Liver Flashcards
(195 cards)
1
Q
What are xenobiotics?
A
Foreign chemical substance not normally found or produced in the body which
cannot be used for energy requirements
Drugs are considered xenobiotics. They’re excreted in urine, bile, sweat and breath.
2
Q
Define lipophilic
A
Able to pass through the plasma membrane to reach metabolising enzymes
3
Q
how are pharmacologically active compounds transported in the blood?
A
Bound to plasma proteins
4
Q
Define microsome
A
a small particle consisting of a piece of endoplasmic reticulum to which
ribosomes are attached, so microsomal enzymes - are just enzymes which can be
found in these microsomes
5
Q
Which reaction do microsomal enzymes mainly catalyse?
A
Mainly phase 1, but can do phase 2 aswell
6
Q
Where are microsomal enzymes loacted?
A
- Liver heptocytes
- SER
7
Q
What is a phase 1 reaction?
A
- Non-synthetic catabolic reaction: oxidation, reduction and hydrolysis.
- Introduces a reactive group to the drug, this is the attack point for conjugation.
- very small increase in hydrophilicity
8
Q
What is a phase 2 reaction?
A
- Synthetic anabolic reactions: conjugation, glucuronidation ( adding glucoronic acid) etc.
- Usually inactivate products and increase hydrophilicity for renal excretion.
9
Q
What are the mechanisms for drug metabolism?
A
Phase 1 and phase 2 reactions. They usually occur sequentially. The aim is to make drugs more polar.
10
Q
Phase 1 reactions: what can happen in an oxidation reaction?
A
- Hydroxylation (add OH group).
- Dealkylation (remove CH side chains).
- Deamination (remove NH).
- Hydrogen removal.
11
Q
Phase 1 reactions: what can happen in a reduction reaction?
A
Add hydrogen, saturate unsaturated bonds.
12
Q
Phase 1 reactions: what can happen in a hydrolysis reaction?
A
Split peptide and ester bonds.
13
Q
What usually catalyses phase 1 reactions?
A
Cytochrome P450.
14
Q
What type of enzyme is cytochrome P450?
A
Microsomal.
15
Q
Give examples of non-microsomal enzymes.
A
Oxidases, esterases, conjugases.
16
Q
What enzyme catalyses glucuronidation reactions?
A
Glucuronosyltransferase (UGT)
17
Q
What kind of enzyme is Glucuronosyltransferase?
A
Microsomal.
18
Q
Is Glucuronosyltransferase involved in phase 1 or phase 2 reactions?
A
Phase 2.
19
Q
What other reaction is Glucuronosyltransferase involved in?
A
The conjugation of bilirubin.
20
Q
Where are non-microsomal enzymes located in cells?
A
- cytoplasm
- mitochondria
of hepatocytes
21
Q
Which reactions are non-microsomal enzymes involved in
A
all conjugation reactions except glucuronidation - carried out by Glucuronosyltransferase (UGT) which is a microsomal enzyme
22
Q
What is the importance of pharmacologically active compounds being lipophilic?
A
It enables them to pass through plasma membranes to reach metabolising enzymes.
23
Q
Why is the aim of drug metabolism to make a drug more polar?
A
so they cannot get
across membranes and thus are easily excreted
24
Q
How do cytochrome p450 enzymes oxidise substances?
A
Uses heme group (Fe2+) to oxidise substances
25
What four things can phase do to drugs?
* Inactivate drugs
* Further activate drug
* Activate drug from pro-drug (inactive form of drug)
* Make a drug into a reactive intermediate (could be carcinogenic or toxic)
26
What can induce or inhibit microsomal enzymes?
Drugs, food, age bacteria, alcohol.
27
What is the aim of drug metabolism?
To make drugs more polar.
28
Where does drug metabolism mostly occur?
In the liver - where the enzymes are.
29
What is iron used for in the body?
- Haemoglobin
- myoglobin
- bone marrow
- cytochrome p450
30
Name some sources of iron
- Meat
- liver
- shellfish
- egg yolk
- beans
- nuts
- cereals
31
where does active absorption occur the most in the body?
Duodenum
32
Around how much-ingested iron is absorbed into the blood each day?
