GI Flashcards
(315 cards)
1
Q
Give 9 functions of the stomach.
A
- Store and mix food.
- Regulate emptying into the duodenum.
- Secrete proteases.
- Dissolve and continue digestion.
- Kill microbes.
- Secrete intrinsic factor.
- Activate proteases.
- Lubrication.
- Mucosal protection.
2
Q
What are the 4 key cell types in the stomach?
A
- Mucous cells.
- Parietal cells.
- Chief cells.
- Enteroendocrine cells.
3
Q
What is gastric acid? How much do we make a day?
A
Hydrochloric acid. We make ~2 litres/day.
4
Q
Which 3 ions are needed for gastric acid secretion?
A
H+, Cl-, and K+.
5
Q
Describe the cephalic phase of activating gastric acid secretion.
A
- Stimulated by sight, smell, taste of food and chewing.
- Parasympathetic nervous system.
- Acetylcholine is released.
- ACh acts directly on parietal cells, triggering gastrin and histamine release.
- Gastrin and histamine stimulate parietal cells.
- Therefore, increases acid production .
6
Q
Describe the gastric phase of activating gastric acid secretion.
A
- Gastric distension.
- Presence of peptides and amino acids.
- Gastrin released, acts on parietal cells, triggers histamine release.
- Histamine then acts directly on parietal cells.
- Therefore, increases acid production.
7
Q
Describe how protein in the stomach has a role in activating gastric acid secretion.
A
- Directly stimulates gastrin release.
- Luminal proteins act as a buffer, mopping up H+, causing pH to rise.
- Decreases somatostatin secretion.
- Allows more parietal cell activity due to lack of inhibition.
- Therefore, increases acid production.
8
Q
Describe the gastric phase of deactivating gastric acid secretion.
A
- Low luminal pH from high H+.
- Low pH inhibits gastrin secretion.
- Therefore, indirectly inhibits histamine release (via gastrin).
- Low pH also stimulates somatostatin release, which inhibits parietal cell activity.
- Therefore, decreases acid production.
9
Q
Describe the intestinal phase of deactivating gastric acid secretion.
A
- Duodenum has higher pH than the stomach at rest.
- Gastric contents entering causes duodenum distension, lower luminal pH, hypertonic contents, and presence of amino acids and fatty acids.
- This triggers the release of enterogastrones: secretin and cholecystokinin (CCK).
- Secretin inhibits gastrin release, and promotes somatostatin release.
- Short and long neural pathways which reduce ACh release.
- Therefore, decreases acid production.
10
Q
Give a simple list of facts about the regulation of gastric acid secretion.
A
- Controlled by the brain, stomach, and duodenum.
- 1 parasympathetic neurotransmitter (ACh = + acid).
- 1 hormone (gastrin = + acid).
- 2 paracrine factors (histamine = + acid, somatostatin = - acid).
- 2 key enterogastrones (secretin and cholecystokinin = - acid).
11
Q
What is an ulcer?
A
A breach in a mucosal surface.
12
Q
Give 4 causes of an ulcer.
A
- Helicobacter pylori infection.
- Drugs (NSAIDs).
- Chemical irritants (alcohol, bile salts, diet).
- Gastrinoma (tumours of gastrin producing cells).
13
Q
Where can peptic ulcers occur?
A
In the stomach, duodenum, and oesophagus.
14
Q
Describe the two ways an ulcer can occur in terms of the mucosal attack/defences.
A
Increased mucosal attack, or decreased mucosal defences.
15
Q
How does the gastric mucosa defend itself? Give 4 ways.
A
- Alkaline bicarbonate-rich mucus, which forms a barrier between acid and epithelial cells.
- Tight junctions between epithelial cells, prevent acid passing between cells to tissue below.
- Replacement of damaged cells, occurs via stem cells in gastric pits.
- Feedback loops, irritation causes surface mucous cells to produce more.
16
Q
What is the purpose of intrinsic factor?
A
To bind to Vitamin B12 taken in in the diet, helping it to be absorbed in the terminal ileum.
17
Q
What is the role of parietal cells?
A
Produce intrinsic factor and gastric acid.
18
Q
What is the role of enteroendocrine cells?
A
Produce gastrin.
19
Q
Describe how helicobacter pylori cause peptic ulcers.
A
- Bacteria lives in gastric mucus.
- Secretes urease, splitting urea into CO2 and ammonia.
- Ammonia and H+ = ammonium.
- Ammonium damages gastric epithelium.
- Inflammatory response.
- Reduced mucosal defence.
20
Q
How do you treat patients with peptic ulcers from helicobacter pylori?
A
- Eradicate the organism
- Proton pump inhibitor.
- 2 antibiotics from: clarithomycin, amoxicillin, tetracycline, and metronidazole.
21
Q
Describe how NSAIDs cause peptic ulcers.
A
- Non-steroidal anti-inflammatory drugs.
- Cyclo-oxygenase 1 needed to synthesise prostoglandins.
- NSAIDs inhibit COX-1, reducing prostoglandin synthesis.
- Mucus secretion stimulated by prostoglandins.
- Inhibits mucus secretion, and reduces mucosal defence.
22
Q
How do you treat patients with peptic ulcers from NSAIDs?
A
- Prostoglandin analogues e.g. misoprostol, to stimulate mucus secretion.
- Reduce acid secretion.
23
Q
Describe how bile salts can cause peptic ulcers.
A
- Duodenal-gastric reflux.
- Regurgitated bile strips away mucus layer.
- Reduce mucosal defence.
24
Q
What is the role of chief cells?
A
Produce pepsinogen (inactive form of pepsin).
25
Why is pepsinogen synthesised rather than pepsin?
Synthesised as a zymogen (in its inactive form), as proteases break down proteins, so if the cell made an active protease it would digest itself.
