GI Flashcards
(342 cards)
1
Q
How is swallowing initiated?
A
When pressure receptors in the wall of the pharynx are stimulated by food or drink, and forced into the rear of the mouth by the tongue
2
Q
What is the nervous supply to the nasopharynx?
A
Maxillary nerve (V2- second branch of trigeminal nerve V)
3
Q
What is the nervous supply to the oropharynx?
A
Glossopharyngeal nerve (IX)
4
Q
What is the nervous supply to the laryngopharynx?
A
Vagus nerve X
5
Q
What muscles manipulate food during chewing and elevate the hyoid bone?
A
The buccinator and supra hyoid
6
Q
How is the pharynx shortened and widened during swallowing?
A
Elevation of the hyoid bone via actions of the muscles of the floor of the palate
7
Q
How is food prevented from entering the trachea?
A
Impulses from the swallowing centre close the glottis. Food tilts the epiglottis over the closed glottis.
8
Q
What is the nervous supply to the pharyngeal constrictor muscles?
A
Vagus X
9
Q
Is the upper third of the oesophagus skeletal or smooth muscle?
A
Skeletal
10
Q
Is the lower two thirds of the oesophagus skeletal or smooth muscle?
A
Smooth
11
Q
What is the ring of skeletal muscle around the oesophagus just below the pharynx?
A
The upper oesophageal sphincter
12
Q
What is the ring of smooth muscle surrounding the oesophagus in the last portion of the oesophagus?
A
The lower oesophageal sphincter
13
Q
What is a peristaltic wave?
A
Waves of muscle contractions that proceed along the oesophagus, compressing the lumen and forcing the food ahead
14
Q
How long does one oesophageal peristaltic wave take to reach the stomach?
A
9 seconds
15
Q
What is the nervous supply that allows the gag reflex?
A
A reflex arc between the glossopharyngeal (IX) and Vagus (X) nerves
16
Q
What are the functions of saliva?
A
Lubricant for mastication
Maintaining oral pH (maintained at 7.4) by the bicarbonate/carbonate buffer system
Release digestive enzyme- salivary alpha amylase released from parotid gland
17
Q
What is the daily secretion of saliva?
A
800-1500 ml
18
Q
What is serous secretion?
A
Alpha amylase for starch digestion
19
Q
What is mucous secretion?
A
Mucins for lubrication of mucosal surfaces
20
Q
What secretion does parotid glands release?
A
Serous
21
Q
What secretion does submandibular glands secrete?
A
Mucous and serous
22
Q
What secretion does sublingual glands secrete?
A
Mucous and serous but mainly mucous
23
Q
What secretion does minor glands secrete?
A
Predominantly mucous but some serous
24
Q
What factors affect the composition and amount of saliva produced?
A
Flow rate Circadian rhythm Type and size of gland Duration and type of stimulus Diet Drugs Age Gender Time of day
25
What are the defences of the oral cavity provided by?
The mucosa
The salivary glands
Palatine tonsils
26
Which salivary glands are continuously active?
Submandibular, sublingual and minor glands
27
What are the epithelial tissues present in salivary glands?
Acinar Cells and ducts
28
What do the ducts do in salivary glands?
Collect to form the large cut entering the mouth. Equipped with channels and transporters in the apical and basolateral membranes enabling transport of fluid and electrolytes
29
What are the two types of acini?
Serous and mucous
30
What do serous acini secrete?
Water and alpha amylase
31
Where are serous acini mainly found?
Parotid glands
32
What do mucous acini secrete?
Mucous (water and glycoproteins)
33
Where are mucous acini found?
Submandibular and sublingual glands
34
What are the two types of intralobular ducts?
Intercalated and striated
35
Describe intercalated ducts
Short narrow duct segments with cuboidal cells that connect acini to larger striated ducts
36
Describe striated ducts
Striated like a thick lawn, and major site for reabsorption of NaCl. Appear striated at the basal end. Basal membrane is highly folded into microvilli for active transport of HCO3 against conc gradient.
37
What ions do ducts secrete?
K+ and HCO3-
38
What ions do ducts reabsorb?
Na+ and Cl-
39
Why is saliva hypotonic?
The epithelium of the ducts reabsorb water
40
How much of the salivary flow are from the major glands?
80%
41
Where are the minor saliva glands found?
The submucosa or oral mucosa of the lips, cheeks, hard and soft plate and the tongue
42
Where is the parotid gland?
Superficial triangular outline between the zygomatic arch, sternocleidomastoid and ramus of mandible
43
Where does the parotid gland enter the mouth?
Near the second upper molar
44
What is the sympathetic sensory innervation of the parotid gland?
Auriculo-temporal nerve which is a branch of the mandibular nerve
45
What is the parasympathetic innervation of the parotid gland?
Glossopharyngeal nerve (stimulates secretion)
46
What are the structures that pass through the parotid gland?
External carotid artery, retromandibular vein and facial nerve
47
What are the two lobes of the submandibular gland, and how are they seperated?
Seperated by the mylohyoid muscle, larger superficial lobe and a smaller deep lobe
48
Where does the submadibular gland empty into the oral cavity?
The sublingual papillae- under tongue
49
What is the parasympathetic innervation of the submandibular gland?
Chorda tympani branch of facial nerve VII
50
What is the sympathetic innervation of the submandibular gland?
Lingual nerve which is derived from the facial nerve VII
51
Where is the sublingual gland?