10%
33
How does iron get into the duodenal epithelial cells?
active transport
34
Once in the duodenal epithelial cells, what is the iron incorporated into?
- Ferritin ( protein-iron complex)
| - storage
35
What is Ferritin?
- Protein iron complex
- storage form of iron
- in the liver
36
What does iron absorption depend on?
body's iron content
37
What happens when the body has plenty of iron in the blood?
- increased concentration of iron causes increased transcription of ferritin
- increased binding of Fe in the intestinal epithelial cells and a reduction of iron in the blood
38
What happens when the body has low levels of iron in the blood?
the production of intestinal ferritin
decreases resulting in a decrease in the amount of iron bound to ferritin thus
increasing the unbound iron released into the blood
39
What is the function of transferrin?
It transports free iron in the plasma to bone marrow. Iron is then incorporated into new RBC.
40
Which cells in the liver store the most iron?
liver ferritin within Kupffer cells
41
What kinds of proteins does the liver synthesise?
1. Plasma proteins.
2. Clotting factors.
3. Complement factors.
42
Give 2 functions of albumin.
1. Maintains capillary oncotic pressure.
| 2. Binds and transports H2O insoluble compounds.
43
What are the main functions of Albumin?
1. Maintains capillary oncotic pressure.
| 2. Allows binding and transport of large hydrophobic compounds e.g. bilirubin, hormones, fatty acids.
44
Why might liver failure result in oedema?
Liver failure may mean less albumin is produced and so you get hypoalbuminaemia. This means the capillary oncotic pressure is reduced and H2O accumulates in the interstitial space - oedema.
45
Where does amino acid degradation occur?
liver hepatocytes
46
Name two main catabolism processes in amino acid degradation
oxidative deamination & transamination
47
What is transamination?
The transfer of an alpha-amino group from an amino acid to a keto-acid.
48
What enzymes catalyse transamination and where are they found?
Aminotransferases, found in the cytosol and mitochondria.
49
What are the products of transamination?
An alpha-keto acid that can go on to the krebs cycle, and glutamate.
50
What is oxidative deamination?
Amino acid catabolism that results in the liberation of the amino group as free ammonia.
51
What is the catalyst in oxidative deamination?
Glutamate dehydrogenase.
52
Where does the ammonia from oxidative deamination go on to?
The urea cycle.
53
What are the consequences of being deficient in the enzymes required for the urea cycle?
NH3 levels would rise and would cross the BBB easily. NH3 would react with alpha keto glutarate to be converted into glutamate meaning you have less alpha ketoglutarate and so the Krebs cycle would be unable to function. This leads to cell damage and neural cell death. due to decreased ATP
54
Glucose-alanine cycle: What reactions take place in muscle?
Glucose is converted to pyruvate via glycolysis. Pyruvate is then converted into alanine via transamination (glutamate -> alpha ketogluterate).
55
What is anabolic nitrogen balance?
A positive balance; nitrogen intake is greater than nitrogen loss.
56
What is nitrogen balance?
A measure of the equilibrium of protein turnover; nitrogen balance = nitrogen intake - nitrogen loss.
5
57
What is catabolic nitrogen balance?
A negative balance; nitrogen loss is greater than intake.
58
Draw the glucose alanine cycle
-
59
What is the glucose-alanine cycle?
A series of reactions in which amino groups and carbons from muscle are transported to the liver.
- gluconeogenesis
- krebs/glycolysis
60
Glucose-alanine cycle: What reactions take place in muscle?
Glucose is converted to pyruvate via glycolysis. Pyruvate is then converted into alanine via transamination (glutamate -> alpha ketogluterate).
61
Glucose-alanine cycle: What reactions take place in the liver?
Alanine is converted to pyruvate via oxidative deamination. NH3 from this reaction goes on to the urea cycle. The pyruvate is converted into glucose via gluconeogenesis.
62
Glucose-Alanine cycle: what is the process by which glucose gets converted into pyruvate in muscle?
Glycolysis.
63
Glucose-Alanine cycle: what is the process by which pyruvate gets converted into alanine in muscle?
Transamination.
64
Glucose-Alanine cycle: what is the process by which alanine gets converted into pyruvate in the liver?
Oxidative deamination.
65
Glucose-Alanine cycle: what is produced when alanine gets converted into pyruvate in the liver?
