GI and appetite Flashcards
(116 cards)
1
Q
What’s in the unstirred layer?
A
IgA, mucus, bicarbonate
2
Q
What are “salvaged carbohydrates”?
A
Ileal bacteria can convert indigestible carbohydrates into SCFAs which can be absorbed and stored as energy, or used directly for fuel by the colonocytes. Up to 80g/day.
3
Q
Which pump is central to chloride ion secretion in the gut?
A
Na+/K+/2Cl- co-transporter
4
Q
“ulcer”
A
mucosal break over 5mm diameter
5
Q
Draw a gastric pit with all the cells
A
”
6
Q
Basal and stimulated stomach secretions are different - how?
A
Basal - Na+ rich - not from parietal
Stimulated - H+ rich, from parietal
7
Q
How does pepsinogen convert to pepsin?
A
In low pH… 3.5-5 = slow,
8
Q
Where does histamine get secreted from? (within the crypt)
A
Base - from ECL cells, in the CORPUS
9
Q
What happens when parietal cells are stimulated?
A
Cytoskeletal rearrangement
- tubulo-vesical membranes fuse with canalicular membrane
- HK pump
10
Q
What stimulates pepsinogen secretion from chief cells?
A
- vagus activity
- low pH
11
Q
What are the four phases of gastric acid secretion?
A
Basal
Cephalic
Gastric
Intestinal
12
Q
Describe basal acid secretion
A
Low in the morning (circadian)
- Regualted by body weight, number of parietal cells, time of day
13
Q
Describe cephalic acid secretion
A
Responsible for 30% of acid secretion
Thought, smell, sight of food
Carried by CN IX (Hering’s) and CN X (Vagus) from medulla; nerves release ACh causing:
- H+ secretion from parietal cells
- Histamine secretion from ECL cells
- Gastrin from G cells
14
Q
Describe gastric phase of acid secretion
A
Responsible for 50%
STRETCH: vagovagal relex - into brain via CN X then back out via CN X causing ACh and GRP release; short reflex - ENS releases ACh
POLYPEPTIDES IN STOMACH
- ACh increased: increased H+
- ACh increased: increased histamine
- GRP increased: increased gastrin
- Low pH also causes somatostatin release (-ve FB)
15
Q
Describe intestinal phase of acid secretion
A
5-10%
CHYME (polypeptides) ENTERING INTESTINE
Gastrin releeased from duodenal G cells - H+ secretion
Entero-oxyntin from “intestinal endocrine cells” - H+
Absorbed amino acids also stimulate H+ secretion
16
Q
How does a small break in mucosa heal?
A
RESTITUTION
Gastric epithelial cells bordering injury migrate to restore it - prostaglandins
17
Q
What chemicals are involved in repair of larger mucosal defects
A
VEGF
EGF
TGF
18
Q
What is zollinger ellison and what is one way of diagnosing?
A
Gastrin secreting adenoma causes v high acid - PUD+++
Minimal stimulation with pentagastrin
19
Q
What is pernicious anaemia?
A
Atrophic gastritis with destruction of parietal cells -> decreased H+ and IF
HYPERGASTRINAEMIA and ACHLORHYDRIA
- -> decreased B12 absorption
- -> decreased somatostatin from D cells
- -> increased gastrin (due to lack of negative FB) = hypergastrinaemia
20
Q
What is reflux w/o PPI response?
A
“non acid reflux”
21
Q
What does a VMH lesion cause?
A
Hyperphagy
22
Q
What does an LH lesion cause?
A
Decrease in weight
23
Q
What does Ob-/- cause?
A
Overeating -> obesity
24
Q
What happens in the brain in response to leptin?
A
Leptin is released by adipocytes, so its an adipostat.
- Leptin causes anorexigenic peptide release from arcuate nucleus (alpha-MSH & CART)
- alpha-MSH and CART act on:
1. AMPK is decreased in VMH which is switched on to inhibit feeding behaviour
2. TSH + ACTH released from anterior pituitary
Also AMPK is increased in skeletal msucle, increasing energy utilisation
25
What happens in the brain in response to lack of leptin?
