GIT case 1-4 Flashcards
1
Q
What is the inverse care law?
A
the places/people that need the most help have the least ressources
2
Q
What is virtue ethics?
A
how we ought to act: being rather than doing
3
Q
maslow’s hierarchy of needs
A
physiological needs safety and security love and belonging self-esteem self actualisation
4
Q
What are the limitations of Shared Decision Making?
A
- not enough info given by doctors to patients
- lack of involvement of patients in decision making to the level they wish
- underused techniques to enable patient recall and understanding
- commission of key info
- language patients do not understand
5
Q
different types of bias in diagnosis?
A
- anchoring (locking diagnosis too early: unable to adjust to ne info)
- availability (similar recent condition)
- confirmation (looking for info to prove theory, rather than disprove)
- diagnosis momentum (acceptance of remade diagnosis without enough skepticism)
6
Q
difference between basic care and clinical care
A
basic: solids, drinks; spoons, straws, assistance
clinical: drips, NG tubes, PEGs, TPN
7
Q
6 activities of processing food
A
- ingest
- propulsion (swallowing and peristalsis)
- mechanical breakdown (chewing, mixing food with saliva, churning of stomach, segmentation)
- digesting
- absorption
- defecation
8
Q
cells of oral mucosa
A
thick stratified squamous epithelium
9
Q
what do defensins do
A
inhibit bacterial growth in oral tissue
10
Q
different types of teeth and what they do
A
incisors (2): slice and cut
canines (1): tear and rip
premolars (2): grind and crush
molars (3): grind (and crush)
11
Q
composition of saliva
A
- water (90%)
- lingual lipases an alpha-amylase (slightly acidic(pH: 6.75-7): optimal condition for enzyme function)
- mucoproteins as mucins (lubricant)
- lysozyme
- IgA
- electrolytes
- calcium and phosphate (dental repair)
12
Q
control of salivation:
A
- salivatory nuclei in medulla and pons
- mechano and chemoreceptors: produce saliva with high H2O content
- food induce production of enzymes
- higher brain centres
- irritation of lower digestive tract
13
Q
enteric nervous system made up of?
what do they respond to, what do they produce
A
- submucosal (Meissner’s) plexus found in submucosa: chemoreceptors: stimulate glands, dilate vessels, secrete hormones/ peptides
- myenteric (Auerbach’s) plexus found in muscular external: mechanoreceptors: descending and ascending fibres that contract/relax circular and longitudinal muscles
14
Q
enteric nervous system pacemaker cells
A
interstitial cells of Cajal: set timing of contraction waves
15
Q
muscle fibres of muscular layer of oesophagus
A
- skeletal in first third (voluntary)
- mixed smooth an skeletal in middle third
- smooth in last third (involuntary)
16
Q
4 histological layers of oesophagus?
A
mucosa
submucosa
muscular layer
adventia (serosa beyond diaphragm)
17
Q
where peristalsis in stomach?
A
lower part
18
Q
what control rate of emptying of stomach?
A
caloric value of contents of duodenum
19
Q
histological parts of stomach that form rugae
A
mucosa and submucosa
20
Q
functions of stomach?
A
storage and mixing digestion (proteina dn nucleic acids) enzyme activation bacteria killing intrinsic factor synthesis (main true function) absorption (alcohol, H2O, drugs, B12)
21
Q
cells present in different parts of stomach
A
- cardia: mucous cells
- body/fundus: all cell types
- pylorus: mucous cells and enteroendocrine / G cells, D cells (antrum)
22
Q
gastric secretions
A
- HCl
- mucus
- pepsinogen
- intrinsic factor
- gastrin
- somatostatin
23
Q
effect of contraction of circular smooth muscle
A
squeezes gut content
24
Q
effect of contraction of longitudinal muscle
A
shortens that portion of gut
25
histological lining of oesophagus?
stratified squamous epithelium (to resist abrasion)
26
role of HCl in stomach
- produces pepsin from pepsinogen
| - acidifies lumen
27
role of gastrin
-stimulate acid production
-stimulate chief cells
-Increases antral muscle mobility and promotes stomach contractions.
Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which increases the rate of gastric emptying
-Plays a role in the relaxation of the ileocecal valve
-Induces pancreatic secretions and gallbladder emptying
-Gastrin contributes to the gastrocolic reflex.
