Liver and friends Flashcards
What is cholestasis?
blockage of bile flow
What is the difference between cholelithiasis and choledocholithiasis?
- cholelithiasis: presence of gallstones
- choledocholithiasis: gallstones in the bile duct
What is cholecystitis vs cholangitis?
- cholecystitis: inflammation of the gallbladder
- cholangitis: inflammation of the bile ducts
What is the pathophysiology behind primary biliary cirrhosis?
- autoimmune condition of small bile ducts
- intralobar ducts affected first
- causes obstruction of bile outflow (cholestasis)
- back pressure leads to fibrosis, cirrhosis and failure
What is the epidemiology behind primary biliary cirrhosis?
- 90% cases occur in women
- occurs in patients with other autoimmune diseases + rheumatoid conditions e.g. arthritis, systemic sclerosis
How does primary biliary cirrhosis present?
- fatigue
- pruritus (itching)
- GI problems and abdominal pain
- jaundice, pale stools
- signs of cirrhosis/failure
What is the physiology behind the presentation of primary biliary cirrhosis?
- bile acids, bilirubin and cholesterol are usually excreted through bile ducts but are obstructed and build up in blood
- bile acids > itching
- bilirubin > jaundice
- cholesterol > xanthelasma
- lack of bile acids in GI > GI disturbance, malabsorption and greasy, pale stools
How is primary biliary cirrhosis diagnosed?
- LFTs: ALP raised, other liver enzymes and bilirubin later in disease
- AMAs +ve in 95% cases
- ESR and IgM raised
- liver biopsy
How is primary biliary cirrhosis treated?
- Ursodeoxycholic acid: reduces intestinal absorption of cholesterol
- Colestyramine effective in 50% cases of pruritus
What is ascites?
- fluid in the peritoneal cavity
- inc pressure in portal system causes fluid to leak out of capillaries in liver and bowel
- lower fluid sensed by kidneys > renin released > aldosterone release > fluid reabsorption > transudative (low protein content)
What are the signs, symptoms and investigations of ascites?
- abdo distention
- shifting dullness (fullness in flank)
- fluid thrill
- transudate low
How is ascites managed?
- low sodium diet
- anti aldosterone diuretic (spironolactone)
- paracentesis
- prophylactic antibiotics if bacterial
What is peritonitis and how is it caused?
- inflammation of the peritoneum
- caused by perforation of the GI tract, bacterial or surgery/trauma
How is peritonitis investigated and managed?
- CXR, serum amylase to rule out pancreatitis, ultrasound/CT
- IV fluids and electrolytes to reverse hypovolaemia
- surgery to repair perforation
How does bacterial peritonitis present?
- Can be asymptomatic so have a low threshold for ascitic fluid culture
- Fever
- Abdominal pain
- Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
- Ileus
- Hypotension
What bacteria most commonly cause bacterial peritonitis and how is it treated?
- Escherichia coli
- Klebsiella pneumoniae
- gram positive cocci e.g. staphylococcus or enterococcus
- treated with cephalosporin e.g. cefotaxime
What is the difference between acute and chronic hepatitis?
- hepatitis: inflammation of the liver
- acute: lasting up to 6 months
- chronic: lasting beyond 6 months
What is the presentation of acute hepatitis?
- GI upset, abdo pain
- jaundice, pale stools/dark urine
- tender hepatomegaly
- liver failure symptoms
- raised transaminase (ALT+AST)
What are the viral causes of acute hepatitis?
- hepatitis: A, B ± D, C, E
- human herpes viruses e.g. HSV, EBV, CMV, VZV
What are the non-viral, infectious causes of acute hepatitis?
- spirochetes
- mycobacteria
- bacteria
- parasites
What are non-infection causes of hepatitis?
- drugs
- alcohol
- Non-alcoholic fatty liver disease
- Pregnancy
- Autoimmune hepatitis
- Hereditary metabolic causes
Where is hepatitis A found and how is it transmitted?
