasound to identify gallstones
Or: MRCP (MRI scan) or CT abdomen & pelvis
Aetiology of gall stones
- Cholesterol supersaturation (diet, hormones)
- Genetic (gallbladder motility)
- Haemoglobin turnover (haemolytic anaemia, cirrhosis, sickle cell)
10% of people have gallstones
And they acount for 30% of all acute presentations
Management of gall stones if not treating directly/straight away
- NSAIDs for mild pain
- IM diclofenac for severe pain
- Change lifestyle
- Decrease fat in diet
Treatment of gallstones
Symptomatic OR asymptomatic and stone blocks CBD:
Elective laproscopic cholecystectomy
Radiological drain (cholesystostomy)
ERCP (endoscopy)
Complications of gallstones that may also be signs
- Acute cholecystitis
- Acute cholangitis
- Obstructive jaundice
- Pancreatitis
What is it called when a gall stone is trapped in the common bile duct?
Choledocholelithiasis
What is a hernia?
Protrusion of an organ through a defect in its containing cavity. Typically bowel
Reducible vs irreducible hernias
Reducible - can be pushed back into place
Irreducible:
- Obstructed - intestinal obstruction
- Strangulation - intestinal ischaemia
- Incarcerated - contents fixed in sac due to size or adhesions
Curative treatment for hernias
Surgery
Other types of hernias
- Umbilical (in neonates)
- Incisional (surgical scars)
- Epigastric
- Obturator (Howship-Romberg sign)
- Diastasis recti
- Spigelian
What is a femoral hernia?
- Bowel herniates through femoral cord
- Female, mid-old age
- Very likely to strangulate due to rigid femoral canal borders
Symptom of femoral hernia
Swelling in upper thigh pointing down
Diagnosis of femoral hernia
- Abdo/pelvic ultrasound if unsure
- BUT usually clinical (based on symptoms)
Borders of the femoral TRIANGLE
Sartorius laterally
Adductor longus medially
Inguinal Ligament superiorly
⛵️
Borders of the femoral CANAL (within the femoral triangle)
Femoral vein laterally
Lacunar ligament medially
Inguinal ligament anteriorly
Pectineal ligament posteriorly
Rolling hiatal hernias
- 20%
- LOS stays in the abdomen
- Part of fundis rolls into thorax
Sliding hiatal hernias
- 80%
- LOS slides into abdomen
What is a hiatal hernia?
- Stomach herniates through diaphragm aperture
- Obese women and 50+ year olds
Symptoms of hiatal hernias
- GORD
- Dysphagia
Diagnosis of hiatal hernias
- Barium swallow (diagnostic)
- Oesophago gastro duodenoscopy
- Chest x-ray
What is an inguinal hernia?
- Spermatic cord herniates through inguinal canal
- In males (obviously
- History of heavy lifting/abdopressure
Direct inguinal hernias
- 20%
- In Hesselbach’s triangle
- Medial to inferior epigastrics
Hesselbach’s triangle
Rectus abdominis medially
Inferior epigastric vessels superiorly/laterally
Poupart’s (inguinal) ligament inferiorly
🪦
Indirect inguinal hernias
- 80%
- Not in Hesselbach’s triangle
- Lateral to inferior epigastrics
Symptoms of inguinal hernias
- Painful swelling in groin
- Points along groin margin
Diagnosis of inguinal hernias
- Usually clinical
- Unsure = AUSS (CT/MRI)
Acute vs chronic pancreatitis
Acute
- Reversible acute inflammation of the pancreas
Chronic
- 3+ month history of pancreatic deterioration
- Irreversible pancreatic inflammation + fibrosis
Causes of acute pancreatitis
Idiopathic
Gallstones
Ethanol🍾🍷🍻
Trauma
Steroids
Mumps/malignancy
Autoimmune
Scorpion stings
Hypercalcaemia/hyperlipidaemia
ERCP
Drugs (azathiprine, NSAIDs, ACE inhibitors, tobacco, thiazides)
Pathophysiology of acute pancreatitis
- Gall stones obstruct pancreatic secretions
- Accumulated digestive enzymes in pancreas
- Host defences soon overwhelmed
- Causes autodigestion -> inflammation + enzymes leak in blood
Symptoms of acute pancreatitis
- Sudden severe epigastric pain radiating to the back (DDx: abdominal aortic aneurysm)
- Nausea and vomiting
- Jaundice
- Pyrexia
- Steatorrhoea
- Grey Turner sign and Cullen sign
Diagnosis of acute pancreatitis
- Blood test first line: High serum amylase/lipase
- Cxr to eclude gastroduodenal perforation
- Abdo ultrasound -> diagnostic for gall stones; CT/MRI for extent of damage
Glasgow score for severity of acute pancreatitis
PaO2 < 8KPa
Age > 55
Neutrophils (WBC > 15x109/L)
Calcium > 2mmol/L
Renal urea > 16mmol/L
Enzymes (LDH > 600iu/L or AST > 200iu/L)
Albumin < 32g/L
Sugar, glucose > 10mmol/L
0-1 - mild pancreatitis
2 - moderate pancreatitis
3+ - severe pancreatitis
Treatment for acute pancreatitis
- Rescuscitation if required
- IV fluid
- IV analgesia
- IV antibiotics for infection/associated cholangitis
- Nil by mouth
- ERCP within 72 hours of pain onset if required
Main complication of acute pancreatitis
Systemic inflammatory response syndrome (SIRS)
2 ≤ out of:
- Tachycardia (90+ bpm)
- Tachypnoea (20+ RR)
- Pyrexia (38°c <)
- High WCC
Causes of chronic pancreatitis
- Alcohol (mc)
Also:
- CKD
- CF
- Trauma
- Recurrent acute pancreatitis
- Cancer
- Autoimmune
Symptoms of chronic pancreatitis
- Epigastric pain radiating to back - exacerbated by alcohol
- Exocrine (eg: steatorrhoea) and endocrine (eg: T2DM) dysfunction
- Pseudocysts or abscesses