Located on the floor of the mouth between mylohyoid muscles and oral mucosa of the floor of the mouth
52
What is the parasympathetic innervation of the sublingual gland?
Chorda tympani branch of the facial nerve VII
53
What is the sympathetic innervation of the sublingual gland?
The lingual nerve which is derived from the facial nerve VII
54
Does sympathetic or parasympathetic stimulation inhibit salivary secretion in the minor glands?
Sympathetic
55
What is xerostomia?
Dry mouth
56
Where do salivary calculi (stones) normally form?
Submandibular gland
57
What are the functions of the stomach?
```
Store and mix food
Dissolve and continue digestion
Regulate emptying into the duodenum
Kill microbes
Secrete protease
Secrete intrinsic factor
Activate proteases
Lubrication
Mucosal Protection
```
58
What do parietal cells produce?
Gastric acid and intrinsic factor
59
What do chief cells produce?
Pepsinogen
60
What do ECL cells release?
Histamine
61
What do G cells release?
Gastrin
62
What do D cells release?
Somatostatin
63
What do glands in the thin walled upper portions of the body of the stomach secrete?
Mucous, hydrochloric acid and pepsinogen
64
What do the glands in the thick walled antrum secrete?
A little acid, mainly gastrin
65
How much hydrochloric acid is produced per day?
2 litres
66
Describe how HCl is made in the stomach
H2O in the parietal cell breaks down into OH- and H+
H2CO3 rapidly disassociates into HCO3- and H+
The H+ ions produced can then react with OH- to regenerate H2O
The H+ ions are actively pumped into the stomach lumen. They pump 1 k+ into the cell for every 1 H+ out.
The K+ ions diffuse back out through K+ channels.
The HCO3- is secreted into the capillary for the exchange of Cl- ions. These Cl- ions then enter the stomach through Cl- channels. In the stomach the H+ ions and Cl- ions react to form HCl.
67
How is H2CO3 produced?
CO2 and H2O from respiration are converted via the enzyme carbonic anhydrase
68
Describe the cephalic phase to increase gastric acid production
This is a parasympathetic response initiated by sight, smell, taste or chewing. Acetyl choline is released and it acts indirectly in parietal cells, triggering the release of gastrin and histamine. These both increase the number of H+/K+ATPase pumps, to increase gastric acid production
69
Describe the gastric phase to increase gastric acid production
Gastrin is released which acts directly on parietal cells, and triggers the release of histamine. These both increase the number of H+/K+ATPase pumps on the membrane of parietal cells, increasing gastric acid production
70
How is the cephalic phase to increase gastric acid production initiated?
Smell, sight, taste or chewing
71
How is the gastric phase to increase gastric acid production initiated?
Gastric distension from the volume of ingested material and the presence of peptides and amino acids
72
How do proteins in the stomach increase acid production?
The proteins act as a buffer thereby reducing the amount of H+ ions, increasing the pH, resulting in decreased secretion of somatostatin which increases parietal cell activity, increasing gastric acid production
73
What is the gastric phase to decrease gastric acid secretion?
A low luminal pH directly inhibits gastrin secretion thereby indirectly inhibiting histamine release. The pH also stimulates somatostatin release which inhibits parietal cell activity.
74
What does somatostatin do?
Inhibit parietal cell activity- less gastric acid secretion
75
What initiates the intestinal phase to decrease gastric acid secretion?
Duodenal distension, low pH, hypertonic solutions, the presense of amino acids and fatty acids
76
What is the intestinal phase to decrease gastric acid secretion?
Locally produced chemical messengers called enterogastrones such as secretin and cholecystokinin (CCK) are released. They also trigger short and long neural pathways which reduce ACh release.
77
What is secretin?
A enterogastrone which inhibits gastrin release and promotes somatostatin release
78
What is an ulcer?
A breach in a mucosal surface
79
Describe helicobacter pylori infection
A bacteria that lives in gastric mucus. It secretes urease which splits urea into CO2 and ammonia. The ammonia reacts with H+ to produce ammonium, which is toxic to gastric mucosa resulting in less mucous being produced. Secreted proteases, phospholipase and vacuolating cytotoxin A can then begin attacking the gastric epithelium, further reducing mucous production. Results in inflammatory response.
80
What is the treatment for helicobacter pylori infection?
Eradicate organism using triple therapy; proton pump inhibitor (increases gastric pH making conditions inhospitable), and antibiotics
81
What does NSAID stand for?
Non-steroidal anti-inflammatory drugs
82
How can NSAIDs cause a stomach ulcer?
NSAIDs inhibit cyclo-oxygenase 1 thus reducing mucosal defence?
83
How is mucous secretion stimulated?
Prostaglandins (cyclo-oxygenase 1 is needed for prostaglandin synthesis)
84
What are the chemical irritants that can cause gastric ulcers?
Alcohol, bile salts (can be refluxed from duodenum)
85
What is a gastrinoma?
A rare tumour of parietal cells causing excessive gastrin release (can cause increased attack on gastric mucosa causing gastric ulcers)
86
What are the synthetic ways to reduce gastric acid secretion?
Proton-pump inhibitors or H2 receptor agonists
87
What are examples of proton-pump inhibitors?
Omeprazole, lasoprazole and esomeprazole
88
What are examples of H2 receptor agonists?
Cimetidine and ranitidine
89
What do H2 receptor agonists do?
