Liver Flashcards
Key presentation of Acute liver failure
Jaundice! Malaise, confusion (hepatic encephalopathy!)
Other signs/symptoms of Acute liver failure
Fetor hepaticus
Asterix
Bleeding
Hypoglycaemia
Liver pain
Nausea
Anorexia
Ix Acute liver failure
Blood tests - INR > 1.5 seconds
Serum LFTs -
in acute, albumin is initially normal
all bilirubin is unconjugated
↑ AST, ↑ ALT
Grading hepatic encephalopathy
What is serum albumin a marker of?
Synthetic function
Useful to gauge severity of CHRONIC liver disease
What does Prothrombin time measure?
Mark of synthetic function
Due to short half-life, sensitive indicator of acute and chronic
Other than acute and chronic liver failure, what can cause a prolonged prothrombin time? When does this commonly occur?
Vitamine K deficiency
In biliary obstruction bc low conc of bile salts = poor absorption of vitamin K
Aminotransferases
Contained in hepatocytes
Leak into blood w/ liver cell damage
Other than the liver, where else can aspartate aminotransferase (AST) be found?
Heart, muscle, kidney, brain
When else can there be high levels on AST (other than liver failure)?
Hepatic necrosis
MI
Muscle injury
Congestive cardiac failure
Other than the liver, where else can alanine aminotransferase (ALT) be found?
More specific to the liver
When is there increased levels of ALT?
Rise only occurs with liver disease
Other than the liver, where else is Alkaline phosphate found?
Bone, intestine, placenta
When is there increased levels of alkaline phosphate?
Both intrahepatic and extrahepatic cholestatic disease
Also hepatic infiltrations (e.g. metastases), cirrhosis
What colour is bilirubin?
Yellow
Dark urine, pale stool, itching? If yes then,
likely to be cholestatic
NOT pre-hepatic
Other Ix for acute liver failure
CT abdomen - to see if Budd-Chiari syndrome
CXR
Pregnancy test
Tx acute liver failure
Treat underlying cause
Treat complications!
How do you treat encephalopathy in liver failure?
Lactulose
How do you treat ascites in liver failure?
diuretics e.g. spironolactone
How do you treat cerebral oedema in liver failure?
Mannitol
How do you treat bleeding in liver failure?
Vitamin K
How do you treat sepsis in liver failure?
Abx
How do you treat hypoglycaemia in liver failure?
dextrose
DDx for acute liver failure
Severe acute hepatitis
Cholestasis
Haemolysis
Causes of acute liver failure
Viral A, B, EBV
Drugs
Obstruction
Vascular ischaemia
CHF
RF acute liver failure
Alcohol
Age
Poor nutrition
Pregnancy
Chronic hep B
Causes chronic liver failure
Viral B, C
Alcohol
Non-Alcoholic steatohepatitis
Autoimmune conditions e.g. Autoimmune hepatitis, 1o biliary cirrhosis, Sclerosing cholangitis
Metabolic conditions e.g. haemochromatosis, Wilson’s syndrome
Vascular conditions e.g. portal hypertension
Key presentation of chronic liver failure
Ascites, Haematemesis, Oedema
Other signs/symptoms of chronic liver failure
Hepatomegaly!
Fetor hepaticus
Anorexia
Easy bruising
Itching
Jaundice, Confusion (rare)
1st line Ix Chronic liver failure
Serum LFTs -
good to gauge severity
falling serum albumin = bad sign
FBC
GS Chronic liver failure
Endoscopy
Ultrasound
CT scan/MRI
Other Chronic liver failure
Biopsy - if degree of inflammation is needed
Tx Chronic liver failure
Lifestyle modification - ↓ alcohol
Antivirals
Liver transplant!
When alcohol enters body, goes to liver and into hepatocytes. What are the 3 pathways it can take?
