Liver and friends Flashcards
Liver failure definition
Hepatic failure occurs when the liver loses the ability to regenerate or repair, so that decompensation occurs. It is characterised by:
- hepatic encephalopathy
- abnormal bleeding
- ascites
- jaundice
Liver failure epidemiology
Globally, viral infection accounts for the majority of cases of liver failure, however, paracetamol overdose is the leading cause in the UK.
Liver failure aetiology
Toxins - chronic alcohol abuse, paracetamol poisoning
Infections - viral heapatitis, adenovirus, epstin-barr virus
Neoplastic - hepatocellular carcinoma or metastatic carcinoma
Metabolic - Wilson’s disease, alpha-1-antitrypsin deficiency
Pregnancy-related - acute fatty liver of pregnancy
Vascular - ischaemia or veno-occlusive disease, Budd-Chiari syndrome
Others - autoimmune liver disease (PBC, PSC), unknown cause - 15%
Liver failure pathophysiology
Dependent on cause
Liver failure signs and symptoms
Mental state showing dowsiness and possibly confusion
Jaundice
Abdominal distention and abdominal masses including:
- possible massive ascites and anasarca (general swelling) due to fluid distribution and hypoalbuminemia
- hepatomegaly and splenomegaly
Cerebral oedema with increased ICP may produce papilloedema (optic disc swelling, seen on fundoscopy)
Liver palms (palmar erythema [reddening of the thenar and hypothenar eminences])
Asterixis (tremor on wrist extension)
Signs of hepatic encephalopathy
Liver failure 1st line investigations
Bloods:
- likely to see iron-deficient anaemia
- may show thrombocytopenia (low platelets)
- raised INR
- markedly raised transaminases (AST and ALT) but alkaline phosphate may be high or normal
- raised bilirubin
- high ammonia
- glucose can be dangerously low
- blood cultures - patients are very susceptible to infection
Imaging:
- doppler ultrasound - look for patents hepatic vein, carcinoma and ascites
- imaging of the head - cerebral oedema
Liver failure management
Conservative: fluids and analgesia
Possibility of liver transplantation should be considered at an early stage
Underlying cause should be assessed and managed
Treat complications:
- ascites - diuretics
- cerebral oedema - Mannitol
- bleeding - Vitamin K
- encephalopathy - Lactulose
- sepsis - sepsis 6, antibiotics
- hypoglycaemia - dextrose
Liver failure complications
Infection is a big problem - spontaneous peritonitis is common
Cerebral oedema may be associated with intracranial hypertension and death
Haemorrhage from oesophageal varices is a major complication
Cholelithiasis (gallstones) definition
The presence of solid concretions in the gallbladder. Usually form in the gallbladder but may enter into the bile ducts (choledocholithiasis). Symptoms occur if a stone obstructs the cystic, bile or pancreatic ducts. In the developed world most gallstone are made of cholesterol.
Cholelithiasis (gallstones) aetiology
Mostly due to cholesterol composed stones forming in the gallbladder.
Around 5% of gallstone are black pigment stones. These consist of polymerised calcium bilirubinate. Patients with chronic haemolytic anaemia, cirrhosis. cystic fibrosis and ilial disease are at a higher risk of black pigment stones.
Brown pigment gallstones result from stasis and infection and form in the bile ducts. May be due to bacterial infection or biliary parasites although in the west they are more commonly from biliary stricture, either inflammatory or neoplastic.
Cholelithiasis (gallstones) risk factors
Age, female sex, overweight, oestrogen (pregnancy/exogenous)
Cholelithiasis (gallstones) pathophysiology
Symptoms and complications result when stones obstruct the cystic and/or bile ducts. Transient obstruction of the cystic duct results in biliary pain (biliary colic). More persistent obstruction leads to acute cholecystitis (inflammation of the gallbladder).
Mirizzi syndrome is an uncommon condition where a large gallstone is impacted in the cystic duct or neck of the gallbladder, compresses the common bile duct and causes obstruction and jaundice.
If gallstones pass into the bile ducts causing obstruction, the result can be biliary and acute cholangitis (inflammation of the bile duct system)
Stone passage through the distal bile duct cab culminate in obstruction at the ampulla. Acute biliary pancreatitis results from the increase in pancreatic ductal pressure and reflux of pancreacticobiliary scretions into the pancreatic duct.
If a gallstone erodes through the gallbladder wall, a cholecystoenteric fistula can develop leading to duodenal obstruction (Bouveret syndrome) or obstruction in the narrowest segment of an otherwise healthy bowel causing gallstone ileus.
