liver top tier Flashcards
liver failure =
types
key features
- Liver failure= liver loses ability to repair
- Acute failure = acute liver injury, previously normal liver
- Acute- on-chronic failure = liver failure as a result of decompensation of chronic liver disease
- Key features = encephalopathy, jaundice, coagulopathy, ascites
liver failure pathophysiology
- injury/death to hepatocytes
- Particular damage in zone 3 around central vein - least blood supply
- Neutrophils kill them
- Apoptosis (due to damage)
- Autoimmune
- Inflammation
- Fibrosis - cirrhosis is irreversible , but fatty liver damage is reversible
- Function decline
fatty liver disease pathophysiology
- two states + their features
- two causes
simple steatosis
- Hepatocytes balloon due to fat accumulation
- perivenular fibrosis (small amounts)
–> inflammation –>
steatohepatitis (= fatty liver disease)
- Hepatocytes balloon due to fat accumulation
- inflammation and fibrosis
- Hepatocytes accumulate cytoskeleton protein as unable to use it due to dysfunction (mallory bodies)
- Neutrophils come to kill em - hepatocyte necrosis
both reversible
this is the case for both causes : alcoholic and non-alcoholic
encephalopathy
- pathophysiology
wernickes’s
- pathophysiology inc cause
- triad presentation
- treatment
- Ammonia not cleared by the liver, builds up in the circulation and passes to the brain
- Astrocytes try to clear ammonia by converting glutamate → glutamine. Excess glutamine causes imbalance in osmotic pressure so fluid into cells → cerebral oedema
- Permanent brain damage as ammonia is neurotoxic (halts Krebs cycle, less ATP)
wernicke’s encephalopathy:
- Thiamine reserves exhausted - malnutrition, alcoholism
- Triad (most don’t have all 3)
- – Ataxia
- – Nystagmus (involuntary eye movements)/ ophthalmoplegia (paralysis / weakness of eye muscles)
- – Confusion
- Acute onset
- Reversible : treat with IV thiamine
causes of acute liver failure
Viral hepatitis +other infections eg, bacteria, parasites
- Rarely C (mainly chronic)
- Cytomegalovirus
- EBV
- Herpes
Drugs
- Drugs started recently are the relevant ones
- Paracetamol overdose is common
- Alcohol,
- antidepressant -amitriptyline
- NSAIDs
- ecstasy , cocaine
- Antibiotics -ciprofloxacin, doxycycline, erythromycin
Vascular
- Congestion (venous congestion from right sided heart failure or obstruction of the hepatic vein)
- Obstruction
chronic causes of liver failure
chronic triggers - acute deterioriation of chronic disease
- Viral hepatitis (not A/e - acute)
- Non alcoholic/ alcholic steatohepatitis
- Autoimmune
- Metabolic liver disease – Genetic - wilsons and A1AT deficiency
- Cancer - hepatocellular carcinoma
- Vascular
Chronic triggers (acute deterioration of chronic disease)
- Constipation
- Drugs
- Infection
- GI bleed
- Alcohol withdrawal
- Low Na, K, glucose
risk factors for non-alc liver failure (conditions, not patient characteristics)
Obesity
Diabetes
Hyperlipidemia
High risk of thrombosis
encephalopathy presentation and test for it
Test: count down in 7s form 100, count animal in a min, spell World backwards, dot-dot, draw 5 point star
1) Altered mood/behaviour, sleep disturbance
2) Drowsy, Confusion, slurred speech, +/- asterixis
3) incoherent, restless, asterixis, stupor
4) Coma
(Liver flap = asterixis – flapping tremor with wrist extended)
liver failure signs
Jaundice Encephalopathy Fever Hypertension Hyper-reflexia Fetor hepaticus = patient smells like pear drops Small liver
acute liver failure symptoms
Jaundice \+ Itching (bile salt collects under skin) \+ Unusual stool/urine Bleeding (coagulopathy) Myalgia GI/abdominal pain Lethargy malaise
chronic liver failure symptoms
Ascites is rare Spider naevus (red vessel skin mark, 5+ is pathological) Bruising Wasting Clubbing (nails) Palmar erythara - red hands jaundice is rare
paracetomol overdose - signs/investigations
Increased prothrombin time ALT/AST rly high - 1000 Metabolic acidosis Raised creatinine Hypoglycaemia -gluconeogenesis is inhibited
liver failure investigations
Bloods
- High bilirubin
- Low albumin
- Long prothrombin time, high INR
- LFTs = enzymes released from hepatocytes due to damage… High AST/ALT
- U/Es
- Low glucose - no gluconeogenesis
- Blood culture