Ammonia which goes on to the urea cycle.
66
Glucose-Alanine cycle: what is the process by which pyruvate gets converted into glucose in the liver?
Gluconeogenesis.
67
What is gluconeogenesis?
Generating new molecules of glucose from non-carbohydrate precursors.
68
Where does the ammonia from oxidative deamination go on to?
The urea cycle.
69
Where does Arginine come from for the urea cycle?
Diet or protein breakdown.
70
What is the product(s) of the urea cycle?
urea
71
Briefly describe the urea cycle.
Arginine is converted to Ornithine and Urea is produced. Ornithine is converted into Citrulline using ammonia and CO2. Citrulline is converted into Arginine using ammonia.
72
Draw the urea cycle
-
73
What does 1 turn of the urea cycle consume?
3 ATP and 4 high energy nucleotides.
74
If you're deficient in the enzymes involved in the urea cycle what might happen?
Ammonia levels in the blood will increase.
75
Where are the enzymes found that are involved in the urea cycle?
mitochondria/cytosol of hepatocytes
76
What is the absorptive state of glucose regulation?
- Ingested nutrients are absorbed from the GI tract into the blood.
- Some nutrients are catabolised and used and the remainder are stored for future use.
77
What is the post-absorptive state of glucose regulation?
- Nutrients are no longer absorbed from the GI tract.
| - Nutrient stores must supply the energy requirements of the body.
78
Name 4 mechanisms of producing glucose in order to maintain blood glucose levels.
1. Glycogenolysis.
2. Gluconeogenesis.
3. Lipolysis.
4. Proteolysis.
79
What is the most common substrate for gluconeogensis?
Pyruvate.
80
How many ATP molecules are consumed per molecule of glucose formed in gluconeogenesis?
6.
81
Name 3 types of lipoprotein and state where they're formed.
1. HDL - formed in the liver.
2. LDL - formed in the plasma.
3. VLDL - synthesised in hepatocytes.
82
What is the function of lipoproteins?
To transport cholesterol through the blood.
83
What is the role of HDL?
Removes excess cholesterol from blood and tissues and secretes into bile/ converts into bile salts
84
What cholesterol is 'good cholesterol'?
HDL.
85
What is the role of LDL?
- formed in plasma
- deliver cholesterol to cells
- high LDL concentration associated with increased deposition of cholesterol in arterial walls
- essential in supplying cells with cholesterol
86
Where are VLDL's synthesised and what is their role?
synthesised in hepatocytes - carries triglycerides from glucose in liver
to adipocytes
87
Briefly describe the mechanism of fat catabolism?
- CoA binds to the end of a fatty acid chain: fatty acyl CoA.
- ATP -> AMP + 2Pi.
- Fatty acyl CoA is a substrate for beta-oxidation.
- Acetyl CoA is split off from FA and 2H+ are transferred to coenzymes.
- H+ enter OP and another CoA attaches to repeat the cycle.
88
What is the function of lipoprotein lipase?
Hydrolyses triglycerides in lipoproteins (chylomicrons & VLDLs) into 3 fatty acids and glycerol.
89
What is the function of hepatic lipase?
It is expressed in the liver and adrenal glands. It converts IDL (intermediate density lipoprotein) into LDL.
90
What is the role of the gallbladder
To store and concentrate the bile
91
What structure lies at the junction between the right mid-clavicular line and the right costal margin?
Gallbladder
92
What structures are found at the porta hepatis?
The portal triad - common hepatic duct, hepatic artery and the hepatic portal vein. Nerves and lymph vessels too.
93
What structure lies most anterior in the portal triad and which most posterior?
The common hepatic duct lies the most anteriorly. The hepatic portal vein is the most posterior (DAV).
94
what structure is in the middle of the hepatic lobule
central vein
95
What are sinusoids and where are they found?
They are specialised blood vessels - fenestrated
- in between hepatocytes
- carry oxygen rich blood from hepatic artery and nutrient rich blood from portal vein
96
What separates the hepatocytes from the sinusoids?
Space of Disse
97
Name the blood supply of the liver and what proportion of blood supply so they deliver?
Hepatic artery - 20%
| Hepatic portal vein - 80%
98
What are sinusoidal macrophages called?
Kupffer cells.
