Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Phase 1 > GI 🤮 > Flashcards

GI 🤮 Flashcards

1
Q

What are the functions of the stomach?

A

Store and mix food
Dissolve and continue digestion
Regulate emptying into duodenum
Kill microbes
Secrete (inactivated) proteases
Secrete intrinsic factor
Activate proteases
Lubrication
Mucosal protection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the purpose of intrinsic factor?

A

Binds to vitamin b-12 and allows it to be absorbed in the ileum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Key cell types in the stomach

A

Mucous cells

Parietal cells

Chief cells

Enteroendocrine cells- produce hormones e.g gastrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe gastric acid secretion in the stomach

A

Hydrochloric acid
Approx 2 litres/day
[H+] >150mM -> need to pump them against the conc. gradient
Parietal cells
Energy dependent
Neurohumoral regulation- part controlled by brain and part by glands near stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens in parietal cells to produce stomach acid?

A

In parietal cells-
-water splits into OH- and H+
-K+ ions into the cell against conc. gradient
-H+ ions out of cell against conc. gradient
-Both processes need ATP
-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the cephalic phase of switching on gastric acid secretion

A

Parasympathetic nervous system
Sight, smell, taste of food, and chewing
Acetylcholine release
ACh acts directly on parietal cells
ACh triggers release of gastrin and histamine
Net effect = increased acid production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the gastric phase of turning on gastric acid secretion

A

Gastric distension, presence of peptides and amino acids
Gastrin release
Gastrin acts directly on parietal cells
Gastrin triggers release of histamine
Net effect = increased acid production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of histamine in the gastric phase?

A

Histamine acts directly on parietal cells

Acts directly but also mediates effects of gastrin and acetylcholine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the protein in the stomach during switching on gastric acid secretion

A

Direct stimulus for gastrin release

Proteins in the lumen act as a buffer, mopping up H+ ions, causing pH to rise:
decreased secretion of somatostatin
more parietal cell activity (lack of inhibition)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the gastric phase of turning off gastric acid secretion

A

Low luminal pH (high [H+])
Directly inhibits gastrin secretion
Indirectly inhibits histamine release (via gastrin)
Stimulates somatostatin release which inhibits parietal cell activity
Negative feedback loop

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What things in the duodenum stimulate the switching off of gastric acid secretion?

A

Duodenal distension- usually not distended
Low luminal pH
Hypertonic luminal contents
Presence of amino acids and fatty acids
Trigger release of enterogastrones:
Secretin (inhibits gastrin release, promotes somatostatin release)
Cholecystokinin (CCK)

And short and long neural pathways, reducing ACh release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Outline the duodenal phase of switching off gastric acid secretion

A

Trigger release of enterogastrones:
Secretin (inhibits gastrin release, promotes somatostatin release)
Cholecystokinin (CCK)

And short and long neural pathways, reducing ACh release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which signalling molecules turn on gastric acid secretion?

A

Gastrin- hormone
Acetylcholine- neurotransmitter
Histamine- paracrine factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which paracrine factors turns gastric acid production off?

A

Somatostatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Define and list the causes of peptic ulcers

A

Definition:
An ulcer is a breach in a mucosal surface

Causes:
Helicobacter pylori infection
Drugs – NSAIDS
Chemical irritants – alcohol, bile salts, ? Dietary factors
Gastrinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does the gastric mucosa defend itself?

A

Alkaline mucus (bicarbonate rich- forms a barrier)
Tight junctions between epithelial cells
Replacement of damaged cells
Feedback loops

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does Helicobacter pylori cause peptic ulcers?

A

Lives in the gastric mucus
Secretes urease, splitting urea into CO2 + ammonia
Ammonia + H+ = Ammonium
Ammonium, secreted proteases, phospholipases and vacuolating cytotoxin A damage gastric epithelium
Inflammatory response
Reduced mucosal defence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do NSAIDs cause peptic ulcers?

A

Non-steroidal anti-inflammatory drugs
Mucus secretion is stimulated by prostaglandins
Cyclo-oxygenase 1 needed for prostaglandin synthesis
NSAIDs inhibit cyclo-oxygenase 1
Reduced mucosal defence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do bile salts cause peptic ulcers?

A

Duodeno-gastric reflux
Regurgitated bile strips away mucus layer
Reduced mucosal defence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How to treat peptic ulcer disease caused by H-pylori?

A

Eradicate the organism!
Triple therapy: 1 proton pump inhibitor
2 antibiotics
clarithromycin
amoxicillin
tetracycline
metronidazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How to treat peptic ulcer disease caused by NSAIDs?

A

Prostaglandin analogues – misoprostol

Reduce acid secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are some proton pump inhibitors?

A

Omeprazole
Lansoprazole
Esomeprazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some H2 receptor antagonists?

A

Cimetidine, Ranitidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe protease secretion

A

Chief cells produce pepsinogen

Synthesised in inactive form (zymogen)

Pepsinogen mediated by input from enteric nervous system (ACh)

Secretion parallels HCl secretion

Luminal activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe protease activation

A

Conversion of pepsinogen to pepsin is pH dependent

Most efficient when pH <2

Positive feedback loop (Pepsin also catalyses the reaction)

Pepsin only active at low pH. Irreversible inactivation in small intestine by HCO3-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Role of pepsin in protein digestion

A

Not essential (protein digestion can occur if the stomach is removed)

Accelerates protein digestion

Normally accounts for ~20% of total protein digestion

Breaks down collagen in meat – helps shred meat into smaller pieces with greater surface area for digestion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the stomach volumes?