- Alcohol dehydrogenase
- Cytochrome P4502E1 (CYP2E1)
- Peroxisomal catalase
Describe the alcohol dehydrogenase pathway
ADH converts alcohol -> acetylaldehyde
∴ NAD+ is converted to NADH and produces ROS
3 stages of alcoholic liver failure
- Fatty liver
- Alcoholic hepatitis
- Cirrhosis
Describe fatty liver process
↑ Alcohol = ↑ NADH
NADH triggers cells to produce ↑ fatty acids
↓ NAD+ = ↓ fatty acid oxidation
∴ ↑ Fat production
∴ FATTY LIVER
Describe a fatty liver
Large, heavy, greasy tender liver
Yellow-ish due to fat deposits
Describe the process of alcoholic hepatitis
Acetylaldehyde can bind to compounds in cell and inhibit them
forms acetylaldehyde adducts, body recognises these as foreign
∴ immune response
∴ inflammation
ALSO, ROS causes lots of damage
∴ ALCOHOLIC HEPATITIS
What can you find during Alcoholic hepatitis?
MALLORY BODIES! (not specific tho)
Key presentation of Alcoholic liver failure
RUQ pain
Other signs/symptoms of alcoholic liver failure
Hepatomegaly
Ascites
Jaundice
Nausea
Vomiting
Diarrhoea
1st line Ix alcoholic liver failure
LFTs - GGT and ALP ↑↑↑
↑ AST and ALT (AST:ALT, 2:1)
FBC - ↓ Platelets, hypoglycaemia
GS Ix alcoholic liver failure
Liver biopsy
Tx alcoholic liver failure
Stop drinking alcohol!! Usually enough to treat
If alcoholic hepatitis, corticosteroids can be used
IV thiamine - prevents Wernicke-Korsakoff’s encephalopathy
Liver transplant - if severe
What can occur after alcohol withdrawal?
How would you treat this?
12-24 hours after - Delirium tremens
Presents w/ seizures, vomiting, headache, sweating, palpitations
Diazepam
Causes of liver cirrhosis
Alcoholic liver disease - common in HICs
NAFLD
Hep B, Hep C - common in LICs
Haemochromatosis
Wilson’s disease
A1AT deficiency
Describe the 2 types of liver cirrhosis
- Micronodular
Regenerating nodules < 3mm in size, uniform involvement
Often caused by alcohol or biliary tract disease - Macronodular
Varying size of nodules
Normal acini seen in larger nodules
Often caused by chronic viral hep
Key presentation of cirrhosis
Compensated - Asymptomatic, sometimes presents w weight loss, weakness, fatigue
Decompensated - Jaundice, pruritus, abdominal pain?
Other signs/symptoms of cirrhosis
Clubbing
Palmar erythema
Spider naevi
Leukonychia
Dupuytren’s contracture
Oedema
Xanthelasma
Bruising
1st line Ix Cirrhosis
LFTs - low albumin, long PT
Liver biochemistry -
↑ AST, ↑ ALT, ↓ Na+, alpha-fetoprotein
Ultrasound/CT - hepatomegaly
If liver is small = severe liver disease
MRI - detects tumours
What does low Na+ indicate with regards to liver disease?
SEVERE liver disease
If alpha-fetoprotein is present in liver biochemistry, what does this indicate?
Hepatocellular carcinoma
GS Ix cirrhosis
Liver biopsy
Describe the Child-Pugh classification
< 7 = best, > 10 = sign of bad prognosis
↑ Risk of variceal bleeding if > 8
Ascites, encephalopathy, ↑ bilirubin, ↓ albumin, long PT -> given 1-3 and added up to give score
Tx Cirrhosis
Treat underlying cause
↓ Salt intake/good nutrition
6 month ultrasound screening for hepatocellular carcinoma
What Tx should you avoid if you suspect a patient has cirrhosis? Why?
NSAIDs and aspirin
May cause GI bleeding/renal impairment
Complications of cirrhosis
Coagulopathy - ↓ in clotting factors II, VII, IX, X
Encephalopathy - liver flap and confusion/coma
Portal hypertension
What is NAFLD characterised by?