28
role of somatostatin
inhibit release of gastrin, insulin, glucagon (an others: look them up)
29
different cells of stomach and function
- surface epithelium cells (HCO3- and mucus)
- goblet cells (mucus)
- mucous cells (mucus and pepsinogen)
- parietal cells (gastric acid and intrinsic factor)
- chief cells (pepsinogen and gastric lipase)
- G cells (gastrin)
- D cells (somatostatin)
- ECL cells (histamine)
- endocrine cells (ghrelin/leptin) (look this up)
30
control of pepsinogen release
vagus nerve: acetylcholine
| gastrin
31
control of HCl release
vagus (acetylcholine)
gastrin (G cells)
histamine (ECC)
other hormones
32
gastric acid secretion inhibited by
- somatostatin (via decrease in gastrin release)
- secretin (via decrease in gastrin release)
- gastric inhibitory peptides and other enterogastrones (directly on parietal cells)
33
phases of gastric secretion
- cephalic (vagus and acetylcholine stimulate G and parietal cells) 40% of secretion
- gastric (distention and reflex activation of enteric neurones+ vagus + digested proteins stimulate G cells) 50% of secretion
- intestinal phase: aa present in bloodstream stimulate parietal cells (10% secretions)
34
gastric and duodenal mechanisms of gastric secretion inhibition
-proteins in stomach at as buffer to keep luminal pH>3, when stomach empties, luminal ph<3: D cells release somatostatin --> reduction in acid secretion
- acidification of duodenal lumen releases secretin: inhibits gastrin secretion
- acidification of duodenal lumen and presence of fatty acids and salt releases gastric inhibitory peptide: acts on parietal cells
35
gastrin: where is it produced and major actions
G cells (antrum-jejenum)
relax cardia, increase antral activity and gastric acid secretion
36
motilin: where is it produced and major actions
duodenum-jejenum
increase gastric acid secretion and stomach activity
37
Gastric inhibitory peptide (GIP): where is it produced and major actions
duodenum-jejenum
"incretin": decrease gastric secretion, enhance insulin secretion, decreases glucagon secretion
38
cholecystokinin (CCK): where is it produced and major actions
small intestine
relaxes stomach (slow stomach emptying), contracts gallbladder, increases pancreatic secretion, satiety, potentiates secretive action of liver, relax sphincter of Oddi
39
secretin: where is it produced and major actions
small intestine
inhibition G cells
relaxes stomach, increases HCO3- secretion by pancreas
40
vasoactive intestinal peptide (VIP): where is it produced and major actions
glands and nerves
increases intestinal electrolyte secretion
41
migrating motor complex
```
done by ENS and ANS
in inter digestive state
release of motilin: stimulates strong sequential contractions by ANS
remove dead cells and sweep anything out
4 phases (3 phase is active one)
```
42
when does inter digestive activity stop?
ingestion of food
gastrin (released by stomach)
CCK
43
what is absorbed in duodenum
iron
carbohydrates
proteins, lipids, sodium and water
(bile salts)
44
what is absorbed in jejenum
carbohydrates
proteins, lipids, sodium and water
(bile salts)
45
what is absorbed in ileum
bile salts
cobalamin (vit B12)
proteins, lipids, sodium and water, potassium
carbohydrates
46
MOA of Orlistat
reacts with serine residues at active site of gastric and pancreatic lipases: prevent breakdown of dietary fat into fatty acids and glycerol: decrease absorption of 30% of dietary fat
47
bariatric surgery
```
BMI>40 kg/m2
Failure to maintain weight loss by non surgical means over period of months/years
-gastric banding
-gastric bypass
-biliopancreatic diversion
```
48
difference in active and passive euthanasia (euthanasia by action or ommission)
passive: withholding consent to lifesaving/prolonging treatment
active: performing action that has lethal effect
49
difference voluntary/non voluntary/involuntary euthanasia
- voluntary: person requested to be killed
- non-voluntary: person made no request and gave no request to be killed
- involuntary: person who is killed made an expressed wish to the contrary
50
def assisted suicide
person provide info/means/guidance to take own life with intention
physician assisted suicide: when doctor involved
51
doctrine of double effect
when harm is a foreseen but intended consequence (i.e. with surgery, or pain medicine)
52
what impermeable to phospholipid bilayer?
- ions
| - polar molecules
53
membrane structure
phospholipid polar heads face interstitial fluid
| sterols: struck integrity
54
different types of membrane transport proteins
- (simple diffusion ie gases)
- channels (passive: driven by electrochemical gradients)
- carriers (passive: driven by electrochemical gradients)
- pumps (active: atpases)
55
function of Na+,K+-ATPase (sodium pump)
- Na+ in, K+ out
- K+ gradient generates membrane potential (-60 mV)
- Na+ gradient for secondary active transport
56
ion channels control
- gated by intracellular or extracellular messengers
| - voltage gated by membrane potential changes
57
uniport
symport
antiport
- facilitated diffusion
- cotransport
- countertransport (exchange)
58
facilitated diffusion
highly lecture carrier protein
passive transport
driven by concentration gradient
59
where are glucose transporters found in the body?
```
GLUT1: red cells, brain, kidney, placenta
GLUT2: liver, intestine
GLUT3: astrocytes, neurones
GLUT4: adipocytes, muscles
GLUT5: intestine
```
60
def secondary active transport
using previously established gradient of ATPases
61
protein family that determines tight junction permeability
claudin family proteins
62
% salivary secretion in unstimulated and stimulated state (gland)?
unstimulated: 25% parotid, 60% submandibular, 7-8% sublingual and 7-8% minor glands
stimulated: 50% parotid, 35% submandibular, 7-8% sublingual and 7-8% minor glands
63
inorganic component of saliva
| and changes with saliva flow
```
from high to low concentration:
Na+ (increase)
HCO3- (increase)
Cl- (increases)
K+ (decreases
```
64
What is secreted in the acinus and secreted and reabsorbed in duct
-secretion in acinus: Na+, Cl-, HCO3-, H20
(isotonic)
-reabsorption in the duct: Na+, Cl-
-secretion in duct: K+, HCO3-
(lower H20 permeability in duct)
(hypotonic)
65
generation of oesophageal peristalsis
swallowing: primary peristalsis
distention: secondary peristalsis
66
oropharyngeal dysphagia
- abnormal bolus transfer to oesophagus
- difficulty initiating swallow
- a manifestation of primary disease
67
oesophageal dysphagia
- abnormal bolus transport through oesophagus
- food stops after initiation of swallow
- oesophagus location of primary disease
68
most likely area of lesion in stroke patients with dysphagia
postcentral and pericentral
69
Chicago classification
achalasia or other obstruction
major motility disorder
minor motility disorder
normal
70
what is achalasia?
failure of ring of muscle fibres (i.e. sphincters) of oesophagus to relax
71
aetiology achalasia
- associated with HLA-DQw1
- may be autoimmune disorder (circulating ab to enteric neurons)
- chronic infections: herpes zestr or measles virus?