DDx: Pancreatic cancer, especially of body and tail
Diagnosis of chronic pancreatitis
- Faecal elastase low (indicator of exocrine function)
- Abdo ultrasound and CCT to detect pancreatic calcification and dilated pancreatic duct (diagnostic)
Treatment of chronic pancreatitis
- Alcohol cessation
- Dietary modification
- Analgesia for abdo pain, first line = NSAIDs
- Pancreatic supplements (eg: enzymes, insulin for DM)
- ERCP or surgery if required
Pathophysiology of primary biliary cholangitis
- Intrahepatic autoimmune jaundice affecting intralobular bile ducts
- Autoantibodies cause intralobular bile duct damage; chronic autoimmune granulomatous inflammation
- Resulting in cholestasis -> Fibrosis, cirrhosis, portal hypertension, infection
Risk factors for primary biliary cholangitis
- Female
- 40-50 years old
- Other autoimmune disease
- Smoking
Complications of primary biliary cholangitis
- Malabsorption of fats + vit ADEK (=steatorrhoea)
- Ostemalacia
- Coagulopathy
Symptoms of primary biliary cholestasis
- Initially often asymptomatic
- Routine test shows high anti-mitochondrial antibodies
- Pruritis + fatigue earliest, then jaundice, then hepatosplenomegaly, + xanthelasma
Diagnosis of primary biliary cholangitis
- LFT
- Rule out acute hepatitis by testing for HepBsAg and HVCAb
- Serology
- Rule out extrahepatic cholestasis via ultrasound
- Liver biopsy
LFT and serology results for primary biliary cholangitis
LFT:
- High ALP
- High conjugated bilirubin
- low albumin
Serology:
95% have anti-mitochondrial antibodies (especially M2)
Liver biopsy results for primary biliary cholangitis
- Portal tract infiltrate (lymphocyte + plasma cell)
- 40% granulamatous
- Portal tract fibrosis
Treatment for primary biliary cholangitis
- Ursodeoxycholic acid (reduces intestinal absorption of cholesterol)
- Colestyramine to treat pruritus
- Consider vitamin ADEK supplements
- May ultimately need liver transplant
Pathophysiology of primary sclerosis cholangitis
- Autoimmune destruction of intra + extralobular hepatic duct
- Blocks the flow of bile out of the liver into the intestines
- Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis
Risk factors for primary sclerosing cholangitis
- Male
- 40-50
- Strong link to IBD (especially ulcerative cholitis)
Presentation of primary sclerosis cholangitis
- 50% asymptomatic until disease advances
- Charcot’s sign
- Pruritis
- Fatigue
- Hepatosplenomegaly
- IBD
Diagnosis of primary sclerosing cholangitis
- Cholestatic LFT
- GS imaging: MRCP
- Biopsy same as PBC
Serology: - HBVsAg/HCVAb -ve
- AMA -ve
- Coelic screen anti tTG -ve
- pANCA +ve in 33-88%
Treatment of primary sclerosing cholangitis
Conservative:
- Colestyramine for pruritis
- Fat soluble ADEK
- ERCP to dilate and stent structures
- Consider liver transplant
Risk factors for alcoholic liver disease
- Chronic alcohol
- Obesity
- Smoking
- Female gender
- Genetic
Stages of alcoholic liver disease
steatosis (fatty liver, undamaged)
alcohol hepatitis (w/ mallory bodies)
alcohol cirrhosis (micronodular)
Symptoms of alcoholic liver disease
- Early stages may be asymptomatic
Later: - Chronic liver failure symptoms
- Alcohol dependency
- Hepatomegaly
Assessing alcohol dependency
- Alcohol use disorder ID test: 10 questions
- Questionnaire with CAGE questions (>2 = dependent!)
- Should you cut down?
- Are people annoyed by your drinking?
- Do you feel guilty about drinking?
- Do you drink in the morning? (eye opening)
Diagnosis of alcoholic liver disease
Bloods
- LFT shows liver damage
- High GGT-
- (gamma-glutamyl transferase (GGT) test measures the amount of GGT in the blood. GGT is an enzyme found throughout the body, but it is mostly found in the liver. When the liver is damaged, GGT may leak into the bloodstream. High levels of GGT in the blood may be a sign of liver disease or damage to the bile ducts)
-
- AST:ALT > 2
- Macrocytic and megaloblastic anaemia
Biopsy to confirm extent:
- Mallory cytoplasmic inclusion bodies
- Inflammation and necrosis in alcoholic hepatitis
Conservative treatment for alcoholic liver disease
- Healthy diet, lower BMI
- Stop alcohol
Pharmacological treatment for alcoholic liver disease
- Consider steroids short term (Maddrey’s discriminant value of 32)
- IV thiamine (Vit B1) so you don’t develop Wernicke Korsakoff syndrome
- Could also give folate
Surgical treatment for alcoholic liver disease
- Consider liver transplant for ESLF cases-end stage liver failure
- Must have abstained from alcohol for 3+ months
Complications of alcoholic liver disease
- Pancreatitis
- Hepatic Encephalopathy
- Ascites
- HCC= Hepatocellular carcinoma
- Mallory-weiss tear
- Wernicke Korsakoff syndrome
Pathophysiology of ALD
- Alcohol dehydrogenase enzymes and cytochromes (2 ways of metabolism)
Alcohol dehydrogenase and acetaldehyde dehydrogenase reduce nicotinamide adenine dinucleotide (NAD) to NADH (reduced form of NAD). Excessive NADH in relation to NAD inhibits gluconeogenesis and increases fatty acid oxidation, which in turn promotes fatty infiltration in the liver.