Fat deposited in liver cells which can interfere with function
Epidemiology of NAFLD
25% of population
3/4 of all obese people
Causes of NAFLD
Fat deposition in liver (insulin resistance)
3 of the following :
Obesity
HTN
DM
Hyperlipidaemia
Hypertriglyceridaemia
Describe the progression of NAFLD
Steatosis -> Steatohepatitis -> Fibrosis –> Cirrhosis
Key presentation of NAFLD
Usually no symptoms
Liver ache in 10%
Other signs/symptoms of NAFLD
Jaundice
Hepatomegaly
Fatigue
Malaise
RUQ pain
Ix NAFLD
LFT - ↑ ALT, sometimes ↑ AST
Liver ultrasound
GS : Biopsy
Tx NAFLD
Diet, exercise, avoid alcohol, weight loss if obese
Stop smoking
Control of DM, BP and cholesterol
How do you calculate a unit of alcohol?
Strength (ABV) x vol (ml) / 1000
= Units
Describe pre-hepatic, hepatic and post-hepatic causes of jaundice
Pre-hepatic
XS breakdown of Hb ∴ ↑ Uncnojugated bilirubin
Hepatic
Hepatocytes don’t take up, metabolise or excrete bilirubin ∴ ↑ Unconjugated AND conjugated bilirubin
Post-Hepatic
Obstruction in biliary system e.g. gallstones
∴ ↑ Conjugated bilirubin
Give some examples of pre-hepatic causes of jaundice
Malaria
Sickle cell anaemia
Foetal Hb in newborns
Give some examples of hepatic causes of jaundice
Viral hepatitis
Drugs
Alcohol
Cirrhosis
Give some examples of post-hepatic causes of jaundice
Gallstones
Pancreatitis
Jaundice key presentation
Yellow discolouration of skin, sclera and mucous membranes
Tx Jaundice
usually no Tx required
Describe Hep A virus
RNA virus, acute only. Notifiable disease!!
100% immunity after infection
Epidemiology Hep A
Endemic in Africa and S. America
Most common acute viral hepatitis in world
Route of transmission of Hep A
Give examples
FAEcal-oral
Ingestion of contaminated food or water, poor sanitation, overcrowding
Hepatitis A is a ____virus
Pircornavirus
When is Hepatitis A maximally infectious?
JUST BEFORE onset of jaundice
Key presentation of Hep A
Prodromal phase (1-2 weeks) -
N+V, fever, malaise (non-specific) + RUQ pain
Icteric phase (~3 months) -
Jaundice, dark urine, pale stools, pruritus
Describe the incubation period of Hep A
Short
15-50 days (mean = 28 days)
Describe the serology of Hep A infection
HAV IgM antibodies = active disease
HAV IgG antibodies = recovery or vaccination
Draw the graph for Hep A serology please
(How levels vary weeks after infection)
Virus in faeces and virus in blood graph
Serum ALT, IgG and IgM HAV
Tx Hepatitis A
Self-limiting
∴ supportive care e.g. anti-emetics, rest, avoid alcohol etc
Manage close contacts by giving human normal immunoglobulin (HNIG) for Hep A within 14 days!!
Vaccine available!
What might be increased in Hep A? Why?
Atypical lymphocytes
i.e. v large lymphocytes
Bc of stimulation from antigens
Describe Hepatitis E virus
RNA virus, acute only! (acc can be chronic in immunosuppressed)
100% immunity after infection
Epidemiology Hep E
Common in elder men and in Indochina
More common than Hep A in UK
High mortality in pregnancy
Mode of transmission Hep E
Give examples
FAEcal-oral
Found in undercooked pork!
Spread by contaminated water, rodents, dogs and pigs
Key presentation of Hep E
> 95% asymptomatic
Complication of HEV
Fulminant hepatitis (rare but increased risk w pregnancy)
Prognosis of HEV
Mortality = 1-2%
(10-20% in pregnant)
Serology of HEV
?
Chronic - HEV RNA
Tx HEV
Supportive management e.g. rest, avoid alcohol, fluids
Consider ribavirin
Describe Hep B
DNA virus, acute AND chronic
Where can Hep B be found?
In semen and saliva
Route of transmission HBV
give examples
Blood borne
e.g. needles, tattoos, sexual, blood products, IVDU, mother to child, dialysis
Key presentation of HBV
Prodromal phase (1-2 weeks)
N+V, fever, malaise (non-specific symptoms) + RUQ pain
Icteric phase (few weeks - 6 months)
Jaundice, dark urine, pale stools, pruritus, athralgia
Complications of HBV
Hepatocellular carcinoma
Fulminant hepatitis
Cirrhosis
HBV serology
Draw graph
HbSAg
ANTI - HbSAg
ANTI - HbCAg
(Susceptible, immune vaccine, immune natural, acute infection, chronic infection)
(IgM + = active infection)
When does HbSAg appear with HBV?