26
How is pepsinogen mediated?
By input from the enteric nervous system (acetycholine).
27
Describe the protease activation of pepsinogen -> pepsin.
- Positive feedback loop.
- Secretion parallel to HCl secretion.
- HCl cleaves pepsinogen -> pepsin.
- This pepsin breaks down pepsinogen -> more pepsin.
- Most efficient at pH <2.
28
Describe the inactivation of pepsin.
Irreversible inactivation in duodenum by HCO3-.
29
Describe the role of pepsin in protein digestion.
- Not essential, protein digestion can occur if the stomach is removed.
- Accelerates protein digestion, and normally accounts for ~20% of total.
- Breaks down collagen in meat, helps shred into smaller pieces = greater SA for digestion.
30
What is the volume of an empty stomach?
~ 50mL.
31
When eating, how much can the stomach accommodate with little increase in luminal pressure?
~ 1.5 L.
32
Give the 3 steps of gastric peristalsis.
- Waves begin in gastric body (weak contractions, little mixing).
- More powerful contractions in gastric antrum, pyloric sphincter closes as peristaltic wave reaches it.
- Little chyme enters the duodenum, antral contents forced back towards the body -> mixing.
33
What is the normal frequency of peristaltic waves?
3/minute.
34
What determines the basic electrical rhythm of the peristaltic waves?
Pacemaker cells in the muscularis propria, called interstitial cells of cajal.
35
Describe the basic electrical rhythm of peristaltic waves, and what happens in an empty stomach.
- Undergo slow depolarisation-repolarisation cycles.
- Waves of depolarisation transmit through gap junctions to adjacent smooth muscle cells.
- Do not cause significant contraction in an empty stomach.
36
Give 2 factors that increase the strength of peristaltic contractions.
- Gastrin.
- Gastric distension (mediated by mechanoreceptors).
37
Give 1 factor that decreases the strength of peristaltic contractions.
- Duodenal distension.
38
Which has a larger capacity, the stomach or the duodenum?
The stomach.
39
What causes dumping syndrome?
Overfilling of the duodenum by a hypertonic solution.
40
Give 8 symptoms of dumping syndrome.
- Vomiting.
- Bloating.
- Cramps.
- Diarrhoea.
- Dizziness.
- Fatigue.
- Weakness.
- Sweating.
41
What is gastroparesis?
Delayed gastric emptying.
42
Give 9 causes of gastroparesis.
- Idiopathic.
- Autonomic neuropathies (e.g. in diabetes mellitus).
- Drugs.
- Abdominal surgery.
- Parkinson's disease.
- Multiple sclerosis.
- Scleroderma.
- Amyloidosis.
- Female gender.
43
Give 7 symptoms of gastroparesis.
- Nausea.
- Early satiety.
- Vomiting undigested food.
- GORD.
- Abdominal pain.
- Abdominal bloating.
- Anorexia.
44
What is receptive relaxation?
Presence of food in stomach makes it relax, then it can stretch without increasing the pressure.
45
Which type of muscle in which parts of the stomach undergo receptive relaxation?
Smooth muscle in the body and the fundus.
46
How is receptive relaxation mediated/coordinated?
- Mediated by parasympathetic nervous system, acting on enteric nerve plexuses.
- Acetylcholine released, triggers nitric oxide and serotonin release by enteric nerves, which mediates relaxation.
- Coordination controlled via the vagus nerve (CN X).
47
What are the 3 pairs of major salivary glands called?
- Parotid.
- Submandibular.
- Sublingual.
48
What % of salivary flow are the major salivary glands responsible for?
80%.
49
Where can the minor salivary glands be found?
In the submucosa of oral mucosa e.g. lips, cheeks, hard and soft palate, tongue.
50
What % of salivary flow are the minor salivary glands responsible for?
20%.
51
Describe the general structure of salivary glands.
Composed of 2 epithelial tissues.
- Acinar cells, which sit around...
- Ducts
Have channels and transporters in the apical and basolateral membranes to enable fluid and electrolyte transport.
52
What are the 2 types of acini?
Serous acinus, and mucous acinus.
53
Describe serous acini.
- Dark staining nucleus in basal 1/3.
- Small central duct.
- Secrete water and alpha amylase.
- Tightly packed.
54
Describe mucous acini.
- Pale staining (foamy).
- Nucleus at base/edge of cell.
- Large central duct.
- Secrete mucous (water and glycoproteins).
55
Which type of acini are present in each of the 3 major pairs of salivary glands?
Parotid = serous acini.
Submandibular = mixed, aka seromucous acini.
Sublingual = mixed, but more mucous acini.
56
Describe the structure of ducts in the salivary glands.
Intralobular ducts -> main excretory duct.
Intralobular ducts = intercalated ducts and striated ducts.
57
Describe intercalated ducts.
Short, narrow duct segments, cuboidal cells that connect acini to larger, striated ducts.
58
Describe striated ducts.
Striped, major site for NaCl reabsorption, basal membrane folded into microvilli (for active transport of HCO3- against conc gradient), microvilli filled with mitochondria for energy to facilitate active transport.
59
What do ducts secrete, and reabsorb?
Secrete: K+ and HCO3-.
Reabsorb: Na+ and Cl-.
60
Describe the process from primary saliva to final saliva.
Primary = NaCl rich, isotonic plasma-like fluid, secreted by acini.
Epithelium of duct does not allow water movement.
Therefore, final saliva = hypotonic.
61
Describe the location of Stenson's duct, and which of the major salivary glands it comes from.
Comes from the parotid gland.
Crosses the masseter, pierces the buccinator, and enters the oral cavity near the second upper molar.
62
Describe the parotid capsule.
Very tough.
63
Give 3 structures that pass through the parotid.
- External carotid and its terminal branches.
- Retromandibular vein.
