OSSF II - Exam 2

Discuss the basic histology of the ruminant stomach

1) Papillae increase the surface area available for absorption 2) Made of stratified squamous epithelium: --> Stratum corneum (keratinized layer of dead cells) --> Cells connected by tight junctions, but ↑ ↑ absorption of water & ions --> Cells continuously renewed in stratum basale 3) Rich blood supply (needed for the high level of absorption) increases 3-4-fold after meals ( ↑ absorption of fermentation products and Na+) 4) 2 layers of smooth muscle 5) 2 neural plexuses → capable of local reflexes, modulated by ANS via the Vagus N. Layering of Fluids, Particles, and Gases Top Layer: Gas layer formed by fermentation: CO2, NH4, H2S, H2, N2, O2 Second from Top: "Floating layer" = raft of plant fibers ↑↑ fermentation → small gas bubbles stuck to the fibers causing them to float The rate of reduction in particle size is slower for less-fermentable substances (e.g., straw with ↑ lignin) so they will remain in the rumen longer. Grains are already finely ground by the time they make it to the rumen so they sink rapidly and move into the omasum faster than grasses. ***Browsers (sheep, goats) have a more homogeneous consistency and undergo diffuse fermentation (fewer layers)***

Describe important aspects of gastric motility (receptive relaxation, mixing and gastric emptying)

1. Receptive relaxation: relaxation (as empty stomach is always slightly contracted) of the proximal portion of the stomach in response to food intake (allows for food storage) --> Reflex process: a) Sensory nerve fibers originate in the stomach (and somewhat in the pharynx) = afferent arm b) Vagal efferent nerve fibers → synapse on postganglionic fibers in the stomach c) Postganglionic fibers release VIP (vasoactive intestinal peptide) and NO, not Ach on the smooth muscle cells of the stomach wall d) Result is relaxation of the muscles of the stomach --> "Vago-vagal reflex": afferent and efferent limbs are carried in the vagus nerve 2. Mixing and digestion: as food moves distally in the stomach, peristaltic contractions occur --> Circular narrowing of the lumen in a proximal ⇢ distal direction (peristaltic contraction) --> Strength of contraction increases as the wave moves towards the pylorus --> Some chyme is forced through the pyloric sphincter (pyloric sphincter also contracts as the wave moves down the stomach, so most of the contents are forced backwards ("retropulsion" mixing divides chunks of food into smaller pieces)) --> Larger food fragments = longer retention time in stomach and Indigestible objects in food often removed by vomiting (e.g. bones) 3. Gastric emptying is determined by a balance of --> Stimulatory mechanisms ( ↑ gastric contractility) originating in the stomach - Neural or Hormonal --> Inhibitory mechanisms originating in the duodenum ( ↓ gastric contractility, closure of pyloric sphincter) - Neural or Hormonal

Explain how H+ release in the stomach is regulated (neuronal, endocrine, paracrine)

3 substances alter HCl secretion 1. Histamine from ECL cells (paracrine) --> Binds to H2 receptors on parietal cells to stimulate HCl secretion 2. Acetylcholine from Vagus N. efferents (neurocrine) --> Binds to Muscarinic receptors on parietal cells to stimulate HCl secretion --> Stimulates ECL cells to release Histamine 3. Gastrin from G cells in the pylorus (endocrine) --> Secreted into the circulation by the G cells in response to gastric distension/stretch, peptides, vagal nerve stimulation --> Binds to receptors on parietal cells and increases HCl secretion directly (short reflex) --> Causes release of Histamine by ECL cells **Parasympathetic nerve (Vagus) impulses increase HCl secretion through multiple pathways (long reflex). It can be direct on parietal cells, indirect on ECL cells (make Histamine) or indirect on G-cells (make Gastrin). Almost all of the HCl secretion into the stomach occurs during the cephalic & gastric phases of digestion --> Cephalic phase (prior to food entry, sight/smell of food) → 30% of the HCl secretion --> Gastric phase (begins with the arrival of food in the stomach, distension) → 60% of the HCl secretion Inhibition of HCl secretion The same duodenal signals that reduce gastric contractility also reduce HCl secretion. At very low pH (< 2.0), gastric D cells release somatostatin which blocks the release of gastrin and histamine via a paracrine mechanism --> Direct inhibitory effect on HCl production → binds to parietal cells and reduces the secretion of HCl --> Indirect inhibitor effect → inhibits histamine release from ECL cells Prostaglandins inhibit gastric acid secretion by blocking the effects of histamine. They also stimulate mucus and bicarbonate secretion (protective function in gastric mucosa). Ingested food buffers high H+ concentrations, particularly proteins. When the stomach begins to empty of ingested food, it loses the buffering capability of food, and the pH drops.

