Hepatobiliary Flashcards
Define acute liver failure
Liver loses its ability to repair and regenerate leading to decompensation. Decompensation is characterised by jaundice, coagulopathy, and hepatic encephalopathy.
Describe the epidemiology of acute liver failure
ALF is the primary indication for liver transplantation in around 8% of cases within Europe.
Describe the aetiology of acute liver failure
Drugs: paracetamol, alcohol.
Viral infection: hepatitis, Epstein Barr virus. Autoimmune hepatitis.
Neoplastic: hepatocellular or metastatic carcinoma.
Metabolic: Wilson’s disease, alpha 1 antitrypsin.
Vascular: Budd Chiari
What are risk factors for acute liver failure
Chronic alcohol abuse, female, chronic hepatitis
Describe the pathophysiology of acute liver failure
Destruction of hepatocytes leads to inflammation and fibrosis. The destruction of the architecture of the nodules of the liver means it cannot perform its functions properly, repair or regenerate.
What are the key presentations for acute liver failure
Jaundice, abnormal bleeding, hepatic encephalopathy (confusion, altered mood, asterixis (liver flap), comatose)
What are the signs and symptoms for acute liver failure
Malaise, nausea, vomiting, confusion, abdominal pain
What is the gold standard investigation for acute liver failure
LFTs: bilirubin, PT/INR, serum AST + ALT, NH3 all raised. Albumin and glucose decreased.
What are the first line investigations for acute liver failure
LFTs: bilirubin, PT/INR, serum AST + ALT, NH3 all raised. Albumin and glucose decreased.
FBC: anaemia, thrombocytopenia, leukopenia. U&E (urea and creatinine raised, deranged electrolytes)
What are further investigations for acute liver failure
Toxicology screen, abdominal USS, blood cultures, EEG for HE
What is the differential diagnosis for acute liver failure
Acute hepatitis, drug or alcohol intoxication, viral infection
What is the management for acute liver failure
1st line – intensive care management, ABCDE, fluids analgesia. Assessment for liver transplant.
Treat underlying causes and complications, e.g., paracetamol overdose
What monitoring is done for acute liver failure
Fluids - urinary and central venous cannulas
Bloods - daily FBC, U&E, LFT and INR
Glucose - 1-4hr + administer IV glucose if needed
What are complications for acute liver failure
Hepatic encephalopathy (lactulose), ascites (diuretics), cerebral oedema (IV mannitol), bleeding (vitamin K), sepsis (sepsis 6, antibiotics)
What is the prognosis for acute liver failure
Survival from ALF is greater than 60% and around 55% of patients will have spontaneous recovery without need for liver transplantation.
The overall one year survival following emergency liver transplantation is around 80%.
Worst prognosis if grade III-IV encephalopathy, age >40 years, low albumin, high INR, DILI. Late onset hepatic failure worse than fulminant failure.
What is the role of the liver
- Storage(i.e. glycogen, iron, vitamins)
- Breakdown(i.e. drugs, toxins, ammonia, bilirubin)
- Synthesis(i.e. bile, cholesterol, coagulation factors, growth factors)
- Immune function(i.e. innate immune protein production, resident immune cells)
Define chronic liver disease
Chronic liver disease is caused by repeated insults to the liver, which can result in inflammation, fibrosis and ultimately cirrhosis.
CLD is generally defined as progressive liver dysfunction for six months or longer. The end result of chronic liver disease is cirrhosis, which describes irreversible liver remodelling.
Describe the epidemiology of chronic liver disease
- CLD represents the fourth commonest cause of years of life lost in those aged under 75.
- In England and Wales an estimated 600,000 patients have CLD.
Describe the aetiology of CLD
Acute liver disease is most common cause, non-alcoholic fatty liver disease.
Acute causes which progress to chronic:
Drugs: paracetamol, alcohol.
Viral infection: hepatitis, Epstein Barr virus. Autoimmune hepatitis. Neoplastic: hepatocellular or metastatic carcinoma.
Metabolic: Wilson’s disease, alpha 1 antitrypsin.
Vascular: Budd Chiar
Describe the risk factors of CLD
Alcohol, obesity, T2DM, drugs, metabolic disease
Describe the pathophysiology of CLD
Destruction of hepatocytes leads to inflammation (hepatitis) which leads to fibrosis (reversible damage). This can progress to cirrhosis - scarring of liver caused by long term liver damage which is irreversible. Cirrhosis can be compensated, with some preserved liver function, or decompensated which causes end-stage liver failure.