Block the receptors for histamine thereby reducing acid secretion
90
What are the protective mechanisms of gastric mucosa?
Alkaline mucus on luminal surface, tight junctions between epithelial cells, replacement of damaged cells, feedback loops
91
Why is pepsin secreted as pepsionogen?
To prevent it digesting the chief cells
92
What ion irreversibly inactivates pepsin?
HCO3-
93
What is essential for vitamin B-12 absorption?
Intrinsic factor
94
What percentage of total protein digestion does pepsin account for?
20%
95
What is the volume of an empty stomach?
50ml
96
What volume can a full stomach accommodate?
1.5L
97
How does the stomach increase in volume?
The smooth muscles in the body and fundus receptive relax
98
What is the nervous supply mediating receptive relaxation?
Parasympathetic nervous system acting on the enteric nerve plexuses with co-ordination provided by afferent input from the stomach via the vagus nerve and the swallowing centre
99
What chemicals mediate receptive relaxation?
Nitric oxide and serotonin
100
What is the direction of the peristaltic waves in the stomach?
From the body towards the antrum
101
What is the pyloric sphincter?
A ring of smooth muscle and connective tissue between the antrum and the duodenum
102
What is the frequency of peristaltic gastric waves determined by?
Pacemaker cells -interstitial cells of cajal, in the muscular propria
103
What is the frequency of peristaltic gastric waves?
3 per minute
104
What can increase the strength of gastric contractions?
Gastrin, gastrin distension
105
What can decrease strength of gastric contractions?
Duodenal distension, increase in duodenal fat, increase in duodenal osmolarity, increase in duodenal pH, increase in sympathetic stimulation, decrease in parasympathetic stimulation
106
What are the symptoms of dumping syndrome?
Vomiting, bloating, cramps, diarrhoea, dizziness, fatigue, weakness, sweating
107
What causes dumping syndrome?
Overfilling of the duodenum by a hypertonic solution
108
What is gastroparesis?
Delayed gastric emptying
109
What happens to the pH of the duodenum, when gastric contents enter?
Duodenal pH falls
110
What are the symptoms of gastroparesis?
Nausea, early satiety, vomiting undigested food, GORD, abdominal pain, anorexia
111
What drugs can cause gastroparesis?
H2 receptor antagonists, proton pump inhibitors, opiod analgesics, diphenhydramine, beta-adrenergic receptor agonists, calcium channel blockers, levodopa
112
What can cause GORD?
Pregnancy, Hiatus hernia, obesity and smoking
113
What percentage of water is absorbed in the small intestine?
80%
114
Which part of the small intestine absorbs the most amount of water?
The jejunum
115
How much of the fluid load is reabsorbed?
98%
116
How is potassium reabsorbed?
K+ is absorbed by passive diffusion in the colon
117
How is chloride reabsorbed?
Cl- is actively reabsorbed in exchange for bicarbonate resulting in the intestinal contents becoming more alkaline
118
What is the absorpitive state?
Ingested nutrients enter the blood from the GI tract. During this state, some of the ingested nutrients provide the energy requirements of the body and the remainder is added to the body's energy stores to be called upon during the post absorptive state
119
What is the postabsorptive state?
The GI tract is empty of nutrients and the body's own stores must supply energy
120
What is the average daily intake of lipid?
70 to 100 ml per day
121
What are the three main important fatty acids we absorb?
Palmitic, stearic and oleic acid
122
Where does triglyceride digestion begin?
In the mouth
123
Where is lipase synthesised?
Pancreas
124
What are triglycerides seperated into under the action of lipase?
Monoglycerides and fatty acids
125
What are examples of emulsifying agents?
Phospholipids, bile salts
126
What does the process of emulsification require?
Mechanical distruption of the large droplets into smaller droplets, and an emulsifying agent
127
How are bile salts formed?
Formed from cholesterol in the liver
128
What are bile salts formed from?
Bile salts, fat soluble vitamins, cholesterol, fatty acids, monoglycerides, and phospholipids
129
What are chylomicrons formed from?
Phospholipids, cholesterol and fat-soluble vitamins
130
What are the three main sources of fatty acids for triglyceride synthesis?
Glucose that enters adipose tissue and is broken down to synthesise fatty acids
Glucose that is used in the liver to form VLDL triglycerides
Ingested triglycerides transported in the blood in chylomicrons and taken up by adipocytes
131
What vitamins are fat soluble?
Vitamin A, D, E and K
132
Where is vitamin C and B (not B12) absorbed and how?
They are absorbed by diffusion in the jejunum
133
Where is vitamin B12 absorbed and how?
It is bound to intrinsic factor and absorbed in the lower portion of the ileum via endocytosis
134
Where is the main site of protein digestion and absorption of protein?
The duodenum
135
How many amino acids are essential?
8
136
Where does protein digestion begin?
The stomach
137
Where is pepsinogen I found?
The HCl secreting region of the stomach
138
Where is pepsinogen II found?
The pyloric region
139
What is the pH of the duodenal cap?
2-4
140
What is the pH in the duodenum?
6.5
141
Where are endopeptidases and exopeptidases produced?
The pancreas
142
What are examples of endopeptidases?
Trypsin, Chymotrypsin and elastase
143
What are examples of exopeptidases?
Carboxyl dipeptidases and the amino peptidases of the brush border
144
Where does the final digestion of peptides occur?
