Week 2 GI Lectures Flashcards
1
Q
Where is bile generated and stored?
A
Generated in the liver
Stored in the gallbladder
2
Q
What are the components of bile?
A
Bicarbonate cholesterol phospholipids bile pigments bile salts
3
Q
What is the lifespan of a RBC?
A
120days
4
Q
What is the daily turnover of Hb?
A
6g/day
5
Q
what are the globin monomers from Hb broken down to?
A
To their constituent amino acids and recycled
6
Q
What is the porphyrin ring converted to?
A
Bilirubin
7
Q
What is converted into bilirubin?
A
The porphyrin ring
8
Q
Why is the porphyrin ring converted to bilirubin?
A
For transport to the liver for modification and excretion
9
Q
What changes haem into biliverdin?
A
Haem oxygenase
10
Q
What are the different stages before the final product of bilirubin is made?
A
Haem –> biliverdin –> unconjugated bilirubin –> conjugated bilirubin
11
Q
How is biliverdin changed into bilirubin?
A
Biliverdin reductase
12
Q
What colour is bilirubin?
A
An orange/ yellow pigment
13
Q
What is responsible for conjugating bilirubin?
A
UDP Glucuronyl transferase
14
Q
What happens when bilirubin become conjugated?
A
It becomes hydrophilic
15
Q
What are the three things that U-bilirubin can turn into?
A
Mesobilinogen
Stercobilinogen
Urobilinogen
16
Q
What does Mesobilinogen turn into and how?
A
Intestinal microflora in the large intestine turns it into mesobilin
17
Q
What does Stercobilinogen
turn into and how?
A
Intestinal microflora in the large intestine turns it into stercobilin
18
Q
What does Urobilinogen turn into and how?
A
Intestinal microflora in the large intestine turns it into Urobilin
19
Q
Why are bile salts/acids required?
A
Oil and water don’t mix so they act as biological emulsifiers
20
Q
What is emulsification?
A
The breakdown of large lipid droplets into small uniformly distributed droplets (1mm or 1000nm) that helps lipase break down triglyceride
21
Q
What does the hydrophobic portion of bile salts/acid bind to?
A
It binds to and disperses large triglyceride lipid droplets
22
Q
What does the hydrophobic portion of bile salts/acid prevent?
A
Prevents large droplets reforming
23
Q
What are the lipid soluble vitamins?
A
A
D
E
K
24
Q
What are micelles?
A
Very small lipid aggregates with hydrophilic (polar) head groups on the outside and hydrophobic (non-polar) tails pointing in
25
What are micelles made up of?
Bile salts, fatty acids, monoglycerides, phospholipids, cholesterol and fat soluble vitamins
26
What happens when micelles constantly break down and reform?
The contents are released each time and some diffuse across the intestinal lining
27
Where do TAGs reform?
They reform in epithelial cells and are packaged into chylomicrons which enter the blood via the lymph
28
Where do the bile salts emulsify the fat globules?
In the intestines
29
What does the digestion of the emulsion droplets by lipases form?
Free fatty acids (monoglycerides) and bile salts
30
What do the bile salts do to free fatty acids (Monoglycerides)?
Form micelles
31
What do absorbed free fatty acids form?
Triglycerides
32
What are the free fatty acids that are absorbed and formed into triglycerides packaged into?
Packaged into chylomicrons for secretion in lacteals
33
Is the sphincter of Oddi contracted or relaxed during the Interdigestive period?
Contracted
34
What is the Interdigestive period?
The time between meals
35
What is the sphincter of Oddi?
A muscular valve that controls the flow of bile and pancreatic fluid into the duodenum
36
How is bile concentrated?
Epithelial cells reabsorb water and electrolytes
37
What does fatty acids and amino acids entering the duodenum after a meal stimulate?
Enteroendocrine cells to release CCK
38
What does CCK stimulate?
Contraction of the gallbladder smooth muscle and relaxation of the sphincter of Oddi
39
What does acidic chyme in the duodenum stimulate?
Release of secretin fron endocrine cells
40
What does secretin do?
