GI Flashcards
Swallowing stage 1: voluntary phase
- Mastication leads to a bolus of food produced. During this stage, the back of the tongue is elevated and the soft palate is pulled anteriorly against it. This keeps the food within the oral cavity and allows the airway to remain open. The duration of this stage varies.
- Inspiration is inhibited and the bolus of food is moved to the oropharynx by the tongue. This leads to the stimulation of the swallowing reflex.
- The buccinator and supra hyoid muscles manipulate food during chewing. They also elevate the hyoid bone and flatten the floor of the mouth.
Swallowing Stage 2: involuntary (pharyngeal) phase
- Once the bolus has been moved to the pharynx, pressure receptors are activated in the palate and anterior pharynx. This signals the swallowing centre in the brain stem which:
- inhibits respiration
- raises the larynx
- closes the epiglottis
- opens the upper oesophageal sphincter
- The soft palate is elevated to close the nasopharynx to allow the passage of food. The true vocal cords also close to prevent aspiration.
- The pharynx is also shortened and widened using longitudinal muscles by the elevation of the hyoid bone via the actions of the muscles of the floor of the palate which depress the mandible if the hyoid bone is fixed, or elevate the hyoid bone and larynx if the mandible is fixed.
- After this, the bolus is moved towards the oesophagus via peristalisis of the pharyngeal constrictor muscles.
- As the tongue forces the food farther back into the pharynx the food tilts the epiglottis backward to cover the closed glottis - this prevents aspiration of food which is a dangerous situation where food travels down the trachea and can cause choking or regurgitated stomach contents are allowed into the lungs causing damage.
Swallowing Stage 3: involuntary oesophageal phase
- The sequential contraction of the circular constriction muscles followed by the depression of the hyoid bone and pharynx.
- Pharyngeal constrictor muscles: 3 overlapping muscles that form the posterior and lateral sides of the pharynx, innvervated by the vagus nerve. They contract sequentially from above down to drive the bolus into the oesophagus.
- Depression of the hyoid bone and pharynx is carried out by the infra hyoid muscle of the neck - they fix the hyoid bone enabling the opening of the mouth. They also depress the hyoid bone and larynx.
The next stage of swallowing occurs in the …
oesophagus
What are the muscles in the oesophagus?
- the skeletal muscle surrounds the upper third of the oesophagus
- smooth muscle surrounds the lower 2/3rds of the oesophagus
Pressure differences in the pharynx and oesophagus?
The luminal pressure in the pharynx at the opening to the oesophagus is equal to the atmospheric pressure and the pressure at the opposite end of the oesophagus in the stomach (in the stomach) is slightly greater than atmospheric pressure. Thus, these pressure differences tend to force both air from above and gastric contents from below into the oesophagus, however this does not occur due to the presence of sphincter muscles at both ends of the oesophagus.
What are the upper and lower oesophageal sphincters? What do they do during swallowing?
- a ring of skeletal muscle surrounding the oesophagus just below the pharynx, and the lower oesophageal sphincter is a ring of smooth muscle surrounding the oesophagus at the last portion of it
- Before food can enter the oesophagus, the upper oesophageal sphincter relaxes. Immediately after the food has passed through, the sphincter closes, the glottis opens, and breathing resumes.
What is the gag reflex?
- The reflex elevation of the pharynx - often followed by vomiting caused by irritation of the oropharynx (the back of the tongue)
- Reflex arc between the glossopharyngeal (IX) and the vagus (X) nerve
Constituents of saliva
water electrolytes bicarbonate bacteriostats mucus enzyme
What is the concentration of sodium, chloride, potassium, calcium and iodide ions in saliva compared to plasma?
sodium and chloride are lower than in plasma
potassium, calcium and iodide are usually higher than in plasma
What is the concentration of bicarbonate in saliva compared to plasma?
a higher concentration in saliva than in plasma to maintain an alkaline environment
What are bacteriostats?
chemicals that prevent the multiplication of bacteria
What enzyme can be found in saliva?
salivary amylase
What are 9 functions that affect the composition and amount of saliva produced?
- Flow rate
- Circadian rhythm (Sleep cycle)
- Type and size of gland
- Duration and type of stimulus that causes saliva to be produced
- Diet
- Drugs
- Age
- Gender
- Time of day
3 glands produce saliva … what percentage is each?
Parotid - 25%
Sublingual - 5%
Submandibular - 70%
Secretion of parotid glands
serous saliva: water secretion rich in enzymes
Secretion of sublingual glands
mucous saliva; viscous secretion containing NO enzymes and large amounts of mucous
Secretion of submandibular glands
MIXED sero-mucous secretion
Which cells are responsible for the volume of saliva secreted and what cells are responsible for the composition of saliva?
acinar = volume duct = composition
Saliva is a –tonic solution
hypotonic
The fluid secreted from the – cells is overall –tonic within the ECF
acini cells
isotonic
-> [Na+]=[K+]
Iodide ions are present at an increased concentration; chloride ions are present at a decreased concentration; bicarbonate is present at the same concentration
During ductal modification, there is little change to volume however concentrations of some of the ions change:
- sodium concentration decreases
- potassium concentration increases
- bicarbonate concentration decreases at rest and increases when stimulated
Resting saliva characteristics
At rest, the acinar secretion ishighly modifiedand has the following characteristics:
- Low volume
- Very hypotonic
- Neutral or slightly acidic
- Few enzymes
Stimulated saliva characteristics
When the production of saliva is stimulated, flow exceeds the ductal cells maximum rate of modification and so the acinar secretion ismodified less:
- High volume
- Less hypotonic than resting saliva
- Alkaline
- Many enzymes
The sympathetic control of salivary production is via the … and results in the release of which neurotransmitter, which acts upon which receptors?
- superior cervical ganglion
- noradrenaline
- alpha and beta-adrenergic receptors
What does the sympathetic control of saliva production result in?
- Decreased production of saliva by acinar cells
- Increased protein secretion
- Decreased blood flow to the glands
Where are the centres which co-ordinate parasympathetic innervation?
medulla
Parasympathetic innervation occurs via which cranial nerves? Which neurotransmitter is released onto which receptors?
- facial and glossopharyngeal
- ACh (acetylcholine)
- M3 muscaronic receptors
(Saliva) What are the results of parasympathetic innervation?
- Acinar cells increase the secretion of saliva
- Duct cells increase HCO3- secretion
- Co-transmitters result in increased blood flow to the salivary glands
- Contraction of myoepithelium to increase the rate of expulsion of saliva
- OVERALL, increased parasympathetic stimulation results in an increased flow of saliva that is more watery in comparison
How long do glycogen stores for a adult male are roughly sufficient to last how many hours?
12
Lipid stores are sufficient to last for
3 months
When can tissue protein be a source of energy supply?
prolonged starvation
The brain and liver represent about 4.6% of body weight yet consume about X% of energy requirement at rest
40%
What fuels does brain use
glucose
ketone bodies
What fuels do muscles use?
glucose
ketone bodies in starvation
tracyglycerol
branched-chain amino acids
What fuels does liver use
amino acids, fatty acids (including short chain acids), glucose and alcohol
What fuels do kidneys use
glucose and ketone bodies (Cortex) and only glucose in medulla
What fuels do small intestines use
ketone bodies (mainly in starvation) and glutamine (amino acid)
What fuel does large intestine use
short chain fatty acids, glutamine
What is the Basal Metabolic Rate? (BMR)
Minimum amount of energy required to keep the body alive at rest
How is BMR measured?
Usually measured by O2 consumption in a person who is awake, restful and fasts for 12 hours
What does BMR decrease with?
age, hypothyroidism, women, period of starvation, decreased muscle mas
What is the unit of BMR measurement?
kcal expended/hr/m2
Where is vitamin A stored?
ito cells in the space of Disse of the liver
What are the functions of vitamin A?
- cellular growth and differentiation
- process of vision
- healthy skin
- reproduction
- embryonic development
- maintenance of bodies mucus membranes
- used in lymphocyte production - immune system
What are sources of vitamin A?
- liver
- dairy products
- oily fish
- margarine
What are symptoms of vitamin A deficiency?
- night blindness
- xerophthalmia (eye fails to produce tears)
- stunted growth
- keratinisation of epithelia
- impaired hearing, taste and smell
- increased susceptibility to infection
What is the solubility of vitamin A?
fat soluble
What are the functions of vitamin C?
- synthesis of collagen, neurotransmitters and carnitine (used in beta oxidation)
- Antioxidant ability - can donate electrons to radical O2 compounds
- Absorption of non-haem iron
What are sources of vitamin C?
- citrus fruits
- green leafy vegetables
- potatoes
- kidney
What are symptoms of vitamin C deficiency?
- initial signs are NON-SPECIFIC
- weakness
- bleeding gums
- hyperkeratosis
- 50-100 days without vitamin C = signs of scurvy
What is the solubility of vitamin C?
water soluble
What are the functions of vitamin B?
important in cell metabolism (synthesis of proteins, DNA and fatty acids) and energy production
Where is B-12 absorbed?
in the terminal ileum
What is required for B-12 absorption?
intrinsic factor
What are symptoms of vitamin B deficiency?
less erythrocyte formation: pernicious anaemia
What is the solubility of vitamin B?
water soluble
Types of vitamin D
- Vitamin D = a group of closely related compounds
- Vitamin D3 (cholecalciferol) is formed by the action of UV radiation from sunlight on a cholesterol derivative in the skin
- Vitamin D2 is derived from plants
How is vitamin D metabolised
Its metabolised by the addition of hydroxyl groups, first in the liver and then in certain kidney cells; the end result of these changes is 1,25-dihydroxyvitamin D - the active hormonal form of vitamin D
Deficiency of vitamin D
Major consequence is decreased intestinal Ca2+ absorption resulting in a decreased plasma Ca2+
- This decrease in detected via a plasma membrane Ca2+ receptor in the parathyroid glands (embedded in the posterior surface of the thyroid gland)
- Resulting in the parathyroid glands releasing PARATHYROID HORMONE (PTH) which exerts multiple actions that increase extracellular Ca2+ concentration:
Solubility of vitamin E
fat soluble
Main function of vitamin E
antioxidant
Vitamin K main function
essential for production of clotting factors
What is malabsorption?
- the inadequate absorption of nutrients from the intestines
- failure to absorb certain minerals, carbohydrates, proteins or facts
What is malabsorption chiefly caused by?
disease of the small bowel
What is giardiasis?
infection which causes the villi to atrophy thus reducing absorption
What is coeliac disease?
Coeliac disease is an auto-immune condition which occurs in genetically disposed individuals, whereby gluten is partially degraded triggering an immune response whereby the system attacks the villi and microvilli resulting in a loss of intestinal brush border surface area resulting in decreased absorption of many nutrients. It results in abdominal distension and muscle atrophy.
What is the most abundant substance in chyme?
Water
How much ingested and secreted water enters the small intestine every day?
8000ml
How much water passes into the large intestine and why is there a decrease from the amount in the small intestine?
only 1500ml passes into the LI since 80% of the water reabsorption occurs in the small intestine
Which part of the GI tract reabsorbs the most water?
jejenum
How much fluid is excreted in stools?
200ml (2%)
Why is a lot of water reabsorbed in the small intestine?
the epithelial membranes of the small intestine are very permeable to water and net water diffusion occurs across the epithelium whenever a water concentration difference is established.
What accounts for most of the actively transported solutes in the small intestine and why?
sodium ions
most abundant solute in chyme
Sodium ions are actively transported from the lumen in the cell membranes of which parts of the GI tract?
ileum
jejenum
Sodium ions are actively transported from the lumen in the cell membranes of which parts of the GI tract?
ileum
jejenum
The contents of the colon is –osmotic
What does this result in?
iso-osmotic
concentration of lumen of colon = that of blood
This means that Na+ is actively transported out of the colon and water follows
Potassium reabsorption in the colon
In general, K+ reabsorption is by passive diffusion, the net movement is determined by the potential difference between the lumen and intestinal capillaries
What can cause severe hypokalaemia?
Diarrhoea
Chloride reabsorption in the colon
Cl- is actively reabsorbed in exchange for bicarbonate resulting in the intestinal contents being more alkaline
There are 2 functional states/periods the body undergoes in providing energy for cellular activities, these are;
- absorptive state
- postabsorptive state
Absorptive state
- During which ingested nutrients enter the blood from the GI tract
- During this state, some of the ingested nutrients provide the energy requirements of the body and the remainder is added to the body’s energy stores to be called upon during the next post-absorptive state
Postabsorptive state
During which the GI tract is empty of nutrients and the body’s own stores must supply energy
3 main important fatty acids we absorb
Palmitic (most abundant)
Oleic
Stearic
Where does triglyceride digestion occur?
to a limited extent in the mouth and stomach but predominantly in the small intestine
What is the major digestive enzyme of triglycerides? Where is it synthesised?
lipase
pancreas
How does lipase catalyse the breakdown of triglycerides?
It catalyses the splitting of bonds linking fatty acids to the 1st and 3rd carbon atoms of glycerol, producing 2 free fatty acids and monoglyceride as products
Since the lipids in ingested food are insoluble in water/hydrophic, what happens?
They aggregate into large lipid droplets in the upper portion of the stomach
What happens to the large lipid droplets?
They are converted into very small droplets via the process of EMULSIFICATION
What does emulsification require
Mechanical disruption of the large droplets into smaller droplets; this is provided by the motility of the GI tract
An emulsifying agent - provided by phospholipids in food and bile salts secreted in bile
What does it mean when something is amphipathic? Which substances are amphipathic?
both hydrophillic and hydrophobic
phospholipids and bile salts
How do phospholipids and bile salts emulsify large lipid droplets?
The non-polar portion of the phospholipids and bile salts associate with the nonpolar interior of the lipid droplet - leaving the polar parts exposed at the water surface - here they repel other lipid droples that are similarly coated with emulsifying agents thereby preventing their reaggregation into larger fat droplets
What does the coating of lipid droplets with emulsifying agent impair?
the accessability of lipids to lipase
How is this impairment overcome?
lipids not being accessible for lipase due to emulsifying agents
The pancreas secretes a protein called colipase which binds to the lipid droplet surface as well as binding to lipase - thereby holding it onto the surface of the lipid droplet
What happens once the large lipid droplets have been emulsified into smaller ones?
They are further converted into smaller droplets under the action of MICELLES
What are micelles made of?
They consist of bile salts with fat soluble vitamins (A, D, E, K) and cholesterol, fatty acids, monoglycerides and phospholipids all clustered together with their polar ends facing outwards and their non-polar ends facing inwards
It is not micelles which are absorbed but instead …
the individual lipid molecules released from the micelle; thus micelles can be regarded as holding stations for lipids
Once in the small intestine, what happens to the fatty acids and monoglycerides released from micelles?
They are re-synthesised into triglycerides in the SER
What does the resynthesisation of triglycerides in the small intestine result in?
The process decreases the cytosolic concentration of free fatty acids and monoglycerides and thus maintains a diffusion gradient for these molecules into the cell from the intestinal lumen.
What happens to the newly reformed triglycerides
They aggregate into small droplets coated by proteins that perform an emulsifying function. The fat droplets then pinch off in the endoplasmic reticulum in VESICLES where they are then processed through the Golgi apparatus where they are modified into CHYLOMICRONS. They then bud off the Golgi in vesicles which then fuse with the plasma membrane and enter the interstitial fluid via exocytosis.
What do chylomicrons contain other than triglycerides?
phospholipids
cholesterol
fat soluble vitamins
Once in the interstitial fluid, where do chylomicrons enter?
lacteals: lymphatic vessels in the intestinal villi rather than into blood capillaries because chylomicrons cannot enter the capillaries due to the basement membrane at the outer surface of the capillaries providing a barrier to diffusion.
Which enzyme catalyses the release of fatty acids from plasma chylomicrons
lipoprotein lipase, since it hydrolyses the triglyceride
What do the released fatty acids do?
They diffuse into adipocyte and combine with alpha-glycerol phosphate synthesised in adipocytes from glucose metabolites to form triglyceride.
Why is glucose essential for triglyceride synthesis?
adipocytes do NOT have the enzyme required for phosphorylation of glycerol to alpha-glycerol, so glycerol can only be produced by reducing dihydroxyacetone phosphate from glycolysis and NOT from glycerol or other fat metabolites
In contrast to alpha glycerol, there are 3 main sources of fatty acids for triglyceride synthesis
- Glucose that enters adipose tissue and is broken down to provide building blocks for the synthesis of fatty acids
- Glucose that is used in the liver to form VLDL triglycerides, which are transported in the blood and taken up by adipocytes
- Ingested triglycerides transported in the blood in chylomicrons and taken up by adipocytes
How are water soluble vitamins absorbed? (recap: which are the water soluble vitamins)
What is the exception?
Vitamins C and B are water soluble
They are absorbed by diffusion or mediated transport in the JEJENUM
Exception = vitamin B12
How is vitamin B12 absorbed?
Vitamin B12 is a very large and charged vitamin. To be absorbed, B12 must first bind to the protein INTRINSIC FACTOR. Intrinsic factor with bound B12 then binds to specific sites on the epithelial cells on the LOWER portion of the ileum where B12 is absorbed via endocytosis.
Which cells secrete intrinsic factor?
parietal cells of the stomach
How many g of protein a day does a healthy adult require?
40-50g
How many essential amino acids are there?
8
Amino acids exist as optical isomers. However, only the X-forms are found in the proteins we utilise. What is X?
L-forms
Where does the digestion of proteins begin?
In the stomach, where the enzyme pepsin cleaves some of the peptide linkages, forming peptide fragments.
Where is pepsinogen I found?
only in the HCl secreting region (mainly the body) of the stomach
Where is pepsinogen II found?
in the pylorus
What bond to pepsins hydrolyse?
the bonds between an aromatic amino acid (tyrosine or phenylalanine) and a second amino acid
What is the optimum pH for pepsins? As a result, where is their activity terminated?
around 1.6-3.2
on exit from the stomach
What is the pH in the duodenal cap?
2-4
What is the pH in the rest of the duodenum (other than cap)
~6.5
Endopeptidases
trypsin
chymotrypsin
elastase
Exopeptidases
carboxyl dipeptidases
the amino peptidases of the brush border (microvilli border)
The final digestion of peptides occurs in 3 locations:
- the intestinal lumen
- the brush border
- within the cell
Where does digestion and absorption of carbohydrates occur?
in the duodenum
Examples of monsaccharides
glucose
fructose
galactose
Important dietary disaccharides
sucrose
lactose
Sugar molecules exist as optical isomers. Which form is utilised in metabolism
D-isomers
linkages in glycogen
alpha 1-4 glycosidic linkages
alpha 1-6 glycosidic linkages in chain branching
linkages in starch
alpha 1-4 glycosidic linkages with some chain branching by alpha 1-6 linkages
Does starch or glycogen have more chain branching?
glycogen has more
What is starch first degraded by?
ptyalin - the alpha amylase of saliva in the mouth
What is the optimal pH for alpha amylase
6.7
What terminates the activity of alpha amylase
gastric acidity
Which part of GI tract is responsible for 95% of starch digestion?
small intestine
What are the products of the first part of starch digestion in the small intestine and why?
Once in the small intestine, pancreatic alpha amylase catalyses alpha 1-4 linkages but NOT alpha 1-6 linkages. Thus the end products are:
- maltose
- maltotriose
- large polymers of glucose with alpha 1-4
- alpha-limit dextrins (branched polymers)
How are these products of starch digestion further digested?
They are further digested by the oligosaccharidases located at the outer portion of the membrane of the microvilli brush border.
Enzymes
- maltase
- lactase
- sucrase
- alpha-limit dextrinase
They are broken down into monosacchardies - glucose, galactose, and fructose
Absorption of hexoses and pentoses
Hexoses and pentoses are rapidly absorbed across the intestinal mucosa; these enter the capillaries which drain into the hepatic portal vein.
The high concentration of X at the mucosal surface facilitates glucose absorption - why?
sodium
because glucose and sodium are co-transported together with SGLT
Absorption of galactose
transported from the lumen by Sodium-glucose transport proteins
Absorption of fructose
Fructose utilises a different carrier and its absorption is independent of luminal Na+ since it is absorbed by facilitated diffusion via a glucose transporter (GLUT)
These monosaccharides then leave the epithelial cells and what happens next?
They enter the interstitial fluid by way of facilitated diffusion via GLUT proteins in the basolateral membranes of the epithelial cells and from these, the monosaccharides diffuse into the blood through capillary pores.
Most ingested carbohydrates are digested and absorbed within the first X% of the …
first 20% of the duodenum
What happens to the carbohydrates entering the hepatic portal vein?
After entering the hepatic portal vein and thus the liver, the liver then converts these carbohydrates into glucose.
What is the major consumer of glucose in the body?
skeletal muscle
During the absorptive state there is a net uptake of glucose by the …
liver
The liver converts glucose into …
glycogen
As well as glycogen, what can the liver convert glucose into?
alpha-glycerol phosphate and fatty acids which are then used to synthesis triglycerides
Where else does the process of converting glucose into alpha-glycerol phosphate (via glycolysis) and fatty acids occur?
adipose tissue cells
Most of the fat synthesised from glucose in the liver is packaged along with specific proteins into molecular aggregates of lipids and proteins known as …
lipoproteins
What are lipoproteins secreted by and where do they enter the blood as?
hepatocytes
VLDLs since they contain more fat than protein and fat is less dense than protein
Due to the large size of VLDLs, they do not easily penetrate capillary walls. What happens instead?
Their triglycerides are hydrolysed mainly to monoglycerides (i.e. glycerol linked to one fatty acid) and fatty acids by the enzyme LIPOPROTEIN LIPASE
Where is lipoprotein lipase located?
on the blood-facing surface of capillary endothelial cells, especially those in adipose tissue
Amino acids, triglycerides and glucose are transported where for conversion to storage molecules?
the liver
After the liver, which storage organs do they travel to?
adipose tissue for fats
muscle for glycogen
Pancreatic hormones in post absorptive state
Insulin for energy uptake into cells (glycogen storage, fat storage, protein synthesis)
Glucagon for energy release (glycogenolysis, gluconeogenesis, ketogenesis)
Adrenal hormones in post absorptive state
Cortisol; preparation for stress response (lipolysis, protein breakdown, gluconeogenesis, glycogen storage)
Adrenaline/noradrenaline; fight or flight gets energy in the bloodstream ready to be utilised (glycogenolysis, gluconeogenesis, lipolysis)
Thryoid hormones in post absorptive state
Thyroxine; generally controls metabolism (glycolysis, cholesterol synthesis, glucose uptake, protein synthesis, sensitises tissues to adrenaline)
Pituitary hormones in post absorptive state
Growth hormone (gluconeogenesis, glycogen synthesis lipolysis, protein synthesis, decreased glucose use)
Somatostatin
Appetite control
Leptin
Ghrelin
Where is leptin released from?
Adipocytes
What does leptin act on?
CNS
Action of leptin in normal weight
suppresses appetite
Action of leptin in obesity
Leptin resistance due to continuous high leptin levels (Stops responding)
Where is ghrelin released from?
stomach
When is ghrelin released? What does it do?
When stomach is empty
Goes to CNS to stimulate appetite
What stops ghrelin release?
gastric distention/stretch
