Liver [COMPLETE] Flashcards
1
Q
What are the two major sources of blood flow to the liver?
A
Portal vein - nutrient rich blood from digestive system
Hepatic artery - oxygenated blood from heart
2
Q
What is the job of the hepatocytes?
A
absorbing nutrients and detoxifying and removing substances from the blood
3
Q
Describe the structure of the liver.
A
Segments made up of lobules of hetapocytes.
Lobules connect to ducts which connect to larger ducts to form the common hepatic duct
Dividded into right and left lobe by middle hepative vein and 8 further sectors by the right, middle and left hepatic veins with each sector having its own blood supply and drainage
4
Q
What is the role of the common hepatic duct?
A
Transporting bile to the gallbladder and duodenum via the common bile duct
5
Q
What are some key functions carried out by the liver? (7)
A
- Protein handling
- Lipid handling
- Carbohydrate handling
- Formation of bile (secretion, bile acid metabolism, bilirubin metabolism)
- Hormone and drug inactivation
- Immunological function
- Storage
6
Q
Liver’s role in protein handling.
A
Making enzymes and proteins responsible for most chemical reactions in the body including blood clotting, repair of damaged tissue and albumin production
7
Q
What is the role of albumin?
A
Transportation of fatty acids and steroid hormones to support pressure and prevent leaking of blood vessels
8
Q
Liver’s role in lipid handling.
A
Production of bile which breaks down fats to make it easier for them to be digested.
9
Q
Liver’s role in carbohydrate handling.
A
The liver is central to glucose homeostasis. Carbohydrates are broken down into glucose and stored in the liver as glycogen –> when energy is needed the liver converts the glycogen back to glucose.
10
Q
What is bile made up of? (5)
A
bile salts
cholesterol
bilirubin
electrolytes
water
11
Q
What are the roles of bile? (3)
A
Carrying away waste and toxins from the liver
Breaking down fats in the small intestine
Essential for vitamin K absorption
12
Q
Liver’s role in hormone and drug inactivation.
A
metabolism including the activation and inactivation of drugs so they can be excreted easier
Cytochrome P450
hormones: thyroid, cortisol, sex hormones, EPO
13
Q
Liver’s role in immunological function.
A
mononuclear phagocyte system - high levels of kupffer cells in the liver so damage to liver can impair its ability to fight infections.
14
Q
Liver’s role in storage. (3 things)
A
- Iron from breakdown of Hb –> ferritin
- Fat soluble vitamins - A, D, E, K, B12
- Copper
15
Q
What is the safe limit of alcohol?
A
No more than 14 units a week spread over 3 or more days
16
Q
What is one unit of alcohol?
A
10ml/8g of pure alcohol
half a pint of beer, lager or cider
half a small glass of wine
17
Q
What are some of the health, economic and social concerns associated with alcohol misuse?
A
- leading cause of liver disease
- increase in crime
- lost productivity
- NHS burden : £21 billion
18
Q
Define an acute liver injury.
A
Acute or sudden deterioration in liver function that occurs quickly with no prior history of liver disease.
19
Q
If untreated what can acute liver injury progress to?
A
Acute liver failure
20
Q
What are some signs/symptoms of acute liver failure? (3)
A
Jaundice
Coagulopathy
Hepatic encephalopathy
Rapid onset - can happen in less than 28 days
21
Q
Can a patient with a pre-existing liver disease have acute liver failure?
A
Yes - acute on chronic liver failure
22
Q
What are some causes of acute liver failure?
A
Drugs - paracetamol overdose is the most common cause in UK
Viral hepatitis - most common cause globally
Autoimmune hepatitis
23
Q
What is chronic liver disease?
A
The gradual destruction of liver tissue over an extended duration - months/years
24
Q
What are some causes of chronic liver disease? (4)
A
Drugs
Alcohol
Viruses
Autoimmune conditions
25
What happens to the liver in chronic liver disease?
Scar tissue replaces normal tissue which reduces bloodflow to the liver --> scar tissue cannot repair itself --> build up of scar tissue (FIBROSIS) --> as more functioning tissue is lost it progresses to cirrhosis and the liver cannot function effectively --> patient shows symptoms of CLD
26
Can mild/moderate fibrosis be reversed?
Yes if treated early
27
What is cirrhosis?
