GI Flashcards
(144 cards)
1
Q
How many muscular layers are on external surface of the GI tract? What are their orientations and roles?
A
2 muscle layers:
inner circular muscle (squeezing and increased pressure, propels)
outer longitudinal muscle (shortens intestine and widens diameter, allows forward movement and mixing)
2
Q
What is the layout of the alimentary system?
A
oral cavity
oesophagus
diaphragm
stomach
small intestine
colon
anus
3
Q
Which sphincters are under voluntary control and what are their roles?
A
upper oesophageal sphincter:
swallowing - controls entry into the tract
external oesophageal sphincter:
defecation - allows exit
4
Q
which plexus supplies the enteric nervous system?
A
Myenteric plexus
lies between inner circular and outer longitudinal muscle layers
submucosal plexus also plays a role
5
Q
what are interstitial cells of cajal and where are they found?
A
intrinsic electrical activity, pacemaker function. Lie in the myenteric plexus
6
Q
What does the Basic Electrical Rhythm (BER) of the gut determine?
A
how often an area of the gut can contract
7
Q
Which area of the intestine has a higher BER and which has a lower BER?
A
proximal intestine has higher
distal intestine has lower
this helps control movement
8
Q
what is the muscular structure of the oesophagus?
A
upper 1/3 - lined by striated muscle (skeletal muscle under voluntary control)
distal 2/3 - involuntary control via enteric nervous system (lined by smooth muscle)
9
Q
what is achalasia?
A
too high lower oesophageal sphincter pressure
hypertonic lower oesophageal sphincter that does not relax in response to swallow
loss of peristaltic function
solid food contents get trapped at lower oesophagus and struggle to make it to the stomach (can result in regurgitation)
10
Q
what is a long term complication of achalasia?
A
over time, can lead to dilation of oesophagus and chronic stasis of food
increased risk of squamous oesophageal cancer
*can be readily treated
11
Q
what role does the oesophagus play in scleroderma?
A
scleroderma is a connective tissue disease
weak lower oesophageal sphincter (absence of LOS pressure)
absent peristalsis
severe oesophagitis
no trouble with swallowing as can easily move past weak sphincter however, can result in reflux as there is no anti-reflux mechanism present
*can lead to oesophagitis and stricture formation
managed with high doses of proton pump inhibitors
12
Q
what is meant by a jackhammer oesophagus?
A
normal oesophageal peristaltic function and normal function of lower oesophageal sphincter.
associated with pain on swallowing
no evident therapies
benign prognosis
*very high pressure = pain
13
Q
what is meant by the interprandial period?
A
cleansing of gut in preparation for next meal
14
Q
What is the Migrating Motor Complex (MMC) and what are the 4 phases?
A
MMC is a cyclic contraction sequence that occurs every 90 minutes.
4 phases:
- prolonged period of quiescence (lack of motor activity)
- increased frequency of contractility
- a few minutes of peak electrical and mechanical activity
- declining activity, merging to next phase 1
*acts to cleanse stomach and intestine
15
Q
Which hormone regulated the Migrating Motor Complex (MMC) and where is it produced? What does it stimulate?
A
Motilin (polypeptide hormone)
Produced by M cells in the small intestine
Stimulates contraction of gastric fundus and enhances gastric emptying
16
Q
What are the functions of the stomach?
A
- act as a reservoir for large volumes of food
- fragment food into smaller particles and mix with gastric secretions so that digestion may begin
- empty gastric contents into duodenum at a controlled rate
17
Q
Which antibiotic is a motilin agonist and can result in diarrhoea?
A
Erythromycin
18
Q
what allows the gastric fundus to accommodate volume increases without increase in pressure?
A
receptive relaxation
19
Q
what is the emptying time from the stomach of inert liquids?
A
20 minutes
20
Q
at what size does digestible food particles leave the stomach
A
when reduced to 2mm
21
Q
what are the 3 phases of meal related motility?
