Liver Anatomy & Functions Flashcards
1
Q
How much cardiac output does the liver produce
A
25%
2
Q
Name the 4 lobes
A
Major- left and right
Minor - caudate and quadrate
3
Q
List the main ducts in the liver
A
Common hepatic
Cystic
From gallbladder
- common bile duct/ joining pancreatic duct at hepatipancreatic ampulla
4
Q
Where do the common bile duct and pancreatic duct join
A
Hepatopancreatic ampulla
5
Q
Name the capsule of connective tissue surrounding the liver
A
Glisson’s capsule
6
Q
What do the hepatic artery and portal vein supply
A
Artery- oxygen rich
Vein- nutrient rich
7
Q
What does the celiac artery filter blood from
A
Stomach spleen and pancreas
8
Q
What does the superior mesentric artery collect blood from
A
Pancreas
SI
Colon
9
Q
What does the inferior mesentric artery collect blood from
A
Colon
10
Q
Where does the portal vein deposit its contents
A
Sinusoids
11
Q
Describe the structure of liver lobules
A
Hexagonal structure containing hepatocytes
Radiate outward from central vein
At each six corners is a portal triad
Contains sinusoids
12
Q
Other terms for hepatic cells
A
Hepatocytes
13
Q
Function of sinusoids
A
Specialised capillaries large and fenestrated
14
Q
Function of kupffer cells
A
Fixed macrophages with phagocytic function
15
Q
Function of stellate cells
A
Storage of vit A, when activated become fibrous
16
Q
Function of basolateral membrane
A
Between hepatocytes and space of disse
Has microvilli
17
Q
Function of apical membrane
A
Makeup bile canaliculi
18
Q
Where is oxygen highest and metabolic pathways that occur
A
Periportal cells
Gluconeogenesis/ b oxidation
Nutrient/ oxygen
19
Q
Where is o2 supply the lowest and metabolic pathways that occur
A
Central vein
Glycolysis
Lipogenesis
B catenin/ signalling
20
Q
Liver injury at periportal cells
A
Autoimmune hep
Iron overload injury
Billiary cirhosis
21
Q
Liver injury at central vein
A
Nafld
Drug alcohol toxicity
Parasite infection fibrosis
22
Q
Describe the route of bile
A
Bile canaliculi to bile duct
Then common hepatic duct
23
Q
Function of bile
A
Emulsify fats
24
Q
What is stored in gallbladder and how is it stimulated
A
Bile not immediately needed for digestion, stimulated by CCK & secretin
25
What are bile acids derived from
Cholestrol
26
Mechanism of Action of bile- how does it work
In conjugation to taurine and glycine, increases polarity of molecules
27
Function of sinusoidql transporter ntcp
Bile acid transporter, symport with sodium
28
Function of oatp sinusoidal transporter
Organic anion transporter protein
Into hepatocyte and blood
29
Function of oct
Into hepatocyte and blood
30
Function of mrp4
Transport drug metabolite back into blood
31
Function of biliary transporter mrp2
Bilirubin transported to bile
32
Function of biliary transporter abcg
Cholestrol
33
Function of biliary transporter mdr3
Pc
34
Function of biliary transporter bsep
Bile salts
35
Function of biliary transporter mdr1
Drug and metabolites
36
Function of biliary transporter bcrp
Steroid derivatives
37
Function of mdr1, abcb1 (p gylcoprotein) in the body
Found in liver gi tract kidneys and brain
Pump materials out of brain,
Activity can be both induced and inhibitted
38
Enzyme which activates bilirubin
Uridine glucournayl transferase
39
Methods of excretion for bile
Feces
Urine
Enterohepatic circulation
40
Functions of liver
Metabolic
Synthesis
Breakdown
Storage of vitamins
Excretion of waste products from blood stream to bile
41
Carbohydrate and lipid metabolism
Gluconeogenesis
Glycogenolysis
Glycogenesis
Cholestrol synthesis
Lipogenesis
42
At basal state what happens to blood sugar levels
Decreased glucose and insulin