Cholelithiasis (gallstones) signs and symptoms
Gallstones themselves are common and are usually asymptomatic unless causing obstruction and/or inflammation.
Right upper quadrant or epigastric pain is the most common symptom of cholelithiasis and is caused by obstruction of the cyctic duct or obstruction and/or passage of a gallstone through the common bile duct.
Biliary pain:
- radiated to the right back or shoulder
- responds to analgesia
- often occurs 1hr after food
- may have associated nausea and vomiting
- becomes increasingly intense then stabilizes
These symptoms together with fever and abdominal tenderness (Muphy’s sign: pain on palpation during inspiration) indicates the development of acute cholecystitis. A distended, tender gallbladder may be palpable in acute cholecystitis
Cholelithiasis (gallstones) 1st line investigations
Biliary colic due to a stone in the neck of the gallbladder or cystic duct is unlikely to be associated with significant abnormalities of tests. Acute cholecystitis is usually associated with moderate leukocytosis and raised inflammatory markers (eg CRP).
FBC - leukocytosis with AC
Bilirubin - may be raised. More significant elevation is consistent with bile duct obstruction
LFTs - elevated alkaline phosphate is consistent with bile duct obstruction
Serum lipase or amylase - identify or exclude acute pancreatitis
Blood cultures - if infection is suspected
Cholelithiasis (gallstones) gold standard investigations
Abdominal ultrasound scan
- may show gallstones, distended gallbladder, thickened gallbladder was
May follow up with MRCP if no bile duct stone seen
Endoscopic retrograde cholangiography - better but less commonly used
Cholelithiasis (gallstones) differential diagnosis
Acute cholangitits: classic findings are fever and chills, jaundice and abdominal pain (charcot’s triad)
Chronic cholecystitis
Peptic ulcer disease
Acute pancreatitis - serum amylase and lipase, inflammation on CT scan
Cholelithiasis (gallstones) management
Analgesia
IV fluids if needed
Antiobiotic therapy (if suspected sepsis)
Laparoscopic cholecystectomy
Percutaneous cholecystostomy if unfit for anaesthesia and surgery
Cholelithiasis (gallstones) prognosis
Intreated acute acalculous cholecystitis has mortality up to 50%
Acute cholangitis defintiion
Previously known as ascending cholangitis, acute cholangitis is an infection of the biliary tree most commonly used by obstruction
Acute cholangitis aetiology
- most common aetiology is cholelithiasis (gallstones) leading to choledocholithiasis (gallstones in the bile duct) and biliary obstruction
- iatrogenic biliary injury leading to strictures of the biliary tree
- sclerosing cholangitis cause up to a quarter of cases
- chronic pancreatitis (with stenosis and stricture of the distal common bile duct)
- radiation-induced biliary injury
- complication of chemo
Acute cholangitis risk factors
Age, gallstones, strictures, surgery on the biliary system
Acute cholangitis pathophysiology
Obstruction of the common bile duct initially results in bacterial seeding of the biliary tress, possibly via the portal vein, and when combined with bacterial contamination, can lead to acute cholangitis. As the bile duct pressure increases, extravasation of the bacteria into the bloodstream occurs. If not recognised and treated this will lead to sepsis.
Acute cholangitis key presentations
Classic presentation is Charcot’s triad: fever jaundic and right upper quadrant pain. Pale stool, pruritus (itch associated with liver disease)
Acute cholangitis 1st line investigations
Transabdominal ultrasound - if there are signs of severe cholangitis or patient is high risk for sepsis
Subsequent abdominal CT scan if ultrasound is inconclusive.
Bloods
- FBC - look at white count
- coagulation profile - PT may be raised with sepsis
- CRP - raised
- LFTs - raised
- U&Es - raised urea with severe disease
- blood cultures - usually gram -ve
Arterial blood gas including lactate is spesis is suspected - low bicarbonate with raised anion gap; metabolic acidosis; raised lactate
Acute cholangitis gold standard investigations
All patients will eventually need biliary decompression most commonly using endoscopic retrograde cholangiopancreatography (ECRP)
Acute cholangitis differential diagnosis
Acute cholecystitis - patients with cholangitis typically have diffuse RUQ pain and not classic Murphy’s sign
Acute cholangitis management
1st line:
- RCP
2nd line:
- surgical biliary decompression
Acute cholangitis complications
Acute pancreatitis, inadequate biliary drainage (symptoms likely to presist and/or worsen), hepatic abscess
Acute cholangitis prognosis
Good in most patients with adequate biliary drainage
Primary biliary cholangitis defintion
A chronic disease of the small intrahepatic bile ducts characterised by progressive bile duct damage (and eventual loss) occurring in the context of chronic portal tract inflammation. Fibrosis develops as a consequence of the initially insult and the secondary effects of bile acids retained in the liver ultimately resulting in cirrhosis.