A
cephalic
gastric
intestinal
22
Q
describe the cephalic phase of meal related motility
A
- secretory phase
- vagally mediated
- sight/smell of food results in increased gastric secretions (HCL and peptin)
*20% of gastric secretion in the cephalic phase
22
Q
describe the gastric phase of meal related motility
A
- stomach expands without increase in pressure
- MMC is replaced by contractions of variable amplitude and frequency, allowing mixing and digestion
- frequency and direction of gastric muscular contractions are controlled by gastric pacemaker zone within proximal gastric body
- pacemaker generates rhythmic depolorisations at a frequency of 3 cycles per minute
23
Q
describe the intestinal phase of meal related motility
A
- liquids leave stomach earlier than solids
- solids undergo mixing and churning
- solids empty completely over 3-4 hours
24
describe the process of gastric emptying
- antral pressures higher than gastric body and duodenum
- as intra-gastric pressure rises, pylorus opens up briefly
- small amount of chyme passes to duodenum and most of gastric contents propelled back up into stomach for further settling and mixing
25
what can duodenal mucosa sense?
- acidity
- osmotic pressure
- presence of fats
- presence of amino acids
-
26
the presence of what in the duodenum inhibits gastric emptying?
presence of fat (causes increased pyloric pressure and reduced emptying)
27
what are the main functions of small intestinal and pancreatic secretions?
- pH control
- carbohydrate digestion
- fat digestion
- protein digestion
28
What does motility in the small intestine consist of?
segmentation and peristalsis
29
What is meant by segmentation in small intestinal motility?
- ring-like contractions along length of small intestines
- contracted areas then relax and are replaced by contractions in areas not previously contracting
- chyme moves backwards and forwards for mixing and absorption
30
What is meany by peristalsis in the small intestinal motility?
- propagates movement of chyme distally
- longitudinal muscle contracts, shortening the gut
- circular muscle then contracts and longitudinal relaxes
- this sweeps chyme downstream
31
What is the main role of the colon?
fluid and electrolyte absorption
32
What are the muscle layers of the colon?
Inner circular muscle layer
Outer longitudinal muscle layer (arranged in 3 strips - taenia coli)
33
What are the major stimuli for contraction of the colon?
- wakening
- meals
34
What is the difference between short spike electrical bursts and long spike electrical bursts in the colon?
short spike electrical bursts - in proximal colon, last <5s and are the basis of haustral contractions in proximal colon
long spike electrical bursts of >10s cause propulsion, with "mass movement" contractions moving over long distances of bowel. During these, faeces are propelled into the rectum
35
How can colonic transit be measured?
By the length of time it takes to expel 50% of ingested radio-opaque markers
36
How long does it take normal subjects to expel 50% of ingested markers in colonic transit measurements?
78 hours
37
What can prolong colonic transit time?
diet (low fibre)
drugs
38
Which drugs are known to reduce colonic motility?
Opiates (via Mu receptor e.g. codeine)
Anticholinergics
Loperamide (imodium)
39
Which drugs are known to increase colonic motility?
stimulant laxatives
prucalopride
Linaclotide
40
Which anal sphincters are under involuntary and voluntary control?
Involuntary control (smooth muscle) - internal anal sphincter
Voluntary control (striated muscle) - external anal sphincter (recruited in reflex reaction to coughing/sneezing)
41
What does rectal distension initiate?
Reflex contraction of the rectal wall
Relaxation of the internal anal sphincter
42
Defecation only occurs if which muscle and sphincter is voluntarily relaxed?
puborectalis muscle
external anal sphincter
43
What is Hirschprung's Disease?
Developmental abnormality, absence of myenteric plexus in distal sigmoid colon + rectum
Rectum remains thin + narrow and does not open
*surgery is very effective for treating
44
what glands is the gastric body mainly lined by
oxyntic gland
45
when is acid secretion at its highest?
after eating
46
why does gastric pH rise/become more alkaline following a meal?
due to buffering of acid by ingested food (protein)
47
what parasympathetic nerve stimulates the release of acetylcholine for the cephalic phase of gastric secretion?
vagus nerve
48
what do ECL cells release (paracrine)?
Histamine
49
Which cells release gastrin (endocrine)?
G cell
50
What do D cells release (endocrine)
somatostatin
51
what is the effect of somatostatin in the gastric phase?
reduces gastric acid secretion
52
What are the 4 components of gastric juice?