Increased glucagon
43
At starved state what happens to blood sugar levels
Decreased insulin and glucose
Increased glucagon
Acetyl CoA supply straight to the brain
44
Hormones involved in glycogen mobilisation
Insulin
Glucagon
Adrenaline
45
Target organs involved in glycogen mobilisation
Liver and muscle
46
Key enzymes regulated from glycogen mobilisation
Glyogen synthase and phosphorylase
47
Function of glycogen phosphorylase
Removal of glucose residues
48
How is glycogen phosphorylase controlled
Kinase - active
Phosphatase- inactive
49
Why is glycogen synthase switched off
Stop a futile cycle
50
Function of glycogen synthase
Regulate synthesis of glycogen
51
Why do we need protein synthesis
Amino acids
Albumin
A/b globulins
Tranferrin
Hormones
52
Why do we need aa for breakdown
Bd insulin and other hormones
Amino acid metabolism
Ammonia to urea
Drug metabolism
53
Enzymes used in amino acid formation
Transaminase
Aminotransferase
54
Function if glutamate dehydrogenase
Release ammonia
And generate nadph
55
Enzyme for glutamine synthesis
Glutamine synthetase
56
Enzyme for glutamine hydrolysis
Glutaminase
57
What can increased urea levels cause
Cerebral oedema
58
Function of orthinine transcarbamylase
Turns carbsmoyl phosphate and orthinie into citrulline
59
Effect of OTc deficiency in urea cycle
Build up of toxic ammonia levels= hyperammonemia
60
Definition of drug metabolism
Process by which biochemical reactions alter drugs into the body
61
Another term for drug metabolism
Drug biotransformation
62
What can cause a loss of pharma activity in liver
Change in structure
63
What are pro drugs and toxic metabolites a product of
Change ins structure
64
Why are substances excreted by liver
Lipophillic xenobiotics are not elimintaed efficiently by kidney
65
What does the process of biotransformation do
Parent drug turned imore polar
66
Difference between phase 1 and phase 2 reactions
Phase 1 unmasks chemical reactive functional group
phase 2 conjugates endogenous molecule onto functional group
67
Examples of phase 1 reactions
Oxidation
Reduction hydrolysis
68
Examples of phase 2 reaction
Sulphation
Glucuronidation
Acetylation
Methylation
69
Describe cytochrome p450
Haem proteins that catalyse monooxygenase reactions
70
What does cytochrome p450 play an important role in
Primary mediators of phase 1 reactions
71
Requirements for p450 catalytic cycle
Molecular oxygen
Nadph
Lipid- membrane bound endoplasmic reticulum
72
How do we classify isoforms of cyp p450
Homology of primary amino acid sequence
73
Why are cytochromes considered first defence against xenobiotics
High catalytic versatility
Broad substrate specificity
74
What do the different overlapping substrates cause in CYP
Different rates of metabolism
75
In a phase two reaction, what will all enzymes be
Transferases
76
What is the effect of phase 11 metabolism
More polar = more water soluble
77
In a glucuronidation reaction what are the reactants
Glucuronic acid WITH
OH
COOH
NH2
SH
Forming an amide ester or thiol bond
78
In a glutathione reaction, what does glutathione perixidase convert glutathione into
Reduced to oxidised
79
In a glutathione reaction, what does glutathione reductase convert glutathione into
Oxidised to reduced
80
In general terms, explain the steps of phase 1 and phase 11 reactions
Drug ——derivative———conjugate
81
What will drug metabolism affect
Drug concentration
82
What useful parameters are used for pharmacokinetics
Half life
Area under the curve
83
Definition of half life
Time taken for concentration of drug to fall by half
84
Definition of cmax
Highest concentration of drug in blood
85
Definition if cmin