During initial infection (1-6 months)
Tx HBV
Acute - supportive
Chronic -
Pegylated interferon-alpha 2a
& Nucleoside analogues e.g. Oral tenofovir or **oral entecav
Epidemiology of HBV
Far East, Africa and Mediterranean
S/E pegylated interferon alpha 2a
Flu-like illness, fever, lethargy, mental issues (anxiety), autoimmune disease, ↓ WBC and platelets
How do you take pegylated interferon-alpha 2a?
SC weekly
How does pegylated interferon-alpha 2a work?
Stimulates immune response - immunomodulatory
How do you take nucleoside/nucleotide analogues?
One tablet a day
S/E of nucleoside/nucleotide analogues
Minimal side effects
Examples of nucleoside/nucleotide analogues
Tenofovir
Entecavir
What should you monitor with tenofovir?
Renal function
How do nucleoside/nucleotide analogues work?
Inhibits viral replication
How does biliary colic present?
Majority are asymptomatic !
Sudden, severe, constant epigastric pain
Can radiate to back
worse after eating large fatty meals
Ix Biliary colic
FBC - ↑ CRP, rule out cholecystitis
LFTs - ↑ ALP
Amylase - rule out pancreatitis
GS : ULTRASOUND
duct dilation, stones, gallbladder wall thickness
RF Biliary colic
5 Fs
Fat
Forty
Fertile
Fair
Female
Tx Biliary Colic
NSAIDs, analgesia
Option cholecystectomy - bc gallstones can recur
Tx Biliary Colic
NSAIDs, analgesia
Option cholecystectomy - bc gallstones can recur
Causes Acute pancreatitis
I GET SMASHED
Idiopathic
Gall stones
Ethanol (alcohol)
Trauma
Steroids
Mumps/malignancy
Autoimmune
Scorpion stings
Hyperlipidaemia and hypercalcaemia
ERCP
Drugs - azathioprine, metronidazole, tetracycline, furosemide
Key presentation Acute pancreatitis
Epigastric pain radiating to back
Relieved by sitting forward
Guarding and tenderness
N+V
Fever
Tachycardia
Anorexia
Cullen’s (periumbilical) and Grey Turner’s (flank) sign
Ix Acute Pancreatitis
Serum amylase ↑
Urinalysis
Serum Lipase
↑ CRP
Abdo ultrasounds, CT, MRI
Describe the Glasgow Scoring system
PANCREAS
PaO2 < 8kPa
Age > 55
Neutrophils (WBCs > 15)
Calcium < 2
uRea > 16
Enzymes (LDH > 600 or AST/ALT > 200)
Albumin < 32
Sugar (Glucose > 10)
0-1 mild pancreatitis
2 moderate
3+ severe
Tx Acute pancreatitis
NBM - to decrease pancreatic stimulation
Analgesics
Prophylactic Abx
Key presentation chronic pancreatitis
Same as acute but longer lasting
Worse after alcohol
Steatorrhoea
Weight loss (malabsorption)
Insulin dependent DM
Tx Chronic pancreatitis
Alcohol cessation
Pancreatic enzyme supplements w PPI - helps digestion
Insulin
ERCP or surgery if req
Key presentation of Acute Cholecystitis
RUQ pain - may radiate to right shoulder
Fatigue
Fever
POS Murphy’s sign
Tenderness & guarding
Ix Acute Cholecystitis
Abdo ultrasound - stones, thick gallbladder walls, fluid around gallbladder
What is acute cholecystitis?
Acute inflammation of the gallbladder
Usually bc of gallstone
Tx Acute cholecystitis
Conservative management before surgery (Abx, heavy analgesia, IV fluids)
Cholecystectomy
What is acute cholangitis?