A

Empty stomach has volume of ~50mL

When eating, can accommodate ~1.5L with little increase in luminal pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is receptive relaxation?

A

The smooth muscles of the stomach relax when stimulated by the presence of food

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What mediates and coordinated receptive relaxation?

A

Mediated by parasympathetic nervous system acting on enteric nerve plexuses

Coordination – afferent input via Vagus nerve

Nitric oxide and serotonin released by enteric nerves mediate relaxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe the mechanism of peristalsis in the stomach

A

Peristaltic waves begin in gastric body
Weak contraction in body (little mixing) towards the pylorus
More powerful contraction in gastric antrum
Pylorus closes as peristaltic wave reaches it
Little chyme enters duodenum
Antral contents forced back towards body (mixing)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Describe the basic electrical rhythm of the stomach

A

Frequency of peristaltic waves determined by pacemaker cells in muscularis propria and is constant (3/minute)

Pacemaker cells (interstitial cells of cajal) undergo slow depolarisation-repolarisation cycles

Depolarisation waves transmitted through gap junctions to adjacent smooth muscle cells

Do not cause significant contraction in empty stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Describe the varying strength of peristaltic contractions

A

Excitatory neurotransmitters and hormones further depolarise membranes

Action potentials generated when threshold reached

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How is the strength of peristaltic contractions increased?

A

Gastrin
Gastric distension (medicated by mechanoreceptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How is the strength of peristaltic contractions decreased?

A

Duodenal distension
Increased Duodenal luminal fat
Increased Duodenal osmolarity
Decreased Duodenal luminal pH
Increased Sympathetic NS action
Decreased Parasympathetic NS action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Describe gastric emptying

A

Capacity of stomach > capacity of duodenum

Overfilling of duodenum by a hypertonic solution causes dumping syndrome:
Vomiting, bloating, cramps, diarrhoea, dizziness, fatigue
Weakness, sweating, dizziness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Describe the response of the duodenum to gastric emptying

A

After duodenum takes in material from the stomach
increased Secretion of enterogastrones
Stimulates neural receptors
Both lead to gastric emptying

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Pathway of glucose in the body

A

Intestine-> blood-> liver -> brain, muscle, RBC, adipocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Describe glucose in the liver

A

insulin stimulates it to take up glucose
Then converted into glycogen or acetyl CoA
From acetyl CoA you can either make ATP from the krebs cycle or converted into triglycerides and then into VLDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Glucose in the muscle

A

Insulin promotes uptake and it is converted to glycogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Glucose in the brain

A

Needs constant supply of glucose from the blood
Converts to ATP via Krebs cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Glucose in RBCS

A

Need constant supply of glucose
Converts it to lactate and pyruvate as no mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Glucose in Adipocytes

A

Uptake stimulated by insulin
Converts to ATP and Triglycerides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Amino acids

A

Absorbed by intestines
In cells converted to protein, other compounds e.g peptide hormones
Can also be used in the krebs cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Triglycerides

A

Absorbed by intestines
Combined with protein
Forms Chylomicrons
Carried in the lymphatic system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Main storage of energy

A

Triglycerides in adipose tissue
Glycogen in liver & muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Describe the release of glucose in a short fast

A

Glycogen broken down into glucose
Stimulated by glucagon
Glycogenolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Describe the release of glucose in a longer fast

A

Not glycogen
AAs, lactate and glycerol broken down in liver and uses it to create glucose
Gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Describe the action of fats during fasting

A

Glucagon stimulates triglycerides to break down into glycerol and fatty acids
gycerol-> glucose
Fatty acids either used by kidneys and muscle or broken down into ketones
Lipolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Describe the release of energy in prolonged fasting

A

Decreased use of ketones in muscles
Fatty acids converted to ketones in the liver (ketogenesis) which can supply the brain rather than glucose so glucose is available for RBCs
Decreased gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What substances can be measured to check metabolism?

A

Glucose, Ketones, Insulin, lactate, Triglycerides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Hormones that regulate fuel metabolism

A

Growth Hormone
Somatostatin
Cortisol- adrenals, stress
Adrenaline+ Noradrenaline- fight or flight
Thyroxine
Insulin + glucagon-> glucose regulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Is insulin anabolic or catabolic and what does it do?

A

Anabolic
Glycogen storage
Fat storage
Protein synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Is glucagon anabolic or catabolic and what does it do?

A

Catabolic
Glycogenolysis
Gluconeogenesis
Ketogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What are DIT and BMR

A

DIT-energy to break down food
BMR- basic amount of energy we need to survive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are the factors contributing to obesity?

A

Genetics
Environment
Energy dysregulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is leptin?

A

Produced by fat cells and acts on the brain
In normal weight
supresses appetite
In obesity
High leptin levels
Leptin resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is ghrelin?

A

Released by stomach cells and stimulates the brain to relax the stomach
Increases before meals
Stimulates appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What functions does the liver perform?

