Liver Dysfunction & Bilirubin Metabolism Flashcards
1
Q
What are the functions of the liver?
A
Key role in iontemediary metabolism
Synthetic function
Detoxification & Excretion
Storage function
Production of bile salts
2
Q
What metabolic processes is the liver involved in?
A
Gluconeogenesis
Glycolysis
Ketogenesis
3
Q
What synthetic functions does the liver have?
A
Plasma proteins
Coagulation factors
Cholesterol
Triglycerides
Lipoporoteins
4
Q
What detox and excretion processes is the liver involved in?
A
Urea cycle (Ammonia to urea)
Bilirubin
Cholesterol
Drug metabolites
5
Q
Which substances does the liver store?
A
Vitamins A, D, E and K and B12
6
Q
What is the function of production of bile salts?
A
Helps with digestion
7
Q
What is cholestasis?
A
Bile cannot flow from the liver to the duodenum
8
Q
What is jaundice?
A
Yellow or greenish pigmentation of the skin and whites of the eyes due to high levels of bilirubin
9
Q
What is hepatitis?
A
Inflammation of the liver tissue
10
Q
What is cirrhosis?
A
Liver does not function properly due to long-term damage characterised by the replacement of normal liver tissue by scar tissue
11
Q
What is steatosis?
A
Abmormal retention of lipids within a cell
12
Q
What is hemochromatosis?
A
Iron storage overload
13
Q
What are liver function tests?
A
Noninvasive methods of screening for liver dysfunction
14
Q
What are the functions of liver function tests?
A
Help in identifying general types of liver disease
Assess severity and allow prediction of outcome
Help in monitoring the treatment of the disease
15
Q
What are the two broad categories of liver tests?
A
Tests to assess hepatic function
Tests to detect hepatic injury
16
Q
What is Group I of LFTs?
A
Markers of liver dysfunction
17
Q
What are the markers of liver dysfunction?
A
Serum bilirubin
Urine
Total protein, serum albumin, and albumin/globulin ratio
Prothrombin time
18
Q
What do you measure within serum bilirubin?
A
Total and conjugated
19
Q
What do measure within the urine test of Group I LFTs?
A
Bile salts and urobilinogen
20
Q
What are Group II LFTs?
A
Markers of hepatocellular injury
21
Q
What are the markers of hepatocellular injury?
A
ALT & AST
22
Q
What are Group III LFTs?
A
Markers of cholestasis
23
Q
What are the markers of cholestasis?
A
ALP
GGT
24
Q
What are the limitations of LFTs?
Why?
A
- Normal LFT values do not always indicate the absence of liver disease
Because the liver has a very large reserve capacity - Asymptomatic people may have abnormal LFT results
25
What is serum albumin?
The most abundant protein in mammals
26
Where is serum albumin synthesised?
The liver
27
What gene encodes serum albumin?
ALB gene
28
Where is serum albumin dissolved?
In the blood stream
29
What is the function of serum albumin?
Primarily a carrier protein for unconjugated bilirubin, steroids, fatty acids and thyroid hormones
Also plays a key role in stabilising extracellular fluid volume by contributing to the osmotic pressure of the plasma
30
What are the normal levels of serum albumin?
3.5 to 5.5 g/L
31
What does the synthesis of serum albumin depend on?
The extent of functioning liver cell mass
32
What is the half life of serum albumin?
20 days
33
In which pathology does the serum albumin levels always decrease?
Chronic liver diseases
34
What is the difference between globulins and albumins?
Globar proteins with higher molecular weights than albumins
Insoluble in pure water but dissolve in dilute salt solutions
35
Where are α & β globulins synthesised?
By the liver
36
What are the normal serum levels of globulins?
16 to 30 g/L
37
Which globulins are known as antibodies?
Active γ globulins
38
High serum levels of IgG are observed in which pathologies?
Autoimmune hepatitis
39
High serum levels of IgA are observed in which pathologies?
Alcoholic liver disease
40
What is prothrombin?
A market of liver function
41
Where is prothrombin synthesised?
In the liver
42
What is prothrombin converted into and when?
Thrombin during coagulation
43
What is the half-life of prothrombin?
6 hours
44
What is prothrombin time?
A blood test that measures how long it taken blood to clot
45
What is the reference range for PT?
12 to 16 seconds
46
When is PT prolonged?
When liver loses more than 80% of its reserve capacity
47
What are other causes of prolonged PT?
Vitamin K deficiency, however, intake of vitamin K has no effect in the case of liver disease
48
Where is ALT found?
Plasma and in various body tissues but most common in the liver
49
What is the function of ALT?
Reversible transfer of an amino group from L-alanine to α-ketoglutarate
50
Which transferase is liver-specific enzyme?
ALT more than AST
51
What is the normal range of ALT?
10 to 55
52
What do high elevations of ALT indicate?
Acute hepatitis
53
What do moderate elevations of ALT indicate?
Alcoholic hepatitis
54
What do minor elevations of ALT indicate?
Cirrhosis, hepatitis C, non-alcoholic steatohepatitis
55
In what cases might ALT levels be elevated but there the individuals are healthy?
In obese but otherwise healthy individuals
56
What is the function of AST?
Reversible transfer of an amino group from aspartate to α - Ketoglutarate
57
What is the normal range of AST?
10 to 40
58
Where is AST found?
In the liver, skeletal muscle, myocardium, kidney, pancreas and RBCs
59
What is AST?
A marker of hepatocellular damage
60
In what cases are there high levels of AST?
Chronic hepatitis, cirrhosis and liver cancer
61
What is ALP?
A homodimeric protein enzyme, containing two zinc atoms crucial to its catalytic function
62
What is the optimal environment for ALP?
Optimally active in alkaline pH environments
63
What is ALP's function under alkaline environments?
To dephosphorylate compounds
64
Is ALP a specific or non-specific marker of liver disease?
Non-specific
65
Where is ALP produced?
In bone osteoblasts
66
What other structures is ALP present on?
Hepatocyte membranę
67
What is the normal range of ALP?
45 to 115
68
When is moderate elevation of ALP seen?
Infective hepatitis, alcoholic hepatitis, and hepatocellular carcinoma
69
When is high elevation of ALP seen?
Obstructive jaundice and interhepatic cholestasis
70
When is very high elevation of ALP seen?
Bone disease
71
What is GGT?
Transferase that catalyses the transfer of gamma-glutamyl functional groups from molecules like glutathione to an acceptor that may be an amino acid or peptide
72
What is the function of GGT?
Key role in gamma-glutamyl cycle
73
What is gamma-glutamyl cycle?
A pathway for the synthesis and degradation of glutathione as well as the drug and xenobiotic detox
74
Where is GGT found?
Microsomal enzyme in hepatocytes and epithelium of small bile ducts and pancreas, kidney and intestines
75
What is the normal range of GGT?
15 to 85
76
When is moderate elevation of GGT seen?
Infective hepatitis and prostate cancers
77
In which cases is GGT increased despite normal liver functions?
In alcoholics, highly sensitive to detecting alcohol abuse
78
What is bilirubin?
A yellow bile pigment
79
What is bilirubin responsible for?
The yellow colour in urine and the brown colour of faeces
Yellow colour of bruises
Yellow colour in jaundice
80
What is the average life span of healthy RBCs?
120 days
81
What happens to senescent RBCs?
They undergo erythrophagocytosis by macrophages in the spleen and liver
82
What happens to global chains when RBCs are broken down?
Break down into amino acids
83
What happens to the heme when RBCs are broken down?
Heme oxygenate converts heme to biliverdin
Biliverdin reductase converts biliverdin to bilirubin
84
What is the function of biliverdin reductase?
Catalyses the conversion of biliverdin to bilirubin by transferring two hydrogen ions to the centrally located C10 carbon of bilirubin
85
What is the linear structure of Bilirubin?
Two dipyrroles joined by a central methene bridge
86
Why is bilirubin insoluble even though it has multiple polar groups?
Because of the internal hydrogen bonding, all polar groups are engaged and central methene bridge becomes buried
87
Why is the conjugation of bilirubin crucial?
It increases its aqueous solubility on preparation for its transport to bile
88
What does albumin function as in regards to bilirubin?
Carrier protein for transporting unconjugated bilirubin through the bloodstream to the liver in order for bilirubin to be conjugated
89
What is unconjugated bilirubin joined with to form conjugated bilirubin?
Glucuronic acid
90
What catalysed the conjugation of bilirubin with glucuronic acid?
Glucuronyl transferase
91
What is the first step of bilirubin conjugation?
Formation of bilirubin monoglucuronide, sufficient soluble for transport
92
In which cases in bilirubin monoglucuronide the predominant form of conjugated bilirubin?
In fetal and early neonatal life
93
What happens if you add another glucuronic acid to bilirubin monoglucuronide?
It becomes bilirubin diglucuronide, which is the fully conjugated form
94
What does conjugated bilirubin do?
Passes through the bile and reaches the intestines
95
What substances deconjugate bilirubin?
Intestinal bacteria
96
What happens to the free bilirubin in the small intestine?
Reduced to urobilinogen and then into stercobilinogen
97
What percentage of bilirubin is converted into stercobilinogen?
Over 80%
98
Where is stercobilin excreted?
In the faeces, gives the brown colour
99
What happens to the remainder urobilinogen?
Reabsorbed from the intestine and enters portal blood
Some of it returns to the liver and is re-excreted (enter-hepatic circulation)
100
What happens to the urobilinogen that does not return to the liver?
Passes through the kidney and is converted into urobilin that is excreted in the urine and gives it its yellow colour
101
What is the bilirubin that is conjugated with the glucuronic acid called?
Direct or conjugated bilirubin
102
What is the bilirubin that is not conjugated with glucuronic acid called?
Indirect or unconjugated bilirubin
103
What is all the bilirubin in the blood called?
Total bilirubin
104
What is the normal levels of the different kinds of bilirubin?
Total: 0.3 to 1mg/dl
Unconjugated: 0.2 to 0.7 mg/dl
Conjugated: 0.1 to 0.3 mg/dl
105
What happens if serum bilirubin > 1?
Hyperbilirubinemia
106
What happens if serum bilirubin > 2?
Jaundice
107
What is neonatal jaundice?
Jaundice in newborns, especially seen in premies
108
When does neonatal jaundice appear?
Appears after 24 hours, picks up after 4 to 5 days and then disappears after 14 days
109
What causes neonatal jaundice?
Bilirubin accumulates as glucurynol transferase is low at birth
Unconjugated bilirubin is increased in blood > albumin
Diffuses into basal ganglia and cause toxic encephalopathy
110
What is the treatment for neonatal jaundice?
Blue fluorescent ligt, convers bilirubin to more polar --> water soluble isomers --> which can be excreted unto bile without glucuronic acid
111
What are the causes for haemolytic jaundice?
Excessive hemolysis
Low haemoglobin levels
Increased levels of indirect bilirubin
Sickle cell anemia, thalassemia, malaria and haemolytic transfusion reaction
112
What causes hepatic jaundice?
Impaired uptake of bilirubin by hepatocytes
Impaired conjugation of bilirubin with hepatocytes
Impaired secretion of bilirubin by hepatocytes
113
What happens to the elevates of both direct and indirect bilirubin in hepatic jaundice?
Both increase
114
What happens to AST and ALT during hepatic jaundice?
Significant increase
115
What happens to aLP during hepatic jaundice?
Moderate increase
116
What can cause hepatic jaundice?
Hepatitis, cirrhosis, Crigler-Najjar syndrome, gilbert's syndrome, dubin-johsnon syndrome, rotor syndrome, drug toxicity
117
What cause obstructive jaundice?
Impaired excretion of bilirubin due to obstruction in the bile flow from the liver to the ntestien
118
What happens to the levels of direct bilirubin in obstructive jaundice?
Increase
119
What happens to ALP levels in obstructive jaundice?
Significant increase
120
What happens to AST and ALT levels in obstructive jaundice?
Moderate increase
121
What can cause obstructive jaundice?
Gallstones, inflammation, carcinoma of head of pancreas
122
What is congenital hyperbilirubinemia?
Bilirubin is elevated in blood due to inherited defects in the bilirubin metabolic pathway
123
What is the Crigler-Najjar syndrome?
Low activity of glucuronyltransferase
124
What does Crigler-Najjar syndrome present like?
Severe hyperbilirubinemia in neonates
Complicated by kernicterus and early death
125
What is Gilbert's syndrome?
Decreased production of glucuronyltransferase due to mutations
126
What population is Gilbert';s syndrome more common in?
In men, 2 to 3% of men
127
How does Gilbert's syndrome present?
Usually asymptomatic
LFT's are normal
128
What is the Dubin-Johnson/Rotor syndrome?
Defect in transfer of conjugated bilirubin into biliary canaliculi
Conjugated hyperbilirubinemia
129