99
Where can stellate cells be found and what is their supposed function?
Space of Disse
| - production of extracellular matrix
100
Where is vitamin A stored? How long can stores last?
Stored in Ito cells in space of Disse. The stores can prevent deficiency for 10 months.
101
Where are Ito cells located?
In the space of Disse.
| Vit D storage
102
Describe the pathway of bile into the GI tract
- bile ducts in hepatic lobules
- Right or left hepatic duct
- common hepatic duct
- cystic duct joins the common hepatic duct allowing bile to enter gall bladder
- common bile duct
- pancreatic duct joins the common bile duct at the ampulla of vater
- enter the 2nd part of dudodenum
- major duodenal papillae
- surrounded by sphincter of Oddi
103
Name 5 components of bile
- Bile salts
- Phospholipids
- cholesterol
- bile pigments
- bicarbonate
104
Why are bile salts, cholesterol and phospholipids stored in mixed micelles in the gallbladder?
- to reduce damage (as they act as detergents) until they are needed
105
What hormones stimulate HCO3- and enzyme secretion?
1. Secretin induces the release of HCO3-.
| 2. CCK induces the release of enzymes.
106
What stimulates CCK?
presence of amino acids and fatty acids
107
What does CCK induce?
Gall bladder contraction and the release of bile. The sphincter of Oddi opens.
- release of pancreatic enzymes
108
What circulation returns bile salts to the liver?
Enterohepatic.
109
How much bile salts do not get recycled?
5% - lost in stool
| liver synthesis more from cholesterol
110
Where and how are bile salts reabsorbed?
- Terminal ileum
| - Na+ coupled transporters
111
What is bile synthesised from?
Cholesterol
112
Cholesterol is insoluble in water, how is it soluble in bile?
incorporation into micelles whereas in blood cholesterol is incorporated into lipoproteins
113
Describe the steps of bilirubin metabolism
1) Haemoglobin is broken down into haem and globin
2) globin is broken down into amino acids used to generate new erythrocytes
3) Haem is broken under the action of hemoxygenase into biliverdin, Fe2+ and CO
4) Fe2+ binds to transferrin and shuttled to bone marrow, incorporated into new erythrocytes
5) biliverdin is reduced under the action of biliverdin reductase into unconjugated bilirubin
6) unconjugated biliverdin is insoluble and toxic
7) bound to albumin and transported to liver
8) glucuronidation occurs : UDP Glucuronyl Transferase: Conjugated bilirubin
114
Describe the steps involved in the recycling of conjugated bilirubin
1) conjugated bilirubin travels to the small intestine until the ileum
2) intestinal bacteria in terminal ileum reduce through a hydrolysis reaction (glucuronic acid removed) forming urobilinogen
3) urobilinogen is lipid soluble around 10% reabsorbed into blood
4) bound to albumin and back to liver, urobilinogen is oxidised into urobilin
5) either recycled into bile or excreted by kidneys - gives urine yellowish colour
6) remaining 90% of urobilinogen is oxidised by different intestinal bacteria to form stercobilin
7) stercobilin is excreted in faeces responsible for brown colour
115
What enzyme converts biliverdin to unconjugated bilirubin.
Biliverdin reductase.
116
What is the function of glucuronosyltransferase?
It transfers glucuronic acid to unconjugated bilirubin to form conjugated bilirubin.
117
What protein does unconjugated bilirubin bind to and why?
- Albumin.
| - It isn't H2O soluble therefore it binds to albumin so it can travel in the blood to the liver.
118
What does conjugated bilirubin form?
Urobilinogen.
119
What is responsible for the conversion of conjugated bilirubin into urobilinogen?
Intestinal bacteria.
120
What can urobilinogen form?
1. It can go back to the liver via the enterohepatic system.
2. It can go to the kidneys forming urinary urobilin.
3. It can form stercobilin which is excreted in the faeces.
121
What is Jaundice?
A yellow discolouration of the skin caused by a high serum bilirubin level
122
in obstructive jaundice where would gallstones be located?
In the common bile duct.
123
What is pre-hepatic jaundice?
When a condition or infection speeds up the breakdown of red blood cells. This causes bilirubin levels in the blood to increase, triggering jaundice.
124
What conditions can cause pre-hepatic jaundice?
Malaria, sickle-cell anaemia, thalassaemia.
125
What is intra-hepatic jaundice?
When there is a problem in the liver – for example, damage due to infection or alcohol, this disrupts the liver’s ability to process bilirubin.
126
What can cause intra-hepatic jaundice?
HepatitisA/B/C, alcoholic liver disease, Gilbert's syndrome, drug misuse.
127
What is Gilbert's syndrome?
A genetic syndrome where the liver has problems breaking down bilirubin at a normal rate. The conjugated bilirubin is normal but the unconjugated bilirubin levels will be elevated.
128
What is post-hepatic jaundice?
When the bile duct system is damaged, inflamed or obstructed, which results in the gallbladder being unable to move bile into the digestive system.
129
What can cause post-hepatic jaundice?
Gall stones, pancreatic cancer, gallbladder cancer, pancreatitis.
130
Why do gallstones form?
Concentration of phosphate becomes too high in relation to other molecules and cholesterol crystallises out of solution
131
Name the five areas of the pancreas
- Uncinate process
- head
- neck
- body
- tail
132
Which parts of the pancreas are retroperitoneal and which part is intraperitoneal
Tail is intraperitoneal and the rest of the pancreas is retroperitoneal
133
Why are the SMA and SMV trapped between the head, neck and uncinate process of the pancreas?
Because the ventral bud rotates posteriorly behind the duodenum to fuse with the dorsal bud trapping the vessels in between.
134
Which artery runs in very close proximity to the duodenum
Gastroduodenal arteries
135
Pancreas development: What does the dorsal bud go on to form?
Neck, body and tail.
136
Pancreas development: What does the ventral bud go on to form?
The head and uncinate process.
137
Where does the pancreas receive its main blood supply from?
Coeliac trunk
138
What does the exocrine pancreas secrete?
- HCO3- (bicarbonate)
| - Digestive enzymes
139
Exocrine pancreas: what is secreted in the buffer phase? What is its function?
HCO3- rich secretion. This protects the duodenal mucosa from gastric acid and buffers material entering the duodenum to a suitable pH for enzyme action.
140
Which enterogastrone stimulates HCO3- release?
secretin
141
Which enterogastrone is responsible for bile secretion and exocrine enzyme secretion?
CCK
142
What affect do secretin and CCK have on the stomach?
- inhibit acid secretion - through inhibiting G cells and causing release of somatostatin
- reduce gastric motility
143
Briefly describe the mechanism of HCO3- secretion.
HCO3- is exchanged for Cl- at the luminal membrane, Cl- moves back out of cell through CFTR channels. H+ is then secreted into blood through H+/Na+ exchanger, then sodium pumped out via Na+/K+ ATPase and then potassium leaves via channel protein on basolateral surface .
HCO3- and H+ come from dissociation of carbonic acid which arise form products of respiration
144
What hormone inhibits pancreatic exocrine secretion?
somatostatin
145
where is somatostatin produced in the pancreas?
islets of Langerhans D cells
146
Name three cells and what they each produce in the islets of Langerhans?
* Alpha cells - produce glucagon
* Beta cells - produce insulin & amylin
* Delta/D cells - produce somatostatin
147
What affect does the parasympathetic vagus nerve have on the acinar cells in pancreas?
stimulation of acinar cells to produce digestive
enzymes
- ready for release through the sphincter of Oddi
148
What layers of the trilaminar disc is the primitive gut derived?
- Endoderm (epithelial lining, hepatocytes of liver & endocrine and
exocrine cells of pancreas)
- visceral mesoderm (muscle & connective
tissue)
149
Describe the boundaries of the foregut, midgut and hindgut of the primitive gut
Foregut - oropharyngeal membrane to liver bud
midgut - Liver bud —> 2/3rds traverse colon
hindgut - 2/3rds transverse colon —> cloacal membrane
150
What week does the liver bud form?
Week 3.
151
What is the liver bud?
An endodermal outgrowth from the distal part of the foregut.
152
What part of the gut has dorsal and ventral mesentery?
Forgeut.
153
When does bile production start?
