Digestion and absorption Flashcards

1
Q

What are the chemical and mechanical digestive mechanisms of the oral cavity and stomach ?

A

Oral:
mechanical - chewing, lubrication
chemical - salivary amylase and lipase
Stomach:
mechanical - churning
chemical - pepsin and gastric lipase

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2
Q

What are the chemical and mechanical digestive mechanisms of the small intestine and large intestine?

A

Small intestine:
Smooth muscle - mechanical: churning and propulsion
Pancreas - chemical: amylase, trypsin, chymotrypsin, carboxypeptidase, elastase, lipase-colipase, phospholipase, cholesterol esterase
Gall bladder - chemical: bile salts
Intestinal brush border - chemical: enterokinase, maltase, lactase etc.
Large intestine:
mechanical: churning, propulsion
chemical: bacterial fermentation

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3
Q

What is the premise of digestion?

A

Each specific segment of the GIT is specialised for chemical and mechanical digestion of food into fundamental components e.g. water and ions, amino acids, monosaccharides, fatty acids
These are absorbed across the mucosa of GIT and into the blood

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4
Q

What are the different carbohydrates digested into?

A

Starch >a-dextrins, maltose, maltotriose > glucose
Trehalose > glucose
Lactose > 2x glucose
Sucrose > glucose, fructose

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5
Q

What are the different lipids digested into?

A

Triglyceride > monoglyceride, 2x fatty acid
Cholesterol ester > cholesterol, fatty acid
Phospholipid > lysolecithin, fatty acid

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6
Q

What is protein digested down into in the stomach vs SI?

A

Stomach:
Protein > amino acids, oligopeptides
SI:
Protein > amino acids, dipeptides, tripeptides
Protein > oligopeptides > amino acids, dipeptides, tripeptides

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7
Q

Through which vessels does the pancreas supply excretion to the rest of the GIT?

A

Flow through the pancreatic duct, into the ampulla of Vater, into the duodenum, controlled by the sphincter of Oddi

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8
Q

What are the different cell types that secrete pancreatic juices, and what do they secrete?

A

Pancreatic acinar cells:
- Enzyme secretion (protease, lipase, amylase)
Pancreatic Duct cells:
- HCO3- secretion and water

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9
Q

What causes acinar cells to secrete enzymes?

A

Stimulation with ACh, CCK or other agonists > intracellular Ca2+ increases and stimulates the exocytosis of enzyme containing secretory granules (zymogen granules) and NaCl rich fluid secretion

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10
Q

What prevents autodigestion in acinar cells containing digestive enzymes?

A

Pancreatic enzymes are contained within zymogen granules in form of proenzymes of mature enzyme
Interior of granules is acidic. Trypsin (enzyme) activity is greatest at pH 8
Also contain serine protease inhibitors e.g. SPINK1 gene - guard against inflammation - mutations lead to pancreatitis

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11
Q

What is the process of converting proenzymes to enzymes to mature enzymes?

A
  • Agonists stimulate the acinar cells
  • Intracellular Ca2+ increases
  • Exocytosis of zymogen granules to release proenzymes into the pancreatic duct into the duodenum
  • Trypsinogen activated by enteropeptidase in duodenal brush border to cleave trypsin
  • Trypsin cleaves trypsinogen to activate more trypsin
  • Trypsin cleaves more proenzymes
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12
Q

How is pancreatic lipase released and become effective?

A

Pancreatic lipase released from the pancreas in active form but is inefficient until bound to colipase:
Trypsinogen cleaves to trypsin by enteropeptidase in brush border
Tryspin will convert procolipase to form colipase
Colipase binds to pnacreatic lipase to make it efficient

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13
Q

How do pancreatic acinar cells secrete NaCl?

A
  • Na-K pump - 3 Na+ out cell, 2K+ in - Na+ gradient across basolateral membrane
  • Na/K/Cl cotransporter produces the net Cl- uptake, driven by Na+ gradient generated by Na-K pump
  • Rise in K+ is shunted by basolateral K+ channels out of cell
  • Intracellular accumulation of Cl- establishes electrochemical gradient that drives Cl- secretion into acinar lumen. Mediated by protein kinases stimulated by increased Ca2+ stimulated by CCK or ACh
  • Movement of Cl- into lumen makes transepithelial voltage more lumen negative, driving Na+ into lumen through tight junctions
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14
Q

How do pancreatic duct cells secrete HCO3- ?

A
  • CO2 and water converted into HCO3 by carbonic anhydrase
  • Produced HCO3 transported into the pancreatic ducts by anion exchanger
  • The source of the luminal Cl- for the exchange is from the cystic fibrosis membrane conductance regulator (CFTR) - activated by cAMP stimulated by secretin
  • Accumulation of anions drive water and Na+ reabsorption paracellulary down transepithelial osmotic and potential gradients = HCO3- risch isotonic fluid
  • H+ accumulation is prevented by Na+/H+ exchange. Allows further conversion of CO2 to HCO3
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15
Q

What is the function of HCO3- secreted by the pancreas?

A

Neutralises stomach acid
HCO3- + H+ -> H2O + CO2
Allows optimal luminal enzironment for chemical digestion in the duodenum

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16
Q

Where is secreting produced from and what stimulates release?

A

Acidic chyme enters the duodenum, stimulates S-cells in crypts of the duodenum to release secretin, if the luminal pH falls below 4.5

17
Q

What is the role of secretin?

A

1) Role in HCO3- secretion:
- pancreatic duct secretion HCO3-
- stimulates HCO3- secretion from Brunner’s gland in duodenum
- regulates HCO3- secretion into duodenum from biliary ducts
2) Stimulates bile secretion from biliary ducts
3) Slows H+ secretion by stomach parietal cells - inhibits gastrin release
4) Decreases motility of the stomach
5) Constriction of pyloric sphincter
= aid neutralisation activity and reduce factors leading to acidic environment > optimal conditions for enzymatic digestion of food

18
Q

What are the phases of GI secretion?

A

Stimuli upregulate GI secretion - stimuli can be divided into three phases:
- Cephalic phase (external environment and mouth)
- Gastric phase
- Intestinal phase

19
Q

What is the cephalic phase of gastrointestinal secretion?

A

Sight, smell and taste of food can elicit salivary, gastric and pancreatic secretions
Secretion therefore triggered before food arrives in the GI tract - feedforward control
Anticipatory response allows prep to receive food:
lubrication with saliva
Ensure acid present in stomach to digest, kill bacteria
Bicarbonate present to neutralise any acidic chyme escaping the stomach
Active enzymes

20
Q

What is the role of the stomach in the cephalic phase?

A

Stimulated by smelling, tasting, chewing and swallowing
Afferent nerve impulses transmitted through vagal nerve nucleus and vagal efferent fibres to stomach
Vagus nerve acts directly on:
- Parietal cells = acid secretion
- Antral G cells = gastrin release
Mediator at the parietal cells = ACh
Mediator at G cell = gastrin-releasing peptide (GRP)
Secretory response to cephalic stimulation depends on meal

21
Q

What is the role of the pancreas in the cephalic phase?

A

Afferent impulses travel to vagal nucleus
Vagal efferent transmissions to pancreas stimulate both duct and acinar cells to secrete
Stimulation is mediated by ACh and has greater effect on enzymatic component than it does on the aqueous component

22
Q

What is the gastric phase composed of?

A

1) Distention:
- Activates mechanoreceptors
- Mucosal distention receptors send signals by vagal afferents > vagal nucleus
- Efferent signals are sent back to G cells and parietal cells by the vagal efferents
- All distention reflexes are mediated cholinergically
2) Digestion of protein:
- Amino acids and peptides stimulate G cells in stomach to secrete gastrin
- Gastrin stimulates acid secretion
- Matches degree of secretion to predicted quantity of food ingested
- pH <3 inhibits gastrin release in response to digested protein

23
Q

What occurs in the intestinal phase of GI secretion?

A

Gastric acid stimulates secretin release from S cells in duodenum
> stimulates water and HCO3- release from duct cells
Fat and protein digestion products stimulate CCK released from I cells in duodenum mainly
CCK stimulates vagal afferent receptors and initiates vagovagal reflexes - depends on cholinergic signalling
Stimulates release of enzymes from acinar cells
Active trypsin in the intestinal lumen inhibits CCK release

24
Q

Gastrin:
Site of secretion
Stimuli for secretion
Effect

A

Site: G cells of stomach
Stimuli: small peptide and amino acids, distention of stomach, vagal stimulation (GRP)
Effect: increases gastric H+ secretion, stimulates growth of gastric mucosa

25
Q

CCK:
Site of secretion
Stimuli for secretion
Effect

A

Site: I cells of duodenum and jejunum
Stimuli: Small peptides and amino acids, fatty acids
Effect: increase pancreatic enzyme and HCO3- secretion, Stimulates contraction of gallbladder and relaxation of sphincter of Oddi, Stimulates growth of exocrine pancreas and gallbladder, inhibits gastric emptying

26
Q

Secretin:
Site of secretion
Stimuli for secretion
Effect

A

Site: S cells of duodenum
Stimuli: H+ in duodenum, fatty acids in duodenum
Effect:
Increased pancreatic HCO3- secretion
Increased biliary HCO3- secretion
Decreased gastric H+ secretion
Inhibits trophic effect of gastrin on gastric mucosa

27
Q

GIP - glucose dependent insulinotropic peptide
Site of secretion
Stimuli for secretion
Effect

A

Site: duodenum and jejunum
Stimuli: fatty acids, amino acids, oral glucose
Effects:
increase insulin secretion form pancreatic B cells
Decrease gastric H+ secretion

28
Q

How are monosaccharides absorped across the intestinal wall?

A
  • SGLT1 on apical memb needed for glucose uptake driven by Na+ electrochemical gradient
  • Maintained by extrusion of Na+ across by Na-K pump on basolateral memb
  • Facilitated diffusion by GLUT5 for fructose absorption
  • Facilitated diffusion by GLUT2 on basolateral membrane for glucose and fructose into interstitial space
29
Q

How are proteins absorbed across intestinal wall?

A

Peptide and amino acid s mainly via Na+ cotransport mechanism
Na+ ion binds and moves down its electrochemical gradient to interior of the cell and pulls amino acid or peptide with it - co-transport
Oligopeptide uptake is via H/oligopeptide cotransporter, PepT1

30
Q

How are fats absorbed across the intestinal wall?

A

Fatty acid/bile salt mixed micelles enter acidic microclimate generated by Na+/H+ exchange at the brush border membrane
Fatty acids become protonated and leave the micelle
Membrane proteins assist uptake of fatty acids:
FAT, FABPpm, FATPs

31
Q

How are lipids absorbed across the intestinal wall?

A
  • Cholesterol, monoglycerides, lysolecithin and free fatty acids are solubilised in lumen in mixed micelles
  • At apical membrane, lipids released from micelle and diffuse down their gradients into cell
  • Inside intestinal epithelial cells, products of lipid digestion are reesterified with free fatty acids on SER to form original fats
  • Reesterified lipids packaged with apoproteins in cholemicrons
  • Chylomicrons packaged into secretory vesicles on golgi apparatus. Migrate to basolateral membranes > exocytosis of cholemicrons > lymph > bloodstream
32
Q

What occurs in lactase deficiency?

A

Inability to break down lactose into glucose and galactose
Accumulation of non-absorbable osmotically active solutes will generate osmotic difference
Draws fluid into intestinal lumen
Osmotic diarrhoea
Excrete large amounts of H2 into breath due to lactose catabolism by colonic bacteria

33
Q

Anti-obesity drugs

A

Need for complete digestion of nutrients for absorption has been utilised for anti-obesity drugs
Orlistat inhibits pancreatic lipase > prevents lipid absorption
Undigested triglycerides cannot cross enterocyte membranes
Common side effect = steatorrhoea - very fatty poo - pale, greasy

34
Q

What deficiencies can occur in Crohn’s disease? What are they associated with?

A

Iron, zinc, magnesium, calcium, vitamin D, vitamin B12
Associated with:
insufficient consumption
insufficient absorption
bleeding losses
losses in diarrhoea