Lecture 5.2: Diseases of the Liver and Pancreas Flashcards
What part of the abdomen is the liver located?
- RUQ
- Right Hyperchondrium
Functions of the Liver (7)
- Bile production
- Carbohydrate, protein and lipid metabolism
- Protein synthesis
- Vitamin D synthesis
- Detoxification
- Vitamin and mineral storage
- Phagocytosis
Types Liver Function Tests? (3)
- Hepatocellular damage
- Cholestasis (bile ducts)
- Synthetic function
What LFTs test for Hepatocellular damage? (2)
- Aminotransferases (ALT/AST)
- γ-Glutamyl transpeptidase (γ-GT/GGT)
What LFTs test for Cholestasis (bile ducts)? (2)
- Bilirubin
- Alkaline phosphatase (ALP)
What LFTs test for synthetic function? (3)
- Albumin
- Prothrombin time (clotting)
- Glucose
What is Jaundice?
- Yellow pigmentation of the skin and sclera
- Caused by accumulation of bilirubin in tissue
Why does Jaundice happen?
Normal metabolism of bilirubin disrupted (including uptake, transport, conjugation and excretion)
What are the 3 ways Jaundice is classifed?
- Prehepatic (haemolytic)
- Hepatic (parenchymal)
- Post hepatic (cholestatic)
When is Bilirubin produced?
Breakdown product of RBCs
How is bilirubin normally processed? (5 Steps)
- Unconjugated bilirubin bound to albumin in blood
- Bilirubin conjugated in liver
- Excreted in bile into duodenum
- De-conjugated into urobilinogen
- Urobilinogen oxidised to form urobilin and stercobilin
→ faeces
What is Pre-Hepatic Jaundice?
- Excessive haemolysis
- Liver unable to cope with excess bilirubin
Lab findings in Pre-Hepatic Jaundice (3)
- Unconjugated hyperbilirubinaemia
- Reticulocytosis
- Anaemia
Causes of Pre-Hepatic Jaundice: Inherited (6)
- Red cell membrane defects (thalassemia)
- Haemoglobinopathies
- Metabolic defects
- Congenital hyperbilirubinaemias
- Hereditary spherocytosis
- Sickle Cell Disease
Causes of Pre-Hepatic Jaundice: Acquired (6)
- Immune
- Mechanical
- Acquired membrane defects
- Infections (malaria)
- Drugs
- Burns
What is Hepatocellular Jaundice?
- Deranged hepatocyte function
- Cell necrosis→ inabilty to metabolise or excrete
bilirubin - Element of cholestasis
Lab findings in Hepatocellular Jaundice (4)
- Mixed unconjugated & conjugated
hyperbilirubinaemia - Increased liver enzymes (AST/ALT) reflecting liver
damage - Normal/Increased ALP (cholestasis (swollen cells))
- Abnormal clotting
Causes of Hepatocellular Jaundice: Inherited (3/5)
- Congenital hyperbilirubinaemias
- Gilbert’s syndrome (common)
- Crigler-Najjar syndrome (rare)
- Dubin-Johnson syndrome (rare)
- Wilson’s Disease
- Autoimmune hepatitis
Causes of Hepatocellular Jaundice: Acquired (6)
- Hepatic inflammation
- Alcohol
- Drugs (i.e. paracetamol)
- Cirrhosis
- Hepatic tumours
- Haemochromotosis
What is Post-Hepatic/Cholestatic/Obstructive Jaundice?
- Obstruction of biliary system
- Intrahepatic
- Extrahepatic
- Passage of conjugated bilirubin blocked
Lab findings in Post-Hepatic Jaundice? (6)
- Conjugated hyperbilirubinaemia
- Bilirubin in urine (dark)
- Pale stools
- No urobilinogen in urine (no bilirubin enters bowel
and so is not converted to urobilinogen) - Increased canalicular enzymes (ALP)
- Normal/increased liver enzymes (ALT and AST)
Causes of Post-Hepatic Jaundice: Extrahepatic (obstruction distal to bile canaliculi) (3/7)
- Gallstones
- Biliary stricture
- Carcinoma
- Head of pancreas
- Ampulla
- Cholangiocarcinoma (bile duct)
- Portal hepatis lymph nodes
- Liver metastases
- Pancreatitis
- Sclerosing cholangitis
Causes of Post-Hepatic Jaundice: Intrahepatic (hepatocyte swelling)
- Hepatitis
- Drugs
- Cirrhosis
- Primary biliary cirrhosis
What is Courvoisier’s Law?
In the presence of a non-tender palpable gallbladder,
painless jaundice is unlikely to be caused by
gallstones
Gallstones formed over a long period of time result in…?
A shrunken fibrotic gallbladder
What is Hepatitis?
Inflammation of the Liver
Lab findings in acute hepatocyte breakdown (2)
- Aminotransferase release (AST/ALT)
- Jaundice
Lab findings in prolonged/chronic hepatocyte damage (3)
- Synthetic failure
- Decreased albumin
- Decreased clotting factors
Causes of Hepatitis (7)
- Infections- viral
- Toxins
- Alcohol
- Drugs
- Wilsons Disease
- Haemochromatosis
- Autoimmune
How is Hepatitis A spread? It is acute of chronic?