72
difference in presentation between achalasia and oesophageal cancer
oesophageal cancer: dysphagia for solids before liquids
achalasia: dysphagia for liquids and solids at the same time
73
diagnosis of achalasia
clinical history
endoscopy (dilated oesophagus)
radiology + fluoroscopy (dilated + beak like narrowing, absence of peristalsis, spastic contractions (=vigorous achalasia with corkscrew appearance))
manometry (elevated resting LES pressure, incomplete LES relaxation, aperistalsis)
74
treatment for achalasia
- botulinum toxin
| - pneumatic dilation
75
treatment for achalasia
- botulinum toxin
- pneumatic dilation
- Hellers Myotomy
76
gastric motility in stomach
-fundus: relaxes on feeding: accommodate food without rise in pressure: vagal control (disorders of funds can cause early satiety)
l-antrum: pump s and churns (3 waves/min): emulsify contents
77
when is CCK stimulated
presence of fatty kids, amino acids or HCl: stimulation of I cells
78
acinus and duct secretion pancreas
acinus: NaCl and H2O
duct: NaHCO3 and H2O
79
hormonal stimulation of pancreatic acinus (enzymes)
CCK
80
hormonal stimulation of pancreatic duct (aqueous)
secretin (which also stimulates bile secretion by liver)
81
role of stomach acid and iron
Fe3 --> Fe2 for absorption in duodenum
82
largest endocrine organ in body
gut epithelium (enteroendocrine cells): "taste" molecules to release appropriate molecules
83
mechanism by which histamine increased release of H+
- stimulate parietal cells
| - increase cAMP: increase number of proton pumps
84
what receptor does PPI act on
H+,K+ ATPase
85
MOA of omeprazole
- weak base, absorbed in SI and enters blood, enters and accumulates in acid spaces (canaliculi and tubulovesicles of parietal cells)
- activated in acid by H+ to sulphenamide form --> cationic so trapped in canaliculi
- irreversable S-S bond with H+-K+ATPase: blocks secretion of new pumps
86
difference between esomeprazole and omeprazole
omeprazole: mixture of optical (R & S) isomers
esomeprazole: S isomer ("more active" in humans)
87
what are long term side effets of PPIs?
reduction in bone density
88
duodenal ulcers causes
- bacterial infection H. Pylori
- NSAIDs
- Zollinger-Ellison syndrome (gastrin-secretin tumour)
- risk factors: smoking, alcohol, caffeine etc
89
def gastritis
inflammation of the stomach lining
90
secretion of secretin
HCl stimulation S cells
91
role of prostaglandin in stomach
- maintains mucus barrier and stimulates HCO3 secretion
| - decreases and production
92
somatostatin secretion stimulation
- increase blood glucose
- increase aa
- increase fatty acids
- increased concentrations of several GI hormones from upper GIT in response to food intake (CCK, GIP, secretin, H+)
93
H pylori virulence factors
- flagella (bacterial motility and chemotaxis to colonise under mucosa)
- urease: neutralise gastric acid + ammonium cytotoxic
- CagA (cytokine associated gene A): affects cell signalling, reduces cell adhesion and changes cell phenotype from epithelial to mesenchymal cells (actin remodelling), IL-8 induction, apoptosis and host cell growth inhibition
- exotoxin: VacA (vacuolating toxin A): induces vacuoles in host cells and pore like structures --> osmotic swelling + causes mitochondrial dysfunction, apoptosis, disrupts epithelial cell barrier and improves H. pylori ability to colonise gastric epithelium
- babA (sialic-acid-binding adhesion): binds to Lewis b ABO blood group antigen on RBC and some epithelium cells ---> DNA breaks in host cells and can lead to cancer-associated gene mutations
- OipA (outer inflammatory protein adhesion): acts as an adhesion and associated with carcinogenesis
- peptidoglycan lipopolysaccharide coating: causes inflam responses and adheres to host cell
- secretory enzymes: mucinase, protease, lipase: gastric mucosal injury
94
Mechanism of H. Pylori living in low pH
- antrum: least acidic region
- "burrow" through mucus + adheres to epithelium
- metabolises urea (C02 + ammonia): increase local pH with NH3 and CO2 release --> control urea influx with H+gated urea channel
- lives in cloud of ammonia
95
mechanism somatostatin decreases acid secretion
inhibitory:
- G cells
- ECL cells
- (parietal cells)
96
treatment H. pylori
quadruple therapy:
- 2 antibiotics (claritheromycin, amoxicillin, metronidazole, tetracycline)
- PPI
- Bismuth compounds: improve antibiotic effectiveness
(Triple therapy; without bismuth)
97
why do we have quadruple therapy
H. pylori divides at pH>5.5 + clarithromycin, amoxicillin and tetracycline all work best in dividing cells
--> PPI: raises pH
-bismuth: blocks H+ influx into H. pylori --> prolonges a less acidic environment as PPI effects wear off
98
NSAIDs and ulcers
-inhibit COX1: decreases PEG2 in mucosa of stomach and duodenum
- PEG2: inhibits parietal cells and increase mucosal protection
- -> inhibition of PEG2: increase H+ and decrease protection
99
location find H. pylori
- mucus layer gastric antrum (especially in gastric pits
| - duodenal gastric metaplasia
100
gastric ulcers mechanism
- H pylori, NSAIDS: decrease mucosal barrier
- mucosa digested by H+ and pepsin
- H+ secretory rates decrease (H+ leaks into mucosa)--> increase gastrin: increase H+ (due to lack of inhibition of H+ on G cells)
101
duodenal ulcers mechanism
- hyperacidity (+ H. Pylori)
- increase H+: HCO3- buffer capacity overwhelmed
- H+ and pepsin damaged to mucosa
- H.Pylori indired actions (in one of two ways)
1. damage to antrum inhibits somatostatin release: increase gastrin: increase H+
2. spread of Pylori to duodenum: inhibits HCO3- secretion
102
def odynophagia
pain on swallowing
103
def meleana
passage of dark tarry stools (containing decomposing stools), usually indication of bleeding in upper GIT (oesophagus, , stomach, duodenum)
104
def peritonitis
inflammation of peritoneum
105
what is succossion splash
when percussing on abdomen, hear and see fluid splashing around due to gastric outlet obstruction
106
Virchow's node
Troisier's sign
VN: left supraclavicular: first place cancer spreads for abdomen, thorax and thoracic duct
TS: clinical finding of a VN
107
red flags for gastric and duodenal disorders
dysphagia, weight loss and older patients
108
investigations to do in gastric and duodenal disorders if no red flags
- H.Pylori (stool antigen, urea breath test, gastric biopsy)
- barium studies: abnormality in stomach wall: stretch with water and barium
- OGD
- pH (for acid reflux) and manometry (pressure)
- BRAVO capsule (for acid)
109
investigations for gastric and duodenal disorders in suspected malignant pathology
- blood tests (FBC, UEs, LFTs, iron)
- OGD (8 biopsies for cancer)
- CT scan (staging: from neck to below pelvis: presence of cancer and staging)
- PET-CT scan
- laparoscopy: key hole surgery
110
benign disease of stomach and duodenum
- gastritis
- peptic ulceration
- GORD (gastroesophagel reflux disease)
- achalasia
- functional disorders (bloating, delayed gastric emptying)
- Crohn's disease
111
risk factors for peptic ulceration
- H. Pylori
- smoking
- NSAIDS
- caffeine
- stress ulcers (Hb drop)
- steroids, Crohn's, drugs
112
where bleeding and perforating ulcers
AUP PUB
| posterior D1 bleed due to gasproduodenal artery haemorrhage
113
hereditary diffuse gastric cancer mutation
CDH1
114
mucus composition
- water and ions (90%)
- proteins (glycoproteins): 5-10%
- mucins (mucus glycoproteins: 1-5%)
115
liquid mucus, think mucus composition
liquid: low percentage of mins
thick: high percentage of mucins
116
different types of mucins in mucus
- free floating mucus: leaves molecules move through (i.e. O2, digested food), binds to other molecules (i.e. bacteria), interferes with delivery of drugs
- membrane associated mucins: attaches mucus to epithelial cell, last line of defence, signal changes to cell
117
mucus barrier layers
- loose layer: beneficial bacteria here
| - adherent layer: compact, very small pore size
118
when are mucins released
mucins stored in packets (preformed molecules) in goblet cells and release when a protective barrier needs to be formed
119
mucin composition
large glycoprotein polymer
- protein at both ends
- glycans (sugars) centrally: 80% of mass (sugar binds to things i.e. leptins on bacteria)
120
different family members of gel forming mucins
```
MUC2
MUC5AC
MUC5B
MUC6
MUC19
```
121
role of mucins
- space filling (gel formation)
- protease resistance (host, viral, bacterial) by sugars
- pathogen binding/evasion/killing
122
how mucins form mucus
entanglement
| cross links
123
pathogen subversion to epithelial mucosal barrier
- flaggelated
- enzyme production that degrade mucins
- toxins the kill epithelial cells or arrest intestinal cell division
- injection of bacterial toxins into epithelial cells
- disable tight junctions between adjacent epithelial cell
124
glycocalyx in cell
another carbohydrate barrier to cell
125
epithelial cell surface transmembrane (Tm) mucins structure
extracellular: carbohydrates + glycocalyx
transmembrane: lipid bilayer and receptors and adhesion molecules
cytoplasmic: cytoskeletal link/signal transduction proteins (+actin cytoskeleton)
126
if pathogen binds to epithelial cll surface transmembrane mucin
extracellular part of mucin becomes detached signalling cytoskeletal link/Signal transduction proteins: replenish barrier
127
where MUC5AC an MUC6 in GIT
corpus and antrum of stomach
128
where MUC2 in GIT
duodenum to colon
129
adhesins of H Pylori
BabA and SabA
130
role of MUC5AC in defence against H Pylori
binding bacteria
131
role of MUC6 in defence against H Pylori
growth inhibition: when glycans on MUC6 eaten by bacteria, causes cell wall synthesis
132
role of MUC1 in defence against H Pylori
shed from cell surface when H Pylori binds (MUC5AC and MUC1 share some glycans)
133
```
NSAIDs :
use
MOA
SE
warnings
```
use: 1. mild to moderate pain 2. pain related to inflammation
MOA: inhibiting cyclooxyrgenase (synthesis of prostaglandins from arachidonic acid)
SE: COX1 inhibition effects: GIT toxicity, renal impairment, CV events
warnings: don't use if: severe renal impairment, heart failure, liver failure, NSAID hypersensitivity
134
COX 1
constitutive form: stimulates PG synthesis: preserve integrity of gastric mucosa, maintains renal perfusion (dilates afferent glomerular arterioles), inhibits thrombus formation in vascular endothelium
135
COX2
inducible form: stimulates PG production that cause inflammation and pain
136
how much pancreatic juice /day
1200-1500 ml
137
enzymes for protein digestion secreted by pancreas
trypsin
chymotrypsin
carboxypolypetidase
elastase
138
enzymes for fat digestion secreted by pancreas
pancreatic lipase
cholesterol esterase
phospholipase
139
zygomens def
proenzyme: inactive form of enzyme
140
pancreatic zygomens and activation
trypsinogen
chymotrypsinogen
procarboxypolypeptidase
activated by trypsin (trypsinogen activated by enterokinase which is secreted by intestinal mucosa when comes into contact with chyme)
141
trypsin inhibitor secreted
secreted by granular cells in acini
142
pancreatic secretion stimulation
- Ach from vagus and other parasympathetic (mainly to acini)
- CCK
- secretin
143
phases of pancreatic secretion
- cephalic phase: 25% (done by vagus, vasoactive peptide, CCK, gastro releasing peptide)
- gastric: distention of stomach, first absorption of nutriments + same hormones as cephalic
- intestinal: 80%: CCK, secretin
144
interaction of sodium bicarbonate from pancreatic secretions and HCl from stomach
1. NaCl and carbonic acid
2. dissociation of carbonic acid: CO2 + H20
- -> CO2 absorbed into blood and respired by lungs
145
neg feedback regulation of pancreatic secretion
- pancreatic polypeptide (released from islets cells): inhib on acing enzyme secretion (local and central effect)
- somatostatin: pancreatic acing inhibition and CNS inhibition
- peptide YY (PYY): released by endocrine cells of distal SI in response to nutriments in ileum: acts on acing cells and via vagal nerve
146
pancreatic lipase action
triglyceride hydrolysis:
| triglyceride --> monoglyceride and 2 free fatty acids
147
amylase action outcome
dissacharides (i.e. maltose) and trisaccharides (i.e. maltotriose)
148
causes of acute pancreatitis
```
Idiopathic (20%)
Gallstones (50%)
Ethanol (25%)
Trauma
Steroids
Mumps
Autoimmune
Scorpion venom
Hyperkalaemia/hyperlipidaemia
ERCP (bile reflux from duodenum)
Drugs
```
149
pathogenesis of acute pancreatitis
causes:
- pancreatic duct obstruction (gallstones, ampullarf obstruction, chronic alcoholism, ductal secretions) --> interstitial oedema --> impaired blog flow --> ischemia
- acinar cell injury (alcohol, drugs, trauma, ischemia, viruses): release of intracellular proenzymes and lysosomal hydrolyses --> activation of enzymes into and extracellular)
- defefective intracellular transport (metabolic injury, alcohol, duct obstruction): delivery of proenzymes to lysosomal compartment --> intracellular citations of enzymes
all of the above lead to acing cell injury and activated enzymes
lesions:
- interstitial inflammation and oedema
- proteolysis (proteases)
- fat necrosis (lipase, phospholipase) + combines with Ca2+ to form insoluble salts
- hemorrhage (elastase)
150
acute pancreatitis signs and symptoms
- abdo and back pain
- nausea and vomiting
- respiratory distress
- fever
- haemorrhage (proctalgia)
- shock (hypotension, tachycardia and oliguria
- elevated serum amylase (for 24 hours)
- elevated serum lipase (72-96h)
- gycosuria
- hypocalcaemia (poor prognosis)
151
def oliguria
low output of urine
152
diagnosis of acute pancreatitis
severe abdo pain
- blood test: amylase ad lipase enzymes in bloodstream
- chest X ray: show calcification (exclude perforation)
- CT: pancreatic necrosis, access or fluid collection
- abdo ultrasound
153
management of acute pancreatitis
- ABC assessment
- assess severity: Glasgow Imrie Score
- Atlanta
- support: replace fluids, NG secretion, analgesia, nutrition
154
acute pancreatitis complications
- acute fluid collection
- pseudocysts
- walled off pancreatic necrosis (WON)
155
causes chronic pancreatitis
- idiopathic (20-30%)
- alcohol 60-70%
- genetic (i.e. cystic fibrosis)
- autoimmune (ie IgG4)
- hyperlipidaemia, hypergyceriaemia
156
pathogenesis of chronic pancreatitis
- ductal obstruction by concretions (increased protein concentration in pancreatic juice creating ductal plugs, can calcify forming calciuli (calcium carbonate precipitates)
- toxic metabolic: direct toxic effect on acinar cells: accumulation of lipids in cigar cells, acing cell loss and parenchymal fibrosis (change from acinar to ductal metaplasia)
- oxidative stress: free radicals: membrane lipid oxidation and activation of transcription factors (attraction of mononuclear cells)--> promotion of fusion of zygomen granules and lysosomes, acid cell necrosis, inflammation, fibrosis
157
sign/symptoms chronic pancreatitis
- pain (epigastric to back and episodic)
- malabsorption, weight loss, steatorrhoea
- diabetes (type 3c)
- jaudince (bile duct obstruction)
158
diagnosis of chronic pancreatitis
- faecal elastase
- endoscopic ultrasound
- CT/MRI
159
management of chronic pancreatitis
- lifestyle, smoking, alcohol
- pain control (analgesia, management diabetes, endoscopic therapy, celiac nerve block, surgery for decompression)
- treat malabsorption croon/pancreatin: combination of protease, lipase and amylase
160
chronic pancreatitis complications
bleeding, obstruction, pancreatic cancer, survival (15-20 years from diagnosis)
161
CHO absorption transporters
- SGLT1: secondary active, Na+ dependent co transport (on apical surface: K+,Na+ ATPase) (for glucose)
- GLUT5 (for fructose)
- GLUT2 (for glucose, galactose)
162
aa absorption transporters
- PePT1 (cotransport with H+)
- XAG- (for anionic aa: aspartate, glutamate: cotransport 2Na, , H+, K+)
- B0: neutral aa: cotransport with Na+
- b0+: cationic aa and cystine (aa)
- PAT1: proline (aa)
163
how do you know if you have with aa transporters
can find them in the urine (as proximal tubal has same transporters
164
B0 transporter deficiency
hartnup disease
165
b0+ transporter deficiency
kidney stones
166
bile salts action on fat
- emulsify large fat droplets: increase surface area for lipase action
- mixed micelles formation: stabilise products of TG hydrolysis while they ar translocated from luminal to apical membrane
167
emulsification process
core body temperature, peristalsis, salivary and pancreatic lipases
168
mechanism of absorption of lipids
- simple diffusion of FA: 50% in undissociated from so lipid soluble
- FFA transporters: FAT and CD36 + SCFA transporters in colon
- MG carrier mediated mechanisms for transport
169
cholesterol absorption
```
duodenum
NPC1L1 (Riemann-Pick C1 Like 1) protein: receptor medicated endocytosis
```
170
drug that inhibits endocytosis of cholesterol
ezetimib
171
SCFA
butyrate, propionate, acetate
- poduced by bacteria fermentation in colon (finer component and incomplete digestion of CHO)
- butyrate good, propionate and acetate bad
172
absorption of SCFA
Secondary active transport:
| SMCT1: SCFA and Na+ cotransport driven by Na+,K+ ATPase
173
H20 absorption
- moves down osmotic gradient
- 8.4L/day, 6.5 in SI, 1.9 in colon
- via junctional complexes between cells OR via SGLT1 and aa transporters (NOT aquaporins)
174
which ions are excreted in faeces
K+ (paracellular absorption diffusion ileum and secretion in LI) and HCO3+ (due to neutralised)
175
osmotic load def
unabsorbed water soluble solutes that increase fluid retention in bowel: lack of enzymes or transporters, damage to mucosal cells, secretion of ions by gut
176
diarrhoea problem
increased osmotic load
177
excretion rate of alcohol
1 unit/hour
178
1 unit of alcohol in pure ethanol
10 ml or 8g
179
alcohol liver disease stages
- acute fatty change (aldehyde pathways instead of H20--> fat) REVERSIBLE
- alcoholic hepatitis (Mallory's hyaline) REVERSIBLE: inflame response causing:
- hepatic fibrosis REVERSIBLE
- cirrhosis IRREVERSIBLE (end stage liver disease, complete modularity, increase turnover of cells so increase risk of developing
- Hepatocellular carcinoma
180
mechanism of alcohol related disease
- direct toxic effect
- indirect metabolite effect
- induction of enzyme systems esp cytochrome p450 (look at how this relates)
- nutritional deficiency esp B group vit
- liver function impairment
181
non alcoholic steatohepatitis (NASH)
- identical features to alcoholic hepatitis
| - associated with obesity, DMT2, hyperlipideamia
182
physical effects of alcohol
fetal alcohol syndrome
- increase risk of head/neck/oral cancer
- alcoholic cardiomyopathy
- systemic hypertension
- peripheral neuropathy
- CNS problems: vit deficiency, Korsakoff's psychosis, Wernicke's encephalopathy
- withdrawal syndromes
183
GIT effects of alcohol
- mouth/upper GIT:increase risk of cancers of upper GIT (esp tongue, ducal mucosa, pharynx, upper oesophagus) esp in spirit use and cig smoke
- oesophagus: squamous carcinoma, varices (chronic liver disease)
- stomach: acute gastritis, acute/chronic ulceration, portal gastropathy
184
what are determinants of alcohol use
socioeconomic structures
political-legal structures
corporate market structures
185
drivers of alcohol use
affordability
availability
acceptability
186
moderators of alcohol use
```
where
what
why
how
who
```
how much and how often
187
consequences of alcohol use
alcohol related health, social and economic harm
188
tools for screening for harmful drinking
CAGE
| AUDIT (FAST and AUDIT-C)
189
what is CAGE
- have you ever attempted to CUT down on drinking
- do you ever get ANNOYED when people complain about your drinking
- do you ever feel GUILTY about things you have done while drinking
- do you ever need a drink to get going in the morning (EYE OPENER)
190
domains and content of AUDIT
- hazardous alcohol use: frequency (of drinking and heavy drinking), quantity
- dependence symptoms: impaired control, increase salience, morning drinking
- harmful alcohol use: guilt, blackouts, alcohol related injuries, other concerns
191
what is IRIS
improved health care response in prevent domestic violence and abuse
192
what is HARKS
popped up on clinicians screen with patient file so clinician knows the patient suffers from domestic abuse and violence and remind them to ask about it:
```
humiliate
afraid
rape
kicks
safety
```
193
2 week referral for oesophageal cancer if
-dysphagia or
-aged 55+ and with any of the following:
upper abdominal pain
reflux
dyspepsia
194
Barrett's oesophagus pathophysiology
-longstanding reflux: squamous epithelium --> columnar epithelium with intestinal metaplasia
(premalignant for adenocarcinoma)
195
oesophageal cancer
types
risk factors
-upper 2/3: squamous cell carcinoma
lower 1/3: adenocarcinoma
-RF: (for SCC) smoking, alcohol, plummer-vinson syndrome, achalasia, corrosive strictures, coeliac disease, radiotherpatry treatment for breast cancer, (for adenocarcinoma):obesity, age, barrette's oesophagus, longstanding heart burn, smoking, breast cancer treated with radiotherapy
196
phases of swallowing
look it up
197
absolute/relative poverty
absolute: standard of living fixed in world and if below you are in poverty
relative: beneath median 60% of country
198
factors affecting poverty
- 0 hour contracts
- housing prices
- universal credit: delayed benefits money + not enough
- inflation
- lack of education
199
5 core dimensions of illness cognitions
```
identity
perceived cause
time line
consequences
cure/control
```
200
self regulatory model
stage 1: interpretation (symptom perception, social messages)
- ->representation of health threat (illness cognitions)
- ->emotional responses to health threat
stage 2: coping (approach coping, avoidance coping)
stage 3: appraisal (was coping strategy effective?)
201
absorption in the colon
- most in proximal colon
- actively transport Na+ in: electrical potential for Cl- absorption and H20
- antiport Cl-/HCO3-
- K+ absorption: H+,K+ ATPase on basolateral side and K channels and K+,Cl- cotransporters (KCC1) on luminal side: necessary to drive Na+ (ENaC) transporter
202
anxiety and physical health
anxiety can make physical health worse by:
1. direct: acute/chronic physical effects of anxiety
2. indirect: influence of behaviours (exercise, social support, diet, smoking)
203
COM-B framework
behaviour affected by
- capability
- motivation (reflective i.e. weighing up and automatic i.e. habit)
- opportunity (physical i.e. time and social i.e. peer pressure)
204
PRIME theory
external environment affects internal environment (percepts, drivers, emotional states, arousal, ideas etc) which are affected by
- Plans
- Evaluation
- Motives
- Impulses
- Responses
- -> theory of decision making in a set moment
205
Health Belief model
reflective motivation: explains intention
demographic variables affected by: susceptibility, severity, costs, benefit, cues to action, health motivation, perceived control
which all lead to likelihood of behaviour
206
control of maximisation of nutrients absorption
-regulating motility
-controlling secretion of digestive juices
(-little control of absorption)
207
receptors of the GIT and receptor activation effect
- mechanoreceptors
- osmoreceptors
- chemoreceptors (acidity and digestive products)
activation causes:
- hormones
- nerves (short and long reflexes)
- paracrine transmission (i.e. release of histamine)
208
main sensory cell f GIT
enteroendocrine cell
209
GLP-1: where is it produced, what does it do
- duodenum-colon by enteroendocrine cells
| - "incretin" (like GIP): enhances insult secretion, inhibits glucagon production
210
gut hormones
- short chain peptides
| - secreted by enteroendocrine cells in mucosa
211
excitatory and inhibitory neurotransmitters of the enteric nervous system
excitatory: acetylcholine, substance P, gastrin releasing peptide
inhibitory: nitric oxide, vasoactive intestinal peptide
212
extrinsic nerves (ANS)
- parasympathetic: preganglionic fibres synapse with ENS: release AChn SP, GRP (excitatory) and NO, VIP (inhibitory) --> vago-vagal reflex
- sympathetic no major role in 'day to day' motility: noradrenaline, decrease motility, decrease blood flow
213
def paracrine and endocrine
paracrine: released locally (binding nearby cell)
endocrine: secreting into systemic circulation
214
enterochromaffin cells
- mechano and chemo sensory cell
- 90% of enteroendocrine cells are enterochromaffin cells
- release serotonin
215
problem with IBS and serotonin
in IBS have too much 5HT because SERT not working properly
216
serotonin and motility
- enterochromaffin cells release 5HT
- 5HT picked up by intrinsic primary afferent neurons
- short reflex: inhibitory motor neurone relax intestines in front of peristalsis mvnt and excitatory motor neurone that contracts intestines behind peristalsis mvnt
- 5HT picked up by excitatory afferent signals to brain (long reflex)
217
drug receptors for trials for IBS
5HT3 antagonists
| 5HT4 agonists
218
control of vomiting
epithelium damaged: increase release of 5HT: stimulate 5HT3R which go to medulla oblongata: "vomiting centre"
(chemoreceptor trigger zone: for blood)
219
def emesis
sudden expulsion of gut/gastric contents through oesophagus and mouth
220
anti-emetics drug receptors
5HT3 antagonists
221
opioid receptors expressed in GIT
mu, kappa, delta (mu is the important one)
222
opioid receptors activation in GIT
G protein (G0):
- activation K+ channels
- Inhibits Ca2+ channels
- -> decrease synaptic transmission:
- main mechanism for analgesia + decrease motility (inhibitory motor neurones not stimulated): increase transit time in colon so more H2O absorbed --> constipation
223
endogenous opioids in GIT
- 4-8 aa
- enkephalins and endomorphins
- -> GPCR: Gi: decrease adenylate cyclase: decrease
224
mechanism for increase intestinal secretion
PEG2 and secretin (secrataguoges): GPCR --> Gs: increase adenylate cyclase
225
opioid antidiarrhoeal drugs
- mu receptor agonists (Loperamide, Diphenoxylate + atropine)
- enkephalinase inhibitors (enhance actions of endogenous enkephalins): Hidrasec
226
primary and secondary peristalsis of oesophagi
primary: continuation of pharyngeal peristalsis
secondary: local reflexes (circular and longitudinal muscles)
227
serosa and advertía: intra/extraperitoneal?
serosa: intra
advent: extra (linked to posterior abodo wall)
228
effects of absence of gut bacteria
```
behaviour
gut homeostasis
immune response under stress
body weight
brain development and gene expression
```
229
use of faecal transplant therapy
Clostridium difficile (spore forming: hard to eliminate with antibiotics)
230
Paneth cells:
- location
- secretions
- stimulations
- base of crypts in SI
- alpha and beta defensives (antimicrobial peptides)
- gut bacteria
231
what secretes IgA
plasma cells
232
how many stem cells does crypts have
6-8
233
zone of cell renewal and differentiation in crypt
stem cell
proliferative zone
differentiation zone
234
where do you find Peyer's patches?
distal jejunum and ileum
235
giardia Intestinalis
- most common intestinal parasite found in the USA
- 10-25 cysts can cause clinical disease
- pathology: villous atrophy + crypt hyperplasia
- enterocyte apoptosis
236
where do you find gut associated lymphoid tissue
just below epithelial cells
237
function of M cells
selective endocytosis of antigens, and transporting them to intraepithelial macrophages and lymphocytes, which then migrate to lymph nodes where an immune response can be initiated
238
where are M cells found
Peyer's patches
MALT
GALT
239
lamina propria lymphocytes types
naive CD4+ T cells differentiate into:
- Th1
- Th2
- Th17
- Treg
Th1, Th2 and Th17 can cause pathology if they are out of control and Treg regulates this
240
innate lymphoid cells
- from common lymphoid progenitor
- rely on IL2R singling
- no T cell receptors
- ILC1, 2 or 3
241
ILC1
- produce IFN gamma
- NK cells are ILC1
- express T-bet
242
ILC2
- also called nuocytes, NKC
- IL5/IL13 producers
- express RORalpha/GATA3
- seen in allergy
- respond to IL25/IL33
243
ILC3
- contributes to mucosal homeostasis
- produce IL17A&F/IL22
- express RORgammat
- respond to IL23
- important in fetal lymphoid organogenesis and GALT formation
244
T cell activation
B7 (on APC) binding to CD28 (on T cell)
245
T cell inactivation
B7 (on APC) binding to CTLA4 (on T cell)
246
what is PD1/PDL1 interaction
PD1: immune suppressive molecule to avoid over-activation
247
types of IBS and cause
ulcerative colitis
crohn's disease
cause: dysregulation of host flora
248
what is the cancer inflammation paradigm
balance between inflammation and cancer
249
hallmarks of cancer
- self-sufficient in growth signals
- insensitivity to anti-growth signals
- avoidance immune destruction
- tumour promoting inflammation
- tissue invasion and metastasis
- limited replicative potential
- sustained angiogenesis
- genomic instability
- deregulated metabolism
- evading apoptosis
250
2 oncogenes of colon cancer
beta-catenin and KRAS
251
3 TSG in colon cancer
APC and p53 and Rb
252
cell signalling pathway
```
ligand
receptor
signalling cascade
transcription factors
gene expression
```
253
what is RAS
a GTPase (when bound to GTP it is on and activates downstream pathway)
254
what does a mutation in RAS cause
locked into active form: conversion from GTP to GDP stops happening
255
which pathway must be dysregulated in colon cancer
Wnt signalling
256
what is Wnt?
growth factor
257
which genes are involved in Wnt signalling
APC and beta catenin
258
Wnt signalling pathway
unstimulated state: Wnt does not bind to receptor and beta-catenin is phosphorylated (and degraded) by Apc
stimulated state: Wnt binds to receptor: inactivation of GSK-3 beta complex: beta-catenin does not get phosphorylated by Apc: activates gene expression in the nucleus and drives cell proliferation
259
how is Wnt signalling dysregulated
- deletion of both copies of APC: beta catenin cannot be phosphorylated (80% of cases)
- point mutation at phosphorylation site of beta catenin: can no longer be phosphorylated (20% of cases)
260
which part of the cell cycle responds to mitogenic GFs and TGF-beta
G1 to the R point
| G1 is only phase that responds to extracellular signals
261
CDKs and cyclins of cell cycle
- G1: CDK4/6, cyclin D
- G1 (from R point) and beginning of S phase: CDK2 and cyclin E
- beginning of S phase: CDK2 and cyclin A
- end of S phase to end of G2: CDK1 and cyclin A
- end of G2 and mitosis: CDK1 and cyclin B
262
what are CDKs
cyclin dependent kinases: enzymes that phosphorylate substrates (bring changes to cell)
263
P53 actions and P21 link
P53: cell cycle arrest (turns up P21 which inhibits CDKs/cyclins), DNA repair, block off angiogenesis and apoptosis (switches on proteins involved in cell death)
264
what is genomic instability
high frequency of mutations within the genome
265
genetic instability in colon cancer
HNPCC: mismatch repair
APC: chromosomal instability
266
what are adenomatous polyps
polyps that carry high risk of cancer
267
FAP
familial adenomatous polyposis (1%)
268
APC
- adenomatous polyposis coli
- chromosome 5q21
- mutated in 80-90% of sporadic colorectal cancers
269
what happens to crypts if APC or beta catenin mutated
zones of proliferation will be higher up in the crypt: forms hyper proliferative zone which can turn into polyp
270
HNPCC
hereditary non-polyposis colon cancer
2-3%
Lynch syndrome (ovary, SI, urinary tract, skin and brain)
-few polyps
-MHS2 and MLH1 mutated (promoter is methylated switching gene off): increases mutation rate
271
what is micro satellite instability
genetic hypermutability
272
mutated pathway of CRC with MSI
TGF-beta (inhibitory pathway): 90% of CRC with MSI: doesn't cause cancer but increase mutations
273
which mutations have highest mutation rate
mismatch repair (not chromosomal)
274
when is immunotherapy used in colon cancer
for higher mutated phenotypes (MSI)
275
metastatic cancer of right sided colon cancer
peritoneal and omental and liver
276
which side of colon cancer has better outcome
left sided
277
3 subtypes of colorectal cancer
pole hyper mutated (1%)
micro satellite instability (8-9%)
micro satellite stability (90%)