- Orexigenic peptides are released from the arcuate nucleus in response to a lack of leptin (AgRP and NPY)
- AgRP and NPY act on:
1. AMPK is increased in VMH to switch it off, and the LH is switched on to stimulated feeding behaviour
2. TSH + ACTH release is inhibited in the anterior pituitary
Also AMPK is decreased in skeletal muscle, decreasing energy utilisation
26
What receptor do two of the "appetite peptides" work by, and what peptides are thet?
AgRP and alpha-MSH
Melanocortin receptor 4 (MC4R)
MC4R defects are the leading cause of genetic obesity
27
What effect does insulin have in the brain?
- Directly stimulates anorexigenic peptide release from the arcuate nucleus
28
What effect does ghrelin have in the brain?
- released from stomach
| - directly causes orexigenic peptide release from the arcuate nucleus
29
What happens to ghrelin levels in obesity?
Go down
30
Reductil (sibutramine)
SNRI
Increased satiety
Withdrawn - CVS effects
31
Reward circuit?
DA release from VTA to N. Acc "mesolimbic system"
32
How do endocannabinoids work in relation to appetite?
Stimulation of nerve fibre causes on-site synthesis of endocannabinoids e.g. 2-AG, anandamide
Released into cleft
Activate pre-synaptic CB1 receptors
Inhibit further stimulation of neurone
33
Delta 9-THC?
Mimics endogenous endocannabinoids
34
1L O2/minute consumption = how much energy?
4.8kCal/min
35
Where do ketone bodies come from?
FA metabolism in the liver (beta oxidation)
36
Where does lactate come from?
Carb metabolism
37
Where does fructose come from?
Sucrose hydrolysis
38
BMR is calculated from...
Weight (kg) x 24kCal or 100kJ/day
39
What effect does fever have on metabolism
Raises by 12% / degree
40
Calculate estimated daily calorie requirement
BMR = weight x 24kcal/day
EDCR = BMR x 30-50% depending on activity
41
Calculate energy deficit for 1kg fat loss
Fat = 85% lipid
0.85 x 1000 x 9 = 7,500
Therefore gain is around 15,000
42
Calculate energy deficit for 1kg protein loss
Protein = 20% protein
0.2 x 1000 x 4 = 800
Therefore gain = 1600
43
Hereditary pancreatitis
Mutation in trypsin makes resistant to intrahepatic inactivation - increased Ca risk
44
Why and how does inhibition of gastric acid secretion happen during digestion?
ACID AND SEMI-DIGESTED FATS cause afferent signals from the stomach ENS to the medulla to give more time for the duodenum to digest the chyme.
Medulla:
1. Inhibits vagal stimulus to the stomach
2. Stimulates sympathetic activity
Enteroendocrine cells secrete secretin and CCK:
1. Gallbladder and pancreas secrete bile and enzymes
2. Gastric emptying / acid secretion is slowed down
3. Pyloric sphincter tightens
45
What is angiogenesis?
New vessels from existing vessels
46
What might be seen in a layer of the duodenum that makes it easily distinguishable in microscopy, and within what layer, and whats the function?
BRUNNERS GLANDS
In SUBMUCOSA
Secrete mucus rich alkaline (HCO3-) secretion in response to acid arriving:
1. Lubricates stomach
2. Protect duodenum from acid content of chyme
3. Provide more neutral environment for enzymes
47
What effect does pepsin have on gastric acid secretion?
Pepsin INHIBITS gastric acid secretion
| and gastrin stimulates it!
48
How would you test for ZE?
Pentagastrin
ZE has increased basal but normal stimulated acid secretion
49
What is achlorhydria?
Lack of hydrochloric acid in the stomach
50
Signs and symptoms of pernicious anaemia?
Anaemia signs
Parasthesias
Sore tongue
Weakness
51
Grading of oesophagitis
```
A = 5mm in length but w/o continuity
C = w/ continuity of 75%
```
52
How to diagnose non-acid reflux
pH monitoring and multichannel intraluminal impedence monitoring
Intraluminal liquid will be detected but without change in pH
53
What are two causes and mechanisms of secretory diarrhoea?