Describe the digestion and absorption of proteins

Absorbable forms of nutrients from proteins are amino acids, dipeptides, and tripeptides (in contrast to carbs which were just monomers). These are produced from proteins by enzymes in the stomach and small intestine (a lot in SI). Proteases are secreted from the pancreas to the duodenum as inactive zymogens that require activation. --> Stomach: pepsinogen is activated to pepsin from the low pH --> SI: trypsinogen is activated to trypsin by enterokinase (brush border enzyme) and then trypsin activates other proteases and more of itself 1. Luminal Phase: Trypsin, chymotrypsin, elastase, carboxypeptidase A, and carboxypeptidase B convert protein to AAs, dipeptides, tripeptides or oligopeptides 2. Membranous Phase: Peptidases on brush border work on the remaining oligopeptide to digest them to AAs, dipeptides, and tripeptides **The products of protein degradation are absorbed across the apical membrane via secondary active transport coupled to Na+ (for AAs) or H+ (for dipeptides and tripeptides). The H+ gradient needed for this co-transporter is generated by a Na/H exchanger in the apical membrane. Amino acids are then transported across the basolateral membrane via facilitated diffusion through channels specific for basic, neutral, and acidic AAs. Dipeptides and tripeptides are either further degraded by peptidases to AAs (follow the AAs out) or can diffuse across the basolateral membrane. Some of these products are taken through the portal vein to hepatocytes that use them for plasma protein and lipoprotein synthesis. Some stay in general circulation to be taken up by various other cells for protein synthesis.

Explain the mechanisms involved in the formation of both the electrolyte (aqueous) and enzymatic components of pancreatic secretion

Aqueous Component Aqueous solution is isotonic and contains Na+, K+, Cl-, and HCO3-. The concentration of HCO3- and Cl- is influenced by flow rate, but Na+ and K+ do not change --> At high flow rates, ductal cells stimulated to secrete more HCO3- rich fluid --> At low flow rates, HCO3- diffuses back into the blood so less Cl- is reabsorbed through the exchanger HCO3- secreted into pancreatic fluid is balanced by H+ entering the blood, which is then used for gastric secretion of HCl. Enzyme Component Amylase & lipase are secreted as active enzymes while proteases are secreted as inactive forms and converted in the duodenal lumen to the active form. Enzymes are stored in zymogen granules until acinar cells are stimulated by PNS stim. or CCK to secrete *** Trypsin(ogen), chymotrypsin(ogen) and (pro)elastase cleave interior peptide bonds *** Lipase cleaves the ester bonds at the 1- and 3-positions, producing FFA and monoglycerides (breaks down fat to glycerol and FAs) *** Amylase cleaves starches and glycogen to maltose

Review bile acid synthesis and secretion

Bile Secretion 1. Hepatocytes continuously synthesize and secrete the constituents of bile: [Bile salts (~50% of bile), Cholesterol (4%), Phospholipids (40%), Bile pigments (e.g. bilirubin) (2%), Water, Ions] 2. Bile flows out of the liver, through the bile ducts, and into the gallbladder for storage (concentrated here from ion and H2O absorption) 3. In response to the presence of fats in the small intestine, CCK is released and causes contraction of the gallbladder and relaxation of the sphincter of Oddi → release of bile into the lumen of the duodenum 4. Bile salts emulsify and solubilize dietary lipids throughout the small intestine, then are absorbed into the portal vein and recirculated back to the liver (enterohepatic circulation) 5. Extraction of bile salts from the portal blood by hepatocytes into bile ***Bile salts function throughout the length of the small intestine, from the duodenum to ileum, before recirculating back to the liver. Conjugation of bile acids into bile salts reduces the passive reabsorption through the lipid bilayer of cell membranes so they remain in the intestinal lumen longer. Bile salts are actively absorbed from the ileum by Na+-dependent secondary active transport Bile Composition Hepatocytes synthesize two primary bile acids from cholesterol (Cholic acid and Chenodeoxycholic acid). These account for the majority of bile salts. Intestinal bacteria modify the primary bile acids to produce secondary bile acids (Deoxycholic acid and Lithocholic acid). Conjugation into bile salts makes the bile acids much more water soluble. --> Phospholipids and bilirubin are secreted into bile by hepatocytes --> Water and ions (including active transport of HCO3-) are actively secreted into bile by bile capillary epithelial cells The majority of what is found in bile is recirculated bile acids and salts and a small amount comes from de novo synthesis from cholesterol.