oxidative stress promotes hepatocyte necrosis and apoptosis in these patients. Free radicals can also induce lipid peroxidation, which can cause inflammation and fibrosis. The alcohol metabolite acetaldehyde, when bound to cellular protein, produces antigenic adducts and induces inflammation.
- Risk of forming reactive O2 species, more overload = more O2 species
- Eventual scar tissue around central veins, adding to portal hypertension
Delirium tremens+ treatment
- Alcohol stimulates GABA receptors and inhibits glutamate receptors
- Chronic alcohol leads to upregulation of glutamate receptors and downregulation of GABA receptors
- Treat wirh IV Chlordiaepoxide or diazepam
Alcohol units
- 1 unit = 8g/10ml pure alcohol
- Recommended no more than 14 units a week for both men and women
Equation:
strength (ABV) x volume (ml)
dividedby
1000
1000
Alcohol withdrawal
6-12 hours: tremours, sweating, headaches
12-24 hours: hallucination
24-48 hours: seizures
24-72 hours: delirium tremens (medical emergency)
Gilbert’s syndrome
- Most common in males
- T1DM
- Autosomal recessive
- Most common cause of hereditary jaundice
Pathophysiology of Gilbert’s syndrome and Crigler Najjar syndrome
- Autosomal recessive
- Deficient or abnormal UGT (UDP101), reducing UGT activity
- Causes an excess in unconjugated hyperbilirubinaemia
(In Crigler Najjar, UGT is completely gone)
Presentation of Gilbert’s syndrome
- 30% asymptomatic
- Typically males around 20
- May present with painless jaundice at a young age
Symptoms of Crigler Najjar syndrome
- More severe than Gilbert’s
- Jaundice
- Nausea and vomiting
- Lethargy
Treatment of Gilbert’s and Crigler Najjar syndrome
- Gilbert’s: Usually no need
- CN: Phototherapy to break down unconjugated bilirubim
Complications of Crigler Najjar syndrome
- More severe progression chances
- Can die from kernicterus in childhood
- Kernicterus is accumulation of bilirubin in the basal ganglia, causing severe neurological deficits
What do all types of hepatitis show?
Interface necrosis
“Piecemeal necrosis” on histology (don’t ask wjhat it looks like bc idk)
Pathophysiology of autoimune hepatitis
- Chronic inflammation of the liver - aka: lupoid hepatitis, very rare
- T helper cell mediated response vs hepatocytes
Risk factors for autoimmune hepatitis
- Female:male, 4:1
- Nitrofurantoin use
- Other autoimmune diseases
- Viral hepatitis
- HLA DR3 or DR4
Type 1 autoimmune hepatitis
- Adult females
- 80% of cases
- ANA - antinuclear antibody (found in many other autoimmune diseases but very specific for Type 1 autoimmune hep)
- ASMA - antismooth muscle antibody
Type 2 autoimmune hepatitis
- Young females
- Rarer
- ALC-1 (antiliver cystosol)
- ALKM-1 (antiliver-kidney microsome)
Presentation of autoimmune hepatitis
- 25% asymptomatic
- Many = jaundice, fever, hepatosplenomegaly
- Anorexia
- Lupus-like rash
Treatment for autoimmune hepatitis
- Corticosteroids - prednisolone
- Immunosuppressants - azathioprine
- Hep A+B vaccination (depending on cause)
- Last resort - consider transplant
Pathophysiology of viral hepatitis
Inflammation of the liver as a result of viral replication within hepatocytes
Virus types of Hepatitis
- All are single-strand RNA
- Apart from Hep B, which is double-strand DNA
Which hepatitis needs to be notified to Public Health England?
All
Which types of hepatitis have 100% immunity after infection?