```
Inflammation = VIP release = increased cAMP = Increased CFTR
Toxin = increased cAMP = increased CFTR
```
54
Colonic reabsorptive capcity
4L/day
55
Osmotic gap cut off for osmotic diarrhoe
>50mOsm/kg suggests poorly absorbed substance
56
Plasma osmolality
290mOsm/kg
57
Epithelium of the small intestine?
Simple columnar with villi + transporters
58
Draw a crypt of Lieberkuhn + villus
```
Enterocytes at top
Goblet cells half way and top of villi
Stem cells at neck of crypt
Neuroendocrine cells near base
Paneth cells in base
```
59
What are the four components of defense of the membranes
Unstirred layer (apical):
1. HCO3- neutralises acid
2. IgA binds antigen
3. MUCUS is a barrier against hydrophobic molecules and binds bacteria
Apical membrane:
4. LIPID BILAYER is a barrier against hydrophilic molecules
60
How much water, roughly, is excreted each day in poop
100mL
61
Where is the majority of nutrients absorbed, and how?
Jejunum
Sodium-nutrient co-transporters (NA-glucose/Na-AA)
62
How is water absorbed?
Passively and transcellularly; along with salt absorption
63
What five things enter the ileum and what happens to them?
```
IF.B12: out by specialised pumps
Bile acids: out by specialised pumps
Fibre: non-digestible carbohydrates
Water: follows salt (transcellular)
Electrolytes: by pumps
```
64
Draw electrogenic and electroneutral sodium transport
.
65
What are the functions of the large intestine bacteria?
1. SCFA salvage from non-digestible carbohydrates
2. Bile acid and bilirubin metabolism
3. Space: less space for pathogens
66
What are the differences between the SI and LI?
SI:
Plicae circularis
VIlli
Peyer's patches
LI:
Taenia coli
Haustra
Epiploic appendages
67
What are the retroperitoneal organs?
SADPUCKER
```
Suprarenals
Aorta/IVC
Duodenum 2&3
Pancrease (not tail)
Ureters
Colon (Asc/Dec)
Kidneys
Eosophagus
Rectum
```
68
What are the four ligaments of the greater omentum and where does it connect
Greater curvature to the TV colon
Gastro colic
Gastosplenic
Gastrophrenic
Splenorenal
69
PP of SAM?
Na+/K+ pump fails
Intracellular sodium goes up and potassium down
Total body sodium therefore goes up and potassium down
70
Management of SAM?
Aim to hydrate and correct sodium
Be careful of impaired cardiac tolerance
Oral fluids if possible; v careful with IV
Reduced osmolarity ORS
IV fluids 15ml/kg over 1 hr with glucose 5% + hartmanns
71
What is a normal skin pinch? and pathological?
```
Normal = immediate
1s = slow
2s = v slow
```
72
When would you give IV fluids instead of ORS?
- Suspected or confirmed SHOCK
- Deterioration despite ORS
- Persistant vomiting of ORS
73
Do you continue breastfeeding in acute diarrhoea?
Yes
74
Signs of overhydration?
```
Tachycardia
Tachypnoea
Cough
Crackles
Hepatomegaly
Peri-orbital oesdema
```
75
S&S and management of hypernatraemic dehydration?
NA+ >150
Jittery, increased tone, hyperreflexia, convulsions
Replace fluid over 48h instead of 24
Replace Na+ slowly
Regular monitoring of serum Na+
76
What % have GORD weekly?
20%
of which 40% have had it for >10y and 20% for >5y
77
Dyspepsia definition
Symptoms: pain or discomfort in upper abdomen
78
PUD definition
Surface breach of mucosa of GIT due to ACID and PEPSIN
79
Meckel's diverticulum?