What are the key presentations of CLD
Jaundice, ascites, abnormal bleeding, hepatic encephalopathy (confusion, altered mood, asterixis (liver flap), comatose), low serum albumin
Describe the clinical manifestations of CLD
Signs
Portal hypertension, oesophageal varices (enlarged veins), caput medusae (cluster of swollen veins in abdomen), spider naevi, palmar erythema, gynecomastia, clubbing, fetor hepatis (sweet musty rotten egg garlic breath), Dupuytren’s contracture, hepatomegaly
Symptoms
Malaise, nausea, vomiting, abdominal pain, pruritis, bleeding
What is the gold standard investigation for CLD
Liver biopsy (distortion of liver parenchyma)
What are the first line investigations of CLD
1st line LFTs: bilirubin, PT/INR, serum AST + ALT, NH3, GGT all raised. Serum albumin and glucose decreased.
FBC: anaemia, thrombocytopenia, leukopenia. U&E (urea and creatinine raised, deranged electrolytes)
What are other investigations for CLD
Abdominal ultrasound, ascites tap
What are the differential diagnosis for CLD
Budd Chiari, portal vein thrombosis, constrictive pericarditis
What is the management for CLD
1st line – prevent progression, lifestyle monitoring (less alcohol, reduce BMI), liver transplant (MELD score – model for end-stage liver disease. Assesses severity and transplant likelihood).
Manage complications: hepatic encephalopathy, ascites, etc.
What monitoring may be done for CLD
-
Hepatocellular Carcinoma -
- Six monthly surveillance with ultrasound +/- AFP (tumour marker) as patients with cirrhosis are at high risk of HCC
What are potential complications with CLD
- Hepatic encephalopathy
- Ascites
- Gastrointestinal bleeding(i.e. variceal bleed)
- Bacterial infections(i.e. SBP)
- Acute kidney injury
- Hepatorenal syndrome
- Hepatopulmonary syndrome
- Hepatocellular carcinoma
- Acute-on-chronic liver failure
What is the prognosis for CLD
2 years without transplant
Describe the breakdown of RBCs
- Red blood cells are broken down, releasing haemoglobin.
- Haemoglobin is broken down into haem and globin, with haem being further broken down into unconjugated bilirubin and iron. Globin and iron from haem is recycled for erythropoiesis.
Describe the properties of unconjugated bilirubin
- Unconjugated bilirubin is abreakdown product of haemfrom senescent red blood cells
- Unconjugated bilirubin isnot water-solubleand requiresconjugationfor excretion in bile
How is unconjugated bilirubin conjugated
-
UGT (UDP-glucuronosyltransferase)in the liver converts unconjugated bilirubin into conjugated bilirubin, making it water-soluble
- Conjugation involves the addition of glucuronic acid to bilirubin
- Conjugated bilirubin is secreted into the bile canaliculi andstored in the gallbladderas a component of bile
What happens to conjugated bilirubin
- When it is released into the intestinal tract, conjugated bilirubin is broken down intourobilinogenand thenstercobilinby bacteria
- Stercobilin is excreted infaeces, giving it a brown colour
- Some urobilinogen is reabsorbed and is either directed back into making bile (enterohepatic circulation) or transported to the kidney and excreted in theurine, giving it a yellow colour
Define cholelithiasis (gallstones)
Cholelithiasis (gallstones) refers to the development of a solid deposit or ‘stone’ within the gallbladder.
Describe the epidemiology of gallstones
- Gallstones affect up to 20% of the population.
- F>M
- Prevalence increases with age, before levelling off in the sixth - seventh decade of life.
- More common in caucasians, Native American’s and Hispanics.
- The vast majority of people with gallstones will remain asymptomatic (80%).
Describe the aetiology of gallstones
Bile is secreted by hepatocytes into the biliary circulation. It is stored in the gallbladder. Bile is composed of bile acids (or salts), phospholipid, bilirubin, cholesterol and water. Imbalance in composition and stasis leads to stone formation.
What are the risk factors for gallstones
5 Fs: Fat, Fertile, Forty, Female, Fair
Family history, rapid weight loss, diabetes and medications
Describe the clinical manifestations of gallstones
Gallstones: biliary colic severe colicky RUQ pain, comes and goes (>30 minutes), worse after eating a fatty meal. Nausea and vomiting.
What is the gold standard investigation for gallstones
Gallstones: abdominal USS (1. Identify stones, 2. Gallbladder wall thickness – inflammation, 3. Duct dilation)
What are the primary investigations for gallstones
Gallstones: raised ALP, normal FBC and CRP, raised bilirubin if gallstone is blocking bile duct
What are the differential diagnosis for gallstones
Pancreatitis, peptic ulcer disease, gallbladder cancer
What is the management for gallstones
Gallstones: NSAIDs/analgesia. Elective cholecystectomy (surgical removal of gallbladder) Bile duct clearance if gallstones in bile ducts (ERCP).
What are the complications of gallstones
Gallstones > cholecystitis > cholangitis. Sepsis
What is the prognosis for gallstones
The majority of patients with gallstones will be asymptomatic. 1-4% of patients develop gallstone-related complications, the most common being biliary colic. 10-20% of those who have had an attack of biliary colic will go on to develop a more serious complication, such as acute cholecystitis.