The intestinal lumen
The brush border
Within the cell
145
Describe the digestion of lactose
Forms beta linkages sinse OH groups lies above the plane of the molecule thus it requires its own enzyme to be broken down.
146
Why are people lactose-intolerant?
They do not have sufficient amounts of beta enzymes
147
What is the most common disaccharide?
Sucrose
148
Which type of isomer of amino acids are found in the proteins we utilise?
L forms
149
Which type of isomer of sugar molecules are utilised in metabolism?
D forms
150
What type of glycosidic linkages are found in glycogen?
Alpha 1-4, and alpha 1-6
151
What type of linkages are found it starch?
Mainly alpha 1-4 and some alpha 1-6 glycosidic linkages
152
What type of linkages are found in cellulose?
Beta 1-4 glycosidic
153
How is starch first degraded?
Ptalin - alpha amylase in the mouth
154
What is the optimal pH for ptyalin?
6.7
155
Where is olgiosaccharidases?
The outer portion of the membrane of the microvilli
156
What are examples of olgiosaccharidases?
Maltase
Lactase
Sucrase
Alpha-Limit dextrinase
157
How is glucose absorbed?
Sodium-glocose cotransporter (facilitated diffusion)
158
What are the roles of liver in the conversion of glucose?
Glucose can be converted to glycogen or alpha-glycerol phosphate/fatty acids
159
Where is lipoprotein lipase located?
The blood-facing surface of the capillary endothelial cells, especially those in adipose tissue
160
What is the equation for BMI?
Weight (KG)/ Height ^2(m)
161
What classifies as obese on BMI?
>30
162
What classifies as overweight on BMI?
>25
163
What classifies as underweight on BMI?
<18.5
164
How long can an adult male last with only glycogen stores?
12 Hours
165
How long can an adult male last with lipid stores?
3 Months
166
What fuels are used by the brain?
Glucose, ketone bodies
167
What fuels are used by muscle?
Glucose, ketone bodies (in starvation), triacyglycerola, branched-chain amino acids
168
What fuels are used by the liver?
Amino acids, fatty acids, glucose and alcohol
169
What fuels are used by the kidney?
Glucose, ketone bodies (cortex), glucose (medulla)
170
What fuels are used by the small intestine?
Ketone bodies (mainly in starvation), glutamine (amino acid)
171
What fuels are used by the large intestine?
Short chain fatty acids, glutamine
172
What is the basal metabolic rate?
Minimum amount of energy required to keep the body alive- decreases with age
173
Where is vitamin A stored?
Ito cells in the space of Disse of the liver
174
What are the functions of vitamin A?
```
Cellular growth and differentiation
Process of vision
Healthy skin
Reproduction
Embryonic development
Maintenance of bodies mucus membranes
Immune system
```
175
What are the sources of vitamin A?
Liver
Dairy products
Oily fish
Margarine
176
What can happen in vitamin A deficiency?
```
Night blindness
Xerophthalmia
Growth retardation
Keratinisation of epithelia
Impaired hearing, tase and smell
Increases susceptibility to infection
```
177
What are the functions of vitamin C?
Synthesis of collagen, neurotransmitters, and carnitine
Antioxidant ability
Absorption of non-haem iron
178
What are the sources of vitamin C?
Citrus fruits
Green leafy vegetables
Potatoes
Kidney
179
What happens in vitamin C deficiency?
Weakness
Bleeding gums
Hyperkeratosis
Scurvy
180
What is the function of B vitamins?
Cell metabolism
| Energy production
181
Where is vitamin B-12 found?
Fish
Poultry
Meat
Eggs
182
What happens in vitamin B deficiency?
Pernicious anaemia
183
Where is vitamin D found?
Vitamin D3- UV radiation
| Vitamin D2- Plants
184
What is the function of active vitamin D?
Stimulates intestinal absorption of Ca2+ and phosphate
185
When is PTH released?
If there is a decrease in calcium ions (low vitamin D)
186
What are the actions of PTH?
Increases reabsorption of bone by osteoclasts- can lead to osteoporosis
Stimulates the formation of 1,25-dihydroxyvitamin D
Directly increases Ca2+ and decreases phosphate ions reabsorption in the kidneys
187
What is the function of vitamin E?
Antioxidant
188
What is the function of vitamin K?
Production of clotting factors (2,7,9,10) in the liver
189
What is giardiasis?
Infection which causes the villi to atrophy thus reducing absorption capacity
190
How does coeliac disease occur?
Autoimmune condition whereby Gluten is partially degraded triggering an immune response whereby the system attacks the villi and microvilli resulting in a loss of brush border surface area, resulting in decreased absorption
191
What are Xenobiotics?
Foreign chemical substance not normally found or produced in the body which cannot be used for energy requirements. Can be absorbed across lungs, skin or ingested. Excreted in bile, urine, sweat and breath.
192
What are the properties of pharmacologically active compounds?
Lipophilic
Non-ionised at pH 7.4
Bound to plasma proteins to be transported in the blood
193
What is a microsome?
A small particle consisting of a piece of endoplasmic reticulum to which ribosomes are attached
194
What is a microsomal enzyme?
Enzymes which can be found in microsomes
195
What type of reactions can microsomal enzymes do?
Mainly phase I reactions but can do phase II
196
Where are microsomal enzymes found?
Mainly in liver hepatocytes but can be found in the kidneys and lungs too
197
What are examples of microsomal enzymes?