- most common type of viral hepatitis worldwide
- spreads through faeco-oral transmission: contaminated food and water
- RNA virus
- mostly in countries with lack of access to safe drinking water and lower socioeconomic backgrounds
How does Hepatitis A present and how is it treated?
- incubation period of 2-4 weeks
- cholestasis: pale stools, dark urine
- 100% immunity after infection
- managed by analgesia
- self-limiting so cannot become chronic
What are the causes of hepatitis E and how is it transmitted?
- faeco-oral transmission
- G1+2: contaminated food and water, poor sanitation
- G3+4: undercooked meat: mammalian zoonotic reservoir
Describe Hepatitis E
- RNA virus
- self-limiting acute hepatitis
- risk of chronic infection from types G3+4 in immunocompromised patients
How is Hepatitis E managed?
- acute: monitor for liver failure/fulminant hepatitis
- chronic: reverse immunosuppression, treat with ribavirin
- avoid undercooked meat
- screen blood donors
What type of virus is Hep B and how is it transmitted?
- DNA virus
- transmitted by blood or bodily fluids
- sharing needles/contaminated household products
- vertical transmission
How does Hep B present?
- incubation 30-180 days (mean 75)
- monitor liver function
- rarely get fulminant hepatitic failure
How can Hep B be prevented?
- Antenatal screening (HBsAg)
- screening and immunisation: followup testing for HBsAb
- blood product screening
How is Hep B managed?
- pegylated interferon-α 2a: weekly subcut injection
- oral nucleoside analogues (inhibit viral replication): tenofovir, entecavir
What type of virus is Hepatitis D and how is it transmitted?
- defective single stranded RNA virus
- can only survive with Hep B
- attaches itself to HbsAg to survive
- transmitted by blood and bodily fluids
How is Hep D tested for and treated?
- test for Hep D antibody, if +ve test for HDV RNA
- treat with pegylated interferon α
What type of virus is Hep C and how is it transmitted?
- RNA virus
- becomes chronic in 75%
- blood and bodily fluids
- blood products, injecting drug use, iatrogenic
How is Hep C diagnosed and treated?
- Hep C antibody then RNA screening
- directly-acting antiviral therapy
- lifestyle modification
Which types of hepatitis do PHE need to be notified of?
- Hep A, B, C, D, E
Describe Type 1 autoimmune hepatitis
- occurs in adults - typically women 40s/50s
- fatigue, symptoms of liver disease
- anti-LKM1 and anti-LC1 autoantibodies
Describe type 2 autoimmune hepatitis
- occurs in children > teens-early 20
- present with acute hepatitis, high transaminases, jaundice
- ANA, anti-actin and anti-SLA/LP autoantibodies
How is autoimmune hepatitis diagnosed and treated?
- liver biopsy
- high dose steroids: prednisolone and immunosuppressants
What are the 3 steps in the progression of alcoholic liver disease?
- alcohol related fatty liver: drinking causes a buildup of fat which reverses after 2 weeks of sobriety
- alcoholic hepatitis: over a long period, alcohol causes inflammation in liver sites. also associated with binge drinking
- cirrhosis: liver is made up of more scar tissue than healthy tissue. Is irreversible
What are the signs of liver disease/cirrhosis?
- jaundice
- hepatomegaly
- spider naevi
- palmar erythema
- bruising
- ascites
What are the typical results of bloods in someone with alcoholic liver disease/cirrhosis?
- FBC: raised MCV
- LFTs: elevated ALT and AST. ALP in advanced stage. Low albumin and elevated bilirubin
- Clotting: elevated PT
- U&Es may be deranged
What are other investigations that can be done for alcoholic liver disease?
- ultrasound
- endoscopy
- CT and MRI
- liver biopsy
How is alcoholic liver disease managed?
- stop drinking alcohol permanently
- nutritional support and high protein diet
- steroids in short term
- refer for liver transplant if severe
What is Wernicke’s encephalopathy?
- alcohol excess leads to thiamine (B1) deficiency
- confusion, oculomotor disturbance and ataxia
- leads to Korsakoff’s syndrome
What is non alcoholic fatty liver disease and how does it present?