Hydrochloric acid, pepsin, mucin and intrinsic factor
53
which cells secrete hydrochloric acid?
parietal cells
54
which cells secrete pepsin?
chief cells
55
which cells secrete mucin?
mucus cells (neck cells)
56
when is intrinsic factor released?
in conditions of low pH
57
what is the function of hydrochloric acid?
- Assists with the breakdown of foodstuffs, allows gastric mixing.
- Kills bacteria, parasites and viruses.
- Optimises pH for action of pepsin
- line of defence
58
what is the function of pepsin?
Breaks down protein to polypeptides to assist transit through stomach and begin digestive process
59
what is the function of mucin?
helps provide protection from auto-digestion by acid and pepsin
60
What is the function of intrinsic factor?
Binds to free vitamin B12 and complex, then absorbed in distal ileum
61
What is the major stimulus for gastric secretion?
via histamine
62
What is histamine inhibited by?
somatostatin
63
What is the function of acetylcholine in gastric secretion?
ACh increases gastric acid production and inhibits the release of somatostatin - releasing the break on gastric acid secretion
64
What is the function of gastrin?
- stimulates ECL cell to produce histamine
- stimulates parietal cell to produce acid
65
What is the function of ACh?
- stimulates G cell to produce gastrin
- stimulates parietal cell to produce acid
66
What is the function of somatostatin?
- inhibits parietal cell acid secretion
- inhibits ECL cell histamine secretion
67
What is the function of histamine?
- stimulates acid secretion by acting on parietal cell via H2 receptor
- stimulates acid secretion by acting on D cell via H3 receptor to inhibit somatostatin production
68
What is the function of gastric acid?
- digestion (converts pepsinogen to pepsin)
- absorption of iron, vitamin B12, calcium
- antimicrobial
69
What epithelium lines the oesophagus?
stratified squamous epithelium
70
What epithelium lines the stomach?
simple columnar epithelium
71
What are the stomach's defence against gastric acid?
prostaglandin rich mucous layer - rich in bicarbonate + physical barrier (gastric mucous)
72
Gastric mucous is produced as a by-product of which cycle?
Arachidonic acid cycle
73
How is the arachidonic acid cycle involved in gastric mucous cycle and how do NSAIDs affect this?
- COX-2 is expressed in the presence of inflammation
- decreased COX activity
- decreased prostaglandins
- decreased GI mucous production
74
What defences does the oesophagus have against acid damage?
- thickening of circular muscle layer
- lower oesophageal sphincter sits at high tonic, transient sphincter relaxation
- pressure in thoracic cavity is lower than in abdominal cavity
- saliva, neutral or alkaline pH, rich in bicarbonate (increased in exposure to acid)
75
What are some causes of acid-peptic disease?
- too much attack (usually due to weakening of defence)
- Zollinger Ellison Syndrome (very rare gastrin producing tumour)
- Helicobacter pylori antral gastritis (inflammation of gastric antrum, increase acid production and decreased somatostatin produced by D cells) *chronic inflammation weakens defences (peptic ulcer disease)
76
What can cause gastric and duodenal ulceration?
- NSAIDs (aspirin) inhibits mucous production
- "stress" ulceration
- Helicobacter pylori corpus/pan gastritis (gastric lining inflamed and impaired gastric production)
- Gastro-Oesophageal reflux disease (impaired physical anti-reflux barrier)
77
What are complications of peptic ulcer disease?
- bleeding (vomiting or diarrhoea of blood)
- tiredness
- breathlessness
- low blood count
- severe abdominal pain (perforation) presence of air bilaterally, under right diaphragm
- pale conjunctiva
78
In which parts of the stomach are ulcers most commonly seen?
Antrum and distal stomach
79
How does H.pylori surround itself in a relatively alkaline environment?
Surrounds itself in urease. Urease is an enzyme that breaks down urea and water into carbon dioxide and ammonia. This buffers gastric acid and can survive in acid rich environments
80
How is H.Pylori detected?
- blood test: serology for antibody (previous infection, only before treatment)
- stool test: H.pylori antigen in faeces
- tests of urease activity: urea breath test and rapid urease test from endoscopic biopsy
- histological biopsy
81
What are the principles of urea breath test?
