LIVER Flashcards
What percentage of the liver is comprised of hepatocytes?
60%
How many blood supplies does the liver have?
hepatic artery - from the heart
portal vein - blood from the bowel
what are the functions of the liver?
1)metabolism
2)synthesis
3)immunological
4)storage
5)secretion
6)homeostasis
what are some examples of substances metabolised in the liver?
products of digestion
bilirubin
steroid hormone
insulin
aldosterone
vitamin D
what is synthesised in the liver?
plasma proteins
clotting factors
cholesterol
urea
what is stored in the liver?
fat soluble vitamins
glycogen
blood reservoir
what is secreted in the liver?
bile and bile salts
what is the function of the liver in homeostasis?
glucose regulation
conversion of glucose to glycogen
what are some potential causes for chronic liver disease?
alcohol
NAFLD/NASH
Immune/autoimmune
drugs
malignancy
HCV/HBV
What are some potential causes for acute liver disease?
HAV/HBV/HEV
ø 3rd trimester of pregnancy
- Drugs
- TPN
- Infection, e.g. malaria
- Ischaemia
- Alcoholic hepatitis
- Acute fatty liver of pregnancy
what increases risk of non-alcoholic fatty liver disease?
T2DM
Obesity
Dyslipidaemia
What may be the first presentation of NAFLD?
cirrhosis/jaundice
What is the non-pharmacological management of NAFLD?
Weight loss
healthy diet
exercise
smoking cessation
2-3 cups of black coffee daily
What is the pharmacological management of NAFLD?
Statins
what co-morbidities can make a HepC (HCV) infection worse?
(1) HIV
(2) Underlying cirrhosis
(3) Liver transplant
(4) Lifestyle
What is the process of chronic liver disease development?
(1) Injury
- e.g. toxin/ virus
(2) Hepatitis or steatohepatitis
(3) Reversible
- if cause is stopped, e.g. alcohol cessation
(4) If insult is not removed
(5) Fibrosis
- scarring + thickening of smooth muscle
(6) Cirrhosis
what is the general classification of liver disease?
1) compensated - asymptomatic due to medication/sufficient healthy liver tissue for normal function
2) decompensated - symptomatic
what is a liver function test?
used to identify patients
struggling with liver/biliary tract
what is the downside of liver function tests when checking for liver disease?
some LFTs reflect liver DAMAGE rather than function
what results from a liver function test are considered a casue for concern?
3 times the upper limit of normal
how should a liver function test be used?
(1) Look for trends
(2) Do not use in isolation
What would a liver function test (LFT) show in acute hepatocellular damage?
HIGH - plasma ALT
HIGH - plasma AST
HIGH - bilirubin (unconjugated)
PROLONGED - prothrombin time
NORMAL - albumin
What would a liver function test (LFT) show in chronic hepatocellular damage?
NORMAL - ALT
NORMAL - AST
LOW - albumin
PROLONGED - prothrombin time
What would a liver function test (LFT) show in cholestasis (blockage of bile duct)?
HIGH - plasma ALP
HIGH - bilirubin (conjugated)
What other investigations can be done alongside a liver function test (LFT)?
(1) Ethanol
(2) Drug history
(3) FBC
(4) Clotting
(5) U+Es
(6) Liver ultrasound
(7) Biopsy
(8) Liver screen
- if obstruction ruled out
- check for viral causes
How is acute liver failure graded?
(1) Hyperacute
- 6-7 days
(2) Acute
- 8-28 days
(3) Subacute
- 29-84 days
In which liver failure grade(s) is cerebral oedema rare?
subacute
In which liver failure grade(s) is cerebral oedema common?
Hyperacute/ acute/ subacute
(1) Hyperacute
(2) Acute
What is the prognosis for each liver failure grade?
Hyperacute - moderate
Acute - Poor
Subacute - Poor
What is used to grade chronic liver disease?
(1) Child’s Pugh Score
(2) MELD
- Model for end-stage liver disease
- OR UKELD
What are the grades for chronic liver disease using the Child’s Pugh Score?
(1) A 5-6 points COMPENSATED
(2) B 7-9 MODERATE
(3) C 10-15 ADVANCED
What is the MELD score used for?
Determining the mortality of end-stage liver disease
What are some common symptoms of liver disease?
(1) Jaundice - yellowing of eye
(2) Spider nevi in upper chest
(3) Ascites - accumulation of fluid in peritoneal cavity
(4) Clubbing of nails
(5) Dilated abdominal veins
(6) Ankle oedema
(7) Bleeding tendency due to decreased prothrombin time
which blood vessel brings blood to the liver from the heart?
hepatic artery
Which blood vessel brings blood to the liver from the bowel?
Portal vein
What are the general functions of the liver?
(1) Homeostasis
(2) Storage
(3) Metabolism
(4) Immunological
(5) Secretion
(6) Synthesis
Name some causes of chronic liver disease.
Alcohol
NASH/ NAFLD
Drugs
Malignancy
Autoimmune
HCV/ HBV
Metabolic, e.g. haemochromatosis
Name some causes of acute liver disease
Drugs
TPN
Ischaemia
Infection
Alcoholic hepatitis
Acute fatty liver of pregnancy
What is non-alcoholic fatty liver disease?
A range of liver diseases
From simple fatty liver -> Non-alcoholic seato-hepatitis -> Fibrosis/ cirrhosis
What patient groups are at higher risk of Hepatitis B?