Define biliary colic
Biliary colic refers to a pain in the RUQ/epigastrium caused by gallstones.
Though termed a ‘colic’ the pain is normally constant lasting from 30 minutes to 6 hours.
Describe the epidemiology of biliary colic
- It is the most common symptomatic manifestation of cholelithiasis (gallstones) affecting around 10-20% of patients.
- Prevalence increases with age
- F>M
- More common in caucasians, Native American’s and Hispanics.
What are risk factors for biliary colic
Risk factors for gallstones:
5 Fs: Fat, Fertile, Forty, Female, Fair
Describe the pathophysiology of biliary colic
The pain occurs when a stone impacts against the cystic duct during contraction of the gallbladder with increased pressures in the gallbladder itself.
Describe the clinical manifestations of biliary colic
- Nausea and vomiting
- Right upper quadrant pain
- Epigastric pain
- Pain may radiate to right shoulder or interscapular region
Episodes typically last 30 minutes - 6 hours. Often worse after ingestion of fatty foods.
Note: there are no signs on abdominal examination. Murphy’s sign negative.
What are the first line investigations for biliary colic
Abdominal ultrasound - can identify gallstones as well as looking for dilation of the CBD and presence of stones in CBD.
LFTs - may show derangement of LFTs - indicative of stones within the biliary system (which can be asymptomatic). It is essential to identify patients with CBD stones prior to any cholecystectomy.
What are the differential diagnosis for biliary colic
- Cholecystitis
- Ascending cholangitis
- Common bile duct stone
- Gastritis
- Peptic ulcer disease
- IBS
- Carcinoma on right side of colon
- Renal colic
- Pancreatitis
Describe the management for biliary colic
NSAIDs/analgesia. Elective cholecystectomy (surgical removal of gallbladder) Bile duct clearance if gallstones in bile ducts (ERCP).
Describe the complications of biliary colic
- Obstructive jaundice:due to**a stone that obstructs the common bile duct; presents with jaundice, pale stools and dark urine
- Cholecystitis:inflammation of the gallbladder results infever,rightupperquadrantpain(usually > 6 hours) and positiveMurphy’s sign
- Ascending cholangitis:infection of the biliary tree results in ‘Charcot’s triad’ (rightupperquadrantpain,feverandjaundice)
- Acute pancreatitis:gallstones are the most common cause
- Gallbladder empyema
- Gallstone ileus:a rare form of small bowel obstruction due to impaction of a gallstone within the lumen of the small intestine via a cholecysto-duodenal fistula
- Gallbladder cancer: gallstones are thought to increase the risk by up to 5-fold
Define acute cholecystitis
Acute cholecystitis refers to inflammation of the gallbladder most commonly occurring due to impacted gallstones (calculous cholecystitis)
Relatively rarely acute cholecystitis occurs in the absence of gallstones (acalculous cholecystitis).
Describe the epidemiology of acute cholecystitis
Acute cholecystitis occurs in 10% of patients with symptomatic gallstones
What are the risk factors for acute cholecystitis
5 Fs: Fat, Fertile, Forty, Female, Fair
Describe the pathophysiology of acute cholecystitis
Cholecystitis: gallstones block the cystic duct, preventing the gallbladder from draining. Bile builds up and distends the gallbladder which can reduce vascular supply and leads to inflammation.
What are the clinical manifestations for acute cholecystitis
Cholecystitis: RUQ pain, may radiate to right shoulder, fever, fatigue, RUQ tenderness. Murphy’s sign: press on GB and inhale, patient will wince in pain and stop inspiration. Nausea and vomiting.
What is the gold standard investigation for acute cholecystitis
Cholecystitis: abdominal USS (gallstones, thick gallbladder walls from inflammation, fluid around gallbladder)
Describe the first line investigations for acute cholecystitis
Cholecystitis: positive murphy’s sign, FBC: raised WCC and CRP, LFTs may be elevated (ALP, bilirubin, AST and ALT)
What are the differential diagnosis for acute cholecystitis
- Pancreatitis
- Peptic ulcer disease
- Cholangitis
- Appendicitis
- Basal pneumonia
Describe the management for acute cholecystitis
Cholecystitis: IV fluids, antibiotics, analgesia. Cholecystectomy surgery within 72 hours of symptoms. ERCP if gallstones in bile ducts.