- Facial nerve and branches to muscles of facial expression.
64
Where can you find the parotid gland on physical examination?
Palpate a finger's breadth below the zygomatic arch.
65
Describe the structure/location of the submandibular glands.
Two lobes separated by the mylohyoid muscle:
- Larger, superficial lobe
- Smaller, deep lobe (in floor of the mouth)
66
Describe the location of Wharton's duct, and which of the major salivary glands it comes from.
Comes from the submandibular glands.
Empties into the oral cavity underneath the tongue.
67
Describe the location of the sublingual glands.
Between the mylohyoid muscle and the oral mucosa of the floor of the mouth.
68
Describe the duct system of the sublingual glands.
Has no large duct, instead drains into Wharton's duct, and has small ducts that pierce the oral mucosa on floor of the mouth.
69
Describe the duct system of the minor salivary glands.
Lacks a branching network of draining ducts, each unit has its own simple duct.
70
Describe the locations in which the minor salivary glands are concentrated.
The buccal, labial, palatal, and lingual regions.
71
Give 3 other locations of minor salivary glands.
- Superior pole of tonsils (Weber's glands).
- Tonsillar pillars.
- Base of the tongue (von Ebner's glands).
72
What is the flow rate of saliva?
0.3 -> 7ml per minute.
73
What is the daily salivary secretion in adults?
Between 800 -> 1500ml per day.
74
Give the pH range of saliva.
6.20 -> 7.40.
75
Give 8 factors that can affect the composition and amount of saliva produced.
- Flow rate.
- Circadian rhythm.
- Type and size of gland.
- Duration and type of stimulus.
- Diet.
- Medications/drugs.
- Age.
- Gender.
76
Give 4 functions of saliva.
- Lubrication for mastication, swallowing, and speech.
- Oral hygiene.
- Maintenance of oral pH ~ 7.20, to prevent damage of tissues or teeth.
- Digestive enzyme, dilutes food to allow taste.
77
Describe saliva's role in oral hygiene/health.
Lubrication, mechanical cleaning, buffering salts, remineralisation, defensive and digestive function.
78
How does saliva maintain oral pH?
Bicarbonate/carbonate buffer system rapidly neutralises acids.
79
Describe oral defence and saliva's role in it.
The mucosa = the physical barrier.
Palatine tonsils = immune surveillance and resistance to infection.
Salivary glands = wash away food particles that bacteria or viruses may use for metabolic support.
80
Which salivary glands are continuously active?
Submandibular, sublingual, and minor salivary glands.
81
Describe the composition of unstimulated saliva.
Dominated by submandibular components.
82
Describe the composition of stimulated saliva.
Resembles parotid secretion, the main component of this.
83
What is contained in 'whole' saliva?
Salivary gland secretions, blood, oral tissues, microorganisms, and food remnants.
84
What happens if salivary output falls? How much does it have to fall for this to occur?
Xerostomia (dry mouth).
Has to fall below 50% of normal flow.
85
What are some problems with xerostomia?
Low lubrication -> oral function becomes difficult.
Low (natural) oral hygiene -> poor pH control -> plaque accumulation, opportunistic infection (especially fungal e.g. candida = thrush).
86
What are the most common causes of xerostomia?
Medication, and irradiation for head/neck cancers.
87
Which 2 conditions may cause xerostomia?
Cystic fibrosis, or Sjorgens syndrome.
88
Describe how obstructive salivary gland diseases occur.
Saliva contains calcium and phosphate ions, these can form salivary calculi (stones) that can cause obstructions.
89
Where is obstructive salivary gland disease most often found?
In submandibular glands (80% cases).
Blocking duct at bend around mylohyoid, or at the exit of the sublingual papillae.
90
Describe how inflammatory salivary gland diseases occur.
Infection secondary to a blockage.
91
Which type of disease/illness/infection is mumps?
A viral infection.
92
Give 4 symptoms of mumps.
- Fever.
- Malaise.
- Swelling of glands (especially parotid).
- Pain especially over the parotid, as the tough capsule does not allow much enlargement.
93
What is the most common type/cause of salivary gland dysfunction to encounter?
Drug side effects. About 500 prescription drugs have a sympathomimetic effect (reduce salivary flow massively, or completely).
94
What % of salivary gland tumours (SGTs) are benign? What is the most common benign SGT?
80%. 65% of these are pleomorphic adenomas.
95
Describe the distribution of SGTs across the different salivary glands?
Parotid = 70% SGTs.
Submandibular = 10%.
Sublingual = less than 1%.
Minor glands = around 20%.
96
Are sublingual tumours almost always benign or malignant?
Malignant.
97
Describe the malignancy %s of SGTs in major vs minor glands.
In major glands, 20% = malignant.
In minor glands, 50% = malignant.
98
What can degenerative salivary gland diseases be a complication of?
Radiotherapy to the head/neck.
99
Name a degenerative salivary gland disease.
Sjogren's syndrome.
100
Which group of people are mainly effected by Sjogren's syndrome?
Post-menopausal women.
101
What other condition may be present alongside Sjogren's syndrome?
Rheumatoid athritis.
102
Give 5 diseases/problems associated with metabolic problems.
- Diabetes.
- Increased BMI.
- High cholesterol.
- Malnutrition.
- Absorption problems.
103
How is glucose produced and where in the body?
Breaking down carbohydrates = glucose, occurs in the intestines.
104
Where and how is glucose transported in the body?
Absorbed into the bloodstream after production, is transported to the liver and various other places such as muscle, the brain, RBCs and adipocytes.
105
Which hormone takes up glucose into the liver?
Insulin.
106
What can glucose be stored as in the liver?
Glycogen.
107
Explain the uses of glucose in the liver.
- Some feeds into Acetyl CoA and Krebs' cycle, makes energy (ATP).
- Acetyl CoA can also be converted into triglycerides.
- Triglycerides combine with proteins = VLDL (very low density lipoproteins).
108
Which hormone takes up glucose into muscle?
Insulin.
109
What can glucose be stored as in muscle?
Glycogen.
110
Describe the brain's relationship with glucose.
Needs a constant supply of glucose from the bloodstream in order to have a constant supply of energy.
111
How is glucose stored in the brain?
It is not, the brain cannot store glucose.
112
How can glucose produce energy for the brain?
Glucose -> Acetyl CoA -> Krebs' Cycle -> ATP.
113
How do RBCs utilise glucose?
To create a source energy, can't make their own ATP as they have no mitochondria.
Instead, convert glucose -> pyruvate and lactate, which can be used as sources of energy.
114
Which hormone takes up glucose into adipocytes?
Insulin.
115
How is glucose utilised in adipocytes?
To produce ATP, or to be converted into triglycerides.
116
How are amino acids formed and when?
Proteins are digested, then broken down into amino acids, which can then go into the bloodstream.
There is constant backwards/forwards of protein and amino acid production.
117
What can amino acids be used for?
- Make various compounds.
- Can feed into Kreb's cycle, and therefore ATP production.
118
How are triglycerides formed?
Fats taken in through the diet are broken down into triglycerides, which are transported through the bloodstream.
119
What can triglycerides be used for?
- They are insoluble, so can combine with proteins.
- Different combinations = different molecules, e.g. chylomicron (in the lymphatic system).
120
Describe what happens to the products of macronutrients during fed state.
Food and macronutrients digested are used as fuels, and oxidised into ATP. Any excess is stored as triglycerides in adipose tissue, or glycogen in the liver and muscle.
121
When we are not eating, what level needs to be maintained?
Blood glucose level.
122
How does our body respond to a short fast?
Glycogenolysis.
- If the body needs more glucose, glycogen is broken down back to it, and released into the bloodstream to maintain blood glucose level.
- Glucose mainly goes -> brain and RBCs, which need a constant supply, but also the rest of the body.
- Hormone that does this is glucagon.
123
How does our body respond to a longer fast?
Gluconeogenesis.
- When glycogen stores are used up, alternative source of glucose is needed.
- Amino acids, lactate fro RBCs, and glycerol from adipose tissue are used. These go to the liver, which uses them to create glucose to release into the bloodstream.
- Mainly for brain and RBCs.
124
Describe what happens to fats/triglycerides during fasting.
Lipolysis.
- Triglycerides in adipocytes can be broken down -> glycerol.
- Glycerol goes to the liver and is used to make glucose.
- Triglycerides also broken down to fatty acids, which are used by kidneys and muscle.
- Fatty acids can also go to the liver and make ketones, an alternative energy source to glucose.
- Glucagon is the hormone that promotes this process.
125
How does our body respond to prolonged fasting?
Ketogenesis.
- After 4/5 days = 'starvation' state.
- Gluconeogenesis decreased, as do not want to overuse amino acids, or necessary muscles will be broken down.
- Fatty acids still creating ketones, so decreased use of glucose necessary, as there is an alternative energy source for the brain.
- Brain uses ketones, keeps glucose available for RBCs which cannot used ketones.
- Muscle will use less ketones.
126
Name the 2 main hormones regulating fuel metabolism from the pancreas.
Insulin.
Glucagon.
127
Name the 3main hormones regulating fuel metabolism from the adrenal glands.
Cortisol.
Adrenaline.
Noradrenaline.
128
Name the 1 main hormone regulating fuel metabolism from the thyroid gland.
Thyroxine.
129
Name the 2 main hormones regulating fuel metabolism from the pituitary gland.
Growth hormone.
Somatostatin.
130
Is insulin an anabolic or catabolic hormone? Why? Give examples.
Anabolic, as it builds complex molecules from numerous simple ones. E.g.
- Glycogen storage.
- Fat storage.
- Protein synthesis.
131
Is glucagon an anabolic or catabolic hormone? Why? Give examples.
Catabolic, as it breaks down complex molecules into numerous simple ones. E.g.
- Glycogenesis.
- Gluconeogenesis.
- Ketogenesis.
132
What does BMR stand for?
Basal metabolic rate.
133
What does DIT stand for?
Diet induced thermogenesis (%).
134
Describe energy balance in terms of weight gain/loss.
In energy in = energy out -> stable weight.
If in > out -> weight gain.
If in < out -> weight loss.
135
Explain the role of the hormone leptin.
Suppresses appetite in normal weight.
136
Explain a problem with the hormone leptin.
In obesity, high leptin levels cause leptin resistance, meaning appetite isn't suppressed as it should be.
137
Where is leptin produced, and what does it act on?
Produced from fat cells, acts on the brain.
138
Explain the role of the hormone ghrelin.
Levels increase before meals and stimulate appetite.
139
Explain a problem with the hormone ghrelin.
Too high levels = appetite is stimulated too much.
140
Where is ghrelin produced, and what does it act on?
Produced in the stomach, acts on the brain.
141
Give 7 functions of the liver.
- Carbohydrate metabolism.
- Fat metabolism.
- Protein metabolism.
- Hormone metabolism.
- Toxin/drug metabolism and excretion.
- Bilirubin metabolism and excretion.
- Storage.
142
Where can ferritin be found in the body?
In the cytoplasm of cells, mainly in the liver. Can also be found in blood serum.
143
Describe ferritin's structure.
- Large spherical protein.
- 24 noncovalently linked subunits, which form a shell around a central core.
- Core contains up to 5000 iron atoms.
144
Describe the relationship between concentration of ferritin and total body iron stores.
Directly proportional.
145
What are the 2 types of cause of ferritin excess?
Excess iron storage disorders.
Non-iron overload disorders.
