GI and appetite Flashcards
What’s in the unstirred layer?
IgA, mucus, bicarbonate
What are “salvaged carbohydrates”?
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.
Which pump is central to chloride ion secretion in the gut?
Na+/K+/2Cl- co-transporter
“ulcer”
mucosal break over 5mm diameter
Draw a gastric pit with all the cells
”
Basal and stimulated stomach secretions are different - how?
Basal - Na+ rich - not from parietal
Stimulated - H+ rich, from parietal
How does pepsinogen convert to pepsin?
In low pH… 3.5-5 = slow,
Where does histamine get secreted from? (within the crypt)
Base - from ECL cells, in the CORPUS
What happens when parietal cells are stimulated?
Cytoskeletal rearrangement
- tubulo-vesical membranes fuse with canalicular membrane
- HK pump
What stimulates pepsinogen secretion from chief cells?
- vagus activity
- low pH
What are the four phases of gastric acid secretion?
Basal
Cephalic
Gastric
Intestinal
Describe basal acid secretion
Low in the morning (circadian)
- Regualted by body weight, number of parietal cells, time of day
Describe cephalic acid secretion
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
Describe gastric phase of acid secretion
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)
Describe intestinal phase of acid secretion
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
How does a small break in mucosa heal?
RESTITUTION
Gastric epithelial cells bordering injury migrate to restore it - prostaglandins
What chemicals are involved in repair of larger mucosal defects
VEGF
EGF
TGF
What is zollinger ellison and what is one way of diagnosing?
Gastrin secreting adenoma causes v high acid - PUD+++
Minimal stimulation with pentagastrin
What is pernicious anaemia?
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
What is reflux w/o PPI response?
“non acid reflux”
What does a VMH lesion cause?
Hyperphagy
What does an LH lesion cause?
Decrease in weight
What does Ob-/- cause?
Overeating -> obesity
What happens in the brain in response to leptin?
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
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
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
What effect does insulin have in the brain?
- Directly stimulates anorexigenic peptide release from the arcuate nucleus
What effect does ghrelin have in the brain?
- released from stomach
- directly causes orexigenic peptide release from the arcuate nucleus
What happens to ghrelin levels in obesity?
Go down
Reductil (sibutramine)
SNRI
Increased satiety
Withdrawn - CVS effects
Reward circuit?
DA release from VTA to N. Acc “mesolimbic system”
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
Delta 9-THC?
Mimics endogenous endocannabinoids
1L O2/minute consumption = how much energy?
4.8kCal/min
Where do ketone bodies come from?
FA metabolism in the liver (beta oxidation)
Where does lactate come from?
Carb metabolism
Where does fructose come from?
Sucrose hydrolysis
BMR is calculated from…
Weight (kg) x 24kCal or 100kJ/day
What effect does fever have on metabolism
Raises by 12% / degree
Calculate estimated daily calorie requirement
BMR = weight x 24kcal/day
EDCR = BMR x 30-50% depending on activity
Calculate energy deficit for 1kg fat loss
Fat = 85% lipid
0.85 x 1000 x 9 = 7,500
Therefore gain is around 15,000
Calculate energy deficit for 1kg protein loss
Protein = 20% protein
0.2 x 1000 x 4 = 800
Therefore gain = 1600
Hereditary pancreatitis
Mutation in trypsin makes resistant to intrahepatic inactivation - increased Ca risk
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:
- Inhibits vagal stimulus to the stomach
- Stimulates sympathetic activity
Enteroendocrine cells secrete secretin and CCK:
- Gallbladder and pancreas secrete bile and enzymes
- Gastric emptying / acid secretion is slowed down
- Pyloric sphincter tightens
What is angiogenesis?
New vessels from existing vessels
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:
- Lubricates stomach
- Protect duodenum from acid content of chyme
- Provide more neutral environment for enzymes
What effect does pepsin have on gastric acid secretion?
Pepsin INHIBITS gastric acid secretion
and gastrin stimulates it!
How would you test for ZE?
Pentagastrin
ZE has increased basal but normal stimulated acid secretion
What is achlorhydria?
Lack of hydrochloric acid in the stomach
Signs and symptoms of pernicious anaemia?
Anaemia signs
Parasthesias
Sore tongue
Weakness
Grading of oesophagitis
A = 5mm in length but w/o continuity C = w/ continuity of 75%
How to diagnose non-acid reflux
pH monitoring and multichannel intraluminal impedence monitoring
Intraluminal liquid will be detected but without change in pH
What are two causes and mechanisms of secretory diarrhoea?
Inflammation = VIP release = increased cAMP = Increased CFTR Toxin = increased cAMP = increased CFTR
Colonic reabsorptive capcity
4L/day
Osmotic gap cut off for osmotic diarrhoe
> 50mOsm/kg suggests poorly absorbed substance
Plasma osmolality
290mOsm/kg
Epithelium of the small intestine?
