Liver and friends Flashcards
What are the functions of the liver?
- oestrogen regulation
- detoxification
- metabolises carbohydrates
- albumin production
- clotting factor production
- bilirubin regulation
- immunity → Kupffer cells in reticuloendothelial system
Acute presentation of liver failure
- malaise
- nausea
- anorexia
- jaundice
rare
- confusion
- bleeding
- pain
- hypoglycaemia
Chronic presentation of liver failure (11)
- ascites
- oedema
- Dupuytren’s contracture
- malaise
- anorexia
- clubbing
- palmar erythema
- xanthelasma
- spider naevi
- hepatomegaly
- bleeding → haematemesis, easy bruising
Progression of chronic liver disease
- chronic liver condition
- liver damage
- liver symptoms
- liver cirrhosis if prolonged
- liver failure and higher risk of HCC
What bloods can be done to investigate liver failure?
- liver function tests LFTs
- liver hepatic enzymes
What can be measured in LFTs?
- serum bilirubin
- serum albumin
- prothrombin time → INR
serum albumin and PT = best indicators of liver function
What can be measured in liver hepatic enzymes?
aminotransferases
- leak into blood when hepatocytes are damaged
- AST
- ALT → more specific in disease
alkaline phosphate ALP
- raised in intra/extra hepatic cholestatic disease of any cause
gamma-glutamyl transferase GGT
What is liver failure?
liver loses its ability to repair and regenerate leading to decomposition
decomposition
- hepatic encephalopathy
- abnormal bleeding
- ascites
- jaundice
Causes of liver failure
- infection → viral hepatitis
- metabolic → Wilson’s, A1AT
- autoimmune → PBC, PSC
- neoplastic → HCC, metastatic disease
- vascular → Budd Chiari, ischaemia
- toxins → PCM, alcohol
Signs of liver failure
- jaundice
- coagulopathy
- hepatic encephalopathy
- fetor hepaticus = sweet and musty breath/urine
Investigations for liver failure
clinical examination
bloods
- raised PT/AST/ALT
- toxicology screen
- FBC, U&E
if ascites present → peritoneal tap with M&C
Management of liver failure
- fluids
- supportive measures
- treat complications
- transplant
How do you treat the complications of liver failure?
- ascites → diuretics
- cerebral oedema → mannitol
- bleeding → vitamin K
- encephalopathy → lactulose
- sepsis → sepsis 6, Abs
- hypoglycaemia → dextrose
What is alcoholic liver disease
effect of long term excessive consumption on liver
- alcoholic related fatty liver
- drinking leads to build up of fat in liver
- reverses in 2 weeks if drinking stops - alcoholic hepatitis
- long term drinking → inflammation in liver sites
- mild version is reversible - cirrhosis
- liver made of scar tissue
- irreversible
Investigations for alcoholic liver disease
- bloods
- US/CT/MRI liver
- endoscopy for varices
- DIAGNOSTIC = liver biopsy
What blood results might you see in alcoholic liver disease
- raised ALT/AST/PT
- markedly raised GGT
- raised ALP in later stages
Management of alcoholic liver disease
- stop drinking
- nutritional support
- steroids improve short term outcomes
- treat complications
- transplant
What are the complications of alcoholic liver disease?
- Wernicke-Korsakoff encephalopathy
- acute/chronic pancreatitis
- oesophageal varices
What is Wernicke-Korsakoff syndrome?
- alcohol excess = B1 deficiency
- presents with ataxia, confusion, nystagmus, memory impairment
- treatment = IV thiamine, no alcohol
What is NAFLD?