146
Give 5 causes of excess iron storage ferritin excess.
- Hereditary haemochromatosis.
- Haemolytic anaemia.
- Sideroblastic anaemia.
- Multiple blood transfusions.
- Iron replacement therapy.
147
Give 3 causes of non-iron overload ferritin excess.
- Liver disease.
- Some malignancies.
- Significant tissue destruction.
148
What is the only known cause of low ferritin?
Iron deficiency.
149
What can low ferritin result in?
Anaemia.
150
What level of ferritin indicates depletion?
Less than 20 micrograms/L.
151
What level of ferritin indicate a complete absence of stored iron?
Less than 12 microgams/L.
152
Give 3 roles vitamins act as.
- Gene activators.
- Free-radical scavengers.
- Coenzymes/cofactors in metabolic reactions.
153
Which vitamins are water soluble?
Vitamins B and C.
154
Which vitamins are fat soluble?
Vitamins A, D, E and K.
155
Do we need a more regular intake of water soluble or fat soluble vitamins? Why?
Water soluble, as they pass more readily through the body.
156
What do RDA and AI stand for?
RDA = recommended daily allowance.
AI = adequate intake.
157
How do we take in vitamin A?
Ingest retinol directly from meat and dairy products, or produce it from carotenes.
158
Give 4 functions of vitamin A.
- Vision.
- Reproduction.
- Growth.
- Stabilisation of cellular membranes.
159
How is vitamin A involved in vision?
Used to form rhodopsin in rod cells in the retina.
160
How is vitamin A involved in reproduction?
In males: spermatogenesis.
In females: prevention of foetal reabsorption.
161
How common is vitamin A deficiency in affluent countries?
Rare, as levels only drop when liver stores are severely depleted.
162
What can cause vitamin A deficiency?
Fat malabsorption.
163
Give 3 clinical features of vitamin A deficiency.
- Night blindness.
- Xeropthalmia.
- Blidness.
164
Give 8 clinical features of acute vitamin A excess.
- Abdo pain.
- Nausea.
- Vomiting.
- Severe headaches.
- Dizziness.
- Sluggishness.
- Irritability.
- Desquamation of skin.
165
Give 6 clinical features of chronic vitamin A excess.
- Joint/bone pain.
- Hair loss.
- Lip dryness.
- Anorexia.
- Weight loss.
- Hepatomegaly.
166
Describe carotenemia.
Reversible yellowing of the skin due to high carotene levels.
Does not cause toxicity/vitamin A poisoning.
167
Give 3 functions of vitamin D.
- Increase intestinal absorption of calcium.
- Reabsorption and formation of bone.
- Reduce renal excretion of calcium.
168
What occurs in vitamin D deficiency? In children? In adults?
Demineralisation of the bone.
Children = rickets.
Adults = osteomalacia.
169
What is our main source of vitamin D?
Direct sunlight on the skin.
170
Give 4 sources of vitamin E.
Spinach, carrots, nuts, and oil.
171
Where can vitamin E be stored?
Non-adipose cells e.g. liver and plasma (labile and fixed pool).
Adipose cells (fixed pool).
172
Give 3 causes of vitamin E deficiency.
- Fat malabsorption (e.g. CF).
- Premature infants.
- Rare congenital defects in fat metabolism (e.g. abetalipoproteinaemia).
173
Give 5 clinical manifestations of vitamin E deficiency.
- Haemolytic anaemia.
- Myopathy.
- Retinopathy.
- Ataxia.
- Neuropathy.
174
Discuss vitamin E excess.
Relatively safe in excess.
175
How is vitamin K taken up and transported?
Rapidly taken up by the liver, then transferred to VLDLs and LDLs, which carry in into the plasma.
176
Describe the body's sources of vitamin K.
K1 = synthesised by plants and present in food.
K2 = synthesised in humans by intestinal bacteria.
K3 and K4 = synthetic.
177
Give 2 functions of vitamin K.
- Responsible for activation of some blood clotting factors.
- Necessary for liver synthesis of plasma clotting factors II, VII, IX and X.
178
How can the function of vitamin K be assessed?
By measuring prothrombin time.
179
What can a deficiency of vitamin K cause?
Haemorrhagic disease of the newborn.
180
How is haemorrhagic disease of the newborn prevented?
Vitamin K injection given to newborn babies.
181
How common is vitamin K deficiency in adults?
Rare, unless on warfarin.
182
Discuss excess of vitamin K.
Excess of K1 = relatively safe.
Excess of synthetic forms = more toxic.
Could result in oxidative damage, red cell fragility, and formation of methaemoglobin,
183
Where do we get vitamin C?
Found in fresh fruit and vegetables.
184
Give 3 functions of vitamin C.
- Collagen synthesis.
- Antioxidant.
- Iron absorption.
185
What is the disease that occurs with severe vitamin C deficiency? Give its symptoms.
Scurvy.
Symptoms include: easy bruising and bleeding, teeth and gum disease, hair loss.
186
Describe treatment of scurvy and its effectiveness.
Treatment with vitamin C, improves symptoms quickly.
Joint pain = gone within 48 hrs.
Full recovery = within 2 weeks.
187
Describe what can happen with an excess of vitamin C.
Doses of >1g/day can cause GI side effects.
188
Give 4 sources of vitamin B12.
Meat, fish, eggs, and milk.
189
Describe the release, transport, and storage process of vitamin B12.
Two active forms - methylcobalamin, and 5-deoxyadenosylcobalamin.
- Released from food by acid and enzymes in the stomach.
- Binds to R proteins to protect it from HCl.
- Released from R proteins by pancreatic polypeptide.
- Intrinsic factor needed for absorption, IF-B12 complex absorbed in terminal ileum.
- B12 stored in the liver.
190
Give 3 causes of vitamin B12 deficiency.