What are the complications of acute cholecystitis
- Gallbladder empyema:acute inflammation results in the gallbladder filling with pus and can lead to perforation
- Gallstone ileus:when a gallstone passes from the biliary tract into the intestine via a fistula resulting in small bowel obstruction
- Acute cholangitis: infection of the biliary tree commonly caused by gallstones which move into the common bile duct
- Obstructive jaundice: if stone moves to CBD
- Procedure-related: bile duct injury
What is the prognosis for acute cholecystitis
Prompt medical management with intravenous antibiotics and identification of sepsis alongside an early laparoscopic cholecystectomy is associated with a very good prognosis. In patients with biliary colic without cholecystitis, early laparoscopic cholecystectomy reduces the risk of future episodes and the risk of cholecystitis. Gallbladder perforation has a mortality of over 30%, whilst untreated acute acalculous cholecystitis has a mortality of up to 50%
What does positive Murphy’s sign mean
Murphy’s sign is indicative of cholecystitis. As the patient breathes out, place your hand below the right costal margin. As the patient breathes in an inflamed gallbladder moves inferiorly, the patient catches their breath. To be considered positive, it should be absent on the left side.
Describe chronic cholecystitis
Chronic inflammation of the gallbladder +/- colic
Describe the pathophysiology of chronic cholecystitis
- Repeated lodging and dislodging of gallstone in CBD, causing inflammation and fibrosis of the gallbladder
- In some cases, there may not be lodging and dislodging of gallstones. Instead, gallstones within the gallbladder can cause irritation to the gallbladder and causes damage this way.
- Overtime, this leads to inflammation, fibrosis and maybe even calcification. This is known as porcelain gallbladder. This makes the gallbladder visible on x-ray
Describe the clinical manifestations of chronic cholecystitis
- Flatulent dyspepsia
- Abdominal discomfort - RUQ pain (esp after meal)
- Distension
- Nausea
- Fat intolerance (fat stimulates cholecystokinin release and gallbladder contraction)
Describe the investigations for chronic cholecystitis
- Ultrasound - to image stone and assess CBD diameter
- MRCP - used to find CBD stones
- X-ray - may show porcelain gallbladder
What are the differential diagnosis of chronic cholecystitis
- If symptoms persist post-treatment, consider:
- Hiatus hernia
- IBS
- Peptic ulcer
- Chronic pancreatitis
- Tumour
Describe the management for chronic cholecystitis
- Cholecystectomy
- ERCP + sphincterectomy prior to surgery
What are the complications for chronic cholecystitis
Increased risk of gallbladder cancer
Define acute cholangitis
Acute ascending cholangitis refers to infection of the biliary tree characteristically resulting in pain, jaundice and fevers.
Describe the epidemiology of acute ascending cholangitis
- Acute cholangitis is relatively uncommon and presents as a complication of gallstones in about 1% of patients.
- Age > 50 years
- Affects men and women equally
- There appears to be greater incidence in caucasians, hispanics and Native Americans - following the distribution of gallstones.
- It occurs following ERCP in around 0.5 - 3%.
- Recurrent pyogenic cholangitis is seen in southeast Asian populations.
Describe the aetiology of acute ascending cholangitis
- Choledocholithiasis
- Benign stricture
- Malignant stricture
What are the risk factors for acute cholangitis
- Gallstones:the most common predisposing factor
- Stricture of the biliary tree:benign or malignant
- Post-procedure injuryof the bile ducts e.g. post-ERCP
Describe the pathophysiology of ascending cholangitis
Ascending cholangitis: infection and inflammation of the bile ducts due to prolonged bile duct blockage from gallstones, or bacterial infection from ERCP procedure (E. coli, klebsiella, enterococcus). Bile isn’t ‘flushing out’ the ducts so bacteria migrate from GI tract and cause biliary tree infection. Bile is prevented from entering the GI tract causing jaundice
What are the key presentations of ascending cholangitis
Ascending cholangitis: Charcot’s triad: RUQ pain, fever, jaundice. Patient may have sepsis.
What is the gold standard investigation for ascending cholangitis
Cholangitis: ERCP endoscopic retrograde cholangio-pancreatography (direct observation of bile duct and stones)
What are the first line investigations for ascending cholangitis
Cholangitis: FBC: raised WCC and CRP, leucocytosis. LFTs: raised ALP, aminotransferases, and bilirubin. Blood cultures. Abdominal USS: bile duct dilation and gallstones
What are the differential diagnosis for ascending cholangitis
- Acute cholecystitis
- Peptic ulcer disease
- Pancreatitis
- Hepatic abscess
- Appendicitis
- Biliary colic
Describe the management for ascending cholangitis
Cholangitis: IV antibiotics (cefuroxime and metronidazole), fluids, blood cultures (sepsis risk). ERCP (bile duct clearance) then cholecystectomy.
What are the complications for ascending cholangitis
- Biliary sepsis:the commonest complication and typically presents with Reynolds’ pentad
- Acute pancreatitis:CBD stones can obstruct the pancreatic duct
- Hepatic abscess
- Risks of ERCP: duodenal perforation, pancreatitis, biliary sepsis, intra-abdominal bleeding
What is the prognosis for ascending cholangitis
The majority of patients recover quickly with effective resuscitation, initiation of antibiotics and adequate biliary drainage. The prognosis is worse if decompression is delayed or emergency surgical drainage is required (rather than non-surgical). Factors that predict a poor prognosis include high fever, hyperbilirubinaemia, hypoalbuminaemia, and older age.