Cytochrome P450, FMOs, UGT
198
What happens in a phase I reaction for a microsomal enzyme?
Biotransforming substances
199
What happens in a phase II reaction for a microsomal enzyme?
Glucuronidation
200
What reactions can non-microsomal enzymes do?
Mainly phase II reactions- all conjugation reactions except glucuronidation
201
What is the aim of drug metabolism?
To make the drugs more polar so they cannot get across membranes and thus are easily excreted
202
Where does drug metabolism mainly occur?
The liver
203
What is the aim of a phase I reaction?
To make the drug more hydrophilic so it can be excreted by the kidneys
204
What type of group is introduced or exposed in a phase I reaction and why?
A hydroxyl group or other reactive site that can be used for conjugation reactions
205
What are the non-synthetic catabolic reactions for a phase I reaction?
Oxidation, reduction and hydrolysis
206
What is functionalisation as part of a phase I reaction?
Introduces a reactive group to a drug
Product is usually more reactive
Small increase in hydrophilicity
207
How are phase I reactions normally catalysed?
Cytochrome P450
208
What is a cytochrome P450 enzyme?
Type of microsomal enzyme involved in Phase I reactions. Uses heme group to oxidise substances. Products of P450 enzymes are more water soluble.
209
What is the overall reaction for a phase I reaction?
NADPH+ H+ +O2 + RH = NADP + +H2O +ROH
210
What are phase II reactions?
Sythetic anabolic reactions known as conjugation reaction. Aims to significantly increase hydrophilicity for renal excretion
211
What is a conjugation reaction?
Attachment of substituent groups to a molecule. Usually inactive products catalysed by transferases.
212
What is a glucuronidation reaction?
Addition of a glucuronic acid group to the drug to make it more hydrophilic. Uses UGT enzyme, and UDPGA co-enzyme to conjugate glucuronic acid. Process forms covalent bonds
213
What are the reactions of asprin?
Phase I: It is a pro-drug so activated upon metabolism by a hydrolysis reaction to salcylic acid.
Phase II: Conjugated with glycine or glucuronic acid, forming a range fof ionised metabolite.
214
What are the reactions of paracetamol?
Predominantly metabolised via a phase II reaction- conjugated with glucuronic acid and sulphate.
If stores of glucuronic acid and sulphate are low, paracetamol will undergo phase I metabolism via oxidation to produce toxic NAPQI.
215
What enzymes are used in the metabolism of alcohol?
Alcohol dehydrognase
| Aldehyde dehydrogenase
216
Where does the homeostatic control of iron balance occur?
The intestinal epithelium in the duodenum- actively absorbs iron from ingested foods
217
What percentage of ingested iron is absorbed into the blood each day?
10%
218
What is ferritin?
A protein-iron complex that acts as as intracellular store for iron
219
What happens when the body stores of iron are low?
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. The absorbed iron that does not bind to ferritin is released into the blood where it is able to circulate around the body bound to the plasma protein transferrin. It transports iron in the blood plasma to the bone marrow to be incorporated into new erythrocytes.
220
Where is most of the iron stored?
In the liver in liver ferritin within kupffer cells
221
What types of proteins does the liver produce?
Plasma proteins, clotting factors and complement factors
222
What are the functions of albumin?
Binding and transport of large hydrophobic compounds
| Maintenance of colloid osmotic pressure
223
What is colloid osmotic pressure?
The effective osmotic pressure across blood vessel walls which are permeable to electrolytes but not large molecules
224
How does albumin maintain osmotic pressure?
Its presence in the plasma means that the water concentration of blood plasma is slightly lower than that of the interstitial fluid meaning there is a net flow of water out of the interstitial fluid into the blood plasma
225
What are Starling forces?
1. Capillary hydrostatic pressure
2. Interstitial hydrostatic pressure
3. Osmotic force due to plasma protein concentration
4. Osmotic force due to interstitial fluid protein concentration
226
How does liver failure cause oedema?
There is a reduction in albumin so less albumin in the blood. This will decrease oncotic pressure and there will be an accumulation of water in interstitial fluid
227
What conditions can cause a decrease in albumin?
Nephrotic syndrome
Haemorrhage
Gut Loss
Burns
228
What do globulins transport?
Lipids by lipoproteins
Iron by transferrin
Copper by caeruloplasmin
229
Where are globulins produced?
Gamma-globulins are not made in the liver, but alpha/beta globulins are made in the liver
230
Which clotting factors are NOT produced in the liver?
Calcium (IV) and von Willebrand factor (VIII)
231
What are complement factors?
A plasma protein which sticks to pathogens. It is recognised by neutrophils and help mark which pathogens to kill
232
What are the 2 primary methods of protein breakdown?
Lysosomal and ubiquitin-proteasome
233
Describe the lysosomal method of protein breakdown
Carried out in the reticulo-endothelial system of the liver which is comprised of sinusoidal endothelial cells, kupffer cells and pit cells. Sinusoidal endothelial cells remove soluble proteins and fragments from the blood through the fenestrations known as sieve plates on their luminal surface. Once in the liver these proteins are then fused into lysosomes. Kupffer cells perform a similar function except they package into phagosomes. Both contain hydrolytic enzymes to break down the protein into amino acids.
