Big Boys Flashcards
Q
how do commensal bacteria regulate digestion?
what happens if we have bacterial overgrowth?
dynamic equilibrium between diet-gut microbiome-bile acid pool size:
normally - we have conjugated bile acids, created by liver. Conjugated bile acids (primary bile acids): more efficient in emulsifying fats because at intestinal pH they become more ionized than the unconjugated bile acids.
Commensal bacteria: participate in the synthesis of bile acids. Microbial enzymes de-conjugate bile acids & make them less effecient: (secondary bile acids).
so we have a pool of primary and secondary bile acids: if have bacterial overgrowth in gut: form too much secondary bile acids = struggle to digest fats
explain luminal, mucosal and post absorptive phases of protein digestion
- *luminal phase**
- stomach: pepsin released by pepsinogen (zymogen / proenzyme). pepsinogen is activated by HCl, which is releaed from parietal cells in the gastric pits.
- small intestine: further digestion from pancreatic enzymes
mucosal phase:
- brush border enzyme: enterokinase converts trypsinogen -> trypsin
then:
trypsin activates:
a) chymotrysinogen -> chymotrypsin
b) procarboxypetidae -> carboxypeptidase
- a.a. enter the epithelial cells via Na-linked secondary active transport across the apical membrane (same system for sugar)
- *post-absorptive phase;**
- a.a. transporte across basolateral membrane by fac. d
describe the absorptive pathway of B12 :)
- *absorptive pathway:**
- bound to dietary protein
- first dissociated by HCl and pepsin, in stomach
- reattaches itself via haptocorrin (from saliva thats now in stomach)
- dissociated from haptocorrin and binds with stomach-derived intrinsic factor
- absorbed only in terminal ileum in enterocytes (although 60-80% still goes into faeces)
- reassociates with transcobalamin and then goes to portal circulation
explain luminal, mucosal and post absorptive phases of llipid digestion
luminal phase
- mouth: lingual lipases
- stomach: gastric lipases
- pancrease: pancreatic lipase bile salts & bile salts
= triglycerides -> free fatty acids & monoglycerides. then form micelles (contain fat soluble vitamins and cholesterol)
- *mucosal phase:**
- simple diffusion (bc membrane of enterocytes are also lipids - so can just diffuse through)
- within enterocytes: molecules are reassembled by GA = chylomicrons
- *post absorptive phase:**
- chylomicrons secreted across basolateral membrane, but are too big to enter blood: enter lympahtic fluid
what do two starting materials do you need before glycogen synthesis?
what do you convert one of ^ into for glycogen synthesis (and how)?
what is the mechanism of glycogen synthesis? (3)
- *glycogen synthesis needs:**
- a primer (protein that glucose will attach to): glycogenin.
- glucose-6-phosphate (G6P)
BUT: NEED TO CONVERT G6P -> UDP-glucose before can be added to glycogen:
- *a) G6P –> G1P
b) G1P –> UDP-glucose** - *glycogen synthesis:**
- UDP-glucose added to glycogenin primer initially, and then non-reducing ends of glucose by enzyme glycogen synthase to create a glycosidic-1-4 bonds
- the UDP is lost and one glucose is added onto the glycogen
- branches are made by branching enzyme: creates a 1-6 glycosidic bonds
crohns diease:
a) definition
b) active disease symptoms? (4)
c) leads to? (4)
d) diagnosis? (2)
- *crohns diease:**
a) definition: chronic inflammation condition that can affect whole GIT, but usualy found localised to small bowel (ileum or colon) - *b) active disease symptoms:**
- diarrhoea
- abdominal pain
- fatigue
- fever
- blood in stool (sig. finding)
- *c) leads to:**
- scarring of bowel epithelium
- ulcers
- fistulas (hole in bowel)
- bowel obstruction
- *d) diagnosis:**
- fecal calprotectin
- colonscopy
ulcerative colitis
- restricted to which region?
- active disease symptoms?
- lead to?
- diagnosis?
- *ulcerative colitis**
- restricted to: colon
- *- active disease symptoms:**
a) bloody diarrhoea
b) abdominal pain
c) fatigue
d) fever
e) weight loss - *- leads to:**
a) perforation of colon
b) severe bleeding
c) dehydration
d) systematic inflammation
e) colon cancer - *diagnosis:**
a) fecal calprotectin
b) colonscopy
what is the GALT?
what does it include (3)
gut assocaited lymphatic tissue
includes:
- peyers patches of small intestine (groupings of lymphoid follicles in the mucus membrane that lines your small intestine)
- lymphatic circ supplying immune cells
- lymphoid aggregrates in large intestine
- intra-epthilial lymphocytes: found inbetwen epi cells
- dentritic cells: grab antigens and take to lymph nodes
Q
describe how the ENS and peristaltic reflex works:
- how this reflex activated? (2)
- describe the difference between the different motor neurons causing ascending and descending wave of peristalsis:
- what type of NT released?
- what does that cause?
- *Activation of enteric reflexes: can be chemical or mechanical.**
- Chemical activation can be through substances from endocrine cells (e.g. 5-HT), nutrients or low Ph
- mechanical via muscle deformation or stretch
- contraction of circular muscle
motor neurons:
Ascending wave of peristalsis: excitatory neuro-transmission to muscle, mostly by the release of acetylcholine. This causes the contraction and initiate the push.
Descending wave of peristalsis: Inhibitory neurotransmission to muscle, mostly by release of the gas nitric oxide
Q
explain the MoA of how HCl is produced xo
A
HCl production:
H+:
in the interstitial space:
- bicarbonate (HCO3) can react with H+ to form H2CO3 (carbonic acid)
- carbonic acid reacts via enzyme carbonic anhydrase and turn into H20 and CO2
- H2O and CO2 can then enter parietal cell
in the parietal cell:
- bicarbonate reforms = useful bc its an important buffer!
- H+ ion is left. pumped via proton pump on apical membrane of parietal cell into lumen
Chlorine:
- when bicarbonate pumped out out of parietal cell into interstitial space, Cl- pumped in.
- when in parietal cell, Cl- then pumped into lumen via CFTR channel :)
= HCl formed
(probs just important to know that uses bicarbonate, CFTR & proton pump is key)
* what are the three ways can stimulate pumping H+ into lumen of stomach? *
* what are the two ways can inhibit stomach pumping H+ into lumen of stomach?
can stimulate pumping H+ into lumen of stomach:
- Ach binding to M3 receptor
- Histamine binding to H2 receptor
- Gastrin binding to CCK2 receptor
all in the parietal cells
- *can inhibit stomach pumping H+ into lumen of stomach**
- somatostatin binding to somatostatin receptor
- prostoglandin binding to prostoglandin receptor
explain the cephalic, gastric and intestinal stage of stomach acid secretions xox
- *Cephalic stage**
1. Stimulation of medulla oblongata: Activation of Vagus nerve – parasympathetic action potentials sent to the stomach - Stimulates gastric acid secretion by chief cells, parietal cells, G cells and ECL cells
2.Mechanoreceptors and chemoreceptors in the mouth also increase parasympathetic signals to the stomach.
- *Gastric stage**
1. Distension of stomach stimulates stretch receptors – local reflex
- Gastric distension activates Vagus nerve – parasympathetic action potentials sent to medulla oblongata, and then to stomach (vago-vagal reflex)
- Stimulates gastric acid secretion by chief cells,, parietal cells, G cells and ECL cells
3.Presence of partly digested peptides stimulates G cells to secrete Gastrin
Intestinal stage
Primarily inhibits gastric acid secretion when FOOD AND ACID ENTERS THE INTESTINES
NERVOUS CONTROL:
It signals the sympathetic system to stop gastric secretions
- Inhibition of parietal and chief cells
HORMONAL CONTROL:
- Cholecystokinin, secretin and GIP (gastric inhibitory protein) produced by duodenum –> inhibit gastric secretions
- Cholecystokinin and GIP released by presence of lipids and carbohydrates
- Secretin released when pH decreases (due to entrance of acidic chyme into the duodenum)
give overview of ETC :)
where does it occur?
- location: inner membrane of matrix
- reduced co-enzymes NADH & FADH used to create a proton gradient across the inner membrane of the mt
- NADH & FADH offload their H+ to proton complexes
- H+ passes from one complex to another (1->4) in a series of REDOX reactions
- As H+ passes from complex to another in REDOX reactions, the energy produced is sufficient to pump protons from the inner maxtrix, across the inner mt membrane, into the inner membrane space
- this creates a proton gradient. protons can only return to the matrix via ATP synthase -> where ATP is produced
Q
ETC:
what happens at complexes 1-4 ?
@ which complexes are protons from transferred from the matrix to the intermembrane space, making a proton gradient?
A
Complex 1
- NADH –> NAD+ + H.
- H+ is transfered to ubiqunione (electron carrier)
Complex 2
- FADH –> FAD + H+
- H+ transfers electrons to ubiqunione
Complex 3
transfers electrons from ubiqunione to cytochrome C
4th protein complex
- electrons fro cytochrome C transferred to 1/2 O2 molecule is the final electron acceptor from electron transport chain. h20 is produced.
- protons pumped at complexes 1, 3 & 4 = proton gradient
explain mechanism of insulin secretion from B langerhan cells
- glucose enters B cells through glucose transport GLUT 1&3
- glucokinase (converts glucose to glucose-6-phosphate) acts as gluocse sensor for insulin secretion
- high Km of glucokinase ensures that the initation of of insulin secretion by glucose only occurs when blood glucose levels are high
- glucose converted to glucose-6-phosphate and to pyruvate & generates ATP through ECT = increases ATP:ADP ratio
- increased ATP:ADP ratio: closes ATP-sensitive K channel on B cell
- causes voltage-gated Ca2+ channels open: Ca moves into the cell
- high intracellular Ca2+ triggers insulin secretion !
what is the hypothalamic-pituitary-adrenal axis (HPA axis)
how is it controlled? (3)
- CRH (corticotropin releasing hormone) from hypo causes release of ACTH from anterior pituitary gland; causes release of cortisol from adrenal gland
- *controlled by:**
- long loop: cortisol controls this system via negative feedback on CRH (more cortisol released, causes inhibition of more cortisol)
- short loop: ACTH causes negative feedback on CRH
- ultrashort loop: ACTH feedbacks back itself & inhibits.