Acute inflammation and infection of bile duct
Cause of acute cholangitis
Due to bile duct obstruction
*Gallstones
Trauma
Surgery
Key presentation of Acute Cholangitis
Charcot’s triad
1. RUQ pain
2. Jaundice
3. Fever + rigors
Reynold’s pentad
Charcot’s triad + confusion + septic shock
Ix Acute Cholangitis
FBCs - Leukocytosis
LFTs - ↑ ALP and bilirubin
↑ CRP
Blood cultures - identify pathogen
Ultrasound +/- ERCP
What is ERCP?
Endoscopy Retrograde Cholangiopancreatography
Tx Acute Cholangitis
Treat Sepsis - Iv Abx, aggressive fluid resus
ERCP and stenting
Cholecystectomy
What is Primary Biliary Cholangitis associated with?
FEMALE !!! (9:1 ratio)
Autoimmune disease
Rheumatoid conditions (e.g. RA)
What is Primary Biliary Cholangitis?
When immune system attack small bile ducts within liver
causes obstruction to outflow of bile = cholestasis
∴ fibrosos, cirrhosis + liver failure
Key presentation Primary Biliary Cholangitis
Fatigue
Pruritus
GI disturbance and abdo pain
Jaundice, pale stools
Xanthoma and xanthelasma
Signs of cirrhosis - ascites, splenomegaly, spider naevi
Ix Primary Biliary Cholangitis
LFTs - ↑ ALP, ↑ GGT, ↑ bilirubin
AMA (anti-mitochondrial antibodies) - most specific to PBC, ANA
Liver biopsy
Tx Primary Biliary Cholangitis
Ursodeoxycholic acid - reduce cholestasis
Cholestryamine - ↓ cholesterol absorption
What is Primary Sclerosing Cholangitis?
When biliary tree is strictured and fibrotic
∴ obstruction of bile out of liver
Key presentation Primary Sclerosing Cholangitis
Jaundice
Chronic RUQ pain
Pruritus
Fatigue
Hepatomegaly
RF Primary Sclerosing Cholangitis
Male
FHx
30 - 40 years
UC!!!!!!!!!!
Ix Primary Sclerosing Cholangitis
LFT
pANCA
ANA
aCL
GS : MRCP!! - may show bile duct lesions or strictures
Tx Primary Sclerosing Cholangitis
Liver transplant
ERCP - can be used to dilate and stent strictures
Cholestryamine
Complications of Primary Sclerosing Cholangitis
Acute bacterial cholangitis
Cholangiocarcinoma
Colorectal cancer
Cirrhosis, liver failure
Causes of Hepatocellular Carcinoma
Viral Hep (B and C)
Alcohol
NAFLD
RF Hepatocellular Carcinoma
Male !!
Presentation Hepatocellular Carcinoma
Non-spec symptoms - weight loss, fatigue, N+V
Liver symptoms - jaundice, ascites, hepatic encephalopathy, pruritus
Ix Hepatocellular Carcinoma
1st line - ABdo ultrasound
GS : ABDO CT !
Serum alpha-fetoprotein = tumour marker for HCC
Tx Hepatocellular Carcinoma
Liver transplant
Cause of Spontaneous bacterial peritonitis
Gram -ve = E.coli, Klebsiella spp
Gram +ve = Strep spp
Presentation Spontaneous bacterial peritonitis
Severe acute abdo pain
Guarding
N+V
Diarrhoea
Fever
Ix Spontaneous bacterial peritonitis
Ascitic tap
Culture
ESR + CRP
Tx Spontaneous bacterial peritonitis
ABCDE
IV Abx (cefotaxime)
Paracentesis
Complications Spontaneous bacterial peritonitis
Septicaemia
Tx Paracetamol overdose
Acetylcysteine - asap
Activated charcoal !!!
Tx Hepatic Encephalopathy
1st line - Lactulose
Rifaximin
Liver transplant
What are the aminotransferase levels in Gilbert’s syndrome?
Normally, normal
Define Gilbert’s syndrome
Decreased levels of UDPGT which results in impaired conjugation of bilirubin.
Presentation of Wernicke-Korsakoff’s encephalopathy
Triad of:
1. Confusion
2. Ataxia
3. Nystagmus
Tx Ascending cholagitis
Abx - IV co-amoxiclav