Stimulates duct cells in the liver to release bicarbonate into the bile which neutralises acid and stimulates bile production
41
Why do bile salts need to be recycled by the enterohepatic circulation?
Bile salts in the body are not enough to fully process the fats in a typical meal
42
Where do transporters move bile salts?
From the digestive tract to the intestinal capillaries
43
Where do bile salts go after they reach intestinal capillaries?
Transported to the liver via the hepatic portal vein
44
What takes up the bile salts from the blood?
Hepatocytes
45
What is hyperbilirubinaemia?
Too much bilirubin in the blood
46
What is jaundice?
Yellowing that is most common in the eyes and sometimes the skin caused by elevated levels of bilirubin
47
What level of total bilirubin may jaundice be visible in the sclera?
over 30mmol/L
48
What level of total bilirubin may jaundice be visible in the skin?
Over 100 mmol/L
49
What is prehepatic jaundice?
Jaundice with the cause before the liver (elevated haemolysis)
50
What is hepatic jaundice?
The cause of the jaundice is in the liver (liver damage)
51
What is post hepatic jaundice?
The cause of the jaundice is after the liver (blockage of bile ducts)
52
What can be used to distinguish between groupings?
Proportion of unconjugated: conjugated bilirubin
53
What can cause pre-hepatic jaundice?
- tropical diseases e.g. yellow fever
- side effect of quinine based anit-malarial drugs
- genetic disorders that aare associated with increased haemolysis (e.g. sickle cell)
54
Why does pre-hepatic jaundice happen?
More RBC breakdown
More haemoglobin
More bilirubin produced (unconjugated bilirubin)
55
What is neonatal jaundice?
common and usually harmless jaundice of new-born babies
56
What causes neonatal jaundice?
- After birth, new-borns must destroy foetal haemoglobin and replace with adult haemoglobin, RBCs have short lifespan
- Undeveloped liver (with lack of glucuronyl transferase) has insufficient capacity to cope with elevated haemolysis
- Inhibitors of conjugation in breast milk
- Bilirubin peaks at 3-5 days and lasts < 14 days
57
How is neonatal jaundice treated?
phototherapy - blue light changes unconjugated bilirubin to a water soluble form that can be excreted
58
What organ takes up unconjugated bilirubin?
The liver takes up unconjugated bilirubin, conjugates it and exports it to the gall bladder
59
What are the three problems that can cause hepatic jaundice?
- impaired uptake of unconjugated bilirubin
- impaired conjugation of bilirubin
- Impaired transport of conjugated bilirubin into bile canaliculi
60
What causes post hepatic jaundice?
Conditions associated with obstruction of hepatic, cystic or common bile duct - prevention of bile being released into the small intestine (cholestasis)
61
What does the severity of gallstone symptoms depend on?
Their location and size, they become increasingly problematic when gallbladder contractions cause stones to move further along the bile ducts
62
What are the symptoms of gallstones in the cystic bile duct?
Painful contractions
63
What are the symptoms of gallstones in the common bile duct?
Steatorrhea, grey faeces, post hepatic jaundice
64
What are the symptoms of gallstones in the Duodenal papilla?
Malnutrition, acute pancreatitis
65
What is the duodenal papilla?
Opening of the pancreatic duct into the duodenum, surrounded by the sphincter of Oddi
66
What is vitamin K required for?
Efficient coagulation
67
What is GGCX?
g-glutamyl carboxylase
68
What is GGCX required for?
To make active coagulation factors II VII IX and X
69
What is the plasma unconjugated bilirubin like in prehepatic jaundice?
Very high
70
What is the plasma unconjugated bilirubin like in hepatic jaundice?
A bit high
71
What is the plasma unconjugated bilirubin like in post hepatic jaundice?
Normal
72
What is plasma conjugated bilirubin like in pre-hepatic jaundice?
Normal or a bit high
73
What is plasma conjugated bilirubin like in hepatic jaundice?
Moderately raised
74
What is plasma conjugated bilirubin like in post hepatic jaundice?
very high
75
What is the urine conjugated bilirubin like in pre-hepatic jaundice?