Define primary biliary cholangitis
Autoimmune disease where T cells attack cells of small bile ducts in the liver causing inflammation. Leads to cholestasis and subsequent leakage of bile into the circulation
Describe the epidemiology of primary biliary cholangitis
- Rare disease with a prevalence of < 0.05%
- Middle-aged:peak incidence between 45 and 60 years old
- Female gender: ten times more common in females
Describe the aetiology of primary biliary cholangitis
Unknown. Genetic predisposition and environmental factors
Describe the risk factors for primary biliary cholangitis
Female, age 45-60, smoking, other autoimmune disease, rheumatoid diseases, past pregnancy, chronic UTI
Describe the pathophysiology of primary biliary cholangitis
Immune system attacks small intralobular bile ducts in the liver which obstructs bile outflow causing cholestasis. Bile acids, bilirubin and cholesterol build up in the blood as they aren’t being excreted in bile. Bile acids cause itching, bilirubin cause jaundice and cholesterol causes deposits in the skin (xanthelasma) and blood vessels. The back-pressure of the bile obstruction and overall disease process leads to fibrosis, cirrhosis, and liver failure.
Describe the key presentations of primary biliary cholangitis
Pruritis, fatigue, Jaundice, xanthelasma
Describe the clinical manifestations of primary biliary cholangitis
Signs:
Pale stools, signs of cirrhosis (hepatomegaly, ascites, spider naevi)
Symptoms:
Abdominal pain, joint pain
What is the gold standard investigation for primary biliary cholangitis
Anti-microbial antibodies (AMA) present
What are the first line investigations for primary biliary cholangitis
LFTs: raised bilirubin, alkaline phosphatase, aminotransferases, GGT. Decreased albumin. Abdominal USS (excludes extrahepatic cholestasis)
What are further investigations for primary biliary cholangitis
Liver biopsy (bile duct lesions and granuloma formation)
What are the differential diagnosis for primary biliary cholangitis
Primary sclerosis cholangitis (AMA would not be found), obstructive bile duct lesion, cholestasis (pregnancy, drug-induced)
Describe the management for primary biliary cholangitis
1st line – Ursodeoxycholic acid (bile acid analogue reduces intestinal absorption of cholesterol and dampens the inflammatory response).
Cholestyramine (bile acid analogue) for pruritis. Liver transplant if severe
What monitoring needs to be done for primary biliary cholangitis
Regular LFT; ultrasound +/- AFP if cirrhotic (with chronic liver diseases, such as hepatitis and cirrhosis, AFP may be chronically elevated).
What are the complications with primary biliary cholangitis
Liver cirrhosis, portal hypertension, steatorrhea, osteoporosis, hypercholesterolaemia, malabsorption
What is the prognosis for primary biliary cholangitis
Portal hypertension, advanced histological stage, and failure to respond to ursodeoxycholic acid are poor prognostic factors. Median survival is approximately 9 years, however, in patients diagnosed at an asymptomatic stage, survival is twice as high compared to those diagnosed at a symptomatic stage.
Define primary sclerosing cholangitis
Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, resulting in strictured ‘beaded’ appearance of bile ducts.
Describe the epidemiology of primary sclerosing cholangitis
Male, heavily associated with IBD especially ulcerative colitis, less common than PBC, more common in northern europe and NA. Mean diagnosis is 40
Describe the risk factors for primary sclerosing cholangitis
Male sex, aged 40-50, inflammatory bowel disease (UC and Crohn’s), family history
Describe the pathophsyiology of primary sclerosing cholangitis
Inflammation of intrahepatic and extrahepatic bile ducts leads to fibrosis and stricturing. This obstructs bile flow causing cholestasis. The biliary strictures lead to build up of bile acids and bilirubin in the blood causing pruritis and jaundice. Ongoing strictures eventually leads to fibrosis, cirrhosis, and liver failure.
Describe the key presentations for primary sclerosing cholangitis
Pruritis, fatigue, Charcot’s triad: RUQ abdominal pain, fever, jaundice, hepatomegaly, IBD signs and symptoms
What is the gold standard investigation for primary sclerosing cholangitis
MRCP (magnetic resonance cholangiopancreatography) – bile duct strictures or lesions
What are the first line investigations for primary sclerosing cholangitis
1st line LFTs: raised bilirubin, ALP, AST and ALT, GGT. Decreased albumin.