Primary biliary cholangitis aetiology
Conventially thought to be an autoimmune disease. Very high incidence of anti-mitochondrial antibodies (over 95% of patients)
Primary biliary cholangitis risk factors
Much more common in women (10:1 F:M), usually presents 55-65yrs. Family history of other autoimmune disease
Primary biliary cholangitis pathophysiology
Progressive damage and destruction of the biliary epithelial cells lining the small intrahepatic bile ducts. Bile ducts are damaged in the context of portal tract inflammation. Bile duct loss is progressive and in the end stages there can be a complete loss of small intrahepatic ducts.
Loss of bile duct cross-sectional area within the liver leads to cholestasis (blocked bile ducts) with bile acid retention. This can cause secondary liver damage which further contributes to bile duct loss.
Fibrosis occurs due to progressive damage and this can lead to cirrhosis. Can also have associated hepatitis.
Primary biliary cholangitis signs and symptoms
Asymptomatic patients are discovered on routine examination or screening to have hepatomegaly, a raised alkaline phosphatase or autoantibodies.
May have significant history of hypercholesterolemia.
Pruritus is usually the first symptom preceding jaundice by a few years. Fatigue may accompany pruritus.
When jaundice appears it is usually associated with hepatomegaly.
In later stages, pruritus is severe and patients are jaundiced.
Pigmented xanthelasma on eyelids may be present as well as cholesterol deposits in the creases of the hands.
Primary biliary cholangitis 1st line investigations
Anti-mitochondrial antibodies - present in 95%, M2 is specific
Serum alkaline phosphatase - high, often only abnormality in biochemistry
Serum cholesterol - raised
Globulins - IgM is raised
Ultrasound - diffuse alteration in live architecture. Obstructuve duct lesions should be excluded.
Liver biopsy - granulomas often present although not specific.
Primary biliary cholangitis differential diagnosis
Obtrsuctive bile duct lesion
Sclerosing cholangitis
Drug induced cholestasis
Infiltrative malignancy within liver
Primary biliary cholangitis management
1st line:
- bile acid analogue - ursodeoxycholic acid
- immunomodulatory therapy - prednisolone
- antipruitic treatment (if needed) - colestyramine
End stage:
- liver transplant
Primary biliary cholangitis complications
- Hypercholesterolemia
- Osteoporosis
- Portal hypertension seocndary to cirrhosis
Acute and chronic pancreatitis definition
Defined by pancreatic inflammation. Not always clinically distinguishable between acute and chronic forms. Acute pancreatitis is a self-limiting and reversible pancreatic injury associated with med-epigatric pain and elevated serum pancreatic enzymes whereas chronic pancreatitis is characterised by recurrent or persistent abdominal pain and progressive injury to the pancreas or persistent abdominal pain and progressive injury leading to scarring and loss of function.
For patients with recurrent attacks of pancreatitis, the cause and type involves distinguishing between 4 entities:
1. recurrent acute pancreatitis: identifiable cause of acute pancreatitis that does not lead to chronic pancreatitis (eg gallstones, drugs, hypercalcemia etc)
2. idiopathic pancreatitis: exhaustive evaluation identifies no cause. Most commonly represents chronic relapsing pancreatitis or define chronic pancreatitis
3. chronic relapsing pancreatitis: patients have relapsin pain not recognised as chronic pancreatitis but have pathological changes in tissue specimens
4. established chronic pancreatitis: hallmark features including reduced exocrine function of the pancreas, malabsorption, diabetes and pancreatic calcifications
Acute and chronic pancreatitis aetiology
Acute pancreatitis (GET SMASHED):
- G: gallstones
- E: ethanol
- T: trauma
- S: steroids
- M: mumps
- A: autoimmune eg SLE
- S: scorpion bites (rare)
- H: hypercalcemia, hypothermia, hyperlipidemia
- E: ERCP
- D: drugs - eg azathioprine, metronidazole, tetracycline, furosemide
Chronic pancreatitis: Main ones are alcohol and idiopathic. TIGAR-O classification - T-toxic-metabolic eg alcohol, smoking - I-idiopathic - G-genetic - A-autoimmune - R-recurrent and severe acute pancreatitis - O-obstructive
Acute and chronic pancreatitis risk factors
Acute: middle aged women (due to gallstones), young-middle aged men (due to alcohol)
Chronic: alcohol, smoking, family history, coeliac disease
Acute and chronic pancreatitis key presentations
Acute:
Usually presents with severe, constant supper abdominal pain (epigastric or LUQ), usually sudden in onset and often radiating to the back with associated nausea/vomiting in 80% of patients
Hypoxaemia
Hyperlipidaemia
Late stage - haemorrhagic
- Grey-turner’s sign (bruising of the flanks)
- Cullen’s sign (oedema and bruising around the umbilicus)
Chronic:
Hallmark clinical features:
- abdominal pain (epigastric, dull, radiates to the back)
- jaundice (rare)
- nausea/vomiting
- decreased appetitie
- exocrine dysfunction: malabsorption with weight loss, diarrhoea, steatorrhoea and protein deficiency
- endocrine dysfunction: diabetes mellitus
Acute and chronic pancreatitis signs and symptoms
Additional non-specific symptoms:
Weight loss, micro-nutrient deficiencies, nausea and vomiting, skin nodules, painful joints, abdo distension, SOB
Acute and chronic pancreatitis 1st line investigations
Acute:
serum lipase or amylase (lipase is better)
FBC - leukocytosis (sepsis), may have raised haematocrit
CRP - may be elevated
LFTs - elevated ALT suggestive of gallstones
Transabdominal ultrasound - looks for gallstones may show pancreatic inflammation
Chronic:
Blood glucose - may be elevated due to insulin resistance
CT - look for pancreatic clarifications or enlargement
Abdo ultrasound
Acute and chronic pancreatitis management
Acute: will vary on aetiology
- fluid resuscitation
- analgesia - may need opioids
- antiemetic - ondansetron
- IV antibiotics if infection strongly suspected or proven
- ERCP if cholangitis is present
- cholecystectomy of gallstones present
Chronic: (for chronic symptoms)
- analgesia
- pancreatic enzyme supplements plus PPIs
- treat underlying cause
Acute and chronic pancreatitis complications
Sepsis, DIC, ARDS
Alcoholic liver disease (ALD) definition
Caused by chronic heavy alcohol ingestion. Alcoholic liver disease has 3 stages of liver damage:
- fatty liver (steatosis)
- alcoholic hepatitis (inflammation and necrosis)
- alcoholic liver cirrhosis
Alcoholic liver disease aetiology
The common aetiological denominator is chronic and heavy alcohol ingestion. Only about 10-20% of chronic heavy drinkers develop severe forms such as alcoholic hepatitis and cirrhosis. The risk increases for obese patients and the progression to fibrosis and even hepatocellular carcinoma is quicker in patients who smoke.
Alcoholic liver disease risk factors
Prolonged and heavy alcohol consumption, hepatits C, female sex, cigarette smoking, obesity
Alcoholic liver disease pathophysiology
Alcohol is mainly metabolised in the liver by alcohol dehydrogenase and cytochrome P-450 2E1. Alcohol dehydrogenase and acetaldehyde dehydrogenase (a metabolite of alcohol) reduce NAD to NADH. Excessive NADH in relation to NAD in the liver inhibits gluconeogenesis and increased fatty acid oxidation, which in turns promotes fatty infiltration in the liver.
Alcohol metabolism also causes an increased production of free radicals
Chronic alcohol exposure activates metabolism in hepatic macrophages which produce tissue necrosis factor (TNF-alpha) and induce production of reactive oxygen species in mitochondria.
Alcoholics are usually deficient in antioxidants such as glutathione and vitamin E. therefore oxidative stress promotes hepatocyte necrosis and apoptosis in these patients. Free radials can also induce lipid peroxidation, causing inflammation and fibrosis. Alcohol metabolites may also induce inflammation. Acetaldehyde damages liver cell membranes. Alcohol also affects the barrier function of intestinal mucosa, producing endotoxemia, which leads to hepatic inflammation.
Alcoholic liver disease key presentations
Patients may be asymptomatic with elevated AST and ALT.
Alcoholic liver disease signs and symptoms
Presence of risk factors
Abdo [ain - RUQ discomfort is common with acute alcoholic hepatitis
Hepatomegaly - may be present with alcoholic fatty liver (steatosis) or alcoholic hepatitis. Hepatomeglay may be a sign in a liver cirrhosis patients suggesting hepatocellular carcinoma
Ascites - very common clinical complication of cirrhosis
Weight loss or weight gain
Alcoholic liver disease 1st line investigations
GGT - more sensitive than AST or ALT for alcoholic liver disease - elevated
AST & ALT - often raised, AST almost always elevated. Classic ration of AST/ALT >2 seen in most causes. Reversal of the ratio suggests viral hepatitis or possible non-alcoholic fatty liver disease
FBC - anaemia and leukocytosis often present
Hepatic ultrasound - may show hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, portal hypertension