Describe the basics of brachydont tooth development

Brachydont teeth arise from dental lamina (primitive epithelium made from the down growth from the surface epithelium of the mandibular arch and maxillary process). Enamel organs (tooth buds) grow from specific zones of the dental lamina. The enamel organ arises from the invaginating dental lamina of the fetal skull. Epithelial cells along concave portion become the inner enamel epithelium and give rise to ameloblasts (make enamel). This structure will shoot up like a rocket. Mesenchyme below this concave rim (outer rim of dental papilla) gives rise to odontoblasts (become dentin). The dental papilla will eventually become the dental pulp and the dental lamina will break down. Formation and mineralization of the hard dental structures occur with the ameloblasts on top of the enamel and the odontoblasts below the dentin (double stuffed oreo). The stellate reticulum and outer enamel epithelium start to collapse along the side of the developing tooth. This induces the formation of cementum (from the outer enamel epithelium). The outer enamel epithelium "collapses" just prior to crown eruption, with the result being that only the root dentin is covered with cementum. Ameloblasts will be gone with tooth eruption and the periodontal ligament will form.

Describe carbohydrates as an energy source. Describe the overall flow of non-protein nitrogen and protein metabolism between ruminant microbes and the ruminant animal

Carbohydrates account for ~85% of the energy in the ruminant diet and its dietary process is similar for lipids. The ruminant gains carbohydrates from starch and cellulose from feed. These are hydrolyzed via enzymes on the outside of the bacterial cell wall into monosaccharides and short-chain polysaccharides. These are then transported into the microorganisms and metabolized by glycolysis (NAD+ is converted to NADH during glycolysis and the regeneration of NAD+ produces methane as a byproduct). Pyruvate is converted to VFAs (waste products for bacteria, energy source for ruminants). Pyruvate can be directly converted to propionate (preferred pathway for propionate production under normal feeding conditions) or it can be converted to lactate and then to propionate and acetate. Pyruvate can also become acetyl-CoA to become acetate and butyrate. Energy production in forestomachs for proteins begins with extracellular degradation by microbes. The small peptides are then transported into microbes and broken down into AAs or VFAs. The microbes then undergo microbial protein synthesis and are passed into the small intestine where the protein is digested and absorbed. **Microbial multiplication so rapid that dietary protein is insufficient for protein synthesis so non-protein nitrogen (NPN) from NH4+ is needed for protein synthesis** Amino acids in the small intestine come from feed proteins that have not been digested by microbes in the rumen (undegraded protein) and microbial proteins synthesized in the rumen. Ruminant microorganisms convert NPN to NH4+, and NH4+ to amino acids and proteins. Urea is a common source of NPN and needs to be paired with fermentable carbohydrates to be an energy source. Urea comes from the liver handling NH4+ and is usually excreted in the urine, however, ruminants can recycle it to be used as nutrients for the rumen microbes. Urea recycling occurs in salivary secretions and the bloodstream (reaches the rumen by diffusion across the epithelium). NPNs can also be supplemented in feed.

Compare and contrast the structure of a brachydont vs a hypsodont tooth and list species that have hypsodont teeth

Canine and Feline Dentition --> heterodont (several types of teeth), thecodont (teeth firmly set in sockets using gomphosis (type of fibrous joint)) and brachyodont (shorter crown:root). Two types of teeth Brachydont --> Short crown, neck, well developed root(s) embedded in bony socket --> Exposed surfaces covered with Enamel --> Cease to grow after eruption --> Found in carnivores, humans, the incisor teeth of ruminants, and all pig teeth except canine teeth (tusks) Hypsodont --> Elongated body (no brachydont-like crown or neck) --> Enamel covers the entire length of the body (invagination of enamel layer) --> 3 different mineralized materials wear at different rates resulting in a complex grinding surface (often a rough, flattish occlusal surface adapted for crushing and grinding) ***uneven wear can lead to sharp edges that cause cheek lacerations*** --> Outer enamel epithelium collapses onto enamel surface early on so cementum both above and below the gingival line --> No terminally developed root structure --> Some grow throughout adult life (e.g. rodent incisors, boar tusks) --> Horses - roots grow for several years and tooth will continue to erupt during that time --> Found in all the teeth of horses, the cheek teeth of ruminants, the canine teeth of pigs (tusks), incisors and cheek teeth of rabbits, guinea pig, chinchillas, rodents

Describe the processes involved in the digestion and absorption of carbohydrates

Carbohydrates are a significant source of energy in the diet of most animals. Only monosaccharides (glucose, galactose, fructose) can be absorbed Degradation of carbohydrates into monomers occurs in 2 steps: 1. Luminal phase → starch and glycogen degraded by amylase (from pancreas) into poly- and disaccharides (maltose [most common breakdown product], lactose, sucrose) ⇢ these are smaller than ingested material but cannot be absorbed by epithelial cells --> Ruminants have very little amylase in pancreatic secretions b/c bacteria in rumen do this work 2. Membranous phase → maltose and other simple carbohydrates broken down to monosaccharides (glucose, galactose, fructose) by enzymes in the apical membrane of the epithelial cells --> Enzymes synthesized in epithelial cells and transported to apical membrane w/ catalytic portion facing the lumen Glucose and galactose then share a Na dependent co-transporter (SGLT-1) to be absorbed across the apical membrane. Fructose uses facilitated diffusion so it cannot be absorbed against its gradient. They are all then transferred across the basolateral membrane using GLUT2. They travel to the portal vein to the liver and then are stored as glycogen or transformed into lipids. Some remain in circulation as glucose to supply other tissues.

Discuss the processes involved in the digestion and absorption of the various lipids including the roles of micelles and chylomicrons

Dietary fat = triglycerides, cholesterol, phospholipids Degradation of fat in the small intestine requires pancreatic enzymes & bile salts. The lipids, however, are insoluble in aqueous environments, so they must be solubilized to be absorbed. Products of absorption are free fatty acids and monoglycerides. The presence of fat in the duodenum causes release of CCK which slows gastric emptying to allow time for the slow process of fat digestion. First step in lipid degradation in the small intestine is the release of bile salts into the duodenum. Bile salts emulsify the fat into droplets which creates more surface area for pancreatic enzymes to access. Colipase displaces some bile salt molecules surrounding the fat droplets, allowing fat-digesting enzymes to get access. --> Lingual, gastric and pancreatic lipase digest triglycerides into monoglycerides and FAs --> Cholesterol ester hydrolase digests cholesterol ester into cholesterol and FAs --> Phospholipase A digests phospholipids into lysolecithin and FAs Following enzymatic degradation into monoglycerides, FAs, cholesterol, lysolecithin, and glycerol, the bile salts solubilize these products into micelles and they are transported to the apical membrane of the intestinal epithelium for absorption. At the apical membrane, the lipids are released and diffuse down concentration gradients into the epithelial cell. Bile salts remain in the intestinal lumen. Products of lipid digestion are reesterified with FFAs on the smooth ER to form triglycerides, cholesterol, and phospholipid (their original molecules). Lipids are packaged with apoproteins to form chylomicrons and chylomicrons packaged into secretory vessels on the Golgi apparatus. Exocytosis of the chylomicrons at the basolateral membrane cause them to enter lymph capillaries as they are too large to enter capillaries. They will enter the blood stream once the lymph drains from the thoracic duct.

Explain the transport processes involved in the digestion and absorption of nutrients in the small intestine

Digestion = chemical breakdown of organic nutrients in food into absorbable molecules → mainly monomers (with some notable exceptions) --> Chemical degradation of polymers occurs by hydrolysis Absorption = movement of absorbable molecules from the intestinal lumen into the blood --> Structure of the small intestine is ideally suited for the absorption of large quantities of nutrients (folds, villi, microvilli) --> Usually via the