IV drug users
Casual sex
Close family members
Babies born to infected mothers
HCPs
in which acute liver failure types is coagulation disorder marked?
drug-induced liver injury, viral hepatitis (such as hepatitis A, B, or E), autoimmune hepatitis, Wilson’s disease, and other acute liver insults.
what is ascites
accumulation of fluid in the abdominal cavity,
Which drugs, generally, can exacerbate ascites and peripheral oedema?
NSAIDs - na and water retention
CCB - as a side effect
corticosteroids - prolonged use = fluid retention
BP medicines - can contribute to fluid retention
thiazolidinediones - pioglitazone can cause fluid retention
treatment for ascites?
diet - reducing salt
medicine - diuretics help eliminate xs fluid, albumin help maintain fluid balance
paracentesis - needle used to drain excess fluid from abdomen
liver transplant - for individuals with advanced liver disease
what is hepatic encephalopathy?
brain dysfunction that occurs as a complication of liver disease, caused by toxin buildup
what are the stages of hepatic encephalopathy?
1)minimal HE, subtle changes in cognitive function without obvious symptoms
2)moderate HE, symptoms like confusion, forgetfulness, disorientation, mood swings
3)severe HE, symptoms worsen - leading to significant confusion, personality changes and potential loss of consciousness
4)comatose state - severe, may enter coma
non-pharm treatment for hepatic encephalopathy
diet changes, low protein = minimal ammonia production, drinking enough to hydrate and flush out toxins
monitoring liver function regularly and follow ups with health professionals
pharmacological treatment for hepatic encephalopathy include
Lactulose: A laxative that helps trap and eliminate ammonia in the gut.
Rifaximin: Antibiotic that reduces the production of ammonia-producing bacteria in the intestines.
L-ornithine L-aspartate (LOLA): Helps lower ammonia levels by supporting the urea cycle in the liver. Zinc supplements: Can aid in reducing ammonia levels and improving cognitive function. Branched-chain amino acids: May help improve protein metabolism and reduce ammonia production.
what is pruritus?
itching of skin occurs
how does chronic liver disease cause pruritus?
Bile salt accumulation: Liver dysfunction can lead to reduced bile flow, causing bile salts to accumulate in the bloodstream. These accumulated bile salts can deposit in the skin, leading to itching.
Skin changes: Liver disease can affect the skin’s ability to retain moisture, leading to dryness and increased sensitivity, which can contribute to itching.
Toxic metabolites: Buildup of toxins in the bloodstream, such as ammonia, due to liver dysfunction can also contribute to pruritus.
Inflammation: Chronic liver disease can lead to systemic inflammation, which may trigger itching sensation in the skin
what is the pharmacological treatment for pruritus secondary to liver failure?
bile acid sequestrants e.g. cholestyramine/colesevelam, help bind bile salts in gut, reducing circ and alleviating itching
antihistamines,
opioid antagonists e.g. naltrexone or naloxone
how is VTE risk evaluated in liver failure?
MELD. high score = incr risk
certain conditions such as ascites/hepatic encephalopathy can incr likelihood of VTE
coagulation profile, monitoring levels of clotting factors and platelets can help evaluate risk of VTE
central venous catheters, presence can incr risk of VTE
bedside assessment, physical examination
which administration route should be avoided in VTE, secondary to liver failure
subcutaneous route, for anticoags
what is a variceal heamorrhage
bleeding from enlarged veins in the eosophagus or stomach, commonly occurs in indv with liver cirrhosis
what causes a variceal haemorrhage?
increased pressure in the portal vein system (portal hypertension) leads to develoment of the varices, which are dilated fragile veins in the eosaphagus or stomach
what is DILI?
DRUG INDUCED liver injury, liver damage due to medicine/herba;/supplemts
what are the types of DILI
type A (Intrinsic), predicatable, direct toxicity, acetaminophen overdose
type B, (idiosyncratic), unpredictable, immunological reactions, e.g. drug reactions caused by abx
describe type a DILI
Type A Drug-Induced Liver Injury (DILI) is considered intrinsic and typically dose-dependent. This means that the liver damage is directly related to the amount of the drug taken. It is a more predictable response to the medication. An example of Type A DILI is an overdose of acetaminophen (Tylenol), where taking too much of the drug can directly harm the liver due to its toxic effects at high doses.
describe type B DILI
Type B Drug-Induced Liver Injury (DILI), also known as idiosyncratic DILI, is unpredictable and not necessarily related to the dose of the drug. This type of liver injury can occur in a small subset of individuals who may have unique reactions to a medication. It involves complex immune responses or metabolic idiosyncrasies that lead to liver damage. An example of Type B DILI is an allergic reaction to a medication like amoxicillin-clavulanate, where the liver is affected due to an individual’s specific immune response to the drug.
What website/ source can be used to identify causative agent(s) of drug-induced liver injury (DILI)?
Livertox database
which drug class has the highest incidence for causing DILI?
abx then NSAIDS
which metabolite of paracetamol is toxic?
is N-acetyl-p-benzoquinone imine (NAPQI). When the liver processes acetaminophen, NAPQI is produced. In normal situations, this metabolite is neutralized by glutathione. However, in cases of overdose or when glutathione levels are depleted, NAPQI can build up and cause liver damage.
what is the antidote for paracetamol?
