Exam # 2 Flashcards
Which segment of the small intestine or proximal large intestines has the highest permeability through its tight junctions?
Jejunum
Which segment of the small intestine or proximal large intestines has the lowest permeability through its tight junctions?
Colon
Which segment of the small intestine or proximal large intestines has the highest resistance through its tight junctions?
colon
Which segment of the small intestine or proximal large intestines has the lowest resistance through its tight junctions?
Jejunum
Where does the water absorption take place in the gastrointestinal tract?
85% of water absorption intestine
takes place in the small intestine (55% in duodenum
and jejunum and 30% in ileum); about 14% is absorbed in the large
intestine
What is required for efficient absorption of water?
- Increasing resorption surface
- Mucosa uptake mechanisms
- High blood perfusion
- Permeability
How are the monovalent ions absorbed?
Na+ transport is very efficient since it represents the driving force for most transport processes Chloride is absorbed by carriers as well as passice through the paracellular pathway K+ is mainly absorbed in the small intestine through the paracellular pathway
List in order of lowest to highest permeability the sections of intestine.
Colon -> Ileum -> Jejunum
List in order of lowest to highest resistance the sections of the intestines.
Jejunum-> Ileum -> Colon
What does calcitriol do?
Increases apical Ca++ channels Increases calbindin synthesis Increase Ca++ ATPase
Where is Mg++ absorbed?
Through Mg++ channels and paracellularly
How is Phosphate absorbed?
Through Na+/Phosphate symporter.
Where is viatmin D produced? What influences its synthesis?
Produced in the kidneys. Synthesis is under the influence of PTH
What is calcium absorption modulated by?
Modulated by vitamin D in intestine
What is calcitriol and what will it stimulate?
Calcitriol is active vitamin D hormone. It will stimulate building/ opening of calcium channels at apical membrane.
What occurs to the diameter of the intestine as we move from oral to aboral?
Diameter decreases as we move through GI tract.
What is haptocorrin and what does it do?
Transcobalamin I. This protects B12 from stomach acid.
What releases B12 from Haptocorrin?
Trypsin
Where is B12 absorbed?
Ileum
Where is iron absorbed ?
Small intestines
What breaks down Fe3+ to Fe2+?
Ferriductase
What is iron important for ?
The development of RBC/ B12
Why is iron oxidized?
So it could be bound to protien (apotransferrin) which is converted to transferrin.
What are the energy poor end products of catabolites?
CO2, H2O, NH3
What are the precursor molecules of complex molecules that are anabolites?
Some amino acids, Sugars, fatty acids, nitrogenous bases.
What are some energy sources in living organisms?
Glucose, Fatty acids, amino acids, ketone bodies, volatile fatty acids.
What are the phases of energy metabolism?
- absorptive phase: during active digestion and absorption of nutritents from the gut.
- Post absorptive phase: between meals, nutrients are being mobilixed from storage pools to tissues.
- Prolonged energy deficiency or food deprivation
What occurs during the absorptive phase of energy metabolism?
- Insulin is released
◦ Glucose is taken up by the liver and converted to glycogen and fatty acids o Fatty acids are sent out of the liver in VLDL to adipose tissue or muscle
◦ Amino acids are used for protein synthesis or are deaminated for gluconeogenesis
What is gluconeogenesis? Glycongenolysis?
Gluconeogenesis: Formation of new glucose
Glycogenolysis: Reuse of glucose.
What occurs during the post absorptive stage of energy metabolism?
◦ Glucagon is released (by liver)
◦ Glycogenolysis and gluconeogenesis are stimulated.
◦ Amino acids are mobilized from muscle.
What is occuring during a period of prolonged energy deficiency or food deprevation?
◦ Glucose and amino acids are conserved
◦ Fatty acids are mobilized in the form of non-esterified fatty acids (NEFAs)
◦ Formation of ketone bodies in the liver (mitochondria)
What happens in terms of carbohydrate utilization in glycolysis?
• Glycolysis: Once in the portal blood, glucose will reach the liver Glucose transport into cells is mediated by GLUT
How many GLUT transporters are there, and are they very specific?
• > 14 different GLUTs (highly tissue-specific, insulin-induced)
What is glycolysis?
- Glycolysis is central ATP producing pathway as it produces energy without O2.
- Red blood cells and muscle take advantage of anaerobic glycolysis.
What is the net gain with glycolysis?
• Net gain:
◦ 2 pyruvate + 2 NADH + 2 ATP
What happens to the pyruvate after glycolysis?
It is converted into lactate.
◦ Pyruvate -> mitochondria
◦ NADH -> electron transport chain -> NAD+
Why is NAD+ important?
NAD+ is needed to make more pyruvate.
What can be formed/ found after chronic inappetence?
increased ketone bodies
What can cause metabolic acidosis?
Increased lactate.
What is Aerobic glycolysis?
• Aerobic glycolysis: direct consumption and formation of ATP is the same as in anaerobic glycolysis, also NADH production is the same but pyruvate is imported into the mitochondria (to produce ACoA that enters into the Krebs cycle) and NADH can be oxidized (regeneration of NAD+) during the electron transport chain. During electron transport chain, 3 ATPs are produced for each NADH molecule that has been oxidized
What is anerobic glycolysis?
• Anaerobic glycolysis: 2 ATPs are generated for each molecule of glucose converted to 2 molecules of lactate (no net production of NADH)
What is the TCA cycle?
• The Tricarboxylic Acid Cycle (TCA)
◦ The TCA aka Krebs cycle or citric acid cycle is the final pathway where carbohydrates, amino acids, and fatty acids converge
‣ TCA is a traffic circle („roundabout“)
◦ The energy provided by the TCA is essential for most animals and humans
◦ TCA occurs close to the electron transport chain
◦ The process is aerobic because oxygen is used as an electron acceptor
◦ It delivers reduced NADH and FADH2
What is gluconeogenesis?
• Gluconeogenesis: Production of glucose from non-sugar molecules such as amino acids, lactate, and glycerol
What can occur during a prolonged fast?
• During a prolonged fast, hepatic glycogen stores are depleted, glucose is then formed from precursors other than carbohydrates (i.e. lactate, pyruvate, glycerol from TAG, and alpha-ketoacids from amino acids)
◦ Important tissues for gluconeogenesis: Liver and kidney
◦ Gluconeogenesis. Important substrates:
‣ Glycerol -> Glycerol Phosphate
‣ Lactate -> Pyruvate
‣ Amino acids -> TCA Cycle -> Oxaloacetate
What is glycogenesis?
- Glycogenesis is a mechanism to store glucose as glycogen in order to mobilize glucose in absence of a dietary source Main stores in the body: skeletal muscle and the liver
- Glycogenolysis is the process by which glucose is mobilized from glycogen granules in order to be sent into the blood and to other tissues
Where does the pentose phosphate cycle occur and what is another name for it?
• The pentose phosphate cycle - occurs in the cytosol (aka “hexose pathway”)
What are the functions fo NADPH in physiologic channels?
An important source of electrons (reductases in the body)
• Carrying electrons to the electron transport chain complexes
• Reducing the enzyme cytochrome P450 (steroid hormone synthesis, bile acid synthesis, detoxyfication, etc)
• Respiratory burst in phagocytic cells (NADPH oxidase produces reactive oxygen species to kill bacteria)
• Synthesis of NO
What are the fate of dietarty lipids in the body?
Fate of dietary lipids in the body—very simplified Short- and medium-chain fatty acids: -> get into the portal circulation (bound to albumin) and reach, finally, the liver
• Chylomicrons: -> TAGs will be converted into free fatty acids and glycerol by the enzyme lipoprotein lipase which is expressed at the capillaries of skeletal muscle, adipose tissue, heart, lung, kidney, liver. FFA can be stored as TAG (adipocytes) or can be used to produce energy (in other cells) or remain in the blood (bound to plasma proteins)
• Chylomicron remnants (i.e. cholesteryl ester, phospholipids, lipoproteins, fat-soluble vitamins) will be endocytosed (receptor-mediated) by liver cells
What is the relevance of fatty acids?
◦ Energy: during a fast period fatty acids are bound to albumin in plasma (free fatty acids) on the way to the tissues (coming from adipose tissue) -> oxidation (energy production in most tissues)
◦ Structural components: phospholipids and glycolipids in the plasma membrane
◦ Hormone precursors: prostaglandins
◦ Energy reserve: TAG in adipose tissues
What is the net gain of B-oxidation of fatty acids?
◦ From 1 palmitoyl CoA that has been oxidized to CO2 and H2O -> 8 ACoA, 7 NADH, 7 FADH2
◦ From these molecules 131 ATP can be generated (minus 2 ATP needed = 129 ATP!)
What occurs in ketone body formation?
◦ The liver (mitochondria) can convert ACoA from fatty acid oxidation into ketone bodies –acetoacetate, 3-hydroxybutyrate (ß-) and acetone—which are important sources of energy during fast periods
◦ During a prolonged fast, fatty acids mobilized from adipose tissue come to the liver yielding much more ACoA than necessary (also fatty acid oxidation produces high amounts of NADH which shifts OAA to malate). The result is the utilization of excess ACoA for ketone bodies formation In peripheral tissues, ketone bodies are converted into ACoA which enters the TCA cycle
What are the Peptides and Polypeptides of physiologic importance?
• Peptides of physiological relevance:
◦ Oxytocin: produced in the hypothalamus (uterine contractions and milk
• secretion)
◦ Antidiuretic hormone (ADH): produced in the hypothalamus and essential for maintenance of water balance
◦ Bradykinin, a vasoactive substance
◦ Angiotensin II, a potent vasoconstrictor
• Polypeptides with physiologic relevance:
◦ Gastrin, stomach hormone, stimulates secretion of gastric glands
◦ CCK, stimulates pancreas and liver secretion
◦ Glucagon, produced by alfa-cells of the pancreas
◦ Atrial Natriuretic Peptide (ANP): produced in the heart (atria), essential for regulation of blood volume and pressure
What are the branch chain amino acids and what do they do in muscle cells?
- Branch-Chain amino acids (BCAA) serve as source of energy in muscle cells Valine, Leucine, Isoleucine After deamination, BCAA are converted into α-ketoacids which enter the TCA. At the same time pyruvate serves as an acceptor of the BCAA‘s amino group yielding to the formation of the amino acid alanine which leaves the muscle and is used by the liver for gluconeogenesis
- Alanine from branch-chain amino acids (BCAA) metabolism represents an important way to eliminate ammonia (NH3) from the body through the formation of urea which occurs only in the liver
What is the extrinsic control of GI tract?
Vagus and splanach nerves, non gi hormones, calcitriol
What is the intrinsic control of the gi tract?
Located in the wall of the GI tract (enteric nervous system of gi tract)
Does the GI tract function with the brain?
No the GI tract functions without the brain. The gut can keep moving outside of the body if provided adequate conditions
What plexus is located between the submucosa and circular muscles? What is its function?
Messiners Plexus, or plexus submucosa
Regulates mucus secretion and food absorption.
What plexus is located in the muscularis externa between the longitudinal and circular muscles? What is its function?
Plexus Myentericus ( Auerbach)
Control of the muscular activity (tone and contractions rhythm)
What are the cells of the GI tract arranged in and how many fibers are found?
- Cells are arranged in bundles of as many as 1000 parallel fibers (longitudinal or circular arranged)
- Within each bundle, muscle fibers are electrically connected with one other through gap junctions
- Each bundle of smooth muscle fibers is partially separated from the next by loose connective tissue, but the muscle bundles fuse with one another at many points and work as a syncytium (from Greek syn = “together“ and kytos = “cell“)
What are the functions of Senory nerve cells?
Detect changes/ stimuli and regulate function
What are mechansensitive cells?
recognize stretching of intestinal wall or volume changes (intraluminal pressure) and induce a response (e.g. gastric phase of gastric acid secretion)
What are chemosensitive cells?
(chemoreceptors): detect the presence of nutrients in the GI lumen, changes in the osmolarity, and changes in the pH and induce a response (e.g. sensibilization of enteroendocrine cells)
What is the function of interneurons?
• Interneurons: Process signals coming from other nerve cells or from the CNS and propagate them to other neurons (motor neurons)
What are motor neurons? What are the three types and their locations?
Induce change in the GI tract in response to a stimulus.
◦ Muscle motor neurons: primary located in the plexus myentericus
◦ Secreto motor neurons: primary located in plexus submucosus
◦ Vaso motor neurons: in both plexuses
What regulates GI function?
• Types of neurotransmitters secreted by enteric neurons
What are examples of the Non adrenerfic non cholinergic NANC substances?
Nitric oxide (NO); inhibitory substance that reduces the motility of the GI tract ‣ VIP (vasoactive intestinal polypeptide); inhibits gastric secretion, and causes vasodilation and relaxation of smooth muscle sphincters ‣ Substance P; excitatory substance, increases secretion and motility of the GI trac
What does the parasympathetic nervous system use to stimulate many GI functions?
Acetylcholine
What do preganglionic fibers of the PNS become integrated with?
fibers of the ENS.
What are the postganglionic neurotransmitters of the ENS?
‣ Acetylcholine (excitatory)
‣ NANC Substances VIP and NO (inhibitory)
What does the sympathetic nervous system use on the GI tract and what is its effect?
• Sympathetic nervous system uses Noradrenaline which has an inhibitory effect on the GI tract.
What has an origin in the medulla oblongota through the vagus nerve?
• Oesophagus, stomach, small intestine, colon, ascenders, pancreas, gallbladder, and liver
What has an origin in the sacral spinal cord through the pelvic nerve?
Colon descend and distal part of GI tract
What is the sympathetic ganglion chain and where are they located?
• On either side of the spinal cord, many sympathetic ganglia are arranged like a string, forming the sympathetic ganglion chain
What is the length of preganglionic and postganglionic neurons? ( are they short or long?)
• Preganglionic neurons have short axons, whereas postganglionic neurons have long axons extending to the target organs
What is the postganglionar neurotransmitter?
• Noradrenaline (inhibitory)
What are the two types of electrical waves of the electrical activity of the GI smooth muscle cells?
◦ The smooth muscle of the GI tract is excited by almost continual, slow, intrinsic electrical activity along the membranes of the muscle fibers.
◦ Two basic types of electrical waves:
‣ Slow waves
‣ Spikes.
What will change the speed and strength of peristalisis?
Peristalisis is always there but neuro component changes speed/ strength of peristalisis
What do slow waves indicate?
Most GI tract contractions occur rhytmically, this rhythm is determined mainly by the frequency of the “slow waves“ in smooth muscle membrane potential Slow waves are not action potentials; they are slow, ondulating changes in the resting membrane potential Intensity about 5 – 15 mV
Slow waves -> no contractions.
What is the frequency of slow waves?
3 – 12 per minute (3 in the stomach, 12 in the duodenum, 8 to 9 in the terminal ileum
What are ICC?
specialized smooth muscle cells, the interstitial cells of Cajal (ICC)
What originates from ICC?
Slow waves
What are the functions of ICC?
◦ ICC are believed to be electrical pacemakers for smooth muscle cells ( similar to purkinje cells in the heart)
◦ ICC form network with each other and are interposed between the smooth muscle cells.
◦ ICC under cyclic changes and membrane Potential due to unique ion channels that periodically open and produce currents.
What are spike potentials?
These are true action potentials Occur automatically when the resting membrane potential of the GI smooth muscle becomes more positive than about -40 mV
What will cause induction of action potentials from slow waves?
◦ Slow waves will only induce an action potential when they reach smooth muscle cells that are (or were previously) sensitized
◦ Each time the peaks of the slow wave become more positive than -40 mV -> spikes potentials appear on these peaks
◦ The higher the slow wave potential rises, the greater the frequency of the spike potentials
What are the 3 reflexes essential to GI function?
1) Reflexes that are integrated entirely within the gut wall: control of GI secretion, peristalsis, formation of mixing contractions, local inhibitory effects, etc
2) Reflexes from the gut to the pre-vertebral sympathetic ganglia and then back to the GI tract: transmit signals long distances to other areas of the GI tract
3)Reflexes from the gut to the spinal cord or brainstem and then back to the GI tract
What are the 3 reflexes from the gut to the prevertebral sympathetic ganglia and then back to the GI tract?
◦ gastrocolic reflex: signals from the stomach that causes evacuation of the colon
◦ enterogastric reflex: signals from the colon and small intestine inhibit stomach motility and stomach secretion
◦ colonoileal reflex: signals from the colon that inhibit emptying of ileal contents into the colon
What are examples of Reflexes from the gut to the spinal cord or brainstem and then back to the GI tract ?
◦ Reflexes from the stomach and duodenum to the brainstem and then back to the stomach to control gastric motor and secretory activity
◦ Pain reflexes that cause general inhibition of the entire GI tract
◦ The defecation reflex which travels from the colon and rectum to the spinal cord and back again to produce the colonic, rectal, and abdominal contractions required for defecation
What is the peristaltic reflex?
Stretching of the intestinal wall during the passage of a bolus triggers a reflex that constricts the lumen behind the bolus and dilates the lumen ahead of it -> coordination of longitudinal and circular musculature -> propulsive movement of the chyme.
What direction does the bolus of chyme travel in the SI?
Oral to aboral
What muscles move proximal to the site of distension during peristalisis?
Proximal to the site of distention -> longitudinal muscle relaxes, circular muscle contracts
What muscles move distal to the site of distention during peristalisis?
longitudinal muscle contracts, circular muscle relaxes
What do excitatory neurons release during peristalisis?
• Excitatory motor neurons release Ach and Substance P -> smooth muscle contraction
What do inhibitory neurons release during peristalisis?
• Inhibitory motor neurons release NO, ATP, VIP -> smooth muscle relaxation
What is the vasovagal reflez?
• The term vagovagal reflex refers to gastrointestinal tract reflex circuits where afferent and efferent fibers of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain
What stimulates the vagus affeent fibers? What does it control?
- The stimulation of the mechanical receptors located in the gastric mucosa stimulates the vagus afferent fibers
- It controls motility of the gastrointestinal muscle layers in response to distension of the GI tract by the chime, e.g. receptive relaxation of the stomach in response to mastication of food and deglutition
What are the divisions of the monogastric stomach and what is its job?
Proximal region ( extension past fundus) is the fastric reservoir, it stores and retains frood as it awaits eventual entry into the small intestine.
Distal region( area of the corpus) is the gastric pump. It grinds and sieves pieces of food into small particles that can be digested by the small intestines.
What is the sequence that causes inflow into the gastric pump
- ) Gastric reservoir ( Tonic relaxation and contraction)
- ) Small peristaltic wave in corpus
- ) Move content into distal ( for mixing / grinding into smaller particles) if particles are not small enough they will go back for another grinding.
- ) Emptying of fluid/ predigested particles into the duodenum ( fluid empty faster than solids) the finest particles go to duodenum.
What occurs during a hypocaloric meal ? Hypercaloric?
Hypocaloric: Stomach empties fast, every contraction of gastric pump will lead to emptying of the pyloric antrum
Hypercaloric: Food will be retained in the proximal part of stomach, food needs more time to mix, and empties slower. Retropulsion is present.
What induces the receptive relaxation (vasovagal reflexes)?
Induced by mastication/ degredation of food which activates mechanoreceptors in pharynx.This triggere vagus center, which causes inhibitory vagus nerve fibers ( which use NAC) which leads to short term relaxation of stomach during food intake.
What induces the Adaptive relaxation (gastr-gastric reflex)?
Food arrives which causes stressing and some fibers are inhibited.
What induces the feed back relaxation reflex ?
When nutrients are reaching duodenum and CCK is released, this induces relaxation due to vagus center. CCK will stop this.
What are the functions of intestinal motility?
◦ Mixing food with digestive juices (GI secretions)
◦ Enhancing contact between intestinal wall and food
◦ Peristalsis, the propulsive movement of the chyme to the distal (aboral) direction
What are the contraction patterns of the small intestine?
- Propulsive pattern and non propulsive pattern
What is the propulsive pattern?
peristaltic waves -> fast aboral migrating contractions (faster in duodenum, medium in the jejunum and very slow in the ileum)
Speed will decrease as you move along GI tract
What is the non propulsive pattern of peristalsis?
Non-propulsive pattern: segmentation contractions -> localized contractions of circular muscle, small segments of the intestine contract tightly dividing the gut into two segments of constricted and dilated lumen
(It doesn‘t contribute significantly to the net aboral propulsion of the ingesta but it is important when nutrient concentration is high!)
What is another word for non propulsive pattern?
Segmentation
What is the duration of contractions of the interdigestive period?
Time in which stomach and small intestine are empty between meals -> it lasts typically 80-120 min
What is Migrating Motoric Complex (MMC) and what does it do?
‣ Helps pushing undigested material out of the intestine
‣ Control of the bacterial population
CLEANS
What are the 3 phases of MMC? What is the duration of each stage?
◦ Phase I: motoric rest, no contractions (GI all quiet, ca. 60-70 min)
◦ Phase II: intermittent and irregular contractions sometimes isolated stronger ones (20-30 min)
◦ Phase III: strong peristaltic contractions starting from the stomach and migrating distally to reach the colon (3-10 min)
How often does phase 3 of MMC occur?
Occurs every 3 minutes
What occurs within the segments of the GI tract during the interdigestive cycle?
Phases will alternate in each segment
Which phase begins first in the stomach and duodenum?
Phase III
Which phase begins first in the jejunum?
Phase II
Which phase begins first in the ileum?
Phase 1
What are the motility paterns in the large intestines? What does each pattern do?
• Motility patterns observed in the large intestine are mainly:
◦ Peristaltic waves
◦ Antiperistaltic waves: oral migrating contractions that impede the movement of ingesta, causing a more intense mixing activity
TRUE or FALSE: • Mixing activity is prominent in the colon of all species
TRUE
What are Haustra?
• In horses and pigs, colonic segmentation is more pronounced and results in the formation of sacculations (=haustra)
What are the 2 types of pathologic contractions and what direction do they move?
• Giant contractions: high amplitude and long-lasting contraction
◦ oral migrating -> vomiting
◦ aboral migrating -> diarrhea
What causes vomiting?
- A defense mechanism and important clinical sign activated in order to eliminate gastrointestinal content
- A complex reflex involving many striated muscle groups and other structures outside the GI tract
- Is coordinated in the brainstem
How is stimuli of vomiting classified? What are the classifications?
Stimuli can be classified according to “when/where they originate“:
1) before food intake (color, smell, emotions, appearance of something) 2) after food intake (particles in intestinal lumen) -> visceral afferents -> vomiting center
3) after absorption (particles in the blood, e.g. drugs, toxins)
- > stimulate the chemoreceptor trigger zone (CTZ) in the area postrema
What are frequent causes of vomiting?
- Pregnancy
- Medications, Toxins, Pain, Irradiation
- Smell/ Touch
- Cerebral Pressure
- Stomach stretching/ Inflammation
- Rotary Movement
What is the sequence of events of vomiting?
1) Antiperistaltic wave originates in duodenum ( vomiting may contain ingesta of intestinal origin)
2. ) Propulsion of ingesta towards stomach
3) Contraction of the abdominal muscles increasing intraabdominal pressure
4) Expansion of chest cavity while the glottis remains closed in order to lower the intrathoracic pressure.
5) Relaxation of LES
6) Opening of UES
What are key indications of vomiting? How can you tell it apart from regurgitation?
Vomiting is not normally one retching episode, and can include nausea, dizziness, ect. Abdominal effort is seen with vomiting. With regurgitation you do not see any signs, and there is a lack of abdominal contraction. It can be a single episode.
What is diarrhea?
- Diarrhea refers to an increase in frequency of defecation or fecal volume
- This increase is often due to increased water content
What is the cause of excess water in the gut?
1) Ingested water
2) Water secreted by glands of the GI tract
3) Water secreted or lost directly through the mucosal epithelium
• Through absorption in the intestine, the amount of secreted water slightly exceeds the amount ingested
• Diarrhea occurs when there is a mismatch between secretion and absorption
What are the two types of diarrhea?
- Malabsorptive diarrhea and hypersecretory diarrhea
What is malabsorption diarrhea? what can cause it?
• Malabsorptive diarrhea: occurs when absorption is inadequate to recover all secreted water
◦ Viral, bacterial, protozoan infections
◦ Destruction of the villi and reduced length (the rate of cell loss is higher than the rate of replacement)
◦ Shortened villi cause a loss of absorptive intestinal surface area
◦ More affected are mature enterocytes that possess the enzymes of the brush border and transport proteins.