- non-alcoholic fatty liver disease
- chronic metabolic syndrome relating to processing and storing energy
- increases risk of heart disease, stroke, diabetes
Stages of NAFLD
- healthy
- steatosis
- steatohepatitis
- fibrosis
- cirrhosis
Risk factors for NAFLD (7)
- obesity
- poor diet, low activity
- T2DM
- high cholesterol
- middle age onwards
- smoking
- high BP
Clinical presentation of NAFLD
- asymptomatic
- N,D&V
- hepatomegaly
Investigations for NAFLD
- US liver for steatosis
- biopsy = DIAGNOSTIC
fibrosis
- enhanced liver fibrosis blood test
- NAFLD fibrosis score
- fibroscan
Management of NAFLD
- weight loss
- exercise
- stop smoking
- control diabetes, BP, cholesterol
- avoid alcohol
- treat fibrosis with vitE or pioglitazone
What investigations should be performed after abnormal LFTs
- US liver
- hepB and C serology
- autoantibodies → autoimmune hep, PBC, PSC
- immunoglobulins → autoimmune hep, PBC
- caeruloplasmin → Wilson’s
- A1AT levels
- ferritin and transferrin saturation → hereditary haemochromatosis
What type of virus is hepA?
RNA
- rarer
- developing world
How is HepA transmitted?
faecal-oral transmission
- contaminated food
- fly vectors
Pathophysiology of HepA
- acute infection
- usually cleared by host immune system
Presentation of HepA
- non specific symptoms → nausea, anorexia, malaise
after 1-2 weeks → liver symptoms
- jaundice
- hepatomegaly
- skin rash
Investigations for HepA
LFTs
- raised ALT, bilirubin
- serology
Treatment for HepA
- vaccine available
- treatment often not required
- generally supportive
Complications for HepA
- rare
- acute liver failure
What type of virus is HepB?
DNA
- present worldwide
Pathophysiology of HepB
- acute infection infects hepatocyte
- usually cleared by cellular response
chronic HBV
- if HBsAg >6 months
- depends on age/immunocompetence
- inflammation can last 10 years → cirrhosis
Presentation of HepB
- similar acute infection
- if chronic, then signs of cirrhosis → jaundice, pruritus etc
Investigations for HepB
- LFTs, serology
if Ag after 6 months, confirm chronic HBV
Treatment for HepB
- vaccine available → at risk
- antiviral treatment → tenofovir = pegylated interferon alpha 2a
Complications of HepB
if chronic, increased risk of cirrhosis, HCC
What type of virus is HepC
RNA
- more common in UK
How is HepB transmitted?
- blood products → IVDU
- sexually → MSM
How is HepC transmitted?
blood/blood products → IVDU>sexually
Pathophysiology of HepC
- acute infection often asymptomatic → allows progression to chronic
- chronic HCV causes slowly progressive fibrosis
Presentation of HepC
- acute = asymptomatic
- later on = signs of chronic liver disease
Investigations for HepC
- LFTs, serology
- if Ag after 6 months, confirm chronic HCV
Treatment for HepC
- revolutionising from interferon based regimens to directly acting antiviral agents
- Ribavirin = expensive
Complications of HepC
- chronic liver disease
- HCC
What type of virus is HepD
RNA
How is HepD transmitted?
- blood borne
- IVDU, sexually
Pathophysiology of HepD
- unable to replicate on its own
- requires concurrent HBV infection
- makes HepB more likely to progress to cirrhosis/HCC
Presentation of HepD
indistinguishable from acute HBV infection
Treatment for HepD
same as HBV
Complications of HepD
cirrhosis, HCC
What type of virus is HepE
RNA
- common in UK
How is HepE transmitted
- faeco-oral transmission
- undercooked meat
Presentation of HepE
- 95% asymptomatic
- usually self-limiting
Investigations for HepE
serology
Treatment for HepE
- often not required
- supportive
Complications of HepE
- rare
- can progress to cirrhosis in immunocompromised
What is liver cirrhosis?
- diffuse pathological process
- fibrosis
- conversion of normal liver to structurally abnormal nodules → regenerative nodules
- final stage of any chronic liver disease
- irreversible but significant recovery if underlying cause treated
Causes of cirrhosis
- alcohol abuse → alcoholic liver disease
- NAFLD
- hepatitis B, C
- haemochromatosis
- Wilson’s
- A1AT deficiency
Investigations for cirrhosis
DEFINITIVE DIAGNOSTIC = liver biopsy
blood tests
- INR/PT high
- LFTs
- FBC → thrombocytopenia
- serum electrolytes
US and CT → hepatomegaly
Treatment for cirrhosis
same as chronic liver disease
conservative
- fluids
- alcohol abstinence
- good nutrition
treat complications of liver failure
DEFINITIVE TREATMENT = liver transplant
Complications of cirrhosis
- ascites
- portal HTN
- varices
- jaundice
- coagulopathy
- hypoalbuminaemia
- portosystemic encephalopathy
What is ascites?
fluid in the peritoneal cavity
Why do you get ascites in cirrhosis
- hypoalbuminaemia → reduced oncotic pressure
- portal HTN → increased hydrostatic pressure
- renal water retention → peripheral arterial vasodilation mediated by NO
Causes of ascites
cirrhosis = commonest cause
4 basic mechanisms
- peritonitis = more leaky
- reduced capillary hydrostatic pressure
- reduced colloid oncotic pressure
- peritoneal lymphatic draining
Types of ascites
transudate
- <25 protein
- portal HTN, budd chiari, low plasma protein, HF
exudate
- > 25 protein
- peritonitis, peritoneal malignancy
Presentation of ascites
- shifting dullness
- weight gain
- abdominal distention
- signs of liver disease
- respiratory distress
Investigations for ascites
DIAGNOSTIC = aspiration
- albumin
- neutrophil count
Treatment for ascites
- salt restriction
- diuretics → furosemide, spironolactone
Complications of ascites
spontaneous bacterial peritonitis SBP
- infection of ascitic fluid
- most common causes = E.coli then K.pneumoniae
Causes of portal HTN
prehepatic
- portal vein thrombosis
intrahepatic
- cirrhosis
- budd chiari
posthepatic
- RHS HF
- IVC obstruction
Symptoms of portal HTN
asymptomatic or symptoms of complications
- ascites
- bleeding varices
What are bleeding varices
- GI bleed with chronic liver disease
- most patients with cirrhosis develop varices
- only 1/3 bleed → often massive
Investigations for varices
- GOLD STANDARD = upper GI endoscopy
Progression of varices
- rupture
- haematemesis
- blood digested
- malaena
Treatment for varices
- beta blocker to reduce CO → reduces portal pressure
- nitrate to reduce portal pressure
- band ligation
- trans jugular intrahepatic portosystemic shunt (TIPSS)
Management of active bleeding varices
- urgent endoscopy/gastroscopy
- fluid resusictation
- terlipressin or octreotide
- balloon tamponade
GOLD STANDARD = endoscopic therapy → band ligation/scleropathy
How do you prevent reoccurrence of varices?
- 60-80% chance of recurrence within 2 years
secondary prophylaxis
- propanolol/isosorbide
- repeat variceal banding
- TIPSS
What is biliary colic?
temporary blockage of the cystic duct by gallstones
What is bile made of?
- cholesterol
- pigments
- phospholipids
What are gallstones?
occur when there is a disturbance to the equilibrium of bile causing solid deposits
made of
- cholesterol → excess production = obesity, fatty diet
- pigment → haemolytic anaemia
- mixed
Risk factors of biliary colic
5 Fs
- fat
- female
- forty
- fair
- fertile
Presentation of biliary colic
- classic colicky RUQ pain → worse after eating large/fatty meals
- referred shoulder pain
- N&V
Investigations for biliary colic
rule out cholecystitis/cholangitis
DIAGNOSTIC = US
- stones
- gallbladder wall thickness
- duct dilation
Treatment for biliary colic
- NSAIDs/analgesia
- optional lap cholecystectomy → gallstones often recur
What is acute cholecystitis
inflammation of the gallbladder
Pathophysiology of acute cholecystitis
- gallstones block cystic ducts
- buildup of bile → distends gallbladder
- vascular supply may be reduced
- inflammation
Presentation of acute cholecystitis
- generalised epigastric pain migrating to severe RUQ pain
- signs of inflammation → fever/fatigue
- pain associated with tenderness and guarding from inflamed gallbladder and local peritonitis
Investigations for acute cholecystitis
- positive murphy’s sign
- inflammatory markers → FBC, CRP
- US gallbladder → thick walls
What is a positive murphy’s sign?
- severe pain on deep inhalation with examiners hand pressed into RUQ
Treatment for acute cholecystitis
- Abs
- early lap cholecystectomy (within 7 days) or wait 6 weeks
- fluids and analgesia
What is ascending cholangitis?
- medical emergency
- bacteria ascending through biliary tree → septicaemia
What are the types of jaundice?
pre-hepatic
- unconjugated bilirubin
- cause = breakdown of RBCs → haemolytic anaemia
hepatic
- unconjugated bilirubin
- cause = hepatitis
post-hepatic
- conjugated bilirubin → itching
- causes = obstruction, stricture, cancer head of pancreas
Presentation of ascending cholangitis
- Charcot’s triad
- Reynolds pentad
What is Charcot’s triad?
- RUQ pain
- jaundice
- fever and rigors
What is Reynolds pentad
- Charcot’s triad
- confusion
- septic shock
Investigations for ascending cholangitis
- amylase/lipase, LFTs, CRP, FBC
- CT/US gallbladder
- MRCP/ERCP
Management of ascending cholangitis
- aggressive fluid resuscitation
- IV Abs → penicillins and aminoglycosides
- pressor support
- ERCP
- cholecystectomy when better
What is primary biliary cirrhosis
- progressive autoimmune destruction of liver and biliary tree
- leads to fibrosis then cirrhosis
- AMA +ve against PDC-E2
Risk factors for PBC
- female
- associated with autoimmune disease
Presentation of PBC
very non-specific
- fatigue
- pruritus
- liver failure symptoms if advanced
Investigations for PBC
- AMA
- LFT → GGT/ALP raised
- US gallbladder
- biopsy
Management of PBC
ursodeoxycholic acid to reduce cholestasis
What is primary sclerosing cholangitis?
progressive sclerosis of biliary tree → chronic cholestasis and ESLD
Causes of PSC
- 80% associated with IBD → UC
- p-ANCA and HLA association
- exact mechanism unknown
Diagnostic criteria of PSC
- ALP >1.5x normal for >6 months
- cholangiography → biliary strictures → beaded appearance
- liver biopsy consistent with PSC
Presentation of PSC
- 50% asymptomatic until advanced
- non specific pruritus and fatigue
- may be diagnosed after presenting with ascending cholangitis
Complications of PSC
predisposed to developing
- HCC
- cholangiocarcinoma
- CRC
Management of PSC
- liver transplant
- non known medical management
What is acute pancreatitis
- sudden inflammation of pancreas
- leads to autodigestion of gland → reversible
Presentation of acute pancreatitis
- severe epigastric pain radiating to back
- N&V
- fever and chills
- haemodynamic instability
- retroperitoneal haemorrhage → Cullen’s and Grey Turner’s signs
What is Cullen’s sign?
superficial oedema with bruising in the subcutaneous fatty tissue around the peri-umbilical region
What is Grey Turner’s sign?
discolouration of the left flank associated with acute hemorrhagic pancreatitis
Complications of acute pancreatitis
- pancreatic pseudocyst
- insulin dependent DM
- ARDS and pleural effusion
- DIC
Causes of acute pancreatitis
I GET SMASHED
- idiopathic
- gallstones
- EtOH
- trauma
- steroids
- mumps/malignancy
- autoimmune
- scorpion stings
- hypertriglyceridaemia/hypercalcaemia
- post ERCP
- drugs → tobacco, thiazides
Pathophysiology of acute pancreatitis
gallstones
- blockage of bile duct → backup of pancreatic juices
- change in luminal concentration causes Ca2+ release inside pancreatic cells
- trypsinogen activated early → autodigestion
alcohol
- contracts Ampulla of Vater
- obstructs bile clearance
- affects Ca2+ homeostasis
What scoring systems are there for acute pancreatitis?
- APACHE
- Glasgow&Ranson
Investigations for acute pancreatitis
- raised amylase, lipase, CRP
- erect chest xray
- CT/US gallbladder
- MRCP
Management of acute pancreatitis
- nil by mouth → bowel rest
- aggressive fluid resuscitation
- analgesia
- Abs if necrotising pancreatitis
- ITU/TPN if required
- ERCP/surgery if required
- treat underlying cause ie gallstones
What is chronic pancreatitis?
- long standing inflammation from irreversible damage to pancreas
- can manifest as persistent pain and malabsorption in episodes
Causes of chronic pancreatitis
- generally caused by chronic alcohol abuse
- CF
- cancer
- autoimmune
- CKD
Pathophysiology of chronic pancreatitis
- obstruction of bicarbonate secretion in pancreatic lumen
- early activation of trypsinogen and autodigestion
- replaced by fibrosis
- can be caused by CF/alcohol → increases trypsinogen activation
Presentation of chronic pancreatitis
- epigastric pain radiating to back → less than acute, better when leaning forward, worse with alcohol
- N&V
- steatorrhea
- weight loss → malabsorption
- insulin dependent DM
Investigations for chronic pancreatitis
- secretin stimulation test
- CT, MRI, MRCP
Management of chronic pancreatitis
- creon
- insulin
- opioids
- alcohol cessation
- dietary modification
- ERCP/surgery if required
What is ERCP?
endoscopic retrograde cholangiopancreatography
What is infective diarrhoea?
- increased stool frequency and volume
- decreased consistency
Causes of infective diarrhoea
viral
- rotavirus → children
- norovirus
- adenovirus
bacterial
- e.coli
- norovirus
- c difficile
parasites → giardia
Abs
other
- anxiety
- food allergy
chronic
- IBS
- IBD
- coeliac
- bowel cancer
Risk factors for infective diarrhoea
- foreign travel
- crowded area
- poor hygiene
Causes of infective diarrhoea
viral
- rotavirus → children
- norovirus
- adenovirus
bacterial
- e.coli
- norovirus
- c difficile
parasites → giardia
Abs
other
- anxiety
- food allergy
chronic
- IBS
- IBD
- coeliac
- bowel cancer
Risk factors for infective diarrhoea
- foreign travel
- crowded area
- poor hygiene
Pathophysiology of haemochromatosis
- mutation in autosomal recessive HFE gene
- increased intestinal iron absorption
- iron accumulates in liver, joints, pancreas, heart, skin, gonads
- organ damage
Presentation of haemochromatosis
- slate grey skin → brownish/bronze
- fatigue, arthralgia, weakness
- hypogonadism eg ED
- chronic liver disease, HF, arrythmia
Pathophysiology of haemochromatosis
- mutation in autosomal recessive HFE gene
- increased intestinal iron absorption
- iron accumulates in liver, joints, pancreas, heart, skin, gonads
- organ damage → liver fibrosis, cirrhosis, HCC
Presentation of haemochromatosis
- slate grey skin → brownish/bronze
- fatigue, arthralgia, weakness
- hypogonadism eg ED
- chronic liver disease, HF, arrythmia
Investigations for haemochromatosis
- bloods → iron study, LFTs
- genetic testing
- MRI → detects iron overload
GOLD STANDARD = liver biopsy
Treatment for haemochromatosis
- venesection
- iron chelation
DEFINITIVE TREATMENT = liver transplant
Complications of haemochromatosis
- cirrhosis
- HCC
- diabetes
- heart disease
What is Wilson’s disease?
- too much copper
- builds up in liver and CNS
Aetiology of Wilson’s
- autosomal recessive
- defective enzyme involved in biliary excretion of excessive copper
Pathophysiology of Wilson’s
Cu2+ accumulates in
- liver → liver symptoms
- basal ganglia → Parkinson’s
- cornea → kayser-Fleischer rings
Presentation of Wilson’s
- depression
- neurotic behavioural patterns
- Parkinson’s symptoms
- hepatitis, cirrhosis
- Kayser-Fleischer ring → copper in cornea, green/brown pigment at outer edge
Investigations for Wilson’s
- serum copper and caeruloplasmin reduced
GOLD STANDARD = liver biopsy
Pathophysiology of A1AT deficiency
A1AT gene
- produced in liver
- inhibits neutrophil elastase → produced with inflammation, infection, smoking
- with A1AT deficiency, elastase breaks down elastic unchecked
- affects lung (alveolar wall destruction) and lung
What is A1AT deficiency?
- autosomal recessive genetic disorder
- results in lung and/or liver disease
Pathophysiology of A1AT deficiency
- A1AT defi
Presentation of A1AT deficiency
lung
- COPD like symptoms
- SOB
- emphysema
liver
- cirrhosis
- hepatitis
- neonatal jaundice
Investigations for A1AT deficiency
- bloods → serum A1AT low
- LFTs, PFTs
- chest xray
- liver biopsy
What is peritonitis
inflammation of the peritoneum
Pathophysiology of peritonitis
- inflammation from infection of irritation
Primary causes of peritonitis
- SBP
- ascites
Treatment for peritonitis
- ABCDE management
- find and treat underlying cause
- IV fluids
- IV Abs → 1. broad spec 2. specific for pathogen
- peritoneal lavage → clean cavity
Investigations for peritonitis
bloods
- FBC, CRP
- amylase → pancreatitis
- hCG → ruptured ectopic pregnancy
- erect chest xray → air below diaphragm
- abdo xray → bowel obstruction
- abdo CT → ischaemia
ascitic tap and blood cultures
Treatment for peritonitis
- ABCDE
What is a hernia?
- protrusion of organ through defect in wall of its containing cavity
What are the classifications of hernias?
- reducible
- irreducible
- obstructed = intestinal flow stopped
- strangulated = blood supply cut off → ischaemia +/- gangrene
What is an inguinal hernia?
protrusion of abdominal contents through inguinal canal
Risk factos of inguinal hernia
- male
- chronic cough
- heavy lifting
- past abdominal surgery
Presentation of inguinal hernia
- swelling in groin/scrotum
- may be painful
- may be reducible
Investigation for inguinal hernia
- clinical diagnosis
- US/CT/MRI
What is a femoral hernia?
bowel come through femoral canal
Presentation of inguinal hernia
- mass in upper medial thigh
- may be cough impulse
- likely to be irreducible and strangulate → due to rigidity of canal’s borders
Investigation for femoral hernia
- clinical diagnosis
- US/CT/MRI
What is a hiatus hernis?
herniation of the stomach through oesophageal aperture of diaphragm
Risk factors of hiatus hernia
- obesity
- female
- pregnancy
- ascites
- advanced age
- skeletal deformities
Other types of hernias
- incisional = through surgical scar
- epigastric = through linea alba above umbilicus
- umbilical = at umbilicus
Investigations for hiatus hernia
- chest xray
- barium swallow
- endoscopy
- oesophageal manometry
Management of hernis
SURGERY
What is the most common type of liver cancer?
hepatocellular carcinoma 80%
- prognosis = 3-6 months if unresectable
Presentation of HCC
- chronic liver failure
- maybe abdominal mass
Risk factors for HCC
- HCV and HBV
- EtOH
- aflatoxin
Investigations for HCC
- LFTs
- clotting studies
- CT/MRI
- ultrasound grounded biopsy
Treatment for HCC
depends on staging
- partial hepatectomy/transplant → curative intention
- chemo to downstage and resect
- palliative chemo to prolong life
What is the most common type of pancreatic cancer
pancreatic adenocarcinoma 90%
- 6% 5 year survival
Presentation of pancreatic adenocarcinoma
- unrelenting epigastric pain worse at night
- obstructive jaundice +/- pain
- weight loss and anorexia
- palpable gallbladder → courvoisier’s sign
- recent diagnosis of DM
- Trousseau’s sign
Investigations for pancreatic adenocarcinoma
- bloods → carbohydrate antigen 19-9 and LFTs
- CT +/- endoscopic US gallbladder
- biopsy with histological confirmation
Management of pancreatic adenocarcinoma
- surgery → Whipple
- chemo → neoadjuvant, adjuvant, palliative
What is Trousseau’s sign?
involuntary contraction of the muscles in the hand and wrist that occurs after the compression with a BP cuff