A

-Carbohydrate metabolism
-Fat metabolism
-Protein metabolism
-Hormone metabolism
-Toxin/Drug metabolism and excretion
-Storage
-Bilirubin metabolism and excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Where is iron used?

A

Haemoglobin in RBCs
Myoglobin in muscles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is ferritin?

A

Large spherical protein consisting of 24 noncovalently linked subunits
Subunits form a shell surrounding a central core.
Core contains up to 5000 atoms of iron.
Ferritin found in the cytoplasm of cells but can also be found in the serum.
Concentration of ferritin is directly proportional to the total iron stores in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Excess iron storage disorders

A

Hereditary haemochromatosis
Haemolytic anaemia
Sideroblastic anaemia
Multiple blood transfusions
Iron replacement therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Examples of non-iron iron overload ferritin excess

A

Liver disease
Some malignancies
Significant tissue destruction
Acute phase response:
-Inflammation
-Infection
-Autoimmune disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Describe ferritin deficiency

A

The only known cause of a low ferritin is iron deficiency.
This can result in anaemia.
Ferritin less than 20 µg/L indicates depletion
Ferritin less than 12 µg/L suggests a complete absence of stored iron.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Describe the importance of vitamins in the diet

A

Usually vitamins are provided in the diet.
Characteristic disorders when someone is vitamin deficient
Recommended daily allowance (RDA)
Adequate intake (AI) where no evidence to determine RDA
Vitamins act as:
Gene activators
Free-radical scavengers
Coenzymes or cofactors in metabolic reactions
Excessive vitamin ingestion can result in toxicity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What are the difference between water soluble and fat soluble vitamins?

A

Water- BC
Fat- ADEK
Water soluble vitamins pass more readily through the body, therefore, require more regular intake than fat soluble vitamins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Describe the types of vitamin A in the body

A

Retinols- Vertebrates ingest retinal directly from meat or produce retinal from carotenes: liver cereals, eggs, dairy
Carotenoids- Tomato, spinach, carrots

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What is vitamin A functions?

A

Vision:
Used to form rhodopsin in the rod cells in the retina.
Reproduction:
Spermatogenesis in male
Prevention of foetal resorption of female
Growth
Stabilisation of cellular membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Describe vitamin A deficiency

A

Rare in affluent countries as vitamin A levels drop only when liver stores are severely depleted.
Deficiency may occur due to fat malabsorption
Clinical Features:
Night blindness
Xeropthalmia
Blindness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Describe vitamin A excess

A

Acute:
Abdominal pain, nausea and vomiting
Severe headaches, dizziness, sluggishness and irritability
Desquamation of the skin
Chronic:
-Joint and bone pain
-Hair loss, dryness of the lips
-Anorexia
-Weight loss and hepatomegaly
Carotenemia:
-Reversible yellowing of the skin
-Does not cause toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Describe Vitamin D functions

A

Increased intestinal absorption of calcium
Resorption and formation of bone
Reduced renal excretion of calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Describe vitamin D deficiency

A

Demineralisation of bone:
Rickets in children
Osteomalacia in adults

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

How vitamin D

A

Sunlight converts 7-Dehydrocholesterol to vitamin D3 (cholecalciferol)
This is combined with dietary vitamin D3 and D2 to form 25-hydroxyvitamin D3 in the liver
Then this is converted to 1,25-dihydroxyvitamin D3 in the kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Describe vitamin E in the body

A

Stored in:
Non-adipose cells such as liver and plasma – labile and fixed pool
Adipose cells – fixed pool
Important antioxidant
Vitamin E requirements:
4 mg/day in men
3 mg/day in women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Describe vitamin E deficiency

A

Deficiency
Caused by:
Fat malabsorption (e.g. cystic fibrosis)
Premature infants
Rare congenital defects in fat metabolism e.g. abetalipoproteinaemia.

Clinical manifestations:
Haemolytic anaemia
Myopathy
Retinopathy
Ataxia
Neuropathy

Vitamin E excess is relatively safe in excess

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Describe vitamin K sources and uptake

A

Vitamin K is rapidly taken up by the liver but then is transferred to very low-density lipoproteins and low density lipoproteins which carry it into the plasma.

Sources:
Vitamin K1 (phylloquinone)
Synthesized by plants and present in food
Vitamin K2 (menaquinone)
Synthesized in humans by intestinal bacteria
Synthetic vitamin K’s:
K3 (menadione)
K4 (menadiol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What are vitamin K functions?

A

Vitamin K is responsible for the activation of some blood clotting factors.
Necessary for liver synthesis of plasma clotting factors II, VII, IX and X.
Can be assessed by measuring prothrombin time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Describe vitamin K deficiency

A

Haemorrhagic disease of the newborn:
Vitamin K injection given to newborn babies
Rare in adults, unless on warfarin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Describe excess vitamin K

A

K1 is relatively safe
Synthetic forms are more toxic
Can result in oxidative damage, red cell fragility and formation of methaemoglobin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Describe vitamin C sources and functions

A

Found in:
Fresh fruit and vegetables
Adults need 40 mg/day

Functions:
Collagen synthesis
Antioxidant
Iron absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Describe vitamin C deficiency

A

Scurvy
Easy bruising and bleeding
Teeth and gum disease
Hair loss

Treatment with vitamin C improves symptoms quickly
Joint pain gone within 48 hours
Full recovery within two weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Describe vitamin C excess