Lowest concentration of drug in blood
86
Factors affecting drug metabolism
Disease-liver
Genetic factors-
Polymorphic distribution
87
Definition of poor metaboliser
Lackijg active gene allele
88
Definition of intermediate metaboliser
Homozygous for 2 reduced activity gene alleles
OR
Heterozygous for inactive allele
89
Definition for extensive metaboliser
Normal complemenet of 2 fully active gene alleles
Expect response to standard dose
90
Definition of ultrarapid metaboliser
More than 2 copies of active gene alleles
91
Three types of activation
Induction
Auto induction
Heteroinduction
92
Concerns regarding clinical implications of cyp induction
Reduction in pharma effect
Induction leads to toxicity
93
3 types of inhibitors
Competitors
Non competitive inhibitors
Irreversible inhibitors
94
Effect of comp inhibitor
Most common
Como for active site
95
Effect of non comp inhib
Form inactive intermediate with enzyme = decreased enzyme activity
96
Effect of irreversible inhib
Substrate inactivates enzyme
Time dependent loss of enzyme activity
Aka suicide inhibitors
97
What is the effect of administering a cyp inhihitor with a drug
Slower rate of clearance
98
Propranolol and metoprolol can have interaction with:
Fluoxetine
Paroxetine
Antidepressants
Quinine
Cyp2d6 inhibitors
99
What can st johns wart interact with
Enzyme inducers
Inducing hepatic cyt p450 and intestinal p glycoproteins
100
Increased blood levels of calcium and statins naturally is due to
Grapefruit juice containing furancoumarins which inhibit cyp3a4 in gut wall and liver
101
Steatosis
Fatty liver due to alcohol
Nonalcoholic fatty liver due to diabetes
102
Cholestasis
Blockage of bile flow leading to jaundice
103
Cirrhosis
Loss of lobular structure
104
Causes of cirhosis
Alcohol abuse
Hep b c
Errors of metab
Adverse drug reaction
105
Symtoms of cirrhosis
Blockage of venous flow leading to hypertension
Biliary obstruction leading to jaundice
Liver cell failure - decreased metabolism
106
Symptoms of portal hypertension
Hypersplenism
Neutropenia
Thrombocytopenia
Marked ascites
107
List Treatment of cirrhosis
Prevention of fibrosis
Limit fluid retention/encephalopathy
Avoid alcohol
Ascites if present reduce salt intake and diuretics
108
Causes of hepatitis
Liver inflammation leading to celullar necrosis
Due to viral/alcohol/drugs
109
Symptoms of acute viral hepatitis
Less than 6 months
Nausea/vomiting
Increased bilirubin
110
Symptoms of chronic viral hep
More than 6 months
Asymptomatic
Fever/fatigue
111
Treatment of viral hepatitis
Rest
Low fat diet
No alcohol
Avoid contact
112
Acute alcoholic hepatitis
Hep inflammation and necrosis
Similer symp to HAV
No alcohol
113
Treatment for Drug induced hep mimick acute viral hep
Drug withdrawal
114
Gallbladder disorder
Treatment methods
Cholangitis
Bile duct inflamed
Vomiting and pain
Antibacterial/IV fluids
Surgery
115
Cholecystisis
Different types
With treatment methods
Inflammation of gall bladder
Acute and chronic
Retained bile in gallbladder
Pain/jaundice
Opioid analgesics
Antibac drugs
116
Overdose of paracetamol can lead ti
Hepatotoxicity
117
Explain the effect of taking paracetamol overdose
Glucuronide saturation = sulphate/gsh conjugate depletion
=== increased toxicity’s
118
List sinusoidal transporters
Ntcp
Oatp
Oct
Mrp4
119
List biliary transporters
MRP2
Abcg 5/8
Mdr3
Bsep
Mdr1
Bcrp
120
What enzyme activates glycogen synthase
Protein kinase a
121
What stops glycogen syntahse
Phosphoproteun phosphatase 1
122
What can CYP450 be also known as
Mixed function oxidase
123
Requirements for mixed function oxidase
Molecular oxygen
Nadph
Lipid (membrane bound endoplasmic reticulum)