Build-up of scar tissue and widespread nodules in the liver combined with fibrosis
28
What are the two types of cirrhosis?
Compensated and decompensated
29
What is compensated cirrhosis?
When the liver is cirrhotic but continues to function
30
What is decompensated cirrhosis?
Cirrhosis has progressed and the liver cannot function adequately
31
What are some signs of decompensated cirrhosis?
Varices
Ascites
32
What is hepatitis?
Inflammation of the liver
33
What is the difference between acute and chronic hepatitis?
Acute: may resolve on it own but may progress to chronic hepatitis or cause acute liver failure
Chronic: can progress to fibrosis, cirrhosis, liver failure or liver cancer
34
What are some causes of hepatitis?
Virus
Drugs
Alcohol
Metabolic disturbances
Autoimmune conditions
35
How much of the liver's mass is made up of hepatocytes?
80%
36
What is cholestasis?
A blockage or reduction of bile flow due to impaired bile secretion or obstruction of the bile ducts
37
What are the two types of cholestasis?
Intrahepatic - in the liver
Extrahepatic - outside the liver
38
What are the causes of cholestasis?
Tumours
Stones
Autoimmune conditions
Pregnancy
Infection
Alcoholic liver disease
Drugs
39
What are the symptoms of cholestasis? (4)
Jaundice
Itching
Nausea and vomiting
Right upper abdominal pain
40
What are the causes of liver disease? (5)
Drugs/toxins (ALCOHOL)
Virus - Hepatitis A, B, C, D, E
Autoimmune conditions
Metabolic
Budd Chiari
41
What autoimmune conditions can lead to liver disease? (2)
Primary biliary Cholangitis - bile ducts inflamed and slowly destroyed
Primary Sclerosis Cholangitis - affects bile ducts inside and outside the liver
42
What metabolic conditions can lead to liver disease?
(3 genetic , 1 acquired)
Genetic
Alpha-1 antitrypsin deficiency
Wilson's disease - excessive copper accumulation
Hemachromotosis (excess iron accumulation)
MASLD - Metabolic dysfunction-associated steatotic liver disease
43
What is MASLD?
The most common cause of chronic liver disease.
Excessive fat in the liver leads to inflammation and damage usually associated with obesity. Used to be called NAFLD (non-alcoholic fatty liver disease)
44
What can uncontrolled MASLD progress to?
MASH - metabolic dysfunction-associated steatohepatitis which can then progress to cirrhosis
45
What is Budd Chiari syndrome?
hepatic vein thrombosis - blood clots that fully or partially block blood flow to the liver
46
Outline the progression of liver disease.
Healthy
Steatosis - usually harmless fat accumulation but can progress to INFLAMMATION
Fibrosis - inflammation leads to scar tissue build-up
Cirrhosis - if fibrosis is untreated which can become decompensated cirrhosis when function is lost
47
What are patients with cirrhosis at a higher risk of?
HCC (hepatocellular carcinoma) - 80-90% of HCC patients have cirrhosis
48
Why is liver disease hard to catch?
Often silent progression by the time symptoms are noticeable it has already professed signifcantly to scarring/fibrosis
49
What are some symptoms of early liver disease (compensated cirrhosis)? (5)
Non-specific symptoms :
Fatigue
Nausea
Vomiting
Abdominal tenderness in URQ
Weight loss
50
What are some late symptoms of decompensated liver disease? (9)
Jaundice
Intense itching
Easy bruising/bleeding
Vomiting blood
Infection
Memory loss
Confusion
Drowsiness
Ascites
51
What is the role of the community pharmacist in the prevention and management of liver disease?
Preventative advice - e.g. dangerous drinking
Early identification and identification of red flag symptoms that would warrant urgent referral.
52
What are some signs of decompensated cirrhosis? (7)
Jaundice
Coagulopathy
Ascites
Variceal bleeding
Clubbing - enlarged fingertips and thick nails
Hepatic encephalopathy
Increase risk of dying from complications
53
Why does gynaecomastia occur in males with decompensated liver disease?
The liver is involved in hormone metabolism --> dysfunction leads to an imbalance between androgens and oestrogens --> enlarged male breast tissue
54
What is ascites?
Accumulation of fluid in the abdominal cavity during advanced liver disease caused by several factors including portal hypertension and reduced albumin production.
55
How does portal hypertension lead to ascites?