A

Doses > 1g/day can cause GI side effects
No evidence that increased vitamin C reduces the incidence or duration of colds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Describe vitamin B12 (Cobalamins)

A

Two active forms:
Methylcobalamin
5-deoxyadenosylcobalamin
Released from food by acid and enzymes in the stomach
Binds to R protein to protect it from stomach acid
Released from R proteins by pancreatic polypeptide.
Intrinsic factor (IF) produced by the stomach needed for absorption.
IF-B12 complex absorbed in the terminal ileum.
B12 is stored in the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Describe vitamin B12 deficiency

A

Causes:
Pernicious anaemia – autoimmune destruction of IF-producing cells in stomach.
Malabsorption – lack of stomach acid, pancreatic disease, small bowel disease.
Veganism

Symptoms:
Macrocytic anaemia
Peripheral neuropathy in prolonged deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What is folate and what is it used for?

A

Folate is found in may foods fortified with folic acid.
Individuals have higher requirements in pregnancy.

Functions as a coenzyme in methylation reactions, DNA synthesis, synthesis of methionine from homocysteine.

86
Q

Describe folate deficiency causes and symptoms

A

Causes:
Malabsorption
Drugs that interfere with folic acid metabolism (anticonvulsants, methotrexate)
Disease states that increase cell turnover (e.g. leukaemia, haemolytic anaemia, psoriasis)

Symptoms:
High homocysteine levels
Macrocytic anaemia
Foetal development abnormalities (neural tube defects)

87
Q
A

Intrinsic pathway activated by contact.
Extrinsic pathway activated by FVII coming in contact with tissue factor.
Initiates a cascade which ultimately results in fibrin clot formation.

88
Q

What are the clotting factors produced in the liver?

A

Produced in the liver
I (Fibrinogen)
II (Prothrombin)
IV
V
VI
VII

89
Q

How can clotting factors be measured and what does prolonged PT show?

A

The performance of the clotting pathways can be measured using:
Prothrombin time (PT) (extrinsic pathway)
International normalised ratio (INR)
Activated partial thromboplastin time (aPTT) (intrinsic pathway)
A prolonged PT may indicate a deficiency in the synthetic capacity of the liver.
Prolonged PT is not specific for liver disease:
DIC
Severe GI bleeding
Some drugs
Vitamin K deficiency

90
Q

What are xenobiotics?

A

Xenobiotics are foreign substances that don’t have nutritional value. Xenobiotic compounds are mostly in the diet, but we also breathe in potential toxins, and importantly the body treats medications as xenobiotics.
These unwanted compounds need to be changed into a safer form by detoxification.

91
Q

What are the 2 main types of xenobiotic transformation reactions

A

Phase 1 and Phase 2, usually make the compounds non-toxic and water-soluble.

92
Q

What does phase I of biotransformation do

A

Functionalisation- non synthethic
Add or expose functional groups- -OH, -SH, -NH2, -COOH

93
Q

What does phase II of biotransformation reactions do?

A

Conjugation- Biosynthetic
Conjugation with endogenous molecules: glucuronic acid, sulphate, glutathione
Covakent bonds formed

94
Q

Are glucuronides polar?

A

Glucuronides are polar (hydrophilic) as the glucuronyl group has a number of hydroxyl groups which make the molecule polar and facilitate excretion in the urine.

95
Q

What detoxidication happens in the liver

A
  • inactivation and facilitated elimination of drugs and other xenobiotics
  • active metabolites formed, with similar or occasionally enhanced activity
  • activation of pro-drugs
  • toxification of less toxic xenobiotics
96
Q

Where in the liver does the detoxification take place?

A

Most biotransformation in the liver occurs in the endoplasmic reticulum, specifically smooth endoplasmic reticulum.

97
Q

Describe cytochrome P450 enzymes genotypes

A

Cytochrome-P450 enzymes are encoded by a superfamily of more than 50 different genes in humans.

98
Q

What features do all P450 enzymes have in common?

A

They are present in the smooth Endoplasmic Reticulum (hence called “microsomal” enzymes).
They all oxidise the substrate and reduce oxygen
They have a cytochrome reductase subunit which uses NADPH,
They are inducible – enzyme activity may be increased by certain drugs, some dietary components, and some environmental toxins eg smoking,
They generate a reactive free radical compound.

99
Q

How can cytochrome P450 be used?

A

As well as enzyme induction by medication, these enzymes can be induced by some dietary components, and some environmental toxins such as smoking.

100
Q

2 most common cytochrome P450 enzymes

A

Induction: one drug can induce numerous cytochrome isoenzymes.
Genetics: Note genetic variation especially in CYP2D6

101
Q

Describe some drug interactions with cytochrome P450

A

One of the commonest mechanisms of drug interactions is via cytochrome P450.
Cytochrome P450 enzymes are inducible, which may accelerate the breakdown of some medications;
- Example; phenytoin and rifampicin can result in enzyme induction with accelerated breakdown of a wide variety of medications (accelerated breakdown);

Cytochrome P450 enzymes can be inhibited by various drugs and foodstuffs (usually takes effect quicker than induction);
- inhibition can result in increased blood concentrations of certain medications (less breakdown).