Serology: no antimicrobial antibodies (AMA), maybe pANCA antibodies
What are the differential diagnosis for primary sclerosing cholangitis
Primary biliary cholangitis/cirrhosis, secondary sclerosing cholangitis, hepatitis
What is the management for primary sclerosing cholangitis
1st line – symptomatic treatment. Ursdeoxycholic acid doesn’t work. Cholestyramine for pruritis (bile acid analogue). Consider liver transplant. Encourage a health lifestyle
What are potential complications for primary sclerosing cholangitis
Portal hypertension, cirrhosis, cholangiocarcinoma, colorectal cancer, hepatic encephalopathy
Describe the prognosis for primary sclerosing cholangitis
Theaverage survivalof patients newly diagnosed with PSC is9.3 to 18 years. Despite the rare nature of this disease, PSC is the5thleading indication for liver transplantationin the USA. For those who receive aliver transplantation, the 5-year survival rate is approximately85%.
Define acute pancreatitis
Sudden and rapid onset inflammation of the pancreas
Describe the epidemiology of acute pancreatitis
- In the UK there are an estimated 30 per 100,000 cases each year and the incidence is increasing globally
- The overall mortality rate in the UK is reported as around 5%, rising to 25% for patients with severe disease.
- In the UK, around 50% of cases are caused by gallstones, 25% by alcohol, and 25% by other factors.
- Increases with advancing age
- Afro-Caribbean ethnicity: risk is 2-3 fold higher in black populations than white
- Sex: alcohol-related pancreatitis is more common in males, whilst gallstone-related pancreatitis is more common in females
- Gallstone pancreatitis is more common in white women >60 years of age, especially among patients with microlithiasis.
Describe the aetiology of acute pancreatitis
I GET SMASHED: Idiopathic, Gallstones, Ethanol (alcohol), Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hyperlipidaemia, ERCP, Drugs (diuretics)
Describe the risk factors for acute pancreatitis
Middle-age woman, young/middle-age man, gallstones (MC women), alcohol (MC men), ERCP, diet, obesity, T2DM, family history
Describe the pathophysiology of acute pancreatitis
Gallstones block flow of bile and pancreatic juices into the duodenum. Reflux of bile into pancreatic duct and prevention of pancreatic juice containing enzymes from being secreted results in inflammation. Cascade of zymogen/enzyme activation which triggers the recruitment of inflammatory cells and the release of inflammatory mediators.
Alcohol is directly toxic to pancreatic cells causing inflammation.
Autoimmune: pancreas releases exocrine enzymes which auto digest the pancreas.
What are the key presentations for acute pancreatitis
Severe epigastric pain radiating to the back, vomiting, abdominal tenderness, hypocalcaemia
What are the clinical manifestations for acute pancreatitis
Signs:
Jaundice, tachycardia, Chvostek sign, grey turner (flank bruising) and Cullen sign (periumbilical bruising), signs of hypovolemia and pleural effusion
Symptoms:
Dyspnoea, fever, nausea and vomiting
What is the gold standard investigation for acute pancreatitis
Serum lipase raised (3 times the upper limit level)
What are the first line investigations for acute pancreatitis
Serum amylase raised (3 times the upper limit level), FBC: leucocytosis with left shift (increase in immature:mature WBCs), raised haematocrit, raised CRP. Raised urea, low calcium.
Imaging: chest x-ray, abdominal USS (gallstones), CT scan (inflammation, necrosis, effusions)
Diagnosis needs 2 of 3: acute abdominal pain, elevated pancreatic enzymes (amylase/lipase), abnormal imaging
What are the further investigations for acute pancreatitis
Glasgow score (severity of pancreatitis): Pao2 low, Age >55, Neutrophils raised, Calcium low, uRea raised, Enzymes raised, Albumin low, Sugar raised (PANCREAS)
What are the differential diagnosis for acute pancreatitis
Abdominal aortic aneurysm, peptic ulcer disease, cholangitis, oesophageal spasm
Describe the management for acute pancreatitis
1st line – ABCDE, IV fluids, analgesia, nil by mouth, oxygen, antibiotics, electrolyte replacement.
ERCP for gallstones, treat complications
What are the complications for acute pancreatitis
Renal failure, ARDS, sepsis, pancreatic abscess, pseudocysts, pancreatic necrosis
Describe the prognosis for acute pancreatitis
25% of acute pancreatitis cases are severe and associated with complications. Severe cases often require critical care input, and are associated with prolonged hospital stay and an increased mortality rate (25%), compared to the overall mortality rate (5%).
What is necrotising pancreatitis
A severe subtype of acute pancreatitis
- Necrosis presents within thefirst 24-48 hoursresulting in the death of portions of the pancreas
- It should be suspected in those who continue to haveabdominal pain, nausea and feverdespite supportive management of acute pancreatitis
- Thekey diagnostic factoris non-enhancing low attenuating pancreatic tissue onCT imaging, which signifies necrosis
- Some hospitals performfine-needle aspirationto determine if necrotic tissue is infected, but false negatives are possible
- Walled-off necrosis(WON) occurs after 4 weeks, at which point percutaneous drainage or open necrosectomy may be indicated;earlynecrosectomy has ahigh mortality rate
- Despite the above, the presence of sepsis and multi-organ dysfunction may warrantearly surgery
- It carries apoor prognosisand has a high risk of becoming infected
Define chronic pancreatitis
Chronic pancreatitis refers to inflammation of the pancreas. Unlike acute pancreatitis, chronic pancreatitis is irreversible. It is characterised by structural changes e.g. fibrosis, calcification and atrophy which leads to a decline in function of the pancreas.
Describe the epidemiology of chronic pancreatitis
- Alcohol is the primary risk factor accounting for 80% of cases, whilst 20% of cases have an unknown cause
- The age at presentation varies with aetiology. Hereditary pancreatitis has a peak age at 10 to 14 years, juvenile idiopathic chronic pancreatitis at 19 to 23 years, alcoholic chronic pancreatitis at 36 to 44 years, and senile idiopathic chronic pancreatitis at 56 to 62 years.
- M>F
- Worldwide prevalence is around 4-5%
Describe the aetiology of chronic pancreatitis
Alcohol consumption, progression from acute pancreatitis, trauma, chronic kidney disease, cystic fibrosis
What are risk factors for chronic pancreatitis
- Alcohol excess
- Smoking
- Family history
- Ductal obstruction e.g. gallstones, tumours, structural abnormalities
- Genetic - cystic fibrosis and haemochromatosis
Describe the pathophysiology of chronic pancreatitis
Repeated bouts of acute pancreatitis can progress to chronic pancreatitis. With each bout of acute pancreatitis, there is ductal dilatation and damage to pancreatic tissue. Fibrotic tissue forms causing narrowing of ducts leading to stenosis.
What are the key presentations for chronic pancreatitis
Severe pain in epigastric region which can radiate to back, steatorrhea, jaundice, loss of exocrine function (no pancreatic enzymes secreted in GI tract, especially lipase), loss of endocrine function (lack of insulin causing diabetes),
What are other symptoms of chronic pancreatitis
Weight loss, nausea and vomiting
What is the gold standard investigation for chronic pancreatitis
X-ray/CT/MRI scan shows calcification of pancreas and dilated ducts
What are the first line investigations for chronic pancreatitis
1st line Faecal-elastase 1 (low), faecal fat (high), pancreatic function tests (decreased function), ERCP for visualisation of ducts, bloods (low/no amylase and lipase)
What are the differential diagnosis for chronic pancreatitis
Pancreatic cancer, acute pancreatitis, abdominal aorta aneurysm, peptide ulcer disease
What is the management for chronic pancreatitis
1st line – control pain (analgesia, NSAIDs) and risk factors (less alcohol, less smoking, obesity)
Replace pancreatic enzymes in deficiency (lipase), nutritional supplements. Insulin for diabetes. ECRP with stenting. Surgery to drain bile ducts
What monitoring is done for chronic pancreatitis
Patients are recommended to be seen yearly for non-invasive testing, to include laboratory blood work and perhaps stool tests to monitor for specific complications, including:
- Cholestasis and biliary obstruction (LFTs)
- Malnutrition
- Baseline bone densitometry in high-risk patients
- Steatorrhoea (qualitative faecal fat)
- Diabetes (glucose).
What complications occur with chronic pancreatitis
Pancreatic exocrine insufficiency, diabetes mellitus, pancreatic calcification, steatorrhea, pancreatic pseudocysts, pancreatic cancer, malabsorption, gastric varices, metabolic bone disease
What is the prognosis for chronic pancreatitis
Almost all patients will develop exocrine insufficiency, and up to 75% will develop endocrine insufficiency. Survival is dependent upon the underlying cause, with a life expectancy of 55-72% in chronic pancreatitis due to alcohol excess.
Define alcoholic liver disease
Effects of long-term alcohol consumption on the liver. Fatty liver > alcoholic hepatitis > liver cirrhosis
Describe the epidemiology of alcoholic liver disease
- The prevalence of alcohol-use disorders among men and women in the European region was 14.8% and 3.5%, respectively, in 2016. In the UK, it is estimated that 24% to 28% of adults drink in a hazardous or harmful way.
- M>F prevalence
- Main cause of liver disease and failure
Describe the aetiology of alcoholic liver disease
Chronic heavy alcohol consumption
Describe the pathophysiology of alcoholic liver disease
Progression of alcoholic liver disease.
1. Fatty liver (steatosis): drinking leads to build up of fat in the liver. Treatment: stop drinking alcohol.
2. Alcoholic hepatitis: long term alcohol drinking causes inflammation in liver sites. Damaged intermediate fibres = bundles of Mallory bodies. Treatment: permanent alcohol abstinence.
3. Cirrhosis: liver is made up of scar tissue instead of healthy liver tissue. Irreversible.
Describe the key presentations for alcoholic liver disease
Early stages (asymptomatic). Later: abdominal pain, hepatomegaly, jaundice, spider naevi (cluster of minute blood vessels under skin), alcohol dependency
Describe the clinical manifestations for alcoholic liver disease
Signs:
Palmar erythema, dupuytren’s contracture (fingers bend towards palm of hand), ascites, hepatic encephalopathy, caput medusae (enlarged superficial epigastric veins), bruising, asterixis (flapping tremor), gynecomastia
Symptoms:
Abdominal pain, fatigue, weight loss, confusion, fever, N+V
What is the gold standard investigation for alcoholic liver disease
Liver biopsy: steatosis, inflammation, Mallory bodies
What are the first line investigations for alcoholic liver disease
LFTS: Gamma-glutamyl transferase (raised), AST and ALT (transaminases - raised), AST:ALT (ratio>2), ALP (alkaline phosphatase - raised), bilirubin (raised), albumin (low),
FBC: anaemia, thrombocytosis, high MCV
What are other investigations for alcoholic liver disease
Ultrasound, CT, alcohol dependence (CAGE and AUDIT)
What are the differential diagnosis for alcoholic liver disease
Hepatitis A B C, acute liver failure
What is the management for alcoholic liver disease
1st line - Completely stopping alcohol consumption. Give chlordiazepoxide for delirium tremens – alcohol withdrawal (tremors, agitation, ataxia, disorientation)
Also: weight loss, stop smoking, corticosteroids for alcoholic hepatitis (prednisolone), liver transplant if severe (must abstain from alcohol for 3 months first)
What are complications for alcoholic liver disease
Wernicke-Korsakoff syndrome (thiamine deficiency), hepatic encephalopathy, renal failure, hepatocellular carcinoma, portal hypertension
What is the prognosis for alcoholic liver disease
Good if you stop alcohol
Define non-alcoholic fatty liver disease
Chronic liver disease with evidence of hepatic steatosis (fat build up) which is not a secondary cause of alcohol consumption. Stages: non-alcoholic steatosis, non-alcoholic steatohepatitis, fibrosis, cirrhosis
What is the epidemiology of non-alcoholic fatty liver disease
- Commonest liver disorder in industrialised western countries
- Affects around 3/4’s of all obese individuals
- Individuals with metabolic syndrome
Describe the aetiology of non-alcoholic fatty liver disease
Metabolic syndrome: obesity, hypertension, diabetes, hypertriglyceridemia, hyperlipidaemia
What are the risk factors for non-alcoholic fatty liver disease
Metabolic syndrome: obesity, hypertension, diabetes, hypertriglyceridemia, hyperlipidaemia. Drugs (NSAIDs, amiodarone)
Describe the pathophysiology of non-alcoholic fatty liver disease
Stages of NAFLD:
1. Non-alcoholic steatosis (fat build up in hepatocytes)
2. Non-alcoholic steatohepatitis (steatosis and inflammation)
3. Fibrosis
4. Cirrhosis
Insulin resistance plays a role. Overtime, insulin receptors are less responsive to insulin so liver increases fat storage and decreases fatty acid oxidation. This means there is less secretion of fatty acids into the blood stream. There is also increased synthesis and uptake of free fatty acids from the blood (known as steatosis).
This ultimately damages lipid membrane, leading to mitochondrial dysfunction and cell death. This generates inflammation. Inflammation + steatosis = steatohepatitis.
Damage also attracts neutrophils to the liver. Chronic steatoheptitis can trigger stellate cells to lay down fibrotic tissue (fibrosis).
The architecture then changes to the point where disease is now classed as cirrhosis
Describe the key presentations for non-alcoholic fatty liver disease
Asymptomatic. Very severe = liver failure signs: Hepatomegaly, jaundice, ascites, pain in upper right quadrant. Absence of chronic alcohol consumption
What are the symptoms of non-alcoholic fatty liver disease
Fatigue, malaise, nausea, vomiting
What is the gold standard investigation for non-alcoholic fatty liver disease
Liver biopsy (steatosis, inflammation, fibrosis)
What are the first line investigations of non-alcoholic fatty liver disease
Deranged LFTs: increased PT/INR, low albumin, increased bilirubin, increased AST and ALT, increased GGT
FBC: anaemia, thrombocytopenia. Lipid profile (raised LDL, cholesterol, triglyceride)
Liver ultrasound (fatty infiltrates)
What are the other investigations for non-alcoholic fatty liver disease
Assess risk of fibrosis with fibrosis score
What are the differential diagnosis for non-alcoholic fatty liver disease
Alcoholic liver disease, hepatitis BC, Wilson’s disease
What is the management for non-alcoholic fatty liver disease
1st line – treat underlying cause and reduce risks (lose weight, exercise, smoking, control diabetes, LDL). Medication: pioglitazone, vitamin E, statins, ACEi.
End stage (cirrhosis irreversible): liver transplant