Scarring in to liver leads to impaired blood flow and increased resistance in the liver's vasculature --> portal hypertension--> --> blood vessels in liver and surrounding organs dilate to alleviate pressure reducing effective circulation --> buildup of fluid
56
How does a reduction in albumin lead to ascites?
Albumin is needed to maintain fluid balance in the blood vessels --> vasodilation and lowered albumin leads the kidney to think there is a low blood volume --> retention of sodium and water leading to ascitic fluid in the peritoneal cavity
57
What are spider naevi?
vascular lesions thought to be caused by hormonal imbalances and circulatory changes
58
What are some complications of liver disease? (5)
Variceal bleeding
Hepatic encephalopathy
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Sepsis
59
What is variceal bleeding?
Varices are expanded blood vessels that occur in order to cope with portal hypertension
usually found in the oesophagus and stomach
they can rupture leading to massive bleeding
60
How are varices detected?
Endoscopy
61
How are varices treated?
Stop causative factor - e.g. alcohol consumption
May be treated using non-selective beta blockers or variceal band ligation depending on size and other risk factors.
62
What is hepatic encephalopathy?
Damaged liver cannot filter out neurotoxins such as ammonia whihc can cross the BBB leading to effect on brain function
63
What are the symptoms of hepatic encephalopathy? (5)
Drowsiness
Confusion
Mood changes
Sleep disturbances
COMA
64
What can trigger a hepatic encephalopathy episode? (3)
Dehydration
Constipation
Infection
65
How is hepatic encephalopathy managed?
Treat causative factors ad prevent reccurence.
Lactulose
Rifamixin
66
What is spontaneous bacterial peritonitis?
Infection of the ascitic fluid
67
Signs of SPB.
Fever
Worsening clinical detoriaration
68
Causative organisms of SPB.
Escherichia coli (gram -)
Klebsiella pneumoniae (gram -)
Streptococcus pneumoniae (gram +)
69
How is SPB managed?
3rd generation cephalosporins such as cefotaxime and person may also need prophylactic antibiotics
70
What is hepatorenal syndrome?
Reduced perfusion to kidneys and kidney failure secondary to liver disease
71
How is hepatorenal syndrome treated? (3)
Stop nephrotoxic drugs
Use of vasoconstrictors such as terlipressin to increase perfusion
Liver transplant in serious cases
72
Why are cirrhosis patients at higher risk of sepsis?
Impaired immunity - liver has a role in immune response
73
How is sepsis in liver disease patients managed?
IV antibiotics and fluids
74
What is the aim of the Decompensated Cirrhosis Care Bundle?
Standardising care nationally
Complete checklist for all patients with decompensated cirrhosis within the first 6 hours of admission.
75
What is the role of liver function tests?
Distinguishing between acute and chronic liver disease
Distinguishing between different types of liver disease
76
What are some key liver function tests/markers?
ALT - alanine aminotransferase
AST - aspartate aminotransferase
GGT - gamma glutamyltransferase
bilirubin
ALP - alkaline phosphatase
Prothrombin time
INR
77
What are ALT and AST and what is their significance to the liver?
Transaminases that are released when hepatocytes are damaged.
- High elevations in acute injury but usually normal in chronic disease
78
What is ALP and what is its significance to the liver?
Found in the cells lining the biliary tract and raised in cholestatic diseases but also in the bones !!!!!
79
What is GGT and what is its significance to the liver?
Found in hepatocytes and biliary cells
non specific but highly significant marker of liver damage and cholestasis
Raised by alcohol excess
80
What does a raised blood bilirubin lead to?
Jaundice
81
What markers are raised in cholestatic diseases?
ALP
GGT
Bilirubin
82
If ALP is high but GGT is normal what is the more likely diagnosis?
Bone disease
83
If ALP is high and GGT is high what is the more likely diagnosis?
Cholestasis
84
What are PT and INR and what are their significance to the liver?
Damage = reduction to clotting factors leading to raised PT and INR
85
What markers help to understand liver function?
ALbumin
Bilirubin
PT
86
Liver marker changes in acute liver disease?
Transaminases HIGH
Raised PT - PT can be used to monitor progression
87
Liver markers in chronic liver disease?
Transaminases normal (depending on cause)
PT raises over time
Albumin LOW
88
Liver markers in cholestasis?
Increased bilirubin
Increased ALP AND GGT
89
Liver markers in hepatitis? (acute in particular)
Increase aminotransferases - ALT and AST
90
Liver markers in cirrhosis?
mostly normal
91
Can LFTs alone provide a diagnosis in liver disease?
No - use of other diagnostics alongside LFTs include biopsy, fibroscan, CT, MRI
92
What is the Child Pugh score?
Looks at cirrhosis mortality, prognosis, risk of surgery and dose reductions/contraindications
93
What are MELD and UKELD?
Model for End Stage Liver Disease + UK Model for End Stage Liver Disease
Looks at if patient can be listed for transplant
94
What non selective beta blockers may be prescribed to patients with liver disease?
Carvedilol and propranolol to treat portal hypertension and prevention of variceal bleeding
95
What is the first line diuretic used in liver disease?
SpironolactoneW
96
What is the role of spironolactone in liver disease?
it is an antimineralocorticoid that addresses hypoaldosteronism in cirrhosis. it acts in the distal tubules to allow for excretion of sodium and water
97
What diuretic may be used alongside spironolactone in liver disease and why?
Furosemide - LOOP DIURETIC that acts in the loop of henle to prevent sodium resorption
98
What is the role of lactulose in liver disease?
Treating hepatic encephalopathy - lactulose draws ammonia into the gut --> lower blood ammonia = lower chance of it crossing BBB and neurological symptoms
99
What is the role of rifamixin in liver disease?
Reducing reccurent HE - rifamixin is a non absorbable antibiotic that works i the gut to reduce the production and absorption ammonia
100
Why might a patient with liver disease be on prophylactic antibiotics?
To reduce the risk of SBP (spontaneous bacterial peritonitis)
101
What antibiotics may be used in the prophylaxis of SBP? (Name, class and coverage)
Ciprofloxacin - fluoroquinolone - broad spectrum
Trimethoprim - antifolate - gram negative
102
What is the role of thiamine in liver disease?
People with excess alcohol consumption often have low Vit B1 which can lead to wernicke's encephalopathy
Thiamine supplementation used to reduce the risk of Wenicke's encephalopathy
103
What is the role of vitamin D supplementation in liver disease?
As the liver metabolises Vitamin D and cannot function properly in cirrhosis patient may require vitamin D supplementation
104
Why might a patient with liver disease be on antivirals?
Liver disease can be due to viruses such as hepatitis B which if untreated can lead to cirrhosis.
105
What antivirals may a person with hepatititis B be taking?
Tenofovir/entecavir - nucleoside analogues that inhibit viral replication
106
What analgesia should be avoiding in patients with liver disease?
NSAIDs due to risk of AKI and bleeding
107
What must be done to the dose of paracetamol in decompensated liver disease?
Paracetamol is okay to use but total daily dose should be lowered
108
What must be done to the dose of opioids in decompensated liver disease?
start low and titrate up as the liver metabolises opioids so dysfunction can cause them to accumulate
109
How do ensure medication is safe and appropriate in patients with liver disease?
- Refer to SPC
- Consider ADME
- AVOID hepatoxic drugs where possible and use reduced doses
- TDM - monitoring efficacy and toxicity
- Monitor renal function
- Start low and monitor if synthetic function is impaired
110
Why are patients with decompensated liver disease given nutritional supplementation?
Malnutrition in 50% of patients
Increases risk of infection, HE and ascites
111
How is paracetamol metabolised and excreted?
Mostly metabolised by sulfation and glucuronidation
HOWEVER, small amount by cytochrome P450 which converts it into the hepatotoxic metabolite NAPQI which is FIRST conjugated with glutathione so that it can be inactivated and then it is excreted
112
What happens in a paracetamol overdose?
Sulfation and glucuronidation pathways are saturated so more paracetamol is broken down by cytochrome P450 so more NAPQI is formed. If glutathione stores become exhausted --> NAPQI accumulated leading to HEPATOTOXICITY
113
What is there a risk of if a patient with liver disease is given the normal dose of paracetamol?
1g QDS - pharmacokinetics of paracetamol are altered so patient could go into acute liver failure
114
What is the lowered dose of paracetamol in liver disease and what risk factors would require a lower dose?
Decompensated liver disease
Chronic alcohol consumption
Maximum daily dose goes from 4g to 3g.