Normal (absent)
76
What is the urine conjugated bilirubin like in hepatic jaundice?
Slightly raised
77
What is the urine conjugated bilirubin like in post-hepatic jaundice?
Moderately raised
78
What is the urine urobilinogen/urobilin like in post-hepatic jaundice?
absent
79
What is the urine urobilinogen/urobilin like in hepatic jaundice?
Slightly raised
80
What is the urine urobilinogen/urobilin like in pre-hepatic jaundice?
Slightly raised
81
What is the stercobilin in the faeces like in pre-hepatic jaundice?
Slightly raised
82
What is the stercobilin in the faeces like in hepatic jaundice?
normal
83
What is the stercobilin in the faeces like in post-hepatic jaundice?
Absent
84
What are the steps for measuring direct (conjugated) bilirubin?
1. Add diazo reagent to serum.
2. Conjugated bilirubin converted to blue/purple diazo derivative of bilirubin (Azobilirubin).
- NB unconjugated bilirubin bound to albumin as not water soluble so does not react with diazo reagent
3. Measurement of absorbance @ 530-545 nm proportional to conjugated bilirubin (not unconjugated).
4. Compare to known standards to calculate concentration
85
What are the steps for measuring total bilirubin?
1. Add diazo reagent with caffeine to serum.
2. Caffeine displaces unconjugated bilirubin from albumin.
- Free unconjugated bilirubin can now react with the diazo reagent
3. Both conjugated and unconjugated bilirubin converted to blue/purple diazo derivative of bilirubin (Azobilirubin).
4. Measurement of absorbance @ 530-545 nm proportional to BOTH conjugated and unconjugated bilirubin
5. Compare to known standards to calculate concentration
86
Is bile pigment measured in faeces?
No - a waste of time/money and visual inspection is easy
87
Summarise the three types of jaundice
```
Pre-hepatic = due to elevated haemolysis e.g. Neonatal jaundice
Hepatic = conditions associated with liver damage e.g Hepatitis
Post-hepatic = blockage in bile release into the intestines e.g Gallstones
```
88
What are the two areas of the GI tract under voluntary control?
Upper oesophageal sphincter and the external anal sphincter
89
What does contraction of the longitudinal muscle allow for?
Shortening of the intestine
90
What are the interstitial cells of cajal?
Cells that have an intrinsic pacemaker function that helps regulate muscular function
91
Which neurotransmitter does the gut muscle not respond well to?
Ach
92
What is the function of the enteric nervous system?
Mediates reflex activity in the absence of CNS input (interprandial period)
93
What extrinsic factors is the enteric nervous system influenced by?
Vagal control and sympathetic control
94
What effect does the influence of vagal control have on the enteric nervous system?
It is excitatory to non-sphincteric muscle
95
What effect does the influence of sympathetic control have on the enteric nervous system?
Inhibitory to non-sphincteric muscle
| Excitatory to sphincteric muscle
96
What are the neurohormonal influences on the enteric nervous system?
Motilin, 5 hydroxy-tryptamine and opioid receptors
97
How is motility function measured in the GI tract?
Pressure (circular muscle function) - catheters used to measure how much pressure muscles exert when the muscle is contracted
Transit - radiolabelled isotopes and dynamic contrast radiology used
98
Where is the sympathetic innervation of the oesophagus from?
The sympathetic trunk
99
Where is the parasympathetic innervation of the oesophagus from?
The vagus nerve
100
Is the upper part of the oesophagus circular or longitudinal muscle?
Circular
101
Is the lower part of the oesophagus circular or longitudinal muscle?
Longitudinal
102
How is a HRM trace information gathered?
A catheter is placed into the nose and all the way down into the stomach. Low pressure shows as blue and high shows as purple
103
Where on a HRM trace should there be tonic pressure?
At the upper and lower oesophageal sphincters. These are shown at the top and bottom of the graph respectively
104
What are examples of oesophageal motility?
- Achalasia
- Nutcracker/jackhammer oesophagus
- Diffuse oesophageal spasm
- Oesophageal involvement in scleroderma
105
What is achalasia?