- Perinicious anaemia (autoimmune destruction of IF-producing cells in stomach).
- Malabsorption: pancreatic disease, small bowel disease.
- Veganism.
191
Give 2 symptoms of vitamin B12 deficiency.
- Macrocytic anaemia.
- Peripheral neuropathy (in prolonged deficiency).
192
What is macrocytic anaemia?
A blood disorder, when your bone marrow produces abnormally large red blood cells.
193
How do we get folate?
From many foods fortified with folic acid e.g. cereal.
194
Which group of the population has higher folate requirements?
Pregnant women.
195
Give 3 causes of folate deficiency.
- Malabsorption.
- Drugs that interfere with folic acid metabolism.
- Disease states that increase cell turnover e.g. psoriasis, leukaemia.
196
Give 3 symptoms of folate deficiency.
- High homocysteine levels.
- Macrocytic anaemia.
- Foetal development abnormalities e.g. NTDs.
197
Give 3 ways of measuring the performance of the pathways of the coagulation cascade.
- Prothrombin time.
- International normalised ratio.
- Activated partial thromboplastin time.
198
What may a prolonged prothrombin time indicate?
A deficiency in synthetic capacity of the liver, however, not specific for liver disease.
Could also be:
- DIC (disseminated intravascular coagulation).
- Severe GI bleeding.
- Some drugs.
- Vitamin K deficiency.
199
What are xenobiotics?
Foreign substances that do not have nutritional value.
200
Give an example of something the body treats as xenobiotics.
Medications.
201
What needs to happen to xenobiotics in the body?
Need to be changed into a safer form by detoxification.
202
Where does detoxification occur?
Mostly in the liver, in the ER (particularly smooth ER). Some occurs in the lungs and small intestines.
203
How many types of xenobiotic biotransformation reactions are there? What are these called?
2 types, named phase I and phase II reactions.
204
What do xenobiotic biotransformation reactions do?
Make the compounds non-toxic and water-soluble.
205
Give an example of a xenobiotic that can skip a phase I biotransformation reaction and go straight to phase II.
Paracetamol; combines with glucuronide, which is carried out by transferases.
206
Give an example of a dietary component that can affect metabolism by the liver.
Grapefruit juice.
207
Give an example of an inducer that affects clozapine metabolism by the liver.
Changes in smoking behaviour.
- Dose may need to increase if someone on clozapine takes up smoking.
- Levels increase after smoking cessation, so dose may need to be reduced to avoid drug toxicity.
208
Give an opiate-based example of an active drug being converted into an active metabolite.
Codeine is de-methylated in the liver to morphine, via a phase I reaction.
209
Give a benzodiazepines-based example of an active drug being converted into an active metabolite.
Diazepam is de-methylated in the liver to nordiazepam, via a phase I reaction.
Nordiazepam is hydroxylated to oxazepam, also phase I reaction.
Oxazepam is metaboliserd by conjugation, a phase II reaction, excreted without a phase I step.
210
Give an example of an inactive drug being converted to an active agent in the liver.
Loratadine -> desloratadine.
211
Where are microsomal enzymes located?
Smooth ER.
Liver, kidneys, lungs, intestinal mucosa.
212
Where are non-microsomal enzymes located?
Cytoplasm and mitochondria.
Hepatocytes and other tissues.
213
Are microsomal enzymes inducible?
Yes; by drugs, diet, environment, etc.
214
Are non-microsomal enzymes inducible?
No, but they have polymorphism.
215
Give 2 examples of microsomal enzymes.
- Mono-oxgenates (CYPs).
- UGTs.
216
Give 4 examples of non-microsomal enzymes.
- Protein oxidases, esterases, amidases, conugases.
217
Which types of reactions are microsomal enzymes involved in?
Majority of biotransformation - oxidative, reductive, hydrolytic, and glucuronidation.
218
Which types of reactions are non-microsomal enzymes involved in?
Non-specific enzymes, catalyse a number of reductive and hydrolytic reactions, as well as conjugation reactions (other than glucuronidation).
219
Give an example of a xenobiotic metabolism which does not fit the category of phase I or phase II biotransformation reactions.
Ethanol metabolism.
220
Give 3 functions of the colon.
- Absorption of water and electrolytes (osmosis).
- Excretion of waste (motility).
- Production of vitamins/regulation of immune system (microbiome).
221
How long is the colon in an adult?
~ 1.5m.
222
Where does the majority of absorption occur in the colon?
The ascending colon and the first part part of the transverse colon.
223
What can happen if the colon is much longer than usual?
Excessive -> redundant colon. Can lead to volvulus or constipation.
224
Give the 6 layers of the colonic wall (lumen -> outward).
- Mucosa.
- Muscularis mucosae.
- Submucosa.
- Muscularis propria.
- Subserosa.
- Serosa.
225
Describe the nerve supply of the colon.
226
What are the 2 parts of the anal sphincter?
Internal anal sphincter and external anal sphincter.
227
Describe the internal anal sphincter.
- Continuation and thickening of rectal smooth muscle.
- Involuntary.
- Controlled by pelvic nerve.
228
Describe the external anal sphincter.
- Striated muscle, circular.
- Voluntary.
229
Give 2 important roles of the anal canal.
- Maintaining continence.
- Evacuating stool.
230
Name the key pelvic floor muscle in supporting the anorectum.
Levator ani muscle.
231
Describe the important aspect of the levator ani muscle.
The puborectalis: sling-like muscle, creates 90 degree angle when contracted, this promotes continence by effectively choking the lower rectum/external sphincter.
232
Explain rectal compliance.
The ability of the rectum to store increasing quantities of stool without the pressure significantly changing.
233
What are the four physiological phases of defecation?
1. Basal.
2. Pre-expulsive.
3. Expulsive.
4. Termination.
234
Describe the basal phase of defecation (colon, rectum, anal sphincter, puborectalis).