- Faecal-oral route
- Usually acute
How is Hepatitis B spread? It is acute of chronic?
- Blood/Body fluids/vertical spread
- Acute and chronic
- May progress to cirrhosis
How is Hepatitis C spread? It is acute of chronic?
- Blood spread
- 50% chronic liver disease
- 30% cirrhosis
- 5% hepatocellular carcinoma
How is Hepatitis D spread?
Hep B co-infection
How is Hepatitis E spread? It is acute of chronic?
- Faecal-oral
- Usually acute
What is Alcoholic Liver Disease?
Liver damage caused by excess alcohol intake
Pathology of Alcoholic Liver Disease (3)
- Fatty change
- Alcoholic hepatitis
- Cirrhosis
Complications of Alcoholic Liver Disease (6)
- Hepatocellular carcinoma
- Liver failure
- Wernicke-Korsakoff syndrome
- Encephalopathy
- Dementia
- Epilepsy
What is Liver Cirrhosis?
- Liver cell necrosis → nodular regeneration and fibrosis
- Increased resistance to blood flow
- Deranged liver function
How much of liver parenchyma can be destroyed before any clinical signs present?
80-90%
Causes of Liver Cirrhosis (7)
- Alcohol
- Hepatitis B or C
- Non-alcoholic fatty liver disease
- Primary biliary cirrhosis
- Autoimmune hepatitis
- Haemochromatosis
- Wilson’s disease
Clinical Features of Liver Cirrhosis
- Liver dysfunction
- Jaundice
- Anaemia
- Bruising
- Palmar erythema
- Dupuytren’s contracture
- Portal hypertenision
- Spontaneous bacterial peritonitis
Investigations for Liver Cirrhosis (6)
- →/↑ALT/AST
- ↑ALP
- ↑Bilirubin
- ↓albumin
- Deranged clotting
- ↓ Na
Management of Liver Cirrhosis (3)
- Stop drinking
- Treat complications
- Transplantation
Signs and Symptoms of Liver Disease (9)
- Hepatic Flap
- Clubbing
- Leukonychia
- Koilonychia
- Jaundice
- Gynacomastia
- Dupuytren’s Contracture
- Odema
- Spider Naevi
What is Portal Hypertension?
Portal venous pressure >12 mmHg due to intrahepatic or extrahepatic portal venous compression or occlusion
Causes of Portal Hypertension (3)
- Obstruction of portal vein
- Obstruction of flow within liver
- Cirrhosis
Clinical Manifestations of Portal Hypertension (5)
- Splenomegaly
- Ascites
- Spider Naevi
- Caput medusa
- Oesophageal/rectal varices
What is stored in the gallbladder?
- Liver produces bile
- Stored in gallbladder
Pathological Processes in the Gallbladder and Biliary Tree (4)
- Obstruction
- Infection
- Inflammation
- Neoplasia
Risk Factors for Gallstones (Cholelithiasis): 5 F’s
Fair
Fat
Fertile
Female
Forty
Risk Factors for Gallstones (Cholelithiasis) (6)
- Increasing age
- Positive family history
- Sudden weight loss - eg, after obesity surgery
- Loss of bile salts - eg, ileal resection, terminal ileitis
- Diabetes
- Oral contraception
Types of Gallstones
- Mixed (80%, Cholesterol with calcium & bile pigment)
- Pure cholesterol (10%, usually solitar, up to 5cm)
- Pigment stones/bilirubin stones (10%, calcium
bilirubinate, multiple, small and black)
What percentage of gallstones are radio-opaque?
~10% are radio-opaque
What percentage of gallstones are asymptomatic?
~70%
Complications of Gallstones (13): Name 5
- Biliary colic
- Impaction of stone in cystic duct
- Gallbladder contraction
- Cholecystitis
- RUQ pain & fever
- Sepsis
- Local peritonism
- Raised white cell count
- Gallbladder mass
- Recurrent acute attacks may become chronic
- Ascending cholangitis
- Obstructive jaundice
- Acute pancreatitis
How does pain due to gallstones present?
- Sudden onset of epigastric/RUQ pain
- Radiates to back
- Lasts 15 minutes up to 24 hours
- Resolves spontaneously or with analgesics
- Associated nausea and vomiting
Management of (Complications of) Gallstones (4)
- Analgesia
- NBM
- IV Antibiotics and fluids
- Surgery – laparoscopic cholecystectomy
What is Charcot’s Triad?
The manifestation of biliary obstruction with:
* Upper Abdominal Pain
* Fever
* Jaundice
What is Ascending Cholangitis?
- A life-threatening condition caused by an ascending
bacterial infection of the biliary tree - Inflammation/infection of the CBD
- Bacteria ascend from CBD junction with the
duodenum - Bile duct is already partially obstructed by gallstones
Management of Ascending Cholangitis (3)
- Resuscitate
- IV broad spectrum antibiotics
- Surgery – endoscopic drainage of CBD
What are the Contents of the Triangle of Calot?