- chronic health condition
- fat deposited in liver cells which can interfere with functioning
- shares risk factors w CVD and diabetes
- normally no symptoms and incidental findings then presents with liver failure symptoms
What are the 4 stages of NAFLD?
- Non-alcoholic Fatty Liver Disease
- Non-Alcoholic Steatohepatitis (NASH)
- Fibrosis
- Cirrhosis
How is NAFLD managed?
- weight loss
- exercise
- stop smoking
- control diabetes, BP, cholesterol, avoid alcohol
- possible treatment with Vit E or pioglitazone
How is NAFLD investigated?
- liver ultrasound
- 1st line: enhanced liver fibrosis
- 2nd line: NAFLD fibrosis score
- 3rd line: Fibroscan
Describe enhanced liver fibrosis testing
- blood test
- measures HA, PIIINP and TIMP-1
- < 7.7 = none to mild fibrosis
- ≤ 7.7 to 9.8 indicates mild fibrosis
- ≥ 9.8 indicates severe fibrosis
Describe NAFLD fibrosis score and fibroscan
- if ELF unavailable
- algorithm of age, BMI, liver enzymes, platelets, albumin
- used to rule out fibrosis but not assess severity when present
- fibroscan: measures stiffness
What is primary sclerosing cholangitis?
- bile duct inflammation
- intrahepatic or extra hepatic ducts become structured and fibrotic
- causes obstruction to bile flow out of liver and into intestines
- leads to hepatitis, fibrosis and cirrhosis
What are the causes and risk factors of primary sclerosing cholangitis?
- genetic, autoimmune, intestinal microbiome and environmental factors
- association with ulcerative colitis
- male
- aged 30-40
- family history
How does primary sclerosing cholangitis present?
- jaundice
- chronic upper right quadrant pain
- pruritus
- fatigue
- hepatomegaly
How is primary sclerosing cholangitis managed?
- liver transplant
- ERCP to dilate and stent strictures
- Colestyramine
How is primary sclerosing cholangitis diagnosed?
- Gold: MRCP: magnetic resonance cholangiopancreatography
- MRI of liver, bile ducts and pancreas
- LFTs show cholestatic picture
- ALP is most deranged
- bilirubin, ALT and AST rise in more severe disease
What is the serology of patients with primary sclerosing cholangitis?
- AMA negative
- HBVsAg and HCVAb negative
- ANA, pANCA, SMA positive
What are gallstones?
- formation of hard stones in gallbladder
- form from cholesterol, bile pigment, or mixed
- lead to acute cholecystitis, acute cholangitis and pancreatitis
What are the risk factors for gallstones?
- 4 F’s
- female, fat, fair, forty, (fertile)
How do gallstones present?
- may be asymptomatic
- severe, colicky, epigastric or RUQ pain
- triggered by meals, lasting 30 mins-8hrs
- associated with nausea and vomiting
How are gallstones diagnosed?
- GOLD: ultrasound: duct dilation, stones, gallbladder wall thickness
What is the pathophysiology and presentation of biliary colic?
- occurs due to inc cholesterol, dec bile salts and biliary stasis
- pain occurs when gallbladder contracts against stone lodged in neck of gallbladder
- colicky RUQ pain
- worse postprandially and after fatty meals
- nausea and vomiting
What is acute cholecystitis?
- inflammation of the gallbladder caused by blockage of cystic duct preventing drainage
- usually from gallstones
How does acute cholecystitis present?
- RUQ pain radiating around side and to right shoulder (due to diaphragmatic irritation)
- pain on inspiration
- fever, nausea, vomiting
- tachycardia and tachypnoea
- Murphy’s sign
- raised inflammatory markers and wbc
What is Murphy’s sign?
- Place hand in RUQ and apply pressure
- ask patient to breathe in
- gallbladder moves downwards during inspiration and comes in contact with hand
- stimulation of inflamed gallbladder results in acute pain and stopping of inspiration
How is acute cholecystitis diagnosed?
- abdo ultrasound
- thickened gallbladder wall, stones/sludge and fluid around gallbladder
- MRCP
How is acute cholecystitis managed?