234
Describe the ubiquitin-proteasome pathway of protein degradation
Occurs in the cytoplasm. Different proteins degrade at different rates. Proteins can be targeted for degradation by the attachment of a small peptide called ubiquitin to the protein. This peptide directs the protein to a protein complex called a proteasome which unfolds the protein and breaks it down to smaller peptides.
235
Where does amino acid degradation and catabolism occur?
The hepatocytes of the liver
236
What does amino acid catabolism produce?
Nitrogen, and a carbon skeleton
237
What are the two main catabolism processes?
Oxidative deamination and transamination
238
Describe oxidative deamination
Results in the liberation of an amino group as free ammonia. Glutamate is the only amino acid that undergoes rapid oxidative deamination. Amino acid gives rise to ammonia molecule and is replaced by an oxygen atom from water to form an alpha-keto acid. The alpha keto-acid can then be used in the Krebs cycle for use in glucose production- gluconeogenesis. The co-enzyme involved is NAD+ (forward reaction), and NADPH (backward reaction). The enzyme that catalyses the reaction is glutamate dehydrogenase.
239
How are high levels of ammonia associated with neurotoxicity?
Ammonia is able to cross the blood brain barrier very easily. Once inside it is converted to glutamate. This means there is a depletion in alpha-ketoglutarate. This results in the Kreb's cycle coming to a halt. This results in irreparable cell damage and neural cell death.
240
Describe transamination
Transfer of an alpha-amino group from amino acid to a keto-acid to form an alpha-keto- acid. If the amino acid alanine is transaminated then the amino group from it is transferred to a keto acid, and results in the formation of pyruvate and glutamate. The enzyme involved for these reactions is aminotransferase and they are found in cytosol of mitochondria. This reaction is readily reversible.
241
What is the most common cause of a positive nitrogen balance?
Pregnancy
242
What is the most common cause of a negative nitrogen balance?
Malnutrition
243
What are the steps of the urea cycle?
Argenine is cleaved by arginase generating urea and ornithine. Then ammonia and CO2 is built up on the ornithine to form citrulline. Another molecule of ammonia is then added to citrulline to regenerate arginine and enable the cycle to go around again.
244
What happens in the post-absorptive state?
Nutrients are no longer absorbed from the GI tract. Nutrients stores must supply the energy requirements of the body
245
What are the three main sources of glucose in the post-absorptive state?
Glycogenolysis
Lipolysis
Protein
246
Where does glycogenolysis occur?
Occurs in the liver and skeletal muscles.
247
How does glycogenolysis in the liver occur?
Glycose-6-phosphate in enzymatically converted to glucose which then enters the blood. Hepatic glycogenolysis begins within seconds of an appropriate stimulus, such as sympathetic nervous system activation. Consequently it is the first line of defence in maintaining the plasma glucose concentration within a homeostatic range. The amount of glucose available here can only supply the bodies requirements for only several hours.
248
How does glycogenolysis occur in skeletal muscle?
Glucose-6-phosphate undergoes glycolysis within muscle to yield ATP, pyruvate and lactate. The ATP and pyruvate are used directly by the muscle cell. However, some of the lactate enters the blood and circulates to the liver and is converted into glucose which can then leave the liver cells to enter the blood. Thus muscle glycogen contributes to blood glucose indirectly by way of the livers, processing of lactate.
249
How does lipolysis occur?
The catabolism of triglycerides in adipose tissue via the hydrolysis of triglycerides to produce glycerol and fatty acids. Glycerol and fatty acids enter the blood via diffusion. The glycerol enters the liver which in turn enzymatically converts it through a series of steps into glucose
250
How does gluconeogenesis occur?
Large quantities of protein in muscle and tissues can be catabolised without significant cellular malfunction. There are limits however, and continued protein loss during a prolonged fast ultimately means disruption of cell function, sickness and eventually death. The proteins supply amino acids, which enter the blood and are taken up by the liver, where they are converted via the alpha-keto acid pathway to glucose, which can then be released into the blood.
251
Which cells store most of the bodies fat?
Adipocytes and hepatocytes
252
What percentage of the bodies energy is stored in triglycerides?
78%
253
What percentage of the bodies energy is stored in proteins?
21%
254
What are the functions of lipids?
Energy reserves
Structural part of cell membrane
Hormone metabolism
255
Where are HDLs formed?
The liver
256
Where are LDLs formed?
The plasma
257
What is the role of HDLs?
Remove excess cholesterol from blood and tissue. They then deliver this cholesterol to the liver which secretes it into the bile or converts it into bile salts
258
What are the roles of LDLs?
The main cholesterol carriers and they deliver cholesterol to cells throughout the body. LDLs bind to plasma membrane receptors specific for a protein component of the LDLs and are taken up by the cells via endocytosis.
259
Why is LDL cholesterol said to be "bad"?
High plasma concentrations can be associated with increased deposition of cholesterol in arterial walls and a higher incidence of heart attacks.
260
What is the role of VLDLs?
Carry triglycerides from glucose in the liver to adipocytes
261
Where are VLDLs synthsised?
Hepatocytes
262
What is the function of adipocytes?
To synthesise and store triglycerides during periods of food uptake and then, when food is not being absorbed from the small intestine, to release fatty acids and glycerol into the blood for uptake and use by other cells in order to provide the energy required for ATP formation
263
How are ATP molecules produced from fatty acids?