102
Q

How is cytochrome P450 inhibited?

A

An example of enzyme inhibition that is sometimes in the popular press is inhibition of a cytochrome P450 by compounds in dietary components such as grapefruit juice.
A lot of medications are metabolised in Phase I by CYP3A4.
Most statins are metabolised by CYP3A4.
By inhibiting metabolism of simvastatin and atorvastatin, grapefruit juice causes increased blood levels with increased risk of side-effects.

103
Q

How does smoking link to clozapine?

A

Changes in smoking behaviour can significantly alter clozapine metabolism.
The clozapine dose may need to be increased if someone on clozapine takes up smoking.
Clozapine levels increase after cessation of smoking, which means a dose reduction of 30-50% may be required to avoid drug toxicity.

104
Q

Describe some conversions from active and inactive drugs to active or inactive metabolites

A

Active Drug to Inactive Metabolite
Phenobarbital Glucuronides etc
Active Drug to Active Metabolite
Codeine Morphine
Diazepam oxazepamInactive Drug to Active Metabolite

Clopidogrel Active drug
Active Drug to Reactive Intermediate
Benzo[a]pyrene Reactive metabolite
(carcinogenic)
Paracetamol NAPQI (toxic)

105
Q

Describe the inactivation of xenobiotic

A

An illustration is Phenobarbital which is a barbiturate derivative with both sedative and anti-epileptic activity, metabolised in classic Phase I & Phase II reactions,

Phenobarbital is relatively lipophilic; drug distributes into fat tissue.
The amount that remains in the plasma is mostly bound to plasma proteins.
only a small fraction of the drug is found freely dissolved in the blood plasma,
Elimination of the unmodified drug is thus very slow, and most of the drug is excreted after enzymatic conjugation.

106
Q

Describe the conversion of active drug to active metabolites in opiates

A

Codeine is a morphine molecule with one hydroxyl group replaced by a methyl group which makes the compound less susceptible to first-pass metabolism (in gut mucosa and liver).
Codeine is active, and is de-methylated in the liver to morphine which is also active.

107
Q

Describe active drug to active metabolites

A

Diazepam is demethylated in the liver (a phase-1 reaction) to nordiazepam (an active metabolite).
Nordiazepam is hydroxylated (also a phase-1 reaction) to oxazepam.
Oxazepam is also an active metabolite, and can be prescribed as a shorter-acting sedative. Oxazepam is metabolised by conjugation (phase-2) and excreted without any phase-1 step.

108
Q

Describe the pro-drug to active drug pathway

A

An inactive drug or pro-drug may be converted in the liver to an active agent.

For example Loratadine, a non-sedating antihistamine, is the prodrug of desloratadine, which is largely responsible for the antihistaminergic effects of the parent compound.
Similarly clopidogrel is a pro-drug. Conversion to the active form varies with variations in CYP activity, including genetic variations.

109
Q

How to tell if it is small or large intestine on an x-ray?

A

Plicae circularis on small bowel Lines go all the way across
Haustral folds on large intestine- lines don’t go all the way across

110
Q

Functions of the colon

A

Absorption of water and electrolytes (osmosis)
Excretion of waste (motility)
Production of vitamins/regulation of immune system (microbiome)

111
Q

Describe redundant colon and the conditions it causes

A

Constipation
twisting of the bowel

112
Q

Describe the layers of the colonic wall from inside to outside

A

Mucosa
Muscularis mucosae
Submucosa
Muscularis propria
Subserosa
Serosa

113
Q

Describe the colonic mucosa

A

Single layer columnar epithelium
Goblet cells- secrete mucin that lubricates the bowel
Lamina Propria - Inflammatory cells- helps maintain immunological homeostasis

114
Q

Describe the muscularis propria

A

Inner circular muscle (CM) – mass movement by peristalsis- contain cells of cajal which regulates the contraction of the bowel
Auerbach Nerve Plexus- myenteric plexus
Longitudinal muscle (LM) – segmental motility- creates haustra

115
Q

Describe the nerve supply to the colon and rectum

A

Enteric Nervous System- little brain
Intrinsic -
Myenteric Plexus
Submucosal Plexus
Extrinsic -
Parasympathetic- anoreactal control- non-conscious control
Sympathetic- conscious control

116
Q

Parasympathetic defecation reflex

A

stretching which stimulates stretch receptors
info to the brain which sends a message via pelvic nerve so they

117
Q

Describe the rectum

A

temporary storage for stool
can store lots with little increase of pressure

118
Q

internal anal sphyncter

A
119
Q

External anal sphyncter

A

ring
conscious control

120
Q

Describe the puborectalis

A

at rest creates 90 degree angle

121
Q

What are the four phases of defecation?