The lower oesophageal sphincter doesn't relax and always stays contracted meaning food can't get through
106
What is a key feature of a barium swallow of a patient with achalasia?
The oesophagus has a birds beak at the end at the lower oesophageal sphincter and the oesophagus is dilated
107
What are the treatment options for achalasia?
- Rigiflex balloon dilatation
- Laparoscopic Heller's myotomy
- POEM
108
What is a laparoscopic Heller's myotomy?
A cut is made in the outer layer of muscle which changes the pressure at the sphincter
109
What is a POEM?
Per Oral Endoscopic Myotomy - cut in the mucosa to reach the muscle layer then cut this and seal mucosa back up
110
What happens to the oesophagus in scleroderma?
Weak lower oesophageal sphincter with absent peristalsis and severe oesophagitis
111
What is nutcracker oesophagus?
It is associated with pain on swallowing. There are no evident therapies.
The patient has a functional swallow and benign prognosis
112
What is diffuse oesophageal spasm?
Very rapid contractions of the oesophagus. Very rare condition
113
What is the migrating motor complex?
A cyclic contraction sequence that occurs every 90 minutes
114
What are the 4 phases of the migrating motor complex?
i) Prolonged period of quiescence
ii) Increased frequency of contractility
iii) A few minutes of peak electrical and mechanical activity
iv) Declining activity merging to next phase I
115
What regulates the migrating motor complex?
Motilin
116
What is the function of the migrating motor complex?
It acts to cleanse the stomach and intestine in between meals
117
What is motilin and where is it made?
Motilin is a polypeptide hormone that is produced by M cells in the small intestine. It is secreted in 90 minute intervals to stimulate the mmc
118
What acts as a motilin agonist?
Erythromycin
119
What are the three phases of meal related motility?
Cephalic
Gastric
Intestinal
120
What is the cephalic phase?
It is a vagally mediated secretory phase. The sight/ smell of food results in increased gastric secretion
121
What mediates the cephalic phase?
Vagus nerve
122
How much of gastric secretion occurs during the cephalic phase?
20%
123
What happens during the gastric phase?
proximal gastric tone reduces and the stomach expands without an increase in pressure
124
What is the MMC replaced by during the gastric phase?
contractions of variable amplitude and frequency, allowing mixing and digestion
125
What controls the frequency and direction of gastric muscular contractions?
Gastric pacemaker zone within the proximal gastric body
126
How does the Gastric pacemaker zone control the frequency and direction of gastric muscular contractions?
The pacemaker generates rhythmic depolarisations at a frequency of 3 cycles per minute which only trigger gastric smooth muscle contractions with additional neurohumoral input
127
What leaves the stomach first solids or liquids?
Liquids
128
What is the emptying time for inert liquids?
20 minutes
129
What size are digestible food particles when they leave the stomach?
2mm
130
How long do solids take to empty completely from the stomach?
3-4 hours
131
What happens at the start of gastric emptying of solids?
An initial lag phase in which little chyme is released to the duodenum
132
What are disorders of gastric emptying?
- Accelerated gastric emptying (dumping syndrome, diarrhoea)
| - Delayed gastric emptying (abdominal pain, vomiting, poorly controlled gastro-oesophageal reflux, malnutrition)
133
What is gastroparesis?
delayed gastric emptying
134
What causes gastroparesis?
- Idiopathic
- Longstanding diabetes with macrovascular disease
- drugs (opiates)
- post viral
135
What are the symptoms of gastroparesis?
- abdominal pain
- nausea and (often delayed) vomiting
- weight loss
136
How is gastroparesis managed (not medication)?
- dietary (small meals frequently, liquid food better than solid, nutritional support (post pyloric feeding))
- Attention to the underlying cause (limit use of trigger medication, post viral may improve with time, diabetes - improve diabetic control)
137
How is gastroparesis managed with medication?
```
- prokinetics
5HT4 agonists (cisapride, metoclopramide)
D2 antagonists (metoclopramide, doperidone)
Motilin agonist (erythromycin)
```
138
How can gastroparesis be managed surgically?