12th week
154
What does the liver divide the ventral mesentery into?
lesser omentum and falciform ligament
155
What does the left umbilical vein become after birth?
ligamentum teres
156
what does the ductus venosus become after birth
ligamentum venosus
157
define intraperitoneal
Double layer of peritoneum that
| completely surrounds the organ
158
define retroperitoneal
The organ is only covered by the
| peritoneum on its anterior side
159
which part of the gut only has dorsal mesentry?
midgut&hindgut
160
When does insulin secretion begin
5th month
161
In which abdominal regions does the liver lie?
Right hypochondriac region, epigastric, extends slightly into left hypochondriac region.
162
What ligament divides the liver into anatomical left and right lobes?
Falciform ligament
163
What structures surround the caudate lobe?
IVC and a fossa created by the ligamentum venosum.
164
Where is the caudate lobe located?
Visceral surface of right lobe, upper aspect.
165
What structures surround the quadrate lobe?
The gall bladder and a fossa created by the ligamentum teres.
166
What structure gives the impression on the visceral surface of the left lobe?
It is the gastric impression, so the stomach.
167
What 2 impressions are there on the visceral surface of the right lobe?
The renal impression from the right kidney and the hepatic impression from the hepatic flexure.
168
What nerves innervate the liver?
Parasympathetic and sympathetic stimulation comes from the celiac plexus. The anterior vagal trunk also gives rise to a hepatic branch.
169
Why are complement factors important?
They form an important part of the immune system that responds to pathogens.
170
What are the fat soluble vitamins?
ADEK
171
How long can liver storage of vitamin D last?
3-4 months
172
What is the function of vitamin D?
Increases calcium reabsorption from the intestinal tract
173
What is the function of vitamin K?
production of clotting factors - 1972
174
What is the importance of glycogen stores?
Storage form of glucose. Ensures blood glucose levels are maintained.
175
What is the second phase of pancreatic secretion?
The enzyme rich phase.
176
What is the epithelium lining of the biliary tree?
Simple cuboidal epithelium.
177
What ducts terminate at the ampulla of Vater?
The pancreatic duct and the common bile duct.
178
At what pH are pharmacologically active compounds non-ionised?
7.4
179
Which type of enzymes can have their activity induced or inhibited?
Microsomal enzymes.
180
In starvation why is it important that amino acids are formed from skeletal muscle degradation?
The amino acids can be used in gluconeogenesis to produce glucose.
181
What must be removed for amino acids to undergo catabolism?
The alpha-amino group.
182
What are the products of oxidative deamination?
- An alpha-keto acid -> krebs cycle
| - Ammonia -> urea cycle.
183
What is the only amino acid to undergo rapid oxidative deamination?
Glutamate.
184
What is the function of vitamin A?
- Vision.
- Lymphocyte production.
- Growth and reproduction.
- Maintains mucous membranes.
185
What is the effect on the efficacy of a drug if microsomal enzymes are induced?
The efficacy of the drug will reduce because the inducer will cause increased metabolism by microsomal enzymes.
186
What is needed for intestinal absorption of vitamin K?
Bile salts - without these clotting factor production will be affected.
187
What cells in the spleen are responsible for RBC break down?
Reticuloendothelial cells.
188
What is the importance of the hepatocyte canalicular surface?
Permits the excretion of bile.
are bound together by tight junctions, gap junctions &
desmosomes which cross both cell membranes.
189
What is the purpose of conjugating bilirubin?
It increases its water solubility for excretion.
190
What is the affect on conjugated and unconjugated bilirubin levels in someone with intrahepatic jaundice?
Increased unconjugated and normal conjugated.
191
What is the affect on conjugated and unconjugated bilirubin levels in someone with pre-hepatic jaundice?
Unconjugated is elevated and conjugated is slightly raised too. You also get slightly raised urobilinogen.
192
What is the affect on conjugated and unconjugated bilirubin levels in someone with post-hepatic jaundice?
Conjugated is elevated and unconjugated is normal. Urobilinogen is decreased/absent.
Urinary bilirubin will be raised.
193
What is the affect on the urine and stools in a patient with post-hepatic jaundice?
Urine will be dark and the stools will be pale.
194
What is the affect on the urine and stools in a patient with intra-hepatic jaundice?
Urine will be dark and stools will be normal or slightly paler.
195
What is the affect on the urine and stools in a patient with pre-hepatic jaundice?
Both normal.