Embryological development
Outpouching of DISTAL ILEUM containing GASTRIC MUCOSA; can therefore secrete acid and cause ulcers
Usually causes painless rectal bleeding (malaena) which stops spontaneously
Requires laporascopic resection
GI bleeding, GI obstruction and abdo pain/cramping can occur
80
Most common causes of acute gastritis
ETOH, drugs
81
Most common cause of chronic gastritis
bacterial (HP)
also autoimmune, chemical
82
Which gastritis is the cancer phenotype?
Pan gastritis causes achlorhydria which increases GASTRIC ulcer risk, cancer phenotype
83
When would you rescope an ulcer?
GASTRIC ULCERS after 6/52 post treatment, to check for healing (cancer doesnt heal well); you would also re-test for eradication of Hp
84
What % of DUs have Hp infection?
95%
85
How many barretts oesophagus go on to develop cancer each year?
1 in 150-200
86
Treatment of Barrett's at different stages?
```
Metaplasia: surveillance 2-5yrly
LGD: RFA + surveillance 6/12 until clear
HGD w/o visible abnormalities: RFA
HGD w/ visible abnormalities: EMR + RFA
Ca: EMR + RFA
```
Oesophagectomy also an option for HGD/Ca!
87
LGD?
Architecture and nucleur polarity preserved
88
HGD?
Distrubed maturation of tissue, complex architecture, loss of polarity, altered onco and tumour suppressor genes
89
What % of dyspepsia have an organic cause?
25%
90
How effective is Hp tx?
90%!
91
Ix / mgmt of dyspepsia?
If ALARMS or >55: USC
If not:
- PPI trial
- Hp T&T
- PPI maintenance if necessary
If continuing:
- consider endoscopy
92
Which type of hernia is associated with GORD?
Sliding
93
Parrots beak on barium swallow
Achalasia - inability of LOS to relax
94
Heartburn following a course of steroids or ABx?
Candida oesophagitis
95
Food sticking, asthma + heartburn?
Eosinophilic oesophagitis
96
Survival rate for adenocarcinoma?
15% 5-yr survival
97
Signet ring cells?
Diffuse gastric adenocarcinoma
Linitis plastica
98
Glandular cancer in stomach
Intetinal gastric adenocarcinoma
99
Oesophageal SCC risks?
Smoking + ETOH
100
Oeophageal SCC survivial?
5-25% 5 year
101
Signet ring cancer in ovaries?
Krukenburg tumours
102
Oesophageal webs
Difficulty swallowing
Iron deficiency anaemia
Choilonychia
Plummer vinson syndrome
103
How does racecadotril work?
Enkephalinase inhibitor
Enkephalins activate delta opioid receptor
Decreases hypersecretion without effect on transit time
104
What pathogen is associated with HUS?
0157:H7
105
Common cause of severe dysenty in under 5s and travellers
Shigellosis
106
Is c diff a commensal
yes in 50%
107
Nurseries / travellers diarrhoea associated with water supplies
cryptosporidium
108
Common cause of diarrhoea and dysentry in developing countries
Entamoeba histolitica
109
Waist size cut off in men/women for action
102cm M
| 88cm F
110
Metabolic syndrome
Large waist
Raised TRIGLYCERIDES
Reduced HDL
HYPERTENSION (>130/85)
Raised plasma GLUCOSE >5.6 random
111
Why is metabolic syndrome important to diagnose?
High link to CVD
112
OGTT value cut offs?
FASTING
Normal 3.6-6
IFG 6.1-6.9
Diabetes 7+
2 HOUR
Normal
113
Hba1c
Glycated haemoglobin
Normal
114
How much calorie restriction is recommended for overweight/obese?
```
500/day for overweight/class I
500-1000/day for class II
```
10% decrease in 6/12
115
Liraglutide / exenatide MOA?
GLP-1 analogue
- increased satiety signals
- increased b cell response (glucose dependent insulin secretion)
- decreased b cell workoad (decreased glucagon, gluconeogenesis, appetite etc)
116
Restrictive, malabsorptive and combined surgeries... which is which?
Gastric banding = restrictive
Lap BPD w/ DS = restrictive
Sleeve gastrectomy = combined
Sleeve bypass = combined