Ingest a drink containing a carbon isotope which enriches urea 13C
If urea is present - breakdown urea to ammonia + CO2
CO2 is secreted in breath (measure concentration of enriched carbon in breath sample)
If no H.pylori, enriched urea will not be broken down in stomach and CO2 excreted in breath will all be 12C
*urease activity = enriched in isotopes
82
What are the principles of gastro-oesophageal reflux disease?
Increasing problem with ageing and obese population
Increased abdominal pressure can affect integrity of gastro-oesophageal junction
weakness in diaphragmatic hiatus, upward movement of part of stomach into chest cavity transiently or permanently
*acid escapes into oesophagus
83
What are the symptoms of gastro-oesophageal reflux disease?
- heartburn
- regurgitation of fluid and food
84
What are the complications of gastro-oesophageal reflux disease?
- benign stricture formation (inflammation and narrowing)
- dysphagia (swallowing difficulties)
- ulceration
- bleeding and iron deficiency anaemia
- columnar metaplasia (more resistant to gastric acid)
- risk of adenocarcinoma (Barrett's oesophagus)
85
Which drugs act locally to treat acid/peptic disorders?
Neutralise acid:
- Antacids (weak alkalis which neutralise acid)
- Alginates (promote mucosal resistance, salts of alginic acid)
- Sucralfate (provides a physical barrier over damaged mucosa)
86
How do alginates work?
Promote mucosal resistance
- in presence of acid, form a gel-like raft, which adheres to the top of the acid "pocket" in the proximal stomach
- release CO2, makes gel "float" to proximal stomach (first to reflux, protective raft) *gaviscon
87
What is the most important mediator of gastric secretion?
histamine
88
How do H2 receptor antagonists work? Give examples
Competitively and reversibly inhibit H2 receptor on parietal cell (acid suppressants)
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
H2 receptor antagonists heal peptic ulcers in 87-94% after 4 weeks of therapy
89
What is the main therapy for reflux disease?
Proton-pump inhibitors inc. omeprazole, lansoprazole
90
What is the mechanism of action of proton-pump inhibitors?
- oral ingestion (concentrates in stomach)
- absorbed via small intestine
- uptake only when ATPase making acid (when proton pump is activated)
- short plasma half life (30-60 mins)
*take within 30 mins before eating
91
What are some adverse effects of proton-pump inhibitors?
- reduction in gastric acid output
- reduced nutrient absorption (iron, calcium, vitamin B12)
- reduced gastric antimicrobial function
- increase in serum gastrin levels
- idiosyncratic (diarrhoea, low magnesium absorption)
- interaction with metabolism of other drugs
92
What are the surgical and medical treatments of duodenal ulcers?
Surgical:
- vagotomy
- subtotal gastrectomy
- antrectomy
Medical:
- H2 antagonists
- proton pump inhibitors
93
What is the negative feedback mechanism of regulation of acid secretion?
D cells release somatostatin and inhibit G cells and further gastrin release
94
How does alkali release by H.pylori block the negative feedback of acid secretion?
Alkali release by the colony of bacteria stop acid blocking D + G cells, infection causes excess acid to be produced (negative inhibitive control has been lost)
95
What is the treatment for H.pylori infection?
antibiotics + acid inhibitors
96
What are the outcomes of H.pylori infection?
50% general population have H.pylori
>80% have no associated disease
5-15% have peptic ulcer disease (duodenal or gastric ulcers)
1-3% have gastric cancer
97
What is the progression to atrophic gastritis and gastric cancer?
H.pylori - superficial gastritis - atrophic gastritis, hypochlorhydria - dysplasia and cancer
98
What are risk factors of developing gastric cancer?
- host genetics
- bacterial strain
- smoking
- diet
- carcinogen
- male gender
- age (more time for damage)
99
What are the physical manifestations of upper GI tract inflammation?
- abdominal pain
- weight loss
- diarrhoea
- dysphagia
- fatigue
- vomiting blood
- anaemia
- vomiting
- nausea
- funny taste (acid reflux)
- ulceration
- cancer
100
What are the cell types of the stomach lining?
- simple columnar epithelium
- each cell contributes to mucus secretion
- mucous cells cover most of internal surface
- adequate gastric acid protection
101
What are the cell types of the oesophagus?