A & E
Acute vs chronic hepatitis
- Acute: First 6 months of liver inflammation
- Chronic: Any inflammation beyond 6 months
Spread of Hep A
- Faeco-oral spread
- Fly vectors
- Picornavirus
Risk factors for Hep A
- Overcrowding
- Poor sanitation
- Shellfish
- Travel - endemic in Africa, Asia, South America, Middle East
Pathophysiology of Hep A
- Incubation for 2 weeks
- Replicates in liver, excreted in bile
- Self limiting within 6 weeks (having it/vaccine gives 100% immunity)
- Acute, mild
Symptoms of Hep A
Prodromal phase (1-2 weeks):
- Malaise
- Nausea and vomiting
- Fever
Then:
- Jaundice - dark urine + pale stools
- Hepatosplenomegaly
- Skin rash
Diagnosis of Hep A
- Bloods: High ESR + leukopenia
- LFT: Bilirubin high when there is jaundice
- Serology:
HAV IgM = acutely infected
HAV IgG = chronically infected
Treatment of Hep A
- Supportive (treatment often not required)
- Travellers vaccine available
Complications of Hep A (Rare)
Fulminant liver failure😶🌫️
Spread of Hep B
- Needles (needlestick injury, tattoo, IVDU)
- Sexual
- Vertical (mother -> child)
- Horizontal (between children)
Blood borne and found in semen and saliva
Risk factors for Hep B
- IVDU
- MSM
- Dialysis patients
- Healthcare workers
- Present worldwide
Symptoms of Hep B
- Similar to Hep A
- 1-2 weeks prodrome
- Then jaundice (dark urine + pale stools), hepatomegaly, uticaria-hives, arthralgia- joint pain
Pathophysiology of Hep B and incubation period
- Acute infection infects hepatocyte, cellular response usually clears it
- Incubation 1-6 months
Serology chart for Hep B
HBsAg: acute, chronic, can be carrier
Anti HBsAg: cleared, vaccine
IgM Anti HBcAg: acute
IgG Anti HBcAg: chronic, carrier, cleared
Hepatitis B antigens and antibodies diagram
Surface antigen: HBsAg. +ve = infection. Vaccine = HBsAg
E antigen: HBeAg. Released during replication. +ve = acute phase. high level = high infectivity
Core antigen: HBcAg. not in blood. Middle of virus(core)
Surface antibody: HBsAb. response to HBsAg. +ve = vaccinated or infected
E antibody: HBeAb. Response to HBeAg. +ve = been through active phase - immune response
Core antibody: HBcAb. response to HBcAg.
IgM is higher in acute infection and lower in chronic.
IgG with positive and negative HBsAg= past infection
Treatment for Hep B
- Peginterferon alfa-2a
- Antiviral therapy
- IV Igs for neonates
Complications of Hep B
- 5-10% of cases progress to chronic liver failure + HCC risk
- HBV-associated decompensation with HCC has the worst prognosis
- 90% cases in children become decompested and associated with poor prognosis. TRANSPLANT
Spread of Hep C
Blood-borne and bodily fluids
- IVDU
- Flavivirus
- IVDU more than vertical/sexual transmission
- More common in the UK, again common in Africa
Symptoms of Hep C
- Often acutely asymptomatic, allowing it to become chronic later on
- Few patients with flu-like symptoms
- Chronic causes a sow progressive fibrosis over years + hepatosplenomegaly
Diagnosis of Hep C
- LFTs
- Serology:
HCVRNA = current infection/diagnoses acute infection
HCVAb = presents within 4-6 weeks of infection, if present after 6 months then it’s chronic
Treatment of Hep C
Direct acting antivirals, expensive 💸
- NS5A-inhibitor (acivir)
- NS5B-inhibitor (buvir)
- Previr
Complications of Hep C
30% cases progress to chronic liver failure (cirrhosis and HCC risk)
Spread of Hep D
- Intravenous drug use
- Sexually transmitted
Pathophysiology of Hep D
- Acute + chronic (like Hep B)
- Dependant on surface antigen of Hep B to replicate, makes Hep B more likely to progress to cirrhosis/HCC
- Clinically indistinguishable from acute Hep B
Diagnosis of Hep D
Manifests as co-infection IgM HDV + IgM HBV
Treatment and complications of Hep D
- Treat Hep B
- Can also use inteferons but not that good lol
Spread of Hep E
- Faeco-oral (undercooked pork)
- Water
- Dogs
- Calicivirus
More on Hep E
- Usually self limiting acute hepatitis (95% are asymptomatic)
- Commoner than Hep A in the UK (endemic)
- Common in Indo-China
Complications of Hep E
- Can cause chronic disease in immunosuppressed
- Can cause fulminant liver failure:
Normal mortality 1-2%
Pregnant ladies 10-20% !!!
Diagnosis of Hep E
Serology:
HEV IgM = acute infection
HEV IgG = recovery, only chronic in immunocompromised patients
Treatment of Hep E
- Supportive, self limiting
- Vaccine only in China! 🇨🇳
Primary vs secondary liver cancer
Primary
- Less common
- Cancer that originates in the liver
- Hepatocellular carcinoma (90%) and cholangiocarcinoma (10%)
- There are also benign primary tumours
Secondary
- More common
- Cancer that originates outside of the liver and metastasises to the liver
Types of benign primary tumours
- Hepatic adenoma
- Focal nodular hyperplasia
- Haemangioma - most common, seen in infants as “strawberry mark” on skin within first few weeks of life 🍓
What does cholangiocarcinoma arise from
- The biliary tree
- Typically adenocarcinomas
Risk factors for cholangiocarcinoma
- Parasitic flukeworms
- Biliary cysts
- IBD
- Primary sclerosing cholangitis
Symptoms of cholangiocarcinoma
- Abdominal pain
- Weight loss
- Puritis
- Fevers
- COURVOISER sign (but pancreatic cancer is usually more comon)you have jaundice and a gallbladder that is enlarged but is not painful.
🌌late constellation of symptoms as tumour is slow growing🌌
Diagnosis of cholangiocarcinoma
- LFT: high bilirubin, high ALP
- High CEA and CA19-9
- First line = imaging: abdominal ultrasound + CT
- ERCP (imaging of biliary tree) - invasive but can be therapeutic and diagnostic
Treatment of cholangiocarcinoma
Majority of cases inoperable as patients present very late
What does hepatocellular carcinoma (HCC) arise from?