Simple columnar with villi + transporters
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
What are the four components of defense of the membranes
Unstirred layer (apical):
- HCO3- neutralises acid
- IgA binds antigen
- MUCUS is a barrier against hydrophobic molecules and binds bacteria
Apical membrane:
4. LIPID BILAYER is a barrier against hydrophilic molecules
How much water, roughly, is excreted each day in poop
100mL
Where is the majority of nutrients absorbed, and how?
Jejunum
Sodium-nutrient co-transporters (NA-glucose/Na-AA)
How is water absorbed?
Passively and transcellularly; along with salt absorption
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
Draw electrogenic and electroneutral sodium transport
.
What are the functions of the large intestine bacteria?
- SCFA salvage from non-digestible carbohydrates
- Bile acid and bilirubin metabolism
- Space: less space for pathogens
What are the differences between the SI and LI?
SI:
Plicae circularis
VIlli
Peyer’s patches
LI:
Taenia coli
Haustra
Epiploic appendages
What are the retroperitoneal organs?
SADPUCKER
Suprarenals Aorta/IVC Duodenum 2&3 Pancrease (not tail) Ureters Colon (Asc/Dec) Kidneys Eosophagus Rectum
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
PP of SAM?
Na+/K+ pump fails
Intracellular sodium goes up and potassium down
Total body sodium therefore goes up and potassium down
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
What is a normal skin pinch? and pathological?
Normal = immediate 1s = slow 2s = v slow
When would you give IV fluids instead of ORS?
- Suspected or confirmed SHOCK
- Deterioration despite ORS
- Persistant vomiting of ORS
Do you continue breastfeeding in acute diarrhoea?
Yes
Signs of overhydration?
Tachycardia Tachypnoea Cough Crackles Hepatomegaly Peri-orbital oesdema
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+
What % have GORD weekly?
20%
of which 40% have had it for >10y and 20% for >5y
Dyspepsia definition
Symptoms: pain or discomfort in upper abdomen
PUD definition
Surface breach of mucosa of GIT due to ACID and PEPSIN
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
Most common causes of acute gastritis
ETOH, drugs
Most common cause of chronic gastritis
bacterial (HP)
also autoimmune, chemical
Which gastritis is the cancer phenotype?
Pan gastritis causes achlorhydria which increases GASTRIC ulcer risk, cancer phenotype
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
What % of DUs have Hp infection?
95%
How many barretts oesophagus go on to develop cancer each year?
1 in 150-200
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!
LGD?
Architecture and nucleur polarity preserved
HGD?
Distrubed maturation of tissue, complex architecture, loss of polarity, altered onco and tumour suppressor genes
What % of dyspepsia have an organic cause?
25%
How effective is Hp tx?
90%!
Ix / mgmt of dyspepsia?
If ALARMS or >55: USC
If not:
- PPI trial
- Hp T&T
- PPI maintenance if necessary
If continuing:
- consider endoscopy
Which type of hernia is associated with GORD?
Sliding
Parrots beak on barium swallow
Achalasia - inability of LOS to relax
Heartburn following a course of steroids or ABx?
Candida oesophagitis
Food sticking, asthma + heartburn?
Eosinophilic oesophagitis
Survival rate for adenocarcinoma?
15% 5-yr survival
Signet ring cells?
Diffuse gastric adenocarcinoma
Linitis plastica
Glandular cancer in stomach
Intetinal gastric adenocarcinoma
Oesophageal SCC risks?
Smoking + ETOH
Oeophageal SCC survivial?
5-25% 5 year
Signet ring cancer in ovaries?
Krukenburg tumours
Oesophageal webs
Difficulty swallowing
Iron deficiency anaemia
Choilonychia
Plummer vinson syndrome
How does racecadotril work?
Enkephalinase inhibitor
Enkephalins activate delta opioid receptor
Decreases hypersecretion without effect on transit time
What pathogen is associated with HUS?
0157:H7
Common cause of severe dysenty in under 5s and travellers
Shigellosis
Is c diff a commensal
yes in 50%
Nurseries / travellers diarrhoea associated with water supplies
cryptosporidium
Common cause of diarrhoea and dysentry in developing countries
Entamoeba histolitica
Waist size cut off in men/women for action
102cm M
88cm F
Metabolic syndrome
Large waist
Raised TRIGLYCERIDES
Reduced HDL
HYPERTENSION (>130/85)
Raised plasma GLUCOSE >5.6 random
Why is metabolic syndrome important to diagnose?
High link to CVD
OGTT value cut offs?
FASTING
Normal 3.6-6
IFG 6.1-6.9
Diabetes 7+
2 HOUR
Normal
Hba1c
Glycated haemoglobin
Normal
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
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)
Restrictive, malabsorptive and combined surgeries… which is which?
Gastric banding = restrictive
Lap BPD w/ DS = restrictive
Sleeve gastrectomy = combined
Sleeve bypass = combined