- endoscopically botulinum toxin is injected to the pyloric sphincter
- Gastric electrical stimulation - two electrodes on the stomach that release high frequency, low amplitude waves.
139
What provides motility in the small intestine during fasting conditions?
the MMC
140
What rate are solids and liquids transported in the small intestine?
The same rate but liquids reach the caecum faster because they are released from the stomach first
141
What are some disorders of small bowel transit?
- Chronic intestinal pseudo-obstruction
| - Acute post-operative ileus
142
What is chronic intestinal pseudo-obstruction?
signs of mechanical obstruction without mechanical occlusion
can be caused by either neuropathic or myopathic aetiology
143
What are symptoms of chronic intestinal pseudo-obstruction?
- chronic abdominal pain
- constipation
- vomiting
- weight loss
144
What is acute post-operative ileus?
Constipation and intolerance of oral intake in the absence of mechanical obstruction after a surgery.
145
How long does acute post-operative ileus last in different parts of the GI tract?
- small intestine - 0-24 hours
- stomach - 24-48 hours
- colon - 48-72 hours
146
What are risk factors for acute post-operative ileus?
- Open surgery (vs laparoscopic)
- Prolonged abdominal or pelvic surgery
- Delayed enteral nutrition
- Peri-operative complications
- Peri-operative opiate analgesia
147
What are two disorders of bowel transit?
- Acute colonic pseudo-obstruction (Ogilvie's syndrome)
| - chronic intestinal pseudo-obstruction
148
What is acute colonic pseudo-obstruction (Ogilvie's syndrome)?
A large bowel parasympathetic dysfunction that can occur after surgery, most commonly cardio or spinal surgery.
149
How is acute colonic pseudo-obstruction (Ogilvie's syndrome) managed?
- gut rest - IV fluids, nasogastric decompression
- IV neostigmine (acetylcholinesterase inhibitor)
- colonoscopic decompression
- surgery
150
What are myopathic causes of chronic intestinal pseudo-obstruction?
- scleroderma
| - amyloidosis
151
What is scleroderma?
A chronic autoimmune disorder that causes connective tissue in the body to harden
152
What is amyloidosis?
An abnormal protein called amyloid builds up in tissues and organs
153
What are neuropathic causes of chronic intestinal pseudo-obstruction?
Parkinson's disease
154
What are endocrine causes of chronic intestinal pseudo-obstruction?
- diabetes
| - severe hypothyroidism
155
What are drug related causes of chronic intestinal pseudo-obstruction?
- Phenothiazines
| - Anti- parkinsonian drugs
156
What is the management of chronic intestinal pseudo-obstruction?
- Nutritional - enteral and parenteral feeding
- Antibiotics for small bowel bacterial overgrowth
- in refractory cases, small bowel transplant
157
What is pacemaker activity like in the colon?
There is no typical pacemaker activity
158
What must the colon do?
- mix material without propulsion (for water absorption)
- act as a storage site
- cause aboral movement of contents
- expel faeces
159
How long are the contractions in the colon?
A mixture of short and long duration contractions
160
What happens to colonic activity in response to a meal?
There is a marked increase (gastrocolic reflex)
161
How long does transit from caecum to rectum take?
1-2 days
162
What are the taenia coli?
Three distinct strips of longitudinal muscle orientated at 120 degrees from each other in the proximal colon
163
What does the intermittent contraction of circular muscle create?
Segments in the colon known as Haustra
164
How is colonic transit measured?
Serial x-rays with radio-opaque markers
No markers left = normal transit
Markers in rectosigmoid = pelvic outlet obstruction
Markers scattered throughout = slow transit constipation
165
What drugs reduce colonic motility?
- opiates
- anticholinergics
- loperamide
166
What is loperamide?
A gut selective opiate mu receptor agonist. It decreases tone and activity of myenteric plexus.
This slows colonic transit leading to increased water absorption Used for symptomatic management of diarrhoea
167
What drugs increase colonic motility?
- Stimulant laxatives
- prucalopride
- linaclotide
168
What are stimulant laxatives?
Drugs that increase gut motility. They alter gut electrolyte transport.