1. Molecule of coenzyme A link to the carboxyl at the end of a fatty acid
2. This step is followed by the breakdown of ATP —> AMP + 2Pi
3. The coenzyme A derivative of fatty acid then proceeds through beta-
oxidation reactions
4. A molecule of acetyl coenzyme A is split off from the fatty acid and two pairs of hydrogen atoms are transferred to coenzymes (one pair to FAD and the
other pair to NAD+)
5. The hydrogen atoms from the coenzymes then enter the oxidative
phosphorylation pathway to form ATP
6. Another coenzyme A attaches to the fatty acid and the cycle is repeated
7. Each passage through this sequence shortens the fatty acid chain by two
carbons atoms until all the carbon atoms have transferred to coenzyme A
molecules
8. These molecules then lead to the production of CO2 & ATP via the Kreb’s
cycle & oxidative phosphorylation
264
What is the role of lipoprotein lipase?
Hydrolyses triglycerides in lipoproteins (chylomicrons and VLDLs) into 2 free fatty acids and 1 glycerol molecule
265
Where is hepatic lipase expressed?
In the liver and adrenal glands
266
What is the role of hepatic lipase?
Converts IDL (intermediate density lipoprotein) into LDL thereby packaging it with more triglycerides to be released in the body
267
What are the roles of bile?
Used to emulsify fats, serves as an excretory pathway for most steroid hormones, many drugs as well as some toxins metabolised by the liver
268
Where does the gall bladder lie?
At the junction of the right mid-clavicular line and costal margin
269
Where does the portal vein collect blood from?
The superior mesenteric vein
270
What does the portal triad consist of?
A hepatic portal vein, hepatic artery, bile duct
271
What is the space of disse?
Where hepatocytes are seperated from the sinusoids
272
Where do substances absorbed from the small intestine end up?
The hepatic sinusoid
273
What is the blood supply to the liver?
80% Portal vein, 20% hepatic artery
274
What are the role of stellate cells?
They are responsible for producing the extracellular matrix in the space of disse
275
How are bile canaliculi bound together?
Tight junctions, gap junctions and desmosomes
276
How is bile pumped towards bile ducts from bile canaliculi?
Actin filaments
277
What does the common bile duct consist of?
Bile ducts which join to form the common hepatic duct. The cystic duct then joins allowing bile to collect in the gall bladder. This then becomes the common bile duct
278
What is the ampulla of vater?
The point at which the pancreatic duct joins the common bile duct
279
Where do the pancreatic duct and common bile duct enter the duodenum?
The major duodenal papilla
280
What is the sphincter of Oddi?
The sphincter around the common bile duct and pancreatic duct to regulate entry of bile into the duodenum
281
What are the six major ingredients of bile?
```
Bile salts
Lecithin
HCO3- and other salts
Cholesterol
Bile pigments
Trace metals
```
282
Where are bile salts manufactured?
Hepatocytes
283
Why are bile salts, cholesterol and lecithin aggregated into mixed micelles?
Bile salts are powerful detergents for their fat emulsification function. However they are also capable of damaging cell membranes and so they are seperated in micelles to reduce damage until they are required.
284
Why is HCO3- needed in bile?
To help neutralise the acids in the duodenum
285
How is the HCO3- rich bile solution secreted?
Via epithelial cells lining the bile ducts
286
How is secretion of the HCO3- rich solution stimulated?
Secretin in response to the presence of acid in the duodenum
287
What stimulates the gallbladder to contract?
Cholecystokin- released due to amino and fatty acids in the duodenum
288
What is enterohepatic circulation?
During the digestion of a fatty meal, most of the bile salts entering the intestinal tract are absorbed by specific Na+ coupled transporters in the jejunum and terminal ileum. These bile salts are returned via the portal vein to the liver where they are once again secreted into the bile. This is driven by secondary active transport coupled to Na+
289
What are bile pigments formed from?
The haem portion of haemoglobin when old/ damaged erythrocytes are broken down in the spleen and liver
290
What colour is bilirubin?
Yellow
291
How is haem broken down?
Under the action of hemoxygenase into biliverdin and Fe2+ and CO
292
How is biliverdin reduced?
Under the action of biliverdin reductase into unconjugated bilirubin
293
What is unconjugated bilirubin bound to to be transported to the liver?
Albumin
294
How is unconjugated bilirubin made conjugated?
Glucuronidation in the liver under the action of UDP glucuronyl transferase
295
How is conjugated bilirubin converted to urobilinogen?
It is reduced through a hydrolysis reaction under the action of intestinal bacteria in the ilium
296
What happens to urobilinogen that is reabsorbed?
It is bound to albumin and transported back to the liver. It is oxidised to urobilin and either recycled into bile or transported to the kidneys where it is excreted in urine- responsible for the yellowish colour of urine.
297
What happens to urobilinogen that is not reabsorbed into the blood?
It is oxidised by another type of intestinal bacteria to form stercobilin and then excreted into the faeces- responsible for its brownish colour
298
What is jaundice?
A yellow discolouration of the skin caused by a high serum bilirubin level (clinically detectable when bilirubin is above 50 micromol/L)
299
What are three main types of jaundice?
Pre-hepatic
Hepatic
Post hepatic
300
What is pre-hepatic jaundice?
Increased breakdown of erythrocytes resulting in increased levels of unconjugated bilirubin. This causes an increased serum unconjugated bilirubin
301
What are the clinical syptoms of pre-hepatic jaundice?
Normal stools and urine
Yellow skin
Enlarged spleen
302
What are the causes of pre-hepatic jaundice?
Malaria, sickle cell anaemia, thalassaemia, physiological jaundice of the newborn
303
What is hepatic jaundice?
The result of hepatocellular celling. Impaired cellular uptake, defective conjugation or abnormal secretion of bilirubin by hepatocytes. The liver is damaged so unable to metabolise the unconjugated bilirubin, resulting in a buildup in serum unconjugated bilirubin. Damage could also mean that conjugated bilirubin is unable to be secreted resulting in a raised serum conjugated bilirubin as well. Increased conjugated and unconjugated bilirubin, decreased urobilinogen.
304
What are the clinical symptoms of hepatic jaundice?
Dark urine
Normal or pale stools
Enlargement of the spleen
Yellow skin
305
What causes hepatic jaundice?
Viral hepatitis, drugs, alcohol hepatitis, cirrhosis, and jaundice of the newborn
306
What is post-hepatic jaundice?
When biliary system is damaged, inflamed or obstructed. Elevated serum conjugated bilirubin.
307
What are the clinical symptoms of post-hepatic jaundice?
```
Dark urine
Pale stools
Normal levels of unconjugated bilirubin
No enlargement of the spleen
Yellow skin
```
308
What causes post-hepatic jaundice?
Gallstones, pancreatic cancer, gallbladder cancer, bile duct cancer, pancreatitis
309
Why can cancer or inflammation of the pancreas cause jaundice?
The head of the pancreas is situated in the duodenal loop which is near the common bile duct, thus any inflammation or cancer of the pancreas can eventually cause obstruction to the duct, causing jaundice
310
Where will pain from acute pancreatitis radiate from?
The back
311
What is gilbert syndrome?
Where there is a shortage of UDP glycerol transferase, meaning only small amounts of conjugation can occur. There will be a normal conjugated bilirubin level but a raised unconjugated bilirubin level
312
How are gall stones formed?
When the concentration of cholesterol in bile becomes high in relation to the concentrations of phospholipids and bile salts, the cholsterol will crystalise out of solution forming gall stones
313
Why do gall stones cause decreased fat digestion and absorption?
The stone may become lodged in the common bile duct, thus preventing the bile from entering the intestines
314
Why can gall stones cause clotting problems or calcium malabsorption?
Decreased absorption of fat soluble vitamins A D K and E.
315
Why can gall stones cause diarrhoea and fluid and nutrient loss?
Some excess fat in the large intestine will be converted into fatty acid derivatives by bacteria that alter salt and water movements leading to a net flow of fluid into the large intestine
316
Is the pacreas retroperitoneal or intraperitoneal?
All retroperitoneal apart from the tail which is attached to the spleen and is intraperitoneal
317
Where does the uncinate process arise from?
The ventral bud
318
What vessels lie inbetween the uncinate process and the head of the pancreas?
The superior mesenteric vein and artery
319
What is the main blood supply to the pancreas?
The coelic trunk
320
What are the divisions of the coeliac trunk at the coeliac axis?
Gastric arteries, hepatic artery, and splenic artery
321
What is the venous drainage of the pancreas?
Mainly the splenic vein which then joins the superior mesenteric vein to form the portal vein
322
What does the exocrine pancreas secrete?
HCO3-
| Digestive enzymes
323
Where do the secretions from the exocrine pancreas arise from?
The acinar tissue of the pancreas
324
What will bile reflux down the pancreatic duct cause and why?
Acute inflammation due to its detergent properties
325
What cells secrete HCO3- in the pancreatic duct?
Duct cells
326
Why is HCO3- secreted in the pancreatic duct?
To protect the duodenal mucosa from the gastric acid and buffer the material entering the duodenum to a pH that is suitable for enzyme action
327
How is the secretion of HCO3- from the pancreas and liver stimulated?
The release of the gastrointestinal hormone secretin in response to the presence of acid in the duodenum
328
What exchanger allows the pancreatic duct cells to pump out HCO3-?
Cl-/HCO3-
329
What cells secrete digestive enzymes at the pancreatic end of the duct system?
Gland cells
330
What does the release of CCK do?
Stimulates the secretion of digestive enzymes and also potentiates the actions of secretin. Stimulates the contraction of the gall bladder and relaxes the sphincter of Oddi
331
Where is CCK produced?
The small intestine
332
What are the naturally active digestive enzymes?
Alpha-amylase and lipase
333
Where is enterokinase found?
Embedded in the luminal plasma membranes of the intestinal epithelial cells
334
What is enterokinase?
A proteolyic enzyme that splits off a peptide from pancreatic trypsinogen forming the active enzyme trypsin
335
What is the role of trypsin?
Activate other pancreatic zymogens by splitting off peptide fragments
336
What is chymotrypsinogen activated into?
Chymotrypsin enzyme
337
What is produced by delta cells in the pancreatic islets?
Somatostatin
338
What do alpha cells in the islets of langerhans produce?
Glycagon
339
What do beta cells in the islets of langerhans produce?
Insulin and amylin
340
What do PP cells in the islets of langerhans produce?
Pancreatic polypeptide
341
What is the blood supply to the liver?
25% from hepatic artery (oxygenated)
| 75% from portal vein (deoxygenated but nutrients)
342
How does blood leave the liver?
The hepatic vein which eventually drains into the inferior vena cava