A
  1. Basal
  2. Pre-expulsive
  3. Expulsive
  4. Termination
122
Q

Describe the basal phase

A

Colon – segmental contractions (mixing)

Rectum - motor complexes (to keep rectum empty)
“braking mechanism”

Anal Sphincter - tonic contraction

Puborectalis - contracted (90o anorectal angle)

123
Q

Describe the pre-expulsive phase in the colon

A

Colon – high amplitude propagating contractions
Mass movement of stool ~8 times day
Gastro-colic reflex

124
Q

Describe the pre-expulsive phase in the rectum

A

Rectum –
Fills causing distension
Rectal compliance (adaptive relaxation)

125
Q

Describe the pre-expulsive phase in the anal sphincter and puborectalis

A

Anal Sphincter –
EAS maintains contraction
Reflex relaxation of IAS (RAIR) – for stool sampling
Puborectalis – remains contracted

126
Q

Describe the expulsive phase

A

Rectum contracts
IAS, EAS and PR relaxes
Valsalva manoeuvre/posture
aid emptying

127
Q

Describe the termination phase

A

Traction loss causes sudden contraction of EAS (“closing reflex”)

Valsalva ceases

Change in posture (to standing)

128
Q

What are some causes of constipation?

A

Consistency of stool
Bowel motility
Physical blockage to the bowel
Pelvic floor disorders

129
Q

Describe a colonic transit study

A
130
Q

Defecating postogram

A

To test for anatomical anomalies
barium paste inserted into anus and then x-rayed

131
Q

Anorectal manometry

A

Probe inserted- allows us to assess pressure
at rest and during

132
Q

Describe causes of faecal incontinence

A

Consistency of stool or frequency of movements
Diseased bowel mucosa
Reduced rectal capacity
Pelvic floor disorder

133
Q

Describe the endo-anal ultrasound

A

looking for circular anal sphynters

134
Q

What is an amino acid?

A

It is the building block of protein. All human proteins can be formed from chains formed of 20 different amino acids.
There are more than 20 amino acids. Some have a role in human health, such as homocysteine, but are not actually incorporated into human proteins.

135
Q

Where do we get protein from

A

Dietary protein (0.75g/kg/day)

136
Q

Where are aas in the body?

A

METABOLIC PRECURSORS
(Glycolysis and TCA cycle intermediates, Acetyl CoA)
Freee aa pool
Proteins (around 10kg)

137
Q

Where is nitrogen lost?

A

Renal excret

138
Q

add in cards

A
139
Q

Describe aa metabolism

A
140
Q

How is dietary protein absorbed

A

Dietary protein — pepsin and HCl in stomach—-> denatured protein——

141
Q

What are essential amino acids?

A

Need to have it in your diet and can’t synthesis it

e.g phenylalanine and valine

142
Q

Conditionally essential meaning

A

Can synthesise them but needs an essential amino acid to make them

143
Q

What are non-essential amino acids?

A

Can synthesise them de novo

144
Q

Some important hepatic proteins

A

ALBUMIN
Coagulation Factors
IGF-1
C-Reactive Protein
Carrier proteins (eg caeruloplasmin)
Apolipoproteins (for lipoproteins

145
Q

slide 15

A
146
Q

How can aas be used in the TCA cycle?

A

Some aas are

147
Q

Degradative pathway length from aas to

A

PKU

148
Q

Describe transamination

A
149
Q

Transamination of alanine

A

Alanine + alpha Ketoglutarate -> pyruvate + glutamate

150
Q
A

no storage of amino acids so take it from bodily protein

151
Q

Describe protein degradation

A

Faulty/aging/obsolete proteins
Signal transduction
Flexible system to meet protein/energy requirements of environment

Main means:
1. PROTEASOME (ubiquitin-dependent)
2. LYSOSOME

152
Q

What is ubiquitin (the mark of death)

A

Small protein

Carboxyl group forms isopeptide bond with multiple Lysine residues

Three enzymes involved:
E1 Ubiquitin-activating enzyme
E2 Ubiquitin-conjugating enzyme
E3 Ubiquitin-protein ligase

Formation of ubiquitin chains (stronger signal, esp if >4)

153
Q

Describe the proteosome

A

caps- interact with ubiquitin
Proteasome

154
Q

What is the N-terminal rule?

A

N-terminal residues determine protein half-life

PEST Sequences (proline, glutamate, serine, threonine)

Cyclin Destruction Box
some are stabilising N- terminal residues e.g alanine and glycine

Some are destabilising N- terminal residues e.g lysine and arginine

155
Q

Describe lysosomal

A

Proteolytic enzymes within lysosome separated from cytosolic components

156
Q

What is macroautophagy?

A

non-selective
ER derived autophagisomes engulf cytosolic proteins/aggregates organelles. Lysosome fuses with this to initiate proteolysis.

157
Q

What is microautophagy?

A

non-selective
Invaginations of lysosomal membrane engulf proteins/organelles.

158
Q

What is chaperone-mediated autophagy?

A

selective
Chaperone protein hsc70, in cytosol and intralysosomal, accompany specific cytosolic proteins in response to stressors (fasting/ oxidative stress etc).

159
Q

What is endocytosis/ phagocytosis of?

A

Extracellular substances.

160
Q

What is cystinosis

A

Genetic condition
Autosomal recessive
1 in 200,000

Defect in transporter leads to cystine accumulation in tissue lysosomes

Eye and kidney problems
Crystalisation occurs

161
Q

What does Alanine do in amino acid catabolism?

A

Glucose-alanine cycle transports nitrogen from amino acid breakdown from the tissues to the liver, whilst recycling a carbon backbone that can be converted to glucose for energy.

162
Q

What does cortisol do in amino acid catabolism?

A

+ Proteolysis
- Protein synthesis
+ Gluconeogenesis

163
Q

What does glutamine do in amino acid catabolism?

