Digestion (week 1) Flashcards
why is digestion important?
every cell in the human body depends on it
Hippocrates: all disease begins in the gut (almost)
40% of people worldwide have some form of a functional gastrointestinal disorder
optimizing digestion = “root cause” or “upsteam” approach
drugs may alleviate symptoms or slow the progression of a disease, but may not restore optimal function
digestive dysfunction underlies many conditions, not just overt gastrointestinal conditions
what is digestion?
the mechanical and chemical breakdown of food
food is reduced to molecules that the body is able to use for energy (ATP), structure, and function
the digestive system is made up of:
-gastrointestinal tract (tube/lumen)
-accessory digestive organs: brain, teeth, tongue, salivary glands, liver, gallbladder, pancreas
digestion is a north to south process
one step will initiate or signal the start of the subsequent step. if we miss any step in the “north” part of the process, it can impact the subsequent steps
3 phases of digestion
Cephalic phase:
-the brain is heavily involved in digestive processes (thought, sight, smell)
-chewing and swallowing
Gastric phase:
-food enters the stomach
Intestinal phase:
-food leaves the stomach and enters the small intestine
North to South function - The Brain
sight and smell trigger salivary glands
cerebral cortez triggers gastric secretions
controls peristaltic movement
monitors hunger, satiety, and primes metabolic hormones like insulin
North to South function - The Mouth
mechanical breakdown of food (mastication)
chemical breakdown of food (enzymes in saliva)
salivary solutes
-salivary amylase (carbs)
-lingual lipase (fats)
direct messaging to the CNS to prepare for the rest of the digestive process
North to South function - The Esophagus
once food is swallowed it becomes a bolus
esophagus: additional salivary glands and peristaltic contractions
lower esophageal sphincter (LES) opens to release food into stomach
the LES closes to prevent reflux from stomach into the esophagus
Anatomy of the stomach
5 regions:
-cardia
-fundus
-body (or corpus)
-antrum
-pylorus
lined with millions of secretory epithelial cells which produce hormones, acids, enzymes
four key types of secretory epithelial cell:
-G cells: secrete hormone gastrin
-Mucoid cells: secrete protective mucous
-Parietal cells: secrete hydrochloric acid and intrinsic factor
-Chief cells: secrete pepsinogen, a proteolytic enzyme
North to South function - The stomach
bolus enters stomach and it expands
the presence of protein and other mechanical & neurological cues stimulate the release of gastrin
gastrin stimulates:
-mucous production
-gastric motility
-secretion of hydrochloric acid (HCl) and intrinsic factor (intrinsic factor helps you absorb vitamin b12)
Roles of stomach acid
hydrochloric acid (HCl)
-lowers PH = increases acidity (average pH 1.5-3.0)
-stimulates release of pepsinogen and gastric for protein and fat digestion
-converts pepsinogen to active form, pepsin
-broke down protein into smaller polypeptides and single amino acids
-reduces the microbial populations of the food
-liberates nutrients from food complexes
-stimulates the release of protective mucous
-stimulates the contraction of the LES
-helps regulate “churn and burn” and gastric emptying
Mucous Membrane
how does the stomach not digest itself? protective mucous
protects from injury, burning, ulcers, etc
contains bicarbonate ions to buffer against HCl
in small intestine, will house beneficial microbes and shuttle nutrients for absorption
North to South function - The stomach
once food leaves the stomach it’s known as chyme
chyme is released through pyloric sphincter into the upper part of small intestine
-the movement of chyme through the pyloric sphincter is known as gastric emptying
gastric emptying will begin within 30 minutes of eating and can take up to 4-5 hours to complete
North to South function - Small Intestine
primary site of absorption
longest portion: 22ft in length
surface area of a tennis court
three sections:
-duodenum
-jejunum
-ileum
ducts to connect to accessory organs (liver/gallbladder and pancreas)
North to South function - duodenum
acidity of chyme triggers small intestine to secrete mucous and two hormones:
-secretin
-cholecystokinin (CCK)
these hormones enter bloodstream, communicate with organs and nervous system
small intestine acting as both digestive organ and endocrine organ
North to South function - HCL
notice stomach acid’s role in north to south function:
-LES tightening
-gastric emptying/pyloric valve regulation
-signal accessory organs and intestinal wall to prepare for meal
secretin’s effect on pancreas
brings pH up to neutral (~7.0)
-inhibiting HCL in stomach
-stimulating the pancreas to release bicarbonate
alkalization protects mucous membranes
pH optimizes pancreatic enzyme function
cholecystokinin’s effect on pancreas
several signals, including CCK, stimulate pancreatic enzymes:
-protease: proteins
-amylase: carbs
-lipase: fats/lipids
pancreas: dual role
-digestive secretions = exocrine
-blood sugar regulation (insulin and glucagon) = endocrine
cholecystokinin’s effect on liver/gallbladder
stimulates the gallbladder to release bile
satiety in brain
dietary fat increases CCK and satiety
bile salts are made in the liver, stored in the gallbladder
help to emulsify dietary fats and fat soluble vitamins
Bile Salts
bile acids are converted to bile salts with both hydrophobic and hydrophilic sides
influence the balance of microbiota in the intestines
recycles via enterohepatic circulation
bile flow allows for:
-elimination of endogenous metabolic waste products
-elimination of exogenous medication and environmental toxins
-cholesterol homeostasis
north to south function: small intestine
chyme moves past duodenum into jejunum and ileum
single cell layer of solumnar epithelial cells, enterocytes
inner mucous membrane comprised of three layers:
-the protective mucosal barrier (covering enterocytes)
-lamina propria connective tissue
-muscle fibers of the muscularis mucosae
epithelial cells spread over peaks and valleys called villi
villi covered in microvilli
-increase surface area of intestines
-nutrient absorption
-produce brush border enzymes
-serve as a selective barrier
two routes of absorption:
-transcellular (through the cell body, major route)
-paracellular (between cells, minor route)
tight junctions hold enterocytes together and regulate paracellular route
Small intestine macronutrient breakdown
Carbs > simple sugars (absorption) or indigestible fibers, resistant starch, or FODMAPs
Proteins > amino acids and polypeptides (max 2-3 amino acids in length)
Lipids > free fatty acids, glycerol molecules, cholesterol esters, and fat soluble vitamins
Peristalsis and Migrator Motor complex
peristalsis: involuntary contraction and relaxation moves contents through intestines
migrator motor complex (MMC) is active during fasted state
MMC involved in regulating metabolism, hunger signals, and maintaining a healthy microbial and immune balance in the intestines
changes in MMC associated with functional GI disorders
north to south function: Large Intestine
ileocecal valve separates small intestine from large intestine
processes leftover chyme containing undigested food particles, water, sloughed off cells, waste for elimination
4 sections:
-cecum and ascending colon
-transverse colon
-descending colon
-sigmoid colon
recycles water and electrolytes
concentrates waste into feces
produces and absorbs vitamins
bowel flora synthesizes:
-vitamins K/B1/B2/B12
-short chain fatty acids: butyrate, acetate, propionate
primary site of the intestinal microbiome
-bacteria
-fungus
-viruses
-live on the surface of mucosa
-feed off of indigestible fiber
remnants form and leave the body as feces
Gastrointestinal transit time
varies: 10-73 hours
average closer to 24-48 hours
-50% of stomach contents emptied in 2.5-3 hours and completely emptied within 4-5 hours
-50% emptying of small intestine within 2.5-3 hours
-transit through the colon 30-40 hours
Varies by: age, gender, physical activity, hydration, metabolic function. thyroid function, GI disorders, dietary composition
Carbohydrate digestion
salivary enzymes begin the breakdown of sugars
minimal chemical or enzymatic carbohydrate digestion in the stomach
pancreatic and brush border enzymes in the small intestine/duodenum break complex carbohydrates down into absorbable monosaccharides:
-glucose, fructose, galactose
-undigested/absorbed resistant starch, fibers, FODMAPs will be passed into the colon for bacterial fermentation and bulking of stool
saccharide is another name for sugar
carbohydrate digestion is based on the ability to break glycosidic bonds between saccharides
microbes have different carbohydrate enzymes
basis for prebiotics, fibers, and some elimination diets
Protein digestion
chewed and swallowed as bolus
HCL and pepsin in stomach cleavage of peptide bonds
amino acids move to small intestine, for additional breakdown by pancreatic proteases
microvilli in small intestine absorb amino acids
carried through bloodstream to parts of body
tissue repair, hormones, enzymes, muscle, etc
Lipid digestion
lingual lipase starts lipid digestion
dietary fat in duodenum triggers release of CCK, which triggers release of bile
bile emulsifies larger fat droplets into small micelles
lipase is released into small intestine by pancreas, which continues fat breakdown
primary dietary lipids include triglycerides, phospholipids, and cholesterol esters
-triglycerides are hydrolyzed into monoglycerides (one glycerol bond to fatty acid chain), free fatty acids, and glycerol molecules
-phospholipids are hydrolyzed into free fatty acids and smaller phospholipid particles
-cholesterol esters are hydrolyzed to free cholesterol and free fatty acids
fat soluble nutrients
lipids are absorbed through the microvilli in the small intestine
pathway depends on size:
-glycerol molecules, short & medium chain fatty acids can be absorbed directly into blood stream
-long chain fatty acids, monoglycerides, fat soluble vitamins, and cholesterol will be incorporated into chylomicrons are absorbed into the lymphatic system
used for energy, stored fuel, immune balance, cell membrane synthesis & regulation, tissue repair, hormone function
Food Combining Diets
the idea that some foods pair well and others do not
some plans categorize by dominant macronutrient, others by pH, etc
largely based on the observation that foods are digested at different speeds and require different enzymes to be digested
physiological perspective:
-humans have always eaten a combination of nutrients
-digestive tract can digest multiple macros at the same time
-whole foods contain multiple macronutrients
-enzymes are released regardless of whether certain macronutrients are present
dietary pH vs systemic pH
pH of blood is tightly managed to ensure survival
pH compartmentalization in different tissues and secretions
breathing regulates system pH by exhaling carbon dioxide
kidneys regulate systemic pH:
-excrete hydrogen ions (H+) into urine
-recycle bicarbonate back into the bloodstream
buffering systems exist within individual cells
acidic foods increase the acidity of urine, but in most healthy individuals, they do not change to systemic pH
diets rich in alkaline minerals are always helpful
individuals with impaired kidney or lung function may need additional care
Nervous System overview
Central nervous system (CNS) includes the brain and spinal cord
Peripheral nervous system (PNS) includes all of the nerves that exist outside of the brain and spinal cord
The PNS is further divided into the sensory division (also called afferent with an “a”) and the motor division (also called efferent with an “e”). You can remember this because “affect” is a verb – so think of being affected by the world around you…the beautiful sights, sounds, and
smells that tell you about your environment. Whereas effect is a noun – it is the result of your response - it is what you create. You receive information from the world through the afferent parts of the PNS, integrate it into the CNS, and then use the efferent nervous system to respond using the efferent nervous system.
Somatic is related to the more superficial parts of the body such as the musculoskeletal system and the skin, and is associated with voluntary functions like moving your body or touch
Visceral is related to the internal organs and glands and is associated with involuntary functions and sensations like heart rate or blood pressure. Visceral/efferent = ANS - autonomic nervous system
Autonomic Balance
Sympathetic Nervous System:
-governs stress response
-fight or flight
-shuttles resources to immediate survival
-decreases gastrointestinal activity
Parasympathetic Nervous system:
-rest and digest
-increases blood flow to GI tract
-activates digestive functions
Autonomic Balance
Dual innervation:
-sympathetic: thoracic nerve branches
-parasympathetic: cranial and sacral nerves
-vagus nerve connects the gut brain
-a dynamic balance between autonomic branches, spoken of in terms of tone or dominance
-vagus nerve connects the gut brain
increasing the parasympathetic tone before eating is an upstream “northernmost” approach to digestive wellness
Enteric Nervous System
“Second brain”
complex neural network in the wall of digestive tract
functions on its own, as well as in coordination with central nervous system and endocrine system
two main plexuses (or systems):
-myenteric plexus: gastric motility
-submucosa plexus: gastric secretions and blood flow regulation
constant cross talk with brain to coordinate appetite, immune response, hormone secretions, intestinal barrier functions, and more
Ghrelin - Neuroendocrine Regulation
-secreted from stomach
-stimulates hunger
-levels increase while fasting and decrease when fed
Leptin - Neuroendocrine Regulation
-secreted from the adipose tissue
-acts as an appetite suppressant
-counter-regulatory to ghrelin’s signal
-tells the brain about food intake need over the long term
-dysregulation can result in leptin resistance and increased appetite
Peptide YY - Neuroendocrine Regulation
-secreted from the ileum and upper large intestine after eating
-slows digestive transit to aid absorption and increase satiety
-high levels are associated with poor food intake, low levels are associated with increased food intake
Glucagon-like peptide-1 (GLP-1) - Neuroendocrine Regulation
-secreted from the small and large intestines
-stimulated by food intake, slows gastric emptying, decreases appetite, and promotes the release of insulin to help regulate blood glucose levels
-GLP-1 receptor agonists are drug targets in the treatment of T2DM
the gut microbiome
trillions of bacteria, fungi, viruses, parasites, and other microbes
~90% gut bacteria are obligate anaerobes (oxygen sensitive) making research challenging
genetic sequencing - human microbiome projects (launched 2007) initiated a new era in microbiome research
metabolic capacity 100x greater than the liver
functions of the gut microbiome
-structural integrity of mucosal lining
-protections against pathogenic organisms
-metabolizes complex carbohydrates to produce SCFA’s
-synthesizes B vitamins and Vitamin K
-helps breakdown and metabolize polyphenols
-converts amino acids into neurotransmitters
-reduce antigenicity of foods and induce oral tolerance
-interfaces with our immune system
Prebiotic
Refers to nutrients, primarily carbohydrates, that preferentially feed strains that are associated with health benefits. The key word here is preferentially – so we are selecting the nutrients that the beneficial strains thrive on, and are simultaneously less likely to fuel the growth of pathogenic strains
Probiotic
Refers to the actual living organisms themselves (used to refer to the food and supplements that contain the microorganisms)
Postbiotic
Refers to the metabolic byproducts from microbes, which are more and more recognized for eliciting biological responses in the host and other members of the microbiota
Resident / indigenous
Strains of microbes that have a stable colony in your GIT. They often colonize in early life, and populations can ebb and flow over a lifetime based on environmental factors like the rest of the microbiota, diet, medications, health status, etc. Resident microbes can adhere to the surfaces of the intestines, taking up those parking places in your intestinal terrain. When we talk about altering the microbiome with prebiotics, we are generally talking about shifting the existing populations of resident microbes by altering their food supply, rather than ingesting new microbes (both are valid approaches).
Commensal
Commensal is another term that often refers to healthy indigenous populations and the way they live in balance with a healthy level of non-competition that allows them all to “eat from the same dish,” so to speak. Webster’s dictionary defines commensalism as “a relation between two kinds of organisms in which one obtains food or other benefits from the other without damaging or benefiting it.”
Transient
Microbiota consumed in things like food or supplements, but only remain in the GIT for 2-3 weeks after ingestion. While they may not adhere and set up permanent
colonies, they can still have a major impact on health while they are present. They can exert influences that help alter the resident terrain as well.
Opportunisitc
Describes microbial populations that are not typically considered pathogenic in normal situations/levels but have become problematic after expanding their population in number or location as a result of certain environmental conditions. These microorganisms may be present in very small amounts in healthy individuals
while the immune system and commensal microbes are able to suppress populations but can escalate into an infection when the host immune system is compromised. An example is the overgrowth of candida that is normally present but may get overgrown after a course of antibiotics depletes the beneficial bacteria populations.
Dysbiosis
-imbalances between the beneficial and harmful microbiota
-changes in population numbers, types, function, or shift in their location
-resident microbes can be healthy or problematic depending on the balance
-no one single type of dysbiosis
-altered ratio between the two major phyla groups, Firmicutes and Bacteroides
-complex ecosystems tend to self regulate = biodiversity is key
Diet & the microbiome
-refined carbohydrates (a-cellular) linked to more inflammatory and less diverse microbial profile
-artificial sweeteners have varying impacts
-excessively high saturated fat and/or undigested protein content can have negative impacts, which are mitigated by the presence of fiber/prebiotics/polyphenols
-diets rich in fruits, vegetables, and fibers are clearly associated with a more robust and diverse gut microbiome
Fermented Foods & Prebiotics
Probiotic rich/fermented foods:
-sauerkraut
-kimchi
-kefir
-miso
-natto
-kombucha
Prebiotic rich foods/indigestible fiber:
-legumes
-dandelion greens
-artichokes
-berries
-garlic, onion, leeks
-asparagus
-bananas
-seaweed
-flax
some dysbiotic conditions like SIBO should be approached with caution
some high FODMAP foods can worsen symptoms of gastrointestinal conditions like IBS
microbiome across a lifetime
begins developing at time of birth, diversity matches adult by 2.5 years
maternal vaginal microbiome is primary source of inoculation in vaginal birth
prenatal exposure to antibiotics and C-section deliveries can delay or alter colonization
research into vaginal seeding and supplementation with pre and probiotic strains to support development of healthy microbiome:
-vaginal seeding: not currently endorsed by major gynecological organizations, research is ongoing
-pre and probiotics shown to restore normal microbial profiles in both infants exposed to antibiotics at birth and cesarian delivery by 6 months of age
prebiotic sugars, fatty acids, and immune factors in breast milk influence colonization
adding prebiotics to formula can promote microbiome diversity similar to breastfeeding
microbiome disruptors
- Age
- Geographical location
- Environmental exposures
- Smoking
- Infections
- Chemical consumption including pesticides, insecticides, and herbicides( glyphosate)
- Chronic antibiotic or prescription medication use
- Poor dental hygiene
- High levels of stress and anxiety, or a history of trauma
- Regular alcohol consumption
- Excessive hygiene/lack of exposure to soil, plants, and other animals
Antibiotics
overuse can promote dysbiosis
degree of impact and return to pre-treatment status depending on:
-microbiota before treatment
-age
-genetics
-diet & lifestyle
-duration of treatment, dosage, antibiotic class
can have far reaching effects throughout the body
concurrent use of oral probiotic supplements mitigates damages and reduces risk of opportunistic infection
GALT
GALT = gut associated lymphoid tissue
~70% of total immune system
~80% of activated B cells
impacts intestinal permeability, food tolerance, immunity against pathogens, self recognition, dampen or amplify systemic inflammation
Peyer’s patches: lymphoid follicles in intestinal mucosa that contain immune cells: macrophages, T cells, B cells, and dendritic cells