- non-keratinised stratified squamous epithelium
- do not secrete mucous
- specialised goblet cells secrete mucous
- less protection against gastric acid
- can be insufficient if excess acid in oesophagus
102
What are the cells of the gastric glands and their secretory products?
surface mucous cells - mucin in an alkaline fluid
mucous neck cells - mucin in an acidic fluid
parietal cells - HCL and intrinsic factor
chief cells - pepsinogen and lipase
G cells - gastrin
D cells - somatostatin
103
What are common upper GI inflammatory conditions?
GORD: gastro-oesophageal reflux disease
Gastritis
Ulcers-oesophageal, gastric and duodenal
Eosinophilic oesophagitis
104
What is GORD?
Gastro-oesophageal reflux disease
- reflux of acidic acid contents
- incompetent lower oesophageal sphincter
- non keratinised squamous epithelial cells do not secrete mucus, less protection against acid
Burning, radiation behind sternum
Bending, lying, jumping
Waterbrash: regurgitation acid contents to back of throat (acid taste)
Causes:
- spicy food
- carbonated drinks
- alcohol
- smoking
- obesity
- pregnancy
- structural abnormality (increased pressure)
- dysphagia (acid related strictures)
105
What is eosinophillic oesophagitis?
- chronic, allergic inflammation
- eosinophils aggregate in oesophagus
- inflammation
- narrowing
- food bolus obstruction
*ridged appearance due to inflammation, interrupts motility
Risk factors: asthma, allergy, environment (dust, dander and pollen) *IgE mediated
106
Describe the gastric and oesophageal pre-cancerous cascade
chronic inflammation
- sustained tissue damage
- damage induced cell proliferation
- tissue repair
metaplasia: cell change from one type to another
dysplasia: cell proliferation leading to atypical cell production
107
What are the 2 most common oesophageal cancers, where do they occur and risk factors?
squamous cell cancer: upper 2/3rds
- smoking
- alcohol
Adenocarcinoma: lower 1/3rd
- GORD
- Barretts
108
What is the metastasis pathway?
Lymph nodes
Lung
Liver
Bones
Adrenal glands
Brain
GORD
Metaplasia
low grade dysplasia
high grade dysplasia
adenocarcinoma
109
What is maltoma?
A lymphoma, H.pylori cancer that can cure with antibiotics
110
What is signet ring cell cancer?
A cancer with a genetic component, globular appearance
111
How much does the liver weigh?
1.5kg
112
What are the functions of the liver?
- amino acid, carbohydrate and lipid metabolism
- storage of proteins, glycogen, fat soluble vitamins and metals
- plasma protein and enzyme synthesis
- detoxification
- production of bile (digestion + absorption of fat)
- immune functions (microbiome)
113
What makes up liver vasculature?
Hepatic artery (30-40% oxygenated blood supply)
Portal vein (60-70% blood supply from gut)
Hepatic vein (back of liver)
114
What makes up the portal triad?
hepatic artery
portal vein
bile ducts
115
Where do the portal triad enter/exit the liver?
porta hepatis
116
What are sinusoids?
micro-vasculature/vessels of the liver
117
What are hepatocytes?
- lie in plates and cords
- exchange material with blood at sinusoidal surface
3 types of surface:
Sinusoidal, intercellular and canalicular (intercellular surface)
118
What are the features of the endothelium of sinusoids?
- fenestrated (have holes, optimised for exchange of material between blood and underpinning cell)
- lacks complete basement membrane (optimised for exchange)
119
What are kupffer cells?
macrophages in the liver
120
what are perisinusoidal cells?
fat storing cells of the liver (vitamin A + D)
121
What makes up the biliary system?
bile canaliculi (small channels/canals)
bile ductules
bile ducts (at centre of portal tracts)
122
What is bilirubin?
haemoglobin breakdown product
123
what are bile acids/salts?
cholesterol-based, act as detergent to help lipid absorption
124
What are characteristics of liver cirrhosis?
- range of changes, diffuse abnormal changes
- pale colour (green/brown) due to bile retention
- nodule formation, change from smooth
- fibrosis
125
What is the 3-fold definition of cirrhosis?
diffuse process with
fibrosis and
nodule formation
126
what causes cirrhosis
- end-stage liver disease
- result of chronic inflammation (hepatitis) over many years
- persistence of injury-causing agent (viral, autoimmune, alcohol)
- fibrous scarring and hepatocyte regeneration
- eventually irreversible + cirrhosis develops
127
What is the pathogenesis of cirrhosis?