- Right Hepatic artery
- Cystic artery
- Any aberrant/accessory ducts
Functions of the Pancreas: Endocrine
- Insulin
- Glucagon
- Somatostatin
Functions of the Pancreas: Exocrine
- Fluid (HCO3)
- Enzymes
- Proteolytic, amylase, lipolytic
What is Pancreatitis?
- Inflammation of the pancreas
- Inflammatory process caused by effects of enzymes
released from pancreatic acini
What changes occur in the Pancreas due to Acute Pancreatitis (3)
- Oedema
- Haemorrhage
- Necrosis
What changes occur in the Pancreas due to Chronic Pancreatitis (5)
- Fibrosis
- Calcification
- Loss of acini
- Duct stenosis
- Parenchymal destruction
Causes of Acute Pancreatitis: GET SMASHED
- Gallstones
- Ethanol
- Trauma
- Steroids
- Mumps
- Autoimmune
- Scorpion bite
- Hyperlipidaemia
- ERCP/Iatrogenic
- Drugs
What causes 80% of Acute Pancreatitis cases? (2)
- Gallstones
- Ethanol
Pathogenesis/Clinical Presentations of Pancreatitis (6)
- Duct obstruction (from juice & bile reflux)
- Acinar damage (from reflux or drugs)
- Tissue destruction (via proteases)
- Fat necrosis (via lipases)
- Blood vessel destruction (via elastases)
- Enzymes digest pancreatic tissue
How does pain caused by acute pancreatitis present?
- Sudden severe epigastric pain
- Penetrates to the back
- Vomiting
- Steadily decrease over 72 hours
What is Cullen’s Sign?
Superficial bruising in the subcutaneous fat around the umbilicus
What is Grey Turners Sign?
An uncommon subcutaneous manifestation of intra-abdominal pathology that manifests as ecchymosis or discolouration of the flanks
What conditions is Cullen’s Sign seen in? (7)
- Acute pancreatitis
- Rectus sheath hematoma
- Splenic rupture
- Perforated ulcer
- Intra-abdominal cancer
- Ruptured ectopic pregnancy
- Complication of anticoagulation
What condition is Grey Turners Sign seen in?
Severe acute necrotizing pancreatitis
Treatment of Acute Pancreatitis
- Supportive – NG tube and IVI (drip and suck)
- Fluid balance
What biochemical changes occur in acute pancreatitis? (4)
- ↑Amylase
- ↓Ca2+
- ↑Glucose
- ↑ALP/Bilirubin
What are the clinical presentations of chronic pancreatitis? (5)
- Pain
- Malabsorption
- Steatorrhoea, wt loss
- DM
- Jaundice
When does pancreatic carcinoma present?
- Late presentation
- Early metastases
- Poor survival rates
Risk Factors for Pancreatic Carcinoma (7)
- Smoking
- Over 60
- High Fat Diet
- Alcohol
- Chronic Pancreatitis
- Diabetes
- Family History
Clinical Features Pancreatic Carcinoma (9)
- Initially symptomless/vague
- Painless progressive obstructive jaundice
- Nausea
- Vomiting
- Pain
- Weight Loss
- Carcinomatosis
- Malabsorption
- Diabetes
How many pancreatic carcinomas are found in the head of the pancreas?
70% in head of pancreas
What is the most common type of pancreatic carcinoma? What percentage of pancreatic carcinomas does it make up?
- Ductal adenocarcinoma
- 90%
What effect does pancreatic cancer invading the pancreatic head have on surrounding structures? (3)
- Can compress and obstruct the bile duct,
- Can compress/obstruct hepatopancreatic ampulla
- If cancer invades posteriorly, it can invade/block
portal venous confluence of splenic vein + SMV
Treatment of Pancreatic Carcinoma
- Surgery (only 10-20%)
- Chemotherapy
- Palliative
Prognosis of Pancreatic Carcinoma
- 5th cause of cancer death in UK
- 5-year survival rate less than 5%
What is Gilbert’s Syndrome?
- Inherited condition
- The faulty gene means that bilirubin isn’t passed into
bile at the normal rate - Thus bilirubin build up in blood
Name 5 causes of obstruction to flow of bile from the liver and gallbladder
- CBD gallstones
- Carcinoma
- Pancreatic Pseudocyst
- Biliary Stricture
- Sclerosing Cholangitis
What is HUS?
- Haemolytic Uremic Syndrome
- A kidney condition that happens when red blood cells
are destroyed and block the kidneys’ filtering system
Symptoms of HUS?
- Vomiting
- Bloody Diarrhea
- Stomach Pain
- Fever
- Chills
- Headache
What causes HUS?
In most cases, HUS occurs after a severe bowel infection with certain toxic strains of the bacteria called E. coli. It may also occur in response to certain medicines, but this is rare.
Treatment of HUS (6)
- Plasma Exchange
- Treatment of high blood pressure
- Maintaining specific levels of fluids and salts
- Blood transfusions
- Kidney dialysis
- Medicine