A

Glutamine is formed from BCAA degradation in the tissues. In the fasting state, it is an important metabolic fuel for the kidney and gut, and provides ammonia to buffer proton diuresis in metabolic acidosis states.

164
Q

What is the role of glucagon in amino acid catabolism?

A

+ Glycogenolysis
+ Gluconeogenesis
+ Amino Acid degradation
+ Ureagenesis
+ Entry of Amino Acids to Liver

165
Q

Describe the role of branched chain aas in amino acid catabolism

A

Isoleucine/Valine/Leucine. Major amino acids that can be oxidised in tissues other than the liver, especially skeletal muscle.-

166
Q

What are the major proteins synthesised in the liver?

A

Most plasma proteins (except for immunoglobulins) including:
Albumin
CRP
Hormone binding globulins
Apolipoproteins
Other transport proteins
Caeruloplasmin
Ferritin
All factors in the complement cascade
Parts of the following pathways:
Inhibitors of clotting
Fibrinolysis
Inhibitors of fibrinolysis
Complement

167
Q

Describe albumin

A

~Properties:
66 kDalton protein
Negatively charged
10-15g produced by the liver per day

Functions:
Plasma oncotic pressure
Carrier protein:
Hormones
Vitamins
Electrolytes (Ca2+, Mg2+, etc)
Drugs

168
Q

What are some causes of hypoalbuminaemia?

A

Inflammation
Liver disease
Renal disease
Burns/trauma
Sepsis
Malnutrition

169
Q

What are some consequences of hypoalbuminaemia?

A

Oedema
Effusions
Carrier protein – may need to adjust for this

170
Q

What are some albumin calculations?

A

Exudates vs Transudates
Adjusting for electrolytes – esp Ca2+
Adjusting for hormone levels – eg free testosterone
Renal disease

171
Q

What are some of the key features of the clotting cascade?

A

Made in liver: Fibrinogen, Prothrombin, Factors V, VII, IX, X, XI, XII, XIII, Protein C, Protein S
Vitamin K: Essential factor to the hepatic gamma-glutamyl carboxylase that adds a carboxyl group to glutamic acid residues on factors II, VII, IX and X
(see slide 9 of protein synthesis and urea cycle lecture)

172
Q

What is the link between chronic liver disease and bleeding?

A

Reduced synthesis of clotting factors
Hepatic dysfunction
Vitamin K deficiency/malabsorption
Reduced synthesis of inhibitors
Production of abnormal/dysfunctional proteins
Enhanced fibrolytic activity
Reduced clearance of activators of fibrinolysis
Reduced production of inhibitors
Reduced hepatic clearance of clotting factors
Disseminated intravascular coagulation
Multifactorial – includes endotoxaemia
Platelet abnormalities
Number
Function
Development of varices!

173
Q

What are some core clinical problems of the urea cycle?

A

15 – Confusion/delirium
16 – Loss of consciousness/coma
23 – Seizure
32 – Deterioration of intellect
34 – Learning difficulty

Most because of toxicity

174
Q

What is the significance of NH4+?

A

It is a product of amino acid breakdown
can either be used again in amino acids or excreted

175
Q

Describe the glucose-alanine cycle

A
176
Q

Describe the Krebs bicycle

A

A

177
Q

What are the 2 ways that ammonia enters the urea cycle?

A
178
Q

How does ammonia lead to neurotoxicity?

A

lead to brain swelling and damage

179
Q
A
180
Q

What are some key features of OTC?

A

Late onset, very variable:
male, 16th birthday, vomiting, encephalopathy, diagnosed, died.
male, 17, Scout camp, drowsy, vomiting, swollen brain, died.
female, 51, protein avoidance, P2+1, ops, 6 admissions 2002-3.
Triad: encephalopathy, resp. alkalosis, hyperammonaemia
Plasma ammonia

181
Q

Describe treatment of urea cycle disorders

A

Avoidance of catabolism, glucose polymers when unwell
Induction of anabolism – give dextrose 10% 2ml/kg/hr -> insulin!
Low dietary protein, arginine, benzoate, phenylbutyrate
Haemofiltration
Liver transplantation, umbilical vein hepatocyte transfusion
Gene therapy: NIH NGVL UPenn trial stopped after death (adenovirus E1 E4 del., fever, multi-organ failure)

182
Q

Give an overview of GI function

A

Take relatively large solids and digest them into smaller molecules that can be absorbed as nutrients, while still serving as a barrier to toxins, bacteria, parasites, etc.

183
Q

Give an overview of the functional anatomy of the GI system

A

GI system is a hollow organ, a tube through the body.

The lumen is “outside” the body’s tissues, but its environment is tightly controlled by the body.

Specialized organs for secretion of enzymes & bile.

Epithelial cells line the entire GI tract and serve as the primary barrier.

Structure maximizes surface area for secretion and absorption (folds, villi, and crypts).

184
Q

Describe the daily fluid balance

A
185
Q

Where does absorption and secretion in the small intestine occur?