Colon - segmental contractions (mixing and absoprtion).
Rectum - motor complexes (bursts of contraction, keeps the rectum empty, a braking mechanism).
Anal sphincter - tonic contraction.
Puborectalis - contracted (90 degree anorectal angle).
235
Describe the pre-expulsive phase of defecation (colon, rectum, anal sphincter, puborectalis).
Colon - high amplitude propagating contraction. Mass movements of stool ~8 times/day (colon -> anorectum), gastro-colic reflex.
Rectum - filling causes distension, rectal compliance.
Anal sphincter - external stays contracted, internal relaxes temporarily for stool sampling.
Puborectalis - remains contracted.
236
Describe the expulsive phase of defecation (rectum, anal sphincter, puborectalis).
Rectum contracts.
Internal and external sphincters relax.
Puborectalis relaxes.
Valsalva manoeuvre.
237
Describe the termination phase of defecation.
Traction loss causes sudden contraction of the external sphincter (closing reflex).
Valsalva ceases.
Change in posture to standing.
238
Define constipation in terms of frequency of stools.
<3 stools per week.
239
Give 2 conditions that can lead to slow bowel. What else could cause constipation?
- Hypothyroidism.
- Diabetes.
Physical blockages such as tumours.
240
What type of disorders may cause obstructive defecation?
Pelvic floor disorders, such as issues with anal sphincter's function.
241
Give 4 diagnostic tests that can be used involving the process of defecation.
- Colonic transit study.
- Defecating proctogram.
- Endo-anal ultrasound.
- Anorectal manometry.
242
Describe a colonic transit study.
Swallow 1 capsule for 3 days containing barium sulphate markers, x-ray later, see how many are left. Normal study = almost all gone.
243
Describe a defecating proctogram.
Insert barium paste into back passage, x-ray to assess anatomy of anal sphincter and surrounding pelvic floor before bearing down, and then as they try to evacuate the paste.
244
Describe an anorectal manometry.
Passing a prove to assess pressure of anal sphincter muscle at rest, and bearing down. There are 256 sensors.
245
What is an endo-anal ultrasound looking for?
Circular muscle of the internal and external anal sphincters to be of uniform thickness, and complete rings.
246
What is faecal incontinence?
Involuntary passage of stool.
247
Give 4 lifestyle factors that can cause loose stool.
Too much:
- Fibre.
- Caffeine.
- Alcohol.
- Spicy foods.
248
What condition may cause reduced rectal capacity?
Crohn's disease.
249
Give 3 groups of medications that can cause loose stools.
- Laxatives.
- Antibiotics.
- NSAIDs.
250
Describe the makeup of an amino acid.
- Amino group.
- Carboxyl group.
- Carbon backbone.
251
Where do humans get their main source of nitrogen?
From dietary proteins.
252
Where do humans have their main loss of nitrogen?
From the gut and kidneys (as urea).
253
How does our body get amino acids?
Some synthesised de novo.
Others termed 'essential' as they must be found in the diet.
254
Discuss the acidity/basicity/neutrality of amino acids.
Can be acidic, basic or neutral.
255
Give an example of a conditionally essential amino acid, and explain why.
Tyrosine can be made from phenylalanine, if someones diet has sufficient phenylalanine they will not need tyrosine in their diet, but if they do not - tyrosine becomes essential.
256
What are amino acids?
Building blocks of proteins and peptides.
257
What affect does essential amino acid deficiency have on nitrogen balance?
Leads to negative nitrogen balance, as if they are not getting an essential amino acid from their diet, it will have to come from a pre-existing protein.
258
Give 5 essential amino acids.
- Phenylalanine.
- Valine.
- Leucine.
- Isoleucine.
- Tryptophan.
259
Give 5 conditionally essential amino acids.
- Cysteine.
- Glycine.
- Glutamine.
- Proline.
- Tyrosine.
260
Give 5 non-essential amino acids.
- Alanine.
- Glutamate.
- Aspartate.
- Asparagine.
- Serine.
261
What is a glucogenic amino acid?
An amino acid that produces gluconeogenic intermediates to produce glucose.
262
What is a ketogenic amino acid?
An amino acid that produces acetyl CoA for ketone bodysynthesis.
263
Which 2 amino acids are solely ketogenic?
- Leucine.
- Lysine.
264
How do amino acids bind to one another?
Peptide bonds: C-terminus of one joins N-terminus of another.
265
Discuss classification of dipeptides, polypeptides and proteins.
Dipeptides = 2 amino acids with a peptide bond.
Polypeptides = number of amino acids with peptide bonds.
Proteins = one or more polypeptides, generally around 50 amino acid residues.
266
Describe the 3 main fates of amino acids.
1. Can be incorporated 'as is' with other amino acids -> peptides and proteins.
2. Modified to form other biomolecules e.g. nucleotide bases and neurotransmitters.
3. Amino group removed and carbon backbone reutilised for energy.
267
How are amino acids stored in the body?
They are not. Any ingested amino acids must be used.
268
Give 3 example of positive nitrogen balance.
- Pregnancy.
- Lactation.
- Anabolic steroids/bodybuilder.
269
Give 3 examples of negative nitrogen balance.
- Severe illness/sepsis/trauma.
- Essential amino acid deficiency.
- Brain injury.
270
Discuss GI proteolysis.
Diet includes some free amino acids, but majority are obtained from dietary protein. Dietary proteins are broken down sequentially in the GI tract to eventually produce amino acids.
271
Which type of cell allows absorption of free amino acids, small peptides and (occasionally) dietary proteins into the portal circulation?
Enterocytes.
272
Which organ creates more circulating proteins (not immunoglobulins)?
The liver.
273
Give 6 important hepatic proteins.
- Albumin
- Coagulation factors.
- IGF-1.
- C-reactive protein.
- Carrier proteins e.g. caeruloplasmin.
- Adolipoproteins.
274
Which hepatic protein is perhaps the most important, and why?
Albumin.
- Responsible for maintaining oncotic presure in blood.
- Important carrier of: sex hormones, magnesium, calcium, drugs, etc.
275
Give 3 non-protein derivatives of glycine.
- Heme.
- Creatinine.
- Purine bases.
276
Give 2 non-protein derivatives of aspartate.
- Purine bases.
- Pyrimidine bases.
277
Give 1 non-protein derivative or arginine.
- Nitric oxide.
278
Give 2 non-protein derivatives of tryptophan.
- Serotonin.
- Melotonin.
279
Give 4 non-protein derivatives of tyrosine.
- Dopamine.
- Catecholamines.
- Thyroid hormones.
- Melanin.
280
What are the catecholamines?
Neurohormones that enable fight or flight response to environmental stimuli.
281
Are all amino acid degradative pathways the same length?
No, they can vary massively.
282
Describe transamination reactions.
Amino groups are removed from amino acids and transferred to acceptor keto-acids to generate the amino acid version of the keto-acid and the keto-acid version of the original amino acid.
283
Name the ketoacid and amino acid that often form one of the ketoacid/amino acid pairs in transamination reactions.
a-ketoglutarate and glutamate.
284
Are transamination reactions reversible?
Yes, by aminotransferase.
285
Describe cystinosis.
-Autosomal recessive genetic condition.
- 1/200,000 chance.
- Defect in transporter leads to a cystine accumulation in tissue lysosomes.
- Eye and kidney problems.
286
Give 1 amino acid that can be synthesised from pyruvate.
Alanine.
287
Give 2 amino acids that can be synthesised from oxaloacetate.
- Aspartate.
- Asparagine.
288
Give 4 amino acids that can be synthesised from alpha-ketoglutarate.
- Glutamate.
- Glutamine.
- Proline.
- Arginine.
289
Give 3 amino acids that can be synthesised from 3-phosphoglycerate.
- Glycine.
- Serine.
- Cysteine.
290
Give 1 amino acid which can be synthesised from phosphoenolpyruvate + ethryos-4-P.
Tyrosine.
291
What is the lifespan of crystallin?
The life of organism.
292
What is the lifespan of haemoglobin?
The life of RBC.
293
What is the half life of ornithine decarboxylase?
11 minutes.
294
What are the 2 main means or protein degradation?
- Proteasome (ubiquitin dependent).
- Lysosome.
295
What is ubiquitin?
A small protein, known as the 'mark of death'.
296
How does ubiquitin work?
Carboxyl group forms isopeptide bond with multiple lysine residues.
297
What are the 3 enzymes involved in ubiquitin binding?
E1: ubiquitin-activating.
E2: ubiquitin-conjugating.
E3: ubiquitin-protein ligase.
298
At what point does the ubiquitin signal for death become significantly strong?
Formation of a ubiquitin chain made up of more than 4 ubiquitins.
299
Which structures regulate which proteins may enter the proteasome for destruction?
The caps.
300
Explain the N-terminal rule.
- The amino acid at the N-terminal determines a proteins half-life.
- There are stabilising N-terminal residues and destabilising ones.
- Stabilising = longer half-life.
- Destabilising = shorter half-life.
301
Give 3 stabilising N-terminal residues.
- Alanine.
- Cysteine.
- Glycine.
302
Give 3 destabilising N-terminal residues.
- Lysine.
- Leucine.
- Tyrosine.
303
Do lysosomes only break down proteins?
No, they can break down a range of things.
304
What are the 2 non-selective protein degradation methods of lysosomes?
- Macroautophagy.
- Microautophagy.
305
Name the selective protein degradation method of lysosomes?
Chaperone-mediated autophagy.
306
What do lysosomes use endocytosis and phagocytosis for?
Extracellular substances, for example when there is an infection.
307
Name 5 key players in amino acid catabolism.
- Alanine (AA).
- Glutamine (AA).
- Cortisol.
- Glucagon.
- Branched-chain amino acids (BCAAs).
308
Give 7 core clinical problems with proteins synthesis in the liver.
- Oedema.
- Abdominal mass.
- Burns.
- Bleeding.
- Haematemesis.
- Rectal bleeding.
- Enlarged liver/ hepatomegaly.
309
Give 6 causes of hypoalbuminaema.
- Inflammation.
- Liver disease.
- Renal disease.
- Burns/trauma.
- Sepsis.
- Malnutrition.
310
Give 3 consequences of hypoalbuminaemia.
- Oedema.
- Effusions.
- Carrier protein (may need to adjust for this).
311
Give 5 core clinical problems with the urea cycle.
- Confusion/delirium.
- Loss of consciousness/coma.
- Seizure.
- Deterioration of intellect.
- Learning difficulty.
312
Discuss ammonia derived from amino acids.
- Extremely toxic.
- Converted to non-toxic urea for urinary excretion.
- Any that evades detoxification as urea, is incorporated into glutamine by glutamine synthetase.
313
Describe the presentation of severe ammonia toxicity.
- Decerebrate posturing (legs extended, internally rotated, arms straight down sides).
- Doll's eyes movements (vestibular-ocular reflex).
314
Describe the presentation of OTC deficiency.
- Late onset.
- Very variable.
- Triad: encephalopathy, respiratory alkalosis, hyperammonaemia.
315
Give 7 treatments for urea cycle problems/ hyperammonaemia.
- Avoidance of catabolism.
- Induction of anabolism.
- Low dietary protein -> decrease ammonia.
- Haemofiltration.
- Liver transplanation.
- Umbilical vein hepatocyte transfusion.
- Gene therapy.