- nil by mouth
- IV fluids
- antibiotics
- NG tube
- ERCP used to remove stones
- cholecystectomy if more severe
What is acute cholangitis?
- infection and inflammation in the bile ducts
- caused by obstruction or infection from ERCP
Which organisms most commonly cause acute cholangitis?
- E. coli
- Klebsiella
- Enterococcus
How does acute cholangitis present?
- Charcot’s triad: RUQ pain, fever, jaundice
How is acute cholangitis diagnosed?
- abdo ultrasound
- CT
- MRCP
- endoscopic ultrasound
How is acute cholangitis managed?
- nil by mouth
- IV fluids
- blood cultures and IV antibiotics
Describe pre-hepatic jaundice
- occurs in excessive haemolysis causing inc bilirubin production
- decreased liver uptake or conjugation > unconjugated bilirubin enters blood
- water insoluble > doesn’t enter urine > hyperbilirubinaemia
- newborns have reduced ability to remove bilirubin
- leads to dark urine (on standing) and stools
Describe hepatocellular jaundice
- results from inability of liver to excrete or conjugate bilirubin due to tissue damage
- hepatocyte damage and cholestasis
- levels of conjugated and unconjugated bilirubin increase
- causes are viral: CMV, EBV, hepatitis and cirrhosis
Describe cholestatic jaundice
- results from obstruction in the bile duct
- liver can conjugate bilirubin but is unable to excrete it
- conjugated bilirubin overspills into blood leading to conjugated hyperbilirubinaemia
- leads to dark urine and pale stools
- caused by gallstones, pancreatic cancer, PBC/PSC
What is the pathophysiology behind jaundice?
- yellow pigmentation of skin, sclera and mucosa
- occurs due to inc plasma bilirubin >35µmol/l
- normally, bilirubin is conjugated within the liver and excreted via bile. The majority of this is digested as urobilinogen and stercobilin
- jaundice occurs when this is disrupted
What are the causes of pancreatitis?
I - idiopathic
G - gallstones
E - ethanol (alcohol - is toxic > inflammation)
T - trauma
S - steroids
M - mumps
A - autoimmune
S - scorpion sting
H - hyperlipidaemia
E - ERCP
D - drugs (furosemide, thiazide diuretics, azathioprine)
How do gallstones cause pancreatitis?
- get trapped at ampulla of Vater
- block flow of bile and pancreatic juice into duodenum
- reflux of bile and prevention of pancreatic enzyme secretion > inflammation
How does pancreatitis present?
- severe epigastric pain radiating through to back
- vomiting
- abdo tenderness
- systematically unwell
How is pancreatitis investigated?
- FBC, U&E, LFT, calcium, ABG
- amylase raised >3x, lipase, CRP raised
- Ultrasound, abdo CT
What is the Glasgow score?
- assesses pancreatitis severity
- 0-1 = mild pancreatitis
- 2 = moderate pancreatitis
- 3+ = severe pancreatitis
What factors are used to calculate the Glasgow score?
- P – PaO2 < 8 KPa
- A – Age > 55
- N – Neutrophils (WBC > 15)
- C – Calcium < 2
- R – uRea >16
- E – Enzymes (LDH > 600 or AST/ALT >200)
- A – Albumin < 32
- S – Sugar (Glucose >10)
How is acute pancreatitis managed?
- ABCDE resus
- IV fluids and analgesia
- nil by mouth
- monitoring and treatment of complications
- antibiotics if required
What is liver cirrhosis?
- Results from chronic inflammation and damage to liver cells
- damage is replaced with scar tissue and nodules form
- inc resistance causes portal hypertension
What are the causes of cirrhosis?
- Hep B + C
- NAFLD
- Alcoholic fatty liver disease
- autoimmune hepatitis
- PBC
What is seen on the ultrasound of someone with liver cirrhosis?
- nodularity of the surface
- corkscrew appearance to the arteries to compensate for reduced portal flow
- enlarged portal vein
- ascites
- splenomegaly
How is cirrhosis managed?