A

Net absorbtion- top of villi
Net secretion- Crypts of villi

186
Q

Describe the movement of H2O and electrolytes in the small intestine

A

Water moves down an osmotic gradient

Electrolytes move down electrochemical gradients

To move against concentration gradients requires energy

Energy is supplied by sodium gradients (generated by the sodium pump) and by proton gradients

187
Q

How do we absorb water

A

Sodium moves from gut into cell then out into the lumen then water follows

Can also go through gap junctions between cells

188
Q

Describe the mechanism of intestinal secretion

A

Chloride ions enter the crypt epithelial cell by cotransport with sodium and potassium; sodium is pumped back out viasodium pumps, and potassium is exported via a number of channels.
Activation ofadenylyl cyclaseby a number of so-called secretagogues leads to generation of cyclic AMP.
Elevated intracellular concentrations of cAMP in crypt cells activate the CFTR, resulting in secretion of chloride ions into the lumen.
Accumulation of negatively-charged chloride anions in the crypt creates an electric potential that attracts sodium, pulling it into the lumen, apparently across tight junctions - the net result is secretion of NaCl.
Secretion of NaCl into the crypt creates an osmotic gradient across the tight junction and water is drawn into the lumen.

189
Q

Factors affecting absorption

A

number and structure of enterocytes
Blood and lymph flows
Nutrient intake
GI motility- hormonal and neural

190
Q

Factors influencing secretion

A

Irritants
Bile
Bacterial toxins

191
Q

What does coeliac disease and what do they present with?

A

Damage to villi
Low iron, B12, calcium, lethargy, osteoporosis

192
Q

Describe cholera

A

Vibrio cholerae can survive in the water without a host for a long enough time to be ingested by its next host.

Cholera is transmitted by either contaminated food or water. Source of contamination is typically other cholera sufferers when their untreated diarrheal discharge is in waterways, groundwater, or drinking water supplies. It rarely spreads from person to person.

Major sources:
In developed world: seafood is typically the cause
In developing world: it is often water

193
Q

How does cholera induce diarrhoea?

A

Cholera toxin released from bacteria in infected intestine
Binds to Intestinal cells
Stimulates adenylate cyclase to produce cAMP
Dramatic efflux of ions and water

Watery Diarrhoea

194
Q

Describe oral rehydration

A

Water passively follows the osmotic gradient

SGLT1- sodium glucose co-transporter which moves Na and glucose from the luminal membrane into the enterocyte

195
Q

Definition of digestion and absorption

A

Breakdown of large, complex organic molecules that can be used by the body.

Mechanical (eg. chewing, churning of food)
Chemical (eg. enzymes)

196
Q

Digestion of carbohydrates

A

Salivary amylase then pancreatic amylase breaks down larger glucose polymers
Then the disaccharides (maltase, sucrase and lactase) break them down into monomers
Enterocytes absorb glucose and galactose through an Na-dependent secondary active transport process, while fructose is absorbed by facilitated transport.

197
Q

Describe the digestion and absorption of proteins

A

Process starts in the stomach with pepsin the continues with trypsin ect in the small intestine

198
Q

Describe the digestion of fats

A

Fat and water separate- enzymes are in water and can’t get to the fat
Bile (an emulsifier) arrives, bile has an affinity for both fat and water and can therefore bring the fat into the water
After emulsification, the fat is mixed in the water solution do the fat-digesting enzymes have access to it

199
Q

Digestive enzymes in the salivary gland and what they target

A

39

200
Q

Digestive enzymes in the stomach and what they target

A
201
Q

Digestive enzymes in the pancreas and what they target

A
202
Q

Digestive enzymes in the intestine and what they target

A
203
Q

What stimulates the pancreas to work?

A

CCk release when you consume food
vagus nerve

204
Q

What are some symptoms of pancreatic failure?

A

Maldigestion symptoms- e.g steatorrhea, weight loss, diahorrea, abdominal pain, bloating

205
Q

Impact of PEI

A

malnutrition- maldigestion/malabsorption

206
Q

Causes of PEI- Parenchymal diseases

A

Chronic pancreatitis
Acute pancreatitis
Cystic fibrosis
Pancreatic cancers
autoimmune pancreatitis

207
Q

Extra-pancreatic diseases

A

Coealic disease

208
Q

Outline H1 histamine receptors

A

Location: Throughout the body, specifically in smooth muscles, vascular endothelial cells, heart and CNS
Type of receptor: G-protein coupled linked to intercellular Gq. which activates phospholipase C
Effect: Mediate an increase in vascular permeability of inflammation induced by histamine
Diseases: Allergies, nausea, sleep disorders

209
Q

Outline H2 histamine receptors

A

Location: Mainly gastric parietal cells, low level can be found in vascular smooth muscle, mast cells, neutrophils, CNS, heart and uterus
Type of receptor: G-protein coupled linked to intercellular Gs
Effect: Increases the release of gastric acid
Diseases: stomach ulcers

210
Q

Outline the H3 histamine receptor

A

Location: Found mostly presynaptically in the CNS, with a high level in the thalamus, caudate nucleus & cortex, also a low level in small intestine, testis & prostate
Type of receptor: G-protein coupled possibly linked to intercellular Gi
Effect: Neural presynaptic receptor may function to release histamine

211
Q

Outline H4 histamine receptors

A

Location: They were discovered in 2000. They are widely expressed in component of the immune systems such as the spleen thymus and leukocytes
Type of receptor: Unknown (most likely also G-protein coupled)
Effect: Unknown

Phase 1 (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions