Summary week 1
Lecture 1
Nutritional physiology: balance between nutritional input and physiological output. The metabolism
keeps this balance via metabolic pathways, metabolic rate or changing energetic efficiencies to
generate either ATP or heat. Disbalance differences in body composition.
- Nutritional input: total daily intake, meal size or pattern, nutrient composition
- Physiological output: physiological status, health status, environment. Metabolic rate
Microbial fermentation: bacteria in the colon use all nutrients that are not yet digested and
absorbed which provides some little energy. This will never produce amino acids.
Why does the digest system not digest itself?
- Activity restricted to presence of food
- Regulation of location
- Enzymes are stored as inactive pro-enzymes
- Non-digestible mucus coasts the walls
- High turnover (replacement) of mucosal cells
2 phases:
1. Post prandial phase (PPM, following the meal)
a. Intake > needs. Mainly anabolic processes to store the energy, but some catabolic
(oxidation) because there is always a metabolic rate.
b. Process:
i. Glucose is absorbed and stored as glycogen in the liver and muscles or
released to fuel brain and muscles. More glucose? converted to
triglycerides and stored in adipose tissue.
ii. Fats are immediately stored in adipose tissue via chylomicrons
iii. Amino acids are absorbed and go to the liver for protein synthesis
After a meal: diet-induced thermogenesis. Largest for proteins, smallests for fat. ME is not
corrected for energetic costs of the DIT in PPM.
2. Post absorptive phase (utilization: not eating for a longer time)
a. Input < needs. Mainly catabolic processes (turnover, oxidation, conversion)
i. examples: glycogen glucose. Aminoacids possible to glucose.
Triglycerides fatty acids
Homeostasis: ability to counteract factors that disturb vital functions and to remain in balance. As
long as you are in balance, there is no weight gain/loss.
Digestive system
- General features and goals
o Transfer and digest nutrients from food
o GI tract is a closed hollow tube of 7m
o One-way transport
o Digestion and absorption is influenced by secretory and motor behavior
- Anatomy
o Mouth: digestion starts with chewing food. Lipase & amylase already start some
digestion
o Oesophagus
o Stomach: some digestion takes place, gastric acid, pepsin, gastric lipase.
, o Small intestine: duodenum, jejunum, ileum
Is about 5 meters and enhances full digestion of food. The most absorption
takes place in the duodenum.
Secretion of hormones, digestion and absorption (large in
duodenum),motility (beweeglijkheid)
o Colon: transverse colon, ascending colon, descending colon
Functions:
Bacterial fermentation, storage and elimination of waste, absorption
of water & ions
o Biliary tree: liver, pancreas, gallbladder
o Other organs: teeth, tongue, salivary glands
Villi and microvilli
Villi
The intestinal mucosa (slijmvlies) is folded into the lumen. Villus are absorptive enterocyte linings of
the lumen of the small intestine. Each villus has:
- Blood capillaries which drain into the portal vein
- Lacteal which drains into the lymphatic system
- A layer of cells at the surface increased surface enhanced absorption
- Cells are close to each other impermeable for everything from the intestine to enter your
body.
In between, there are mucus secreting goblet cells. They produce mucus protect the intestinal
cells from attack by digestive enzymes into the lumen.
Microvilli (also referred to as Brush Border)
There are also finger like foldings on/of the cell membrane of a single enterocyte (cells that line the
inner surface of the large and small intestine). These also increase the surface area. And they contain
digestive brush border enzymes, so the nutrients can be directly taken up. Microvilli are not cells.
4 layers in the GI tract (from inside the stomach, lumen to outside):
1. Mucosa: secretion and absorption
2. Submucosa / muscular mucosa: vascular layer for support
3. Muscularis: contractions movement through the GI tract
4. Serosa: protective outside layer, outside of the small intestine
,GI tract muscles
In the antrum of the stomach, there is the biggest layer of muscles to mix everything that is inside
and in the fundus of the stomach the most microvilli. In the esophagus the thinnest layer of muscles
not much absorption.
Gut retention = the time between having amino acids in your lumen and seeing them in circulation. It
takes time before amino acids (or triglycerides) are released in the blood flow.
Innervation
CNS
1. A stimuli is sensed by mechanical or chemical sensors
2. These sensors send a signal to:
a. Your brain and spinal cord (CNS) and from there to ENS
b. Enteric nervous system (ENS) senses the interior of the GI tract
3. CNS and ENS activate effectors motility, secretion, blood flow
a. By many neurons with many projections to the villi and the muscle layers
Communication
3 mechanisms of communication mediate responses:
1. Endocrine: hormones in the circulation.
a. A sensor cell senses a nutrient, releases a hormone, elsewhere a target cell becomes
activated gastrin
2. Neurocrine: neurons that release messengers and neurotransmitters
a. GRP, Acetylcholine
3. Paracrine: local cell-to-cell communication. Only affects neighbor cells
a. Somatostatin
Motor behavior
2 different aspects:
1. Segmentation: chopping the food content.
a. Circular muscles contract and relaxes, thereby creating segments in the intestine
chyme is broken up and mixed with digestive juices brings nutrients into contact
with the intestinal lining
2. Peristalsis: the movement of the bolus through the small intestine
a. Circular muscles are contracted (Ach) in the propulsive segment and circular muscles
are relaxed (VIP / NO) in the receiving segment.
Absorption/diffusion
3 different processes:
1. Simple diffusion: cross freely into cells, no energy needed. = passive diffusion
2. Facilitated diffusion: a specific transporter catches the compound, then its transported to the
other side of the cell and released. No ATP needed.
3. Active transport: these nutrients move against a concentration gradient, this requires ATP to
trap the nutrient onto the transporter! In this case, your body must know that the payoff is
higher.
Digestive, interdigestive state and MMC
During interdigestive phases you don’t eat but your GI tract is not in rest. Every 90 min or so, several
things happen such as gallbladder contraction, pancreatic secretion, gastric secretion etc.
Migrating motor complex
o Phase I 40 min REST
, o Phase II 40 min Start peristalsis
o Phase III 10 min Max peristalsis
This flushes the content, prevents bacterial stasis is the final cleaning of non-digestible parts
Transit time in humans:
- Stomach: 1 to 5 hours
- Small intestine: 1 ½ hours
- Large intestine 1 to 2 days
Lecture 2
Cephalic phase
1. A stimulus (auditory, cognitive, visual, olfactory) NOT TASTE
2. In the higher brain centers there is a signal to the dorsal vagal complex (DVC)
Three things happen:
It sends the neurotransmitter Acetylcholine (signal = food is coming)
a. Ach binds to the chief cells release pepsinogen (because of a lot of HCL)
pepsinogen is converted to pepsin
b. Ach binds to parietal cells release HCL
Secretion of gastrin releasing peptide secretes gastrin in the blood circulation which goes
back to the top part of the stomach more release of pepsinogen and HCL positive
feedback
The DVC sends signals via the parasymphatic outflow via the vagus nerve.
Effector responses
c. Salivary secretion
d. Gastric secretion (acid, pepsinogen by the parietal and chief cells, intrinsic factor)
e. Pancreatic enzyme secretion (via sphincter of Oddi)
f. Gallbladder contraction
g. Relaxation of the spincter of Oddi
Effector responses of the cephalic phase are meal dependent:
- Sham feeding: high acid output
- Bland meal: low acid output
- A meal that you really like: high acid output
Oral phase (mouth, saliva, esophagus
The mouth
When food is in the mouth (saliva) it is called bolus. Saliva is made of:
- Mucins for lubrication
- Amylase for digestion of starch
- Lipase for digestion of fat
- Lysozyme which is antibacterial
- IgA for immune protection
Amylase has the highest activity at pH 7-8 but it can still work around pH 5-6 (for 50%). Low pH in
stomach so:
- When starch meets amylase, starch makes a micro-environment around the amylase to
protect it from the low pH in the stomach amylase can work more efficiently.
The esophagus
The bolus goes through the pharynx (keelholte). There are 2 spincters in the esophagus:
UES: upper esophageal sphincter: normally closed to not swallow everything
,LES lower esophageal sphincter: between esophagus and stomach. Normally closed to inhibit
backflow of gastric acids.
- Resting phase: LES closed, UES slightly opened
- After swallowing: the pressure moves due to neutrotransmitters peristaltic movement.
o First: relaxation of LES (low pressure)
o Lastly: increased pressure in the LES
circular muscles contract (Ach) /relax (NO/VIP) and push the food trough
so Ach causes contraction (closing of sphincters) and NO & VIP cause relaxation (opening)
Gastric phase
Parts of the stomach from up to below:
1. cardia
2. fundus
3. body
4. atherum
5. pylorus pyloric sphincter
function by region:
1. LES and Cardia (no low pH)
a. Secrete mucus and HCO3- prevents reflux, regulates entry of food and belching
2. Fundus and body
a. Secretion of H+, mucus, intrinsic factor, HCO3, pepsinogens, lipase function of
reservoir (collect the food), tonic force
3. Antrum and pylorus
a. Secretion of mucus and HCO3 mixing, grinding, regulation of emptying
Pyloric sphincter: gatekeeper from stomach to duodenum.
Like the cephalic phase, there is a signal again from the DVC. What is different?
- Stomach is communicating back to the brain: mechanoreceptors that detect the distension of
the stomach send the signal through the vagal system to the brain that signals must be
strengthened
o MORE relaxation of the stomach, more H+ and pepsinogen secretion, more
gastrin secretion, more pancreas secretion……
- Stomach is communicating to itself: now there is protein in the stomach:
1. Pepsin digests protein into oligopeptides
2. Oligopeptides function as second messenger bind to cells at the anthrum
3. These cells release more gastrin in the blood
4. Gastrin goes back to the body part of the stomach and stimulates H+ and pepsinogen
secretion
So in sum: what happens with proteins at gastric pH = 2
- Ingested proteins are denatured (to secondary and tertiary structure)
- Pepsinogen activated to pepsin because of H+
- pH optimum for pepsin is 2, the stomach needs 2 hours before this is arrived.
Pepsin is an endopeptidase (cuts non-terminal amino acids) which prefers aromatic amino acids
(mainly leucine and methionine) and cuts it into oligopeptides.
Gastric cells:
1. Surface cells/neck cells
a. Secrete: mucus, HCO3, peptides
, b. Function: lubrication and protection of the epithelium of the stomach mucus lays
on top of the stomach
2. Parietal cells
a. Secrete: H+ and intrinsic factor
b. Function: protein digestion and binding of B12
3. Chief cells
a. Secrete: pepsinogen, gastric lipase
b. Function: protein and triglyceride digestion
4. Endocrine cells
a. Secrete: gastrin, histamine, somatostatin
b. Function: regulation of acid secretion
5. G cells, ECL cells and D cells explained below
B12 is stored in the liver so it has to go through the intestinal system first:
1. The protein salivary haptocorrin (in the salvia) recognizes B12, makes a shield around it and
carries it until the stomach
2. In the stomach: Proteases (enzymes that destroy proteins) are secreted by the pancreas.
Before it gets destroyed, the cells of the stomach produce intrinsic factor that takes over the
duty and binds to B12
3. At the terminal ileum, B12 is absorbed back in the circulation and stored in the liver
Neurotransmitters by the vagal nerves
1. Ach binds to:
a. (as mentioned) Chief and parietal cells pepsinogen and HCl in the lumen of the
stomach
b. Enteroendocrine cells (ECL) secrete histamine in the local lamina propria
(connective tissue before the muscolaris and the serosa) histamine stimulates the
parietal cells to amplify the release of HCL
2. Gastrin release peptide binds to:
a. G cells secrete gastrin in the blood gastrin binds to parietal cells more
release of HCL
So parietal cells are stimulated by histamine from ECL, by Ach and by gastrin from G cells.
How do we stop eating?
A lot of acid secretion (low pH) in the antrum D cells in the antrum of the stomach produce
somatostatin acts on the G cells in the lumen G cells stop releasing gastrin
A second group of second messengers: free fatty acids communicate from stomach to intestine
Free fatty acids in the stomach increase the release of CCK in the duodenum contract gallbladder,
relaxation of sphincter of Oddi, pancreatic enzyme secretion o.a. lipase!! (more digestion/absorption
needed)
3 motor responses during the gastric phase:
- Emptying:
o Digestive phase: duodenal cluster unit. Particles are sized down to 2 mm
Stomach can feel the energy of the nutrient. It ALWAYS releases 8.5 KJ/min
to digest. So a fat meal takes longer to digest
o Interdigestive phase: migratory motor complex to make sure that the stomach is
emptied fully.
- Mixing and grinding: antral peristalsis