- ultrasound
- endoscopy
- high protein, low sodium diet
- MELD score
- possible transplant
What are varices?
- portal hypertension causes back pressure where the portal system anastomoses with the systemic venous system
- causes swollen, torturous vessels
- occur at: gastro-oesophageal, ileocaecal junctions, rectum, anterior abdo wall
How are varices treated?
- propanolol reduces portal htn by acting as non-selective β blocker
- elastic band ligation
What is high ALT/AST indicative of?
- Alanine aminotransferase and aspartate aminotransferase
- markers of hepatocellular injury
- if ALT + AST slightly inc and ALP inc a lot = obstruction
- ALT + AST high compared to ALP = hepatocellular injury
What is ALP?
- alkaline phosphatase
- enzyme originating in the liver
- raised ALP indicates biliary obstruction if present with RUQ pain and jaundice
- can also be caused by liver + bone malignancy
What is endoscopic retrograde cholangio-pancreatography (ERCP)?
- inspiring endoscope down to sphincter of Oddi to clear stones in bile ducts
- can take X-rays and diagnose pathology, clear stones, insert stents
- can lead to cholangitis and pancreatitis
What does HBsAg indicate?
- Hep B surface antigen
- active infection
What does HBeAg indicate?
- E antigen: marker of viral replication
- indicates high infectivity
- patient is in acute phase
- if negative but HbeAb is positive then virus has stopped replicating
What does HBcAb indicate?
- hep B antibodies
- can be used to distinguish acute, chronic and past infections
- IgM: active infection
- IgG: past infection where HBsAg is -ve
What does HBsAB indicate?
- past or current infection or vaccination
- immune response to HBsAg
- other viral markers needed
What does HBV DNA show?
- direct count of the viral load
What is Wilson’s disease and what type of inheritance is it?
- excessive accumulation of copper in body and tissues
- caused by mutation on chromosome 13
- autosomal recessive
What are hepatic and psychiatric problems of Wilson’s?
- Kayser-Fleischer rings
- hepatitis and cirrhosis
- ranging from depression to psychosis
- haemolytic anaemia
- renal tubular acidosis
- osteopenia
What neurological symptoms arise from Wilson’s?
- dysarthria
- dystonia
- Parkinsonism: tremor, bradykinesia, rigidity
How is Wilson’s diagnosed?
- serum caeruloplasmin (protein that carries copper in the blood)
- GOLD: liver biopsy
- 24hr urine copper assay elevated
- Kayser-Fleischer rings
How is Wilson’s disease treated?
- copper chelation
- penicillamine
- trietene
What is haemochromatosis?
- iron storage disorder resulting in excessive total body iron and iron deposition in tissues
- mutations in human haemochromatosis protein (HFE)
- autosomal recessive
What are symptoms of haemochromatosis?
- chronic tiredness
- joint pain
- pigmentation: bronze/slate-grey
- hair loss
- erectile dysfunction/ammenorrhoea
- memory and mood disturbance
How is haemochromatosis investigated?
- high serum ferritin and high transferrin saturation
- genetic testing
- liver biopsy: Perl’s stain for Fe conc in parenchymal cells
What is the management of haemochromatosis?
- venesection
- monitoring serum ferritin
- avoid alcohol
- genetic counselling
What is α 1 antitrypsin deficiency?
- abnormality in the gene for a protease inhibitor called α-1 antitrypsin
What is the pathophysiology behind α 1 antitrypsin deficiency?
- elastase secreted by neutrophils and digests connective tissue
- A1AT produced in liver and inhibits elastase
- coded for by chromosome 14
- autosomal recessive defect
How does A1AT affect the liver and lungs?
- liver: A1AT is produced in the liver and the mutation can get trapped leading to cirrhosis and hepatocellular carcinoma
- lungs: excess of enzymes attack connective tissue leading to bronchiectasis and emphysema
How is A1AT diagnosed?
- low serum α1AT
- liver biopsy shows cirrhosis and acid Schiff positive globules
- genetic testing
- high res CT thorax
How is A1AT managed?
- stop smoking
- symptomatic management
- organ transplant