- hepatocyte injury
- progressive liver cell loss
- hepatocyte regeneration
- hyperplastic nodules
- chronic inflammation
- fibrosis
- architectural abnormality
- ischaemia
- cirrhosis
128
What are the most common causes of liver cirrhosis?
alcoholic or metabolic (drugs)
hepatitis incl. viral (B+C)
auto-immune disease
Biliary disease
Unknown (cryptogenic)
Haemochromatosis (genetic disease/iron overload)
129
What are some complications of cirrhosis?
- liver failure
- portal hypertension (increased resistance to blood flow through liver, increased pressure in portal circulation, causing: portal-systemic shunts and varices, ascites, splenomegaly
- hepatocellular (liver) cancer
130
What are some effects of liver failure?
- altered intermediary metabolism e.g. impaired synthesis of urea and glycogen (low blood sugar)
- reduced albumin and other transport proteins
- coagulation disorders (clotting factors)
- reduced complement, prone to infection
- jaundice (failure to secrete bile properly)
- altered xenobiotic metabolism e.g. drugs and the effect of drug levels
- circulatory and endocrine (hormonal) disturbances
131
What are the 2 main blood supplies to the liver?
Hepatic artery (from heart)
- supplies oxygen rich blood from heart to liver
- provides 20-30% of blood supply to liver
Portal vein (from gut)
- supplies nutrient rich blood from the digestive tract
- provides 70-80% of blood to liver
132
What are the functional cells of the liver?
Hepatocytes:
- 70% of volume of liver
- regenerative
- perform major functions of liver
Kupffer cells:
- immune cells
- macrophages acting as phagocytes
133
What is an acinus in the liver?
micro-circulatory unit of liver
134
What are the 3 zones of acinus?
Zone 1: closer to afferent arteriole *periportal zone
heavily oxygenated
- respiratory chain
- citric acid cycle
- fatty acid oxidation
- gluconeogenesis
- urea synthesis
- production and bile excretion
Zone 2: ill-defined intermediate area
Zone 3: closer to the terminal hepatic veins *perivenular zone
- glycolysis
- glutamine synthesis
- xenobiotic metabolism
135
In which zones of the acinus carry out oxidative and metabolic processes?
Oxidative functions: carried out in zone 1
Metabolic processes requiring lower oxygen: zone 3
136
What role does the liver play in carbohydrate metabolism?
storage: glycogen
release: glycogenolysis
- gluconeogenesis (synthesis of glucose from other sources e.g. lactate, pyruvate, glycerol and alanine)
- glucose as energy substrate (glycolysis, citric acid cycle, synthesis of fatty acids and triglycerides)
- conversion of fructose and galactose to glucose phosphates (citric acid cycle)
137
What are phase 1 reactions?
a suitable polar group is made available, occurs in the smooth endoplasmic reticulum mediated by cytochrome P450 to produce hydroxylated or carboxylated compounds
138
What are phase 2 reactions?
subsequent conjugation with glucuronic acid, acetyl or methyl radicals or glycine, taurine or sulphate
139
What is the composition of bile?
water, electrolytes, phospholipids, bile salts or acids, bile pigments, cholesterol, haem waste products and other substances from blood
140
What is the function of bile?
bile acids needed for fat absorption
mechanism to remove cholesterol waste
141
What is the process of excretion at the excretory system (to remove excess bile acids, cholesterol and bilirubin)
Begins at the bile canaliculi, enters the hepatic ducts then to the common hepatic and bile duct
142
Describe metabolism of bilirubin
intestinal bacteria degrade conjugated bilirubin to form urobilinogen
80% is oxidised to stercobilin and excreted in feaces, giving stool brown colour
20% is absorbed by extra-hepatic circulation to be recycled through the liver and re-excreted, enters systemic circulation to be filtered by kidney and excreted in urine
143
What are the livers 3 central roles in metabolism?
Synthesis: serum proteins
Detoxification/degradation: ammonia
Regulation: blood glucose