- Lipids
ultrasound/MRI/CT
- look for biliary obstruction
- Nodular outline=cirrhosis
- tumours
- varices
- Liver/Spleen size
- Grades encephalopathy - electroencephalogram
- dopple
Microbiology- determine cause (is it infection)
- Ascites fluid
- Urine culture
- Blood culture
- Viral serology/ immunology - Look for antigen/ antibodies of virus, and autoantibodies
biopsy
liver failure management
- Symptom management
- – Eg analgesia - opiates paracetamol, be careful
- Treat underlying cause
- – N-acetyl cystine (NAC) for paracetamol poisoning - and glucose if hypoglycemic
- – Gallstone removal/crushing/dissolution
- – Cancer treatment
- – Antivirals
- Electrolyte balance, acid base balance
- Correct clotting defects - give IV platelets, vitamin K, plasma
- Liver transplant
- Careful with drug prescription (eg hypoglycaemic/constipation/blood thinned effects)
- Antihypertensives - not ACEi
- Proton pump inhibitors to reduce GI bleed risk
- Mannitol for raised intercranial pressure
- Monitor glucose and give IV if necessary
what drug is given for paracetamol poisoning
N-acetyl cystine (NAC
liver failure complications
Hypoglycaemia Bleeding (coagulopathy) Encephalopathy Varices Vulnerable to infection Malnutrition Impotence Amenorrhea
risk factors/ causes for pancreatitis
I GET SMASHED Idiopathic Gallstones (f) Ethanol - alcohol (m) Trauma (kids) Steroid Mumps Autoimmune Scorpion venom Hyperlipidemia ERCP - endoscopic retrograde cholangiopancreatography (following this) Drugs (eg corticosteroids, NSAIDs, diuretics)
Pregnancy
neoplasia/malignancy
pancreatitis pathophysiology
- Inflammation of pancreatic gland, initiated by acute injury
- Premature activation of pancreatic enzymes (eg amylase!) which cause pancreatic inflammation by enzyme mediated autodigestion
- Prematurely activated enzymes digest vessel walls in pancreas, causing leakage of fluid into tissues → oedema, inflammation, hypovolemia, potential haemorrhage
- Destruction of islet of langerhans → less beta cells → less insulin→ hyperglycaemia
- Lipolytic enzymes cause fat necrosis → skin discolouration (Cullen’s Grey turner’s local, bruise-like).
- The released fatty acids bind to Ca → white precipitates in fat and potentially hypocalcemia
Chronic = irreversible fibrosis
pancreatitis signs
Hypovolemia Tachycardia Jaundice Fever Dehydration Hypotension Cullen’s sign = periumbilical bruising Grey Turner’s sign = left flank bruising
pancreatitis symptoms
Oedema Pain - Upper abdominal / epigastric/central abdominal - Radiates to back - Relieved by sitting forward Anorexia nausea/ vomiting Tetany = intermittent muscle spasms (due to hypocalcaemia)
pancreatitis invesitgations
Bloods
- Inflammation - high wbc
- High glucose
- Raised serum amylase - 3x! But drops quite quickly
- Raised serum lipase
- Cultures -see if infection
Temperature
HR
BP
Urine
- Raised urine amylase
Imaging
- CXR/Ultrasound – Maybe gallstones (cause)
- CT/MRI- see necrosis extent
- CXR - excludes perforation differential diagnosis
how is pancreatitis scored
and why
Glasgow + Ranson /APACHE 2 scoring systems
Factors = age, neutrophils, calcium, glucose (obesity/conditions too in APACHE2 ) in first 48/24 h
for prognosis and treatment
pancreatitis management
- Nil by mouth. Nasogastric tube for supplements – reduce pancreatic enzyme release
- fluid replacement (Crystalloid / saline IV) - (lost in third-space sequestration = goes somewhere in body, not balancing with ECF)… to increase urine flow rate and stabilise vital signs (Temp, HR, breathing rate, BP)
- Analgesia - opiates
- Antibiotics - if proven infection (blood cultures)
- Surgical drainage of fluid collections/cysts
- Insulin - in glucose needs correcting (Take over liver functions)
- Calcium correction (liver function impaired)
- Cholecystectomy - may cause recurrent episodes
- Stop risk factors (alcohol, smoking)
- Enzyme replacement ? if chronic
- LMW heparin = DVT/PE prophylaxis
complications of pancreatitis
Hyperglycaemia Hemorrhage - shock Hypocalcemia Renal failure ARDS - acute respiratory distress Coagulopathy , thrombosis Fistulae
If bursts → digests insides = necrosis
Bile duct strictures
Steatorrhea
Low insulin- diabetes
how bad is alcoholic liver disease.
main cause of liver death
alcoholic liver disease risk factors/ cause
alcohol - do not need to be alcoholic / dependent
some genetic component
how does fibrosis cause portal hypertension
due to increased vascular resistance which is due to cirrhosis and architectural distortion (decreased outflow) and splanchnic vasodilation (increased inflow)
how does portal hypertension cause varices
New vessels form + small vessels vasodilate
Shunts
alcoholic liver disease pathophysiology
- Ethanol metabolised in liver, resulting in increase in NADH /NAD ratio. This causes increased fatty acid synthesis and less fatty acid oxidation → fatty acid accumulation, which are esterified to glycerides (tri/di). these is defective balance between free fatty acid oxidation (breakdown) and synthesis (to triglycerides)
- Also causes impaired carbohydrate and protein metabolism → centrilobular necrosis of hepatic acinus
- Hepatocytes become swollen with fat (steatosis)— fatty liver , but no cell damage → reversible!
- Sometimes, collagen in deposited around central hepatic veins (perivenular)→ fibrosis → cirrhosis
- Alcohol also enhances the effect of toxic metabolites of drugs on the liver
- Kupffer cells release TNF-alpha → ROS is released → tissue injury, fibrosis
- fibrosis –> portal hypertension –> varicies
- Polymorphonuclear leukocytes infiltrate → hepatocyte necrosis
- and alcoholic cirrhosis
fatty liver presentation
often no symptoms
nausea, vom , diarrhea
hepatomegaly
alcoholic hepatitis presentation
- Few symptoms
- Mild jaundice
- Signs of chronic liver disease - ascites, bruising, clubbing, dupuytren’s contracture (fingers bend towards palm due to fibrosis in tendons)
- Abdominal pain, if severe
- hepatomegaly
- ankle oedema
alcoholic cirrhosis presentation
final stage of alcoholic liver disease
- alcohol dependancy
- Signs of chronic liver disease - ascites, bruising, clubbing, dupuytren’s contracture (fingers bend towards palm due to fibrosis in tendons)
alcoholic liver disease investigation
- Liver biopsy → histology - see fatty infiltration
- Liver function tests - raised
- ultrasound/CT shows fatty infiltration
- Coagulopathy (prothrombin, INR), higher serum bilirubin seen in alcoholic hepatitis and cirrhosis
alcoholic liver disease management
Alcohol cessation
- Treat withdrawal with lorazepam / diazepam
- Diet - high in vitamins and proteins, reduce salt intake
- IV thiamine to prevent encephalopathy after withdrawal
- Treat infections (hepatitis)
- Liver transplant (if sober )
- Avoid aspirin/NSAIDs if severe
non alcoholic liver disease cause
diet induced!!– high fructose/ fat intake
metabolic syndrome
- central obestiy
- dyslipidaemia
- hypertension
- impaired glucose tolerance
- insulin resistance
alcoholic liver disease - cause?
ethanol –> acetyl coA –> fatty acids
final stage of liver disease=
- features
cirrhosis (fibrosis)
- irreversible
- hepatocyte necrosis
- hyperplastic nodule formation (deterioration of architecture)
- shrunk liver
causes of liver cirrhosis
aka causes of liver disease - as liver cirrhosis is end stage liver disease!
chronic viral hepatitis - B, C (most common worldwide) alcoholic liver disease (most common in west) haemochromatosis non-alcoholic liver disease medications/drugs coeliac wilsons A1AT deficiency autoimmune hepatitis billiary cirrhosis
liver cirrhosis presentation
parotid glands swell asterexis spider naevi jaundice hepatosplenomegaly (small liver i thought) ascites abdominal pain clubbing nail changes muscle cramps caput medusae palmar erythema dupuytren's contracture bruising ankle swelling oedema loss of body hair
liver cirrhosis complications + their pathophysiology
portal vein drains from gut to liver.
ineffective draining due to
1) increased vascular resistance
2) architectual distortion (decreased outflow)
–> increase in pressure (so there is backflow. this is called portal hypertension
the high BP causes splanchnic dilation to compensate but this increases inflow
- ascites
- varicocele
- cardiomyopathy
- varicies
- clubbing
- dupuytrens contracture
- spider naevi, palmar erythema, caput medusae
- carcinoma
- spontaneous bacterial peritonitis
- hepatic encephalopathy
- coagulopathy
cirrhosis pathophysiology
- liver damage
- hepatocyte necrosis/ apoptosis
- ROS released
stellate cells usually dormant, activated in cirrhosis (ROS) - further stimulating macrophages (kupffer cells) to release cytokines (TNFalpha, IL6, IL18, TGF)
— further necrosis !
— TGF causes stellate cells to become myofibroblasts - which secrete collagen (fibrosis) - stellate cells secrete chemokines –> attract more innate immune cells
- inflammation! –> necrosis and fibrosis
- function reduces (fibrosis is nonfuncitioning ofc)
types of cirrhosis
cirrhosis has regenerating nodules (non damaged) within fibrous septa
micronodular = <3mm nodules, uniform. caused by alcohol / billiary tract disease
macronodular - varies in size, caused by chronic viral hepatitis
portal hypertension causes
Cirrhosis
portal vein/IVC obstruction
R heart failure
schistosomiasis (infection)
cirrhosis management
- Good nutrition inc reduced salt intake
- Hep A/B vaccination
- Avoid hepatotoxins
- – NSAIDs - may cause GI bleed/ renal impairement
- – alcohol
- Treat ascites (fluid restriction, low salt diet, spironolactone (K sparing diuretic) + paracentesis + albumin infusion)
- Ultrasound screening for hepatocellular carcinoma - 6monthly
- Treat underlying cause to prevent worsening
- Liver transplant if no response to therapy (last resort)
varicies
=?
- whats worrying
- treatment
new vessels form + small vessels vasodilate
shunts
if rupture –>
- abdominal pain
- acute blood loss - hypotension (pallor), rectal bleeding
- chronic liver damage
- ascites
- splenomegaly
- life threatening if oesophageal
endoscopy to find source of bleeding
- B blocker to reduce pulse rate to decrease portal pressure
- Liver transplant,
- variceal banding, - using endoscopy
- Balloon tamponade to reduce bleeding by placing pressure on varice (if banding fails)
- TIPS - shunt from portal vein to hepatic vein
- Resuscitate if hemodynamically unstable – blood transfusion, vitamine k and platelets and vasopressin/somatostatin (vasoconstriction)
- prophylactic antibiotics
biliary colic =
pain associated with gallstone obstruction of cystic or common bile duct .
Intermittent, comes and goes
what do chole and choledocal and cholang refer to
Chole = gallbladder Choledocal = bile duct (large) cholang = bile duct (small, intrahepatic)
what is cholecystitis
presentation
dif diagnosis and how to differentiate
complications
Cholecystitis, = gallbladder inflammation (as a result of gall stone obstruction)
- Progresssive pain
- Palpable GB
- Murphys sign (catch in breath when RUQ pressed)
- Sepsis signs
- rarely!!!! mainly no - Jaundice (Mirizzi)
Pancreatitis (serum amylase high) Appendicitis Peptic ulcer (endoscopy) Liver abscess (US) Pneumonia (CXR) MI (ECG) Perforated bowel
- Perforation (–> air)
- Abscess
ascending cholangitis =
presentation
treatment and its complications
bile duct inflammation
Travels up
Due to choledocolithalis (bile duct stones)
Charcots triad
- Fever
- Jaundice (not in cholecystitis)
- RUQ pain
ERCP = endoscope + pull out stone Complications - Pancreatitis (irritation → inflammation → goes up) - Bleeding - failure - unremoved
mirizzi’s syndrome
stone in gallbladder (neck) presses on bile duct causing jaundice
empyema =
gallbladder fills with pus
primary sclerosing cholangitis (PSC)
- gender
- presentation
- investigations
- treatment
- complications
diffuse inflammation, long term, causing scarring of bile ducts (not just common bile duct) , causing stricture
m>f or m=f different sources
Fatigue
Anorexia
Indigestion
Jaundice (+ pruiritus)
LFTS: Alk phos, bilirubin
ANA, P-ANCA (antinuclear antibody, perinuclear anti-neutrophil cytoplasmic antibodies)
MRI
Liver transplant
- Low prognosis
Complications
- UC
biliary dyskinesia =
- presentation
- who (age, gender)
- treatment
= pain with no gall stones (no pathology)
= dyskinesis refers to inability to move, gall bladder ineffective squeezing of bile out
RUQ pain after fatty food
Women >50
Remove gall bladder
primary billiary cirrhosis PBC vs primary sclerosing cholangitis PSC
associated with what disease
increased risk of ?
associated
PBC - RA, sjorgrens
PSC - IBD
increased risk
PBC - hepatocellular carcinoma
PSC -cholangiocarcinoma
primary billiary cirrhosis PBC vs primary sclerosing cholangitis PSC
gender
PBC - f»M
PSC - m>f
primary billiary cirrhosis PBC vs primary sclerosing cholangitis PSC
age
PBC- 40-60
PSC - 10-30
primary billiary cirrhosis PBC vs primary sclerosing cholangitis PSC
diagnosis
PBC \+AMA (anti mitochondrial antibody) raised IgM liver biopsy US high ALP
PSC ANCA (anti-neutrophil cytoplasmic antibodies) ANA antibiody liver biopsy US/MRI
primary billiary cirrhosis PBC vs primary sclerosing cholangitis PSC
presentation
both: fatigue, pruiritus
PBC : xanthelasma (demarcated yellow cholesterol deposits around eye)
sore joints
dry eyes
PSC : jaundice
charcots triad (fever (inc rigors), RUQ pain, jaundice)
can have xanthelasma?
gallstones epidemiology
- typical person
- race
female
fat
fertile
forty (rare before 30)
more common = scandivians, s america.
less common = asia, africa
gallstone risk factors
- Female
- age – 40, fertile
- Pregnancy (reduced gallbladder motility)
- smoking
- High cholesterol diet/ fatty food (excess cholesterol pigment)
- contraceptive pill
- Rapid weight loss
conditions
- Crohns
- Sickle cell
- Primary biliary cirrhosis
- Obesity
- liver cirrhosis
- diabetes (reduced gallbladder motility)
- haemolysis (excess pigment)
cholestasis =
causes
presentation
Bile static - not going anywhere
Due to obstruction
- Cholelithiasis
- Choledocal lithilasis
- Tumours
signs/symptoms
- Jaundice + itchy + dark urine + pale stools
- RUQ pain - intermittent colic
- Can be painless
- Weight loss, low appetite
- Lethargy
- Steatorrhea (no fat absorbed) - float
gallstone types
- form where
- made of
both form in gall bladder mainly. due to stasis
cholesterol gallstone (majority)
- large, often solo
- excess cholesterol or deficiency of bile salts / phospholipids (Relative)
bile pigment stones
- formed mainly of Ca2+
- small, crumbly, fragile, irregular
- hemolysis –> bilirubin increased –> excess
- can be black or brown (different composition)
gallstone symptoms
Pain (= biliary colic) Sudden onset epigastric/RUQ Severe, constant, crescendo Intermittent, comes and goes Radiation to R shoulder Often mid evening- late / post prandial Can be painless - most are asymptomatic Associated with nausea/vomiting Jaundice + itching + dark urine + pale stools Weight loss, low appetite Lethargy Steatorrhea (not fat absorbed = fat in stools = float)
Can be asymptomatic
Don’t need to treat
NOT
Flatulence
Fat intolerance
Dyspepsia (impaired digestion)
murphys sign. =
indicates what
Breathe in an press in RUQ and LUQ
Positive = painful RUQ only
positive in ascending cholangitis, cholecystits
what does gallbladder look like in acute cholecystitis
small gallbladder, thick walls
acalculous cholecystitis
gallbladder inflammation due to cause that is not gallstones
what is risk of chronic billiary inflammation
will go to dysplasia then neoplasia
general investigations into biliary diseases
imaging - stones, cancers, inflammation, fluid (eg around gallbladder), duct dilation
bloods
- wbc,
- LFTs - AST/ALT, bilirubin, alkaline phosphate
examination
- tender RUQ
gallstone treatment
stone dissolution
- for cholesterol stone
- by increasing bile salt (rare)
- by reducing cholesterol- statins
laproscopic cholecystectomy - Gallbladder removal
- For any symptomatic complication of gallstones
antibiotics
surgery to remove stones
- balloon, basket, crushing, stent placement
- ERCP
analgesia, fluids
biliary colic vs acute cholecystitis vs cholangitis
- which have which of the following
- RUQ pain
- fever / high WBC
- jaundice
biliary colic = RUQ pain
acute cholecystitis = RUQ pain + fever/high WBC
cholangitis = all 3 : RUQ pain + fever/high WBC and jaundice (this is charcots triad)
courvoisiers sign
painless jaundice + palpable gallbladder = pancreatic / billiary cancer (until proven otherwise)
what is painless jaundice + palpable gall bladder (until proven otherwise)
pancreatic/ biliary cancer
courvoisiers sign