They have short, dramatic effects
169
What is prucalopride?
A gut selective 5HT4 receptor agonist that increases gut motility
170
What is linaclotide?
A minimally absorbed guanylate C receptor agonist that increases secretion of chloride and HCO3 into the lumen
- -> increases intestinal fluid
- -> speeds colonic transit
171
What is the internal anal sphincter?
A smooth muscle sphincter that is under involuntary control. In resting conditions this provides greatest component of contraction
172
What can cause anal sphincter weakness?
- Muscle (sphincter) damage
| - Damage to the pudendal nerve
173
What can cause anorectal constipation?
- Hirschrung’s disease
- Obstructive defecation (paradoxical contraction of puborectalis and external sphincter during defecation)
- Rectocele
- Anal fissure (associated pain on defecation)
174
What is Hirschprung's disease?
Failure of the neural crest cells to the distal colon. The affected segment is aganglionic and contracted. The proximal colon is dilated
175
How is Hirschprung's disease managed?
Surgical resection of the affected colon
176
What happens if there is injury to T12 or above?
| IN TERMS OF THE COLON
- Reflex bowel
- Damage to upper motor neurones
- Reflex arc intact
- Tonic anal sphincter
- Bowel opens spontaneously but without control
- Reflex can be initiated by rectal stimulation (e.g. suppository)
177
What happens if there is injury to the sacral nerve roots?
| IN TERMS OF THE COLON
- Lower motor neurone injury
- “Flaccid bowel”
- No reflex arc
- Slow stool propulsion through colon
- Flaccid anal sphincter --> incontinence
- Management based on manual evacuation of stool
178
What does the conventional LFTs profile include?
- bilirubin
- albumin
- alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
- Alkaline phosphatase
- gamma glutamyl transferase (γ-GT)
- total protein
179
What are some reasons LFTs might be done?
- well person screening
- to investigate unexplained symptoms
- to investigate symptoms and signs suggestive of liver disease
- for pre-operative or baseline assessment
- to monitor the progress of established liver disease and assess the response to treatment
180
What is unconjugated hyperbilirubinaemia?
Indirect bilirubin is >85% of total bilirubin.
| Occurs with increased bilirubin production or defects in hepatic uptake or conjugation (e.g. gilberts disease)
181
What is conjugated hyperbilirubinaemia?
Occurs in inherited or acquired defects in hepatic excretin.
| Direct bilirubin is >50% of total bilirubin
182
What does AST stand for?
Aspartate
183
What does ALT stand for?
Aminotransferase
184
What are the two aminotransferases?
AST and ALT
185
What is the function of AST and ALT?
They take part in gluconeogenesis by catalysing the transfer of amino groups from aspartic acid or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid respectively
186
What do the levels of AST and ALT in LFTs show?
They are markers of hepatocellular injury
187
What is AST (sGOT)?
Glutamate oxalo-acetate transaminase
This is present in cytosolic and mitochondrial isoenzymes.
It is found in in liver, cardiac and skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes and red cells.
It is less specific/sensitive for the liver
188
What Is the plasma half life for AST (sGOT)?
48hours
189
What is ALT (sGPT)?
Glutamate pyruvate transaminase is a cytosolic enzyme with similar tissue distribution as AST but the activity in extra hepatic tissues is much lower
190
What does an increase of ALT signify?
liver disease
191
What is the plasma half life of ALT (sGPT)?
18 hours
192
What is GGT?
y-glutamyl transferase is a microsomal enzyme that is present throughout the in liver, cardiac and skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes and red cells
193
What is the function of GGT?
the transfer of glutamyl groups from gamma-glutamyl peptides to other peptides or amino acids
194
What are the GGT results used for?
It has specificity for liver disease but useful to either identify raised ALP of liver origin or chronic alcohol consumption
195
When would plasma activity of GGT be raised?
Those with chronic liver disease will have higher plasma GGT activity than those without significant liver disease
196
What is ALP and what is its function?
Alkaline phosphatase
| Hydrolyses phosphate esters in alkaline solutions
197
Where is the liver derived isoenzyme of ALP found?
The exterior surface of the bile canalicular membrane
198
Where does the serum activity of ALP come from?
Mainly the liver and bone isoenzymes with some from intestinal (and placental during pregnancy)
199
What does prothrombin time measure?
the rate of conversion of prothrombin to thrombin and reflects a vital synthetic function of the liver
200
What are Kupffer cells?
macrophages in the liver that act as phagocytes
201
What are hepatocytes?
Cells that make up 70% of the volume of the liver. They are regenerative and perform the main functions of the liver
202
Where is zone 1 of the acinus?
Closest to the afferent arteriole (centre of the acinus)
203
What are the functions of zone 1 of the acinus?
- respiratory chain
- citric acid cycle
- fatty acid oxidation
- gluconeogenesis
- urea synthesis
- bile production
204
What is zone 2 of the acinus?
Ill defined area
205
Where is zone 3 of the acinus located?
Closer to the terminal hepatic veins (outside of the acinus)
206
What are the functions zone 3 of the acinus?
- glucolysis
- glutamine synthesis
- Xenobiotic metabolism
207
What is gluconeogenesis?
Synthesis of glucose from other sources, e.g. lactate, pyruvate, glycerol and alanine
208
What are the products fatty acids can be turned into?
- Cholesterol -->steroids
- prostaglandins
- Phospholipids
- Glycolipids
209
What is nitrogen converted to in the liver?
Converted into urea and then excreted by the kidneys
210
What is biotransformation and excretion?
A process used for detoxification but can generate toxic or carcinogenic metabolites
211
What are the 2 phases of reaction in biotransformation and excretion?
- phase 1 reactions in the smooth endoplasmic reticulum mediated by cytochrome P450 to produce hydroxylated or carboxylated compounds
- Phase 2 reactions: subsequent conjugation with glucuronic acid, acetyl or methyl radicals or glycine, taurine or sulphate
212
What happens to urobilinogen that is created by intestinal bacteria from conjugated bilirubin?
- 80% - oxidised to stercobilin and excreted in faeces (giving stool its brown colour)
- 20% - recycled - absorbed by extra-hepatic circulation to be recycled through liver and re-excreted --> enters systemic circulation to be filtered by kidney and excreted in urine
213
What different types of metabolic disorder of the liver can you get?
- of amino acid metabolism
- of bile acid synthesis and metabolism
- of carbohydrate metabolism
- of bile flow and excretion
- of mitochondrial function
- of peroxisomal function
- of copper metabolism
214
What types of mitochondrial damage can you get?
- Inhibition of beta oxygenation of fatty acids
- -> Leads to micro-vesicular steatosis
- Interference with oxidative phosphorylation
- -> Leads to insufficient ATP generation
- Impairment of the respiratory chain
- -> Leads to excess ROS with lipid peroxidation
- Increase in permeability transition
- -> Leads to apoptosis
215
What are different types of metabolic dysfunction within the liver?
- essential product deficit – e.g. G-6-P deficiency (glycogen storage I)
- precursor accumulation – e.g. OTC deficiency (hyperammonaemia)
- Alternative pathway activation – e.g. amino-acidopathy
- Combinations of above
216
What are different consequences of toxic damage to the liver?
```
- Mitochondrial damage
Drugs (antivirals, salicylate, valproate, tetracycline)
Toxins (hypoglycin, atractyloside)
- Endothelial damage to hepatic veins
Drugs (cytotoxic drugs)
Toxins (Senecio, aflatoxin, pyrrolizidine)
- Glutathione depletion and cell death
Drugs (paracetamol)
Hypoxic ischaemia
```
217
What are mechanisms of centrilobular necrosis?
- Sepsis
- shock induced ischaemia
- congestive heart failure
- toxicity from drugs and poisons
218
What are clinical patterns of metabolic disease involving the liver?
- New-born acute metabolic crisis - mimics sepsis
- Severe vomiting and failure to thrive
- Recurrent episodes of vomiting and encephalopathy with acidosis
- Progressive retardation or seizures with hepatomegaly
- Hepatomegaly with/without jaundice and failure to thrive/grow normally