Liver parenchyma
Risk factors of HCC
- Chronic hepatitis virus - C and B
- Decompensated liver cirrhosis
What does HCC metastasise to?
- Lymph nodes, bones, lungs
- Via haematogenous spread (hepatic/portal veins)
Symptoms of HCC
- Signs of decompensated liver failure (jaundice, ascites, HE…)
- Signs of cancer (TATT, unexplained weight loss, nausea, vomiting…)
- May have irregular hepatomegaly
Diagnosis of HCC
- High serum AFP
- Imagine: first line ultrasound, CT for confirmation
- Biopsy is diagnostic but often avoided to prevent seeding of tumour elsewhere
Treatment for HCC
- Surgical resection of tumour
- In decompensative cirrhosis -> liver transplant
- Prevantative: Hep B vaccineas hep b can cause hcc
What is pancreatic cancer?
- Adenocarcinoma (in most cases) of the exocrine pancreas
- Of ductal origin
- Typically affects the head of the pancreas
Risk factors for pancreatic cancer
- Males
- 60+
- Smoking
- Alcohol
- DM
- Family history/genetics (PRSS-1 gene mutation)
- Chronic pancreatitis
What parts of the pancreas does pancreatic cancer usually target?
- Head - 60%
- Body - 25%
- Tail - 15%
Presentation of pancreatic cancer of the head
Courvoisier sign
- Painless jaundice
- Pale stools + dark urine
- Palpable gall bladder
General presentation of pancreatic cancer
- Epigastric pain radiating to the back, worse at night (relieved sitting forward)
- Trousseau sign - migratory thrombophlebitis
- Weight loss and anorexia
- Recent diagnosis of DM
- Nausea
- Vomiting
- Constipation
Referral for pancreatic cancer
- Over 40 + jaundice - 2 week wait referral for suspected cancer pathway
- Over 60 + weight loss + one other symptom - direct access CT scan within 2 weeks
Management of pancreatic cancer
- Mainly palliative due to very poor prognosis, 5 year survival rate of 3%
- Surgery (Whipple’s procedure) + post-op chemo if no mets
Diagnosis of pancreatic cancer
- CT scan and histology from a biopsy
- CA19-9 tumour marker (non-specific)
- CT TAP scan (thorax, abdomen pelvis) for staging
Ammonia
- Neurotoxic - causes irreversible brain damage
- Because it stops the Krebs cycle
Symptoms of liver failure
- RUQ pain
- Hepatomegaly
- Jaundice
- Nausea and vomiting
- Ascites
- Bruising or muscle wasting
Aetiology of acute liver failure
- Viral: Viral hepatitis, CMV, EBV
- Autoimmune hep (more chronic)
- Drugs: paracetamol overdose, alcohol, ecstasy
- HCC
- Metabolic: Wilson’s, haemochromatosis, A1ATD
- Budd Chiari syndrome
Fulminant liver failure
- Rare syndrome of massive multiacinar necrosis
- Rapid
- Caused by paracetamol overdose in 50% of cases in the UK
Types of fulminant liver failure
Hyperacute - Hepatic encephalopathy within 7 days of jaundice
Acute - Hepatic encephalopathy within 8-28 days of jaundice
Subacute - Hepatic encephalopathy within 5-26 weeks of jaundice
Pathophysiology of acute liver failure
- Declined liver function
- Liver loses regeneration/repair ability -> irreversibly damaged
- In patient with previously normal liver
West Haven criteria grades 1-4 of hepatic encephalopathy
- Altered mood, sleep problems
- Lethargy, mild confusion, asterixis, jaundice
- Marked confusion, solmonence, ataxia
- Comatose
Presentation of acute liver failure and their diagnosis
- Jaundice - hyperbilirubinaemia
- Coagulopathy - raised PT/INR over 1.5
- Hepatic encephalopathy - EEG
- Extent of liver damage: biopsy GOLD STANDARD
Top 3 are main characteristics
Diagnosis of acute liver failure
- Bloods
- Imaging
- Microbiology
Bloods for acute liver failure
- LFTs show liver damage (High bilirubin, low albumin, high PT/INR)
- High serum AST + ALT
- High NH3
- Low glucose
Imaging for acute liver failure
- EEG to grade HE
- Abdominal ultrasound to check for Budd Chiari syndrome
Microbiology for acute liver failure
- To rule out infections
- Blood culture, urine cultire, ascitic tap
Treatment of acute liver failure
- ITU, ABCDE, fluid, analgesia
- Treat underlying cause and complications
Treatments for complications of liver failure
- High ICP: IV mannitol
- HE: Lactulose (increases NH3 excretion)
- Coagulopathy: Vit K
- Ascites: Diuretics, esp spironolactone
- Sepsis: Sepsis 6 pathway
Cause of failure with lung pathology
Alpha 1 antitrypsin deficiency
Risk factors for chronic liver failure
- Alcohol
- Obesity
- T2DM
- Drugs
- Inherited metabolic diseases/existing autoimmunity
Assessing prognosis and requierd treatment for chronic liver disease
✨Child-Pugh score✨
- Considers bilirubin, ascites presence, serum albumin, PT/INR, hepatic encephalopathy
A: 100% 1 year survival
B: 80% 1 year survival
C: 45% 1 year survival
End stage liver failure
- Decompensated cirrhosis
- A high risk factor for developing hepatocellular carcinoma
Presentation of chronic liver failure
- Same as acute +
- Portal hypertension
- Oesophageal varices
- Caput medusae- the appearance of a network of painless, swollen veins around your bellybutton
- Spider naevi- dilation of preexisting central arterioles from which numerous thin-walled capillary branches radiate like red spider legs, carrying away freely flowing blood
- Palmar erythema- a rare condition that makes the palms of the hands turn red.
- Gynecomastia
- Clubbing 🕺
- Fetor hepaticus - chronic bad breath due to liver
- Dupuytren contracture- an abnormal thickening of tissues in the palm of the hand. The thickened tissues may develop into a hard lump. Over time it can cause 1 or more fingers to curl (contract) or pull in toward the palm.
Diagnosis of chronic liver failure
- Liver biopsy to determine extent (fibrosis vs cirrhosis)
- LFT, imaging, ultrasound, ascitic tap culture
Treatment of chronic liver failure
- Prevent progression (decrease alcohol and BMI, avoid drugs)
- Consider liver transplant if decompensated liver failure
- Manage complications
Progress of chronic liver failure
hepatitis/ cholestasis —> fibrosis (reversible damage) —-> cirrhosis (irreversible) —> compensated (some extent of liver function) OR decompensated (ESLF)
Aetiology of chronic liver failure
- ALD (Most common)
- NAFLD
- Viral: Hep B, C, D
- Budd Chiari syndrome
- Drugs
- Autoimmine
- PBC + PSC
Pathophysiology of liver cirrhosis
- The result of chronic inflammation and damage to liver cells
- When liver cells are damaged, they are replaced with scar tissue, fibrosis, and nodules within the liver
- Increased resistance leading to portal hypertension
Aetiology of liver cirrhosis
- Alcoholic liver disease (most common cause in developed world)
- Non-alcoholic fatty liver disease
- Hepatitis B
- Hepatitis C
Complications of liver cirrhosis
- Ascites
- Portal hypertension
- Varices
- Jaundice
- Spider naevi + caput medusae
- Coagulopathy
- Hypoalbuminaemia -> oedema
- Portosystemic encephalopathy
- Hepatorenal and hepatopulmonary syndromes
Diagnosis of liver cirrhosis
- LFTs show liver damage (most accurate)
- FBC: thrombocytopenia
- ALT, AST, ALP are all deranged
- Definitive = liver biopsy
Treatment for liver cirrhosis
- Definitive = liver transplant
- Conservative: fluids, analgesia, alcohol abstinence, good nutrition
- Treat complications
Compensated vs decompensated cirrhosis
Compensated - liver is able to override ability to function
Pathophysiology of alpha 1 antitrypsin (A1AT) deficiency
- Autosomal recessive muttion of serdina-1 gene (protease inhibitor) on chromosome 14 causes deficiency of A1AT
- A1AT normally inhibits NE-neutrophil elastase, NE degrades elastic tissue
Lungs: - Degrades elastic tissue
- Alveolar duct collapse
- Air trapping
- Characteristic panacinar emphysema
Liver: - Soon becomes fibrotic; cirrhosis + HCC risk
- A1AT is made by the liver so fibrotic will make synthetic liver function even worse - catch 22
Presentation of A1AT deficiency
- Young/mid aged man with little to no smoking history but COPD-like symptoms
Lung symptoms: - Dyspnoea
- Chronic cough
- Sputum production
- Barrel chest - chest becomes expanded in size
- Pink puffer- fast, labored breathing may cause their skin to appear red or pink temporarily
Liver symptoms: - Jaundice
Diagnosis of A1AT deficiency
- Serum A1AT < 20mmol/L
- Barrel chest on exam, cxr shows hyperinflated lungs
- CT = panacinar emphysema
- LFT shows obstruction (FEV1:FVC < 0.7)
- Genetic testing
Treatment for A1AT deficiency
- If smoking, stop
- Manage ephysema, eg: inhalers (SABAs and LABAs)
- Consider hepatic decompensation patients for liver transplant
Pathophysiology of haemachromatosis
- Autosomal recessive mutation of HFE gene (chromosome 6)
- Excess Fe uptake by transferrin-1 and low hepcidin synthesis (hepcidin regulates Fe homeostasis)
- Fe accumulation and fibrosis of liver (+ pancreas, kidney, heart, skin, ant. pituitary)
Normal Fe vs Fe in haemochromatosis
- Normal: 3-4g
- Haemochromatosis: 20-30g
Risk factors for haemochromatosis
- Male
- 50s
- Genetics
- Can be due to excess transfusions (secondary)
Symptoms of haemochromatosis
- Fatigue
- Joint pain
- Hypogonadism (due to anterior pituitary damage)
- Slate grey/bronze skin
- Liver cirrhosis symptoms
- Osteoporosis
- Heart failure
Gross Fe overload triad
- Bronze statue skin
- Hepatomegaly
- T2DM
Diagnosis of haemochromatosis
- Fe studies
- Genetic test
- Liver biopsy (assess degree of damage with Perl’s Prussian blue stain)
Fe studies results in haemochromatosis
- High serum Fe
- High ferritin
- High transferrin saturation
- Low total iron-binding capacity
Treatment of haemochomatosis
- First line: Venesection 3-4 times a year for life
- If contraindicated; desfernoxamine (chelation therapy)
- Lifestyle, decrease Fe in diet, avoid fruits
Pathophysiology of Wilson’s disease
- Autosomal recessive mutation of ATP7B gene on chromosome 13
- Impaired biliary copper excretion and transport bound to caeruloplasmin
- Excess Cu accumulation in liver, basal ganglia and cornea
The three features of Wilson’s disease
Hepatic
- Chronic hepatitis
- Liver cirrhosis
Neurological
- Assymetrical parkinsonism
- Memory issues
- Dysarthria (difficulty speaking because the muscles you use for speech are weak) and dystonia - movement disorder that causes the muscles to contract involuntarily
- Depression
- Full psychosis
Opthamological
- Kayser-Fleischer rings - Cu deposits in in cornea, greenish brown ringed appearance
Diagnosis of Wilson’s disease
- 24 hour urine Cu tests: low serum copper and caeruloplasmin
- AST:ALT >4.5
- Liver biopsy - High Cu, hepatitis
- MRI brain: cerebellar + basal ganglia degeneration
Management of Wilson’s disease
- 1st line - D-Penicillinamine (Cu chelation, lifelong)
- Diet change: avoid food high in Cu, shellfish, mushroom
- Last resort -> liver transplant
Risk factors for NAFLD
- Obesity
- T2DM
- Hypertension
- Hyperlipidaemia
- Middle aged onwards
- Family history
- Drugs (NSAIDs, amiodarone)
Stages of NFALD
- Hepatosteatosis (NAFLD)
- Non-alcoholic steatohapatitis (NASH)
- Fibrosis
- Cirrhosis
Symptoms of NAFLD
- Typically asymptomatic, findings are incidental
- If v.severe, present with signs of liver failure
Diagnosis of NAFLD
- first line Deranged LFTs (High PT/INR, low albumin, high bilirubin) high everything else
- AST:ALT < 1
- FBC: thrombocytopaenia, hyperglycaemia
- Enhanced liver fibrosis blood tests if fibrosis suspected (comes under lft) ELF
- Abdominal ultrasound to confirm
Fib 4 score (second line) - Assess risk of fibrosis using non-invasive method
Enhanced liver fibrosis blood test for assessing fibrosis
- Measure three markers - HA, PIIINP and TIMP-1
- <7.7 = none-mild fibrosis
- ≥7.7 - 9.8 = moderate fibrosis
- ≥9.8 = severe fibrosis
FIB-4 score for assessing fibrosis
> 2.67 = advanced -> refer to hepatology specialist
Management of NAFLD
- Weight loss
- Exercise
- Control diabetes, blood pressure and cholesterol
- Stop smoking
- Avoid alcohol
- Vitamin E to improve liver function
- Pioglitazone to decrease insulin resistance
Complications of NAFLD
- HE
- Ascites
- HCC
- Portal hypertension
- Oesophageal varices
Treatment for paracetamol overdose
- Activated charcoal within 1 hour of ingestion - Sticks to paracetmol to ensure it’s not absorbed (adsorption), decreases all intestinal absorption
- Followed by IV N-Acetyl Cysteine - Increases availability of glutathione to get rid of excess NAPQI
Paracetamol metabolism
- 95%: Phase II conjugation -> excreted
- 5%: Phase I conjugation -> NAPQI (hepatotoxic) -> Phase II conjugation -> glutathione (antioxidant) -> excreted
How does paracetamol overdose work?
- Shunting phase 1 pathway as phase 2 is too saturated
- Glutathione depleted
- Hypertoxicity of NAPQI in liver and inflammation
Pathophysiology of ascites
Accumulation of fluid in the peritoneal cavity
How can liver cirrhosis cause ascites?
- Hypoalbuminaemia (reduced plasma oncotic pressure)
- Portal hypertension (increased hydrostatic pressure)
- Renal water retention
Cirrhosis is the most common cause of ascites (50% of patients develop ascites within 10 years
Aetiology of ascites
- Cirrhosis (70%)
- Malignancy
- Heart failure
- TB
- Pancreatitis
Symptoms of ascites
- Abdominal distension (severe = risk of SBP!)
- Pain/discomfort = malignant
- Signs of liver disease
- May have jaundice and puritis
- Shifting dullness
Treatment of ascites
- Treat underlying cause
- Diuretic to increase Na+ excretion (spironolactone) + socium restriction
- Paracentesis -which a needle is inserted into the peritoneal cavity to obtain ascitic fluid (or indwelling drain for smaller volume)
- Peritoneovenkus shunting - relieves ascites by transferring fluid through a one-way valve from the peritoneal cavity into the superior vena cava.
Diagnosis of ascites
- Shifting dullness on exam
Imaging: x-ray, uss, CT abdomen
Ascitic tap: - Cytology (WCC counts) + MC+S
- Protein measurement: transudate + exudate
Transudate testing for ascites
- <30g/L protein (low)
- Serum albumin ascitic gradient is <11g/L
- Clear fluid
- Fluid due to high hydrostatic pressure - portal htn, budd chiari, constructive pericarditis, CHF, nephrotic syndrome
Exudate testing for ascites
- ≥30g/L protein (high)
- Serum albumin ascitic gradient is ≥11g/L
- Cloudy fluid
- Fluid due to inflammation mediated exudation, or low oncotic pressure - malignancy, peritonitis, pancreatitis
What is SAAG?
- Serum albumin ascites gradien
- SAAG >1.1g/dL = portal hypertension, suggesting nonperitoneal cause of ascites
Classification of ascites
Stage 1: Detectable only after careful examination/uss
Stage 2: Easy detectable but relatively small volume
Stage 3: Obvious, not tense ascites
Stage 4: Tense ascites (large)
Prehepatic jaundice
- Unconjugated hyperbilirubinaemia due to increased RBC breakdown
- Mainly caused by haemolytic anaemias
- Urine bilirubin negative and urobilinogen high
Intrahepatic jaundice
- Conj/unconj hyperbilirubinaemia, may be mixed
- Dark urine - raised bilirubin in urine and raised bile salts, decrease in urobilinogen
- Parenchymal disease: HCC, ALD/NAFLD, hep, hepatotoxic drugs (eg: rifampicin), Gilbert syndrome, Crigler-Najjar syndrome
Post hepatic jaundice
- Conjugated hyperbilirubinaemia due to biliary obstruction
- Pale stools + dark urine as bilirubin can’t reach GI tract and builds up in urine
- Caused by biliary tree pathologies (eg: choledocholelithiasis, cancers)
- High bilirubin and low urobilinogen in urine
What is jaundice?
- aka: icterus
- Yellowing of skin/eyes/mucous membranes due to accumulation of conjugated or unconjugated bilirubin
- Sign of liver dysfunction
Four signs to look for when a patient presents with jaundice
- Courvoisier sign
- Charcot triad
- Reynold’s pentad
- Murphy sign
Investigations for jaundice
- Bloods
- LFTs
- First line imaging - ultrasound
Normally:
- No bilirubin in urine
- Urobilinogen in urine
Biliary tree pathology
- Choledocholithiasis
- Pancreatic cancer
- Cholangiocarcinoma
- Mirizzi syndrome
- Drug induced cholestasis
- Autoimmune (PBC+PSC)
- GALLSTONES
Pathophysiology of oesophageal varices
- Portal hypertension results in collateral blood shunting to gastroesophageal veins
- Typically small, become oesophageal varices at the cardia and lower oesophagus
Presentation of haemorrhage of oesophageal varices
Haematemesis (vomiting blood)
DDx: Mallory-Weiss tear
- Tear in oesophageal mucosa
- Very acute history
- Increased abdominal pressure
Diagnosis of oesophageal varices
Oesophagogastroduodenoscopy
Acute treatment for oesophageal varices
Acutely:
- Resus until haemodynamically stable
- Consider blood trasfusion (Hb < 70g/L or <80g/L w cardiac comorbidity)
Stopping bleeding of oesophageal varices
- IV terupressin (SST is CI)
- Variceal banding
- Transjugular intrahepatic portosystemic shunt - decreases portal pressure by diverting blood to other larger veins, SE = hepatoencelopathy
Preventing bleeding of oesophageal varices
- Non-selective beta blocker (eg: propanolol) + nitrates
- Repeat variceal banding
- Last resort: liver transplant (decompensate cirrhosis)
Pathophysiology of portal hypertension
- Normal pressure in portal vein = 5-8mmHg
- Cirrhosis = increased resistance to flow, leads to splanchnic dilation and compensatory increased CO
- Fluid overload in portal vein (10+ = bad, 12+ = very bad)
Causes of portal hypertension
Prehepatic: Portal vein thrombosis
Intrahepatic: Cirrhosis (mc in UK), schistomiasis (mc worldwide)
Post hepatic: Budd chiari, RHS heart failure, constrictive pericarditis
Symptoms of portal hypertension
- Mostly asymptomatic
- Present when oesophageal varices rupture
- (90% of portal hypertension cases develop oesophageal varices, 1/3 of these rupture)
Primary and secondary peritonitis
Primary
- Ascites
- Spontaneus bacterial peritonitis (infection) (mc)
Secondary
- Underlying cause, eg: bile, malignancy
Peritonitis can also be classified as acute or chronic
Bacterial causes of SBP
- Gram -ve = e.coli + klebsiella (colliform rods)
- Gram +ve = stap.aureus (cocci)
Chemical causes of SBP
- Bile
- Old clotted blood
- Ruptured ectopic pregnancy
- Intestinal perforation
(which get ultimately infected)
Presentation of SBP
Sudden onset severe abdo pain (and shoulder tip pain) then collapse + septic shock, fever
- Rigidity helps pain (DDx: renal colic)
- Poorly localised -> more localised
+ ascities usually
Symptoms and signs of underlying conditions
Treatment of SBP
- Treat underlying cause; IV fluid + IV antibiotics
- Urinary catheterisation + GI decompression
- IV Broad spectrum antibiotic therapy
- Analgaesia
- Surgery = peritoneal lavage
Complications of SBP
- Septicaemia if not treated early
- Subphrenic/pelvic abscesses
- Paralytic ulcers
What is spontaneous bacterial peritonitis?
Peritonitis (infection of the peritoneum), that happens without a hole or a tear.
Ascitic fluid is affected
Diagnosis of SBP
- Ascitic tap shows neutrophilia
- Cultures (mc+s) show causative organism
- High ESP and CRP
- Exclude pregnancy as cause (b-hCG test) and bowel obstruction (abdo xR)
- Cxr shows air under diaphragm -> indicates perforated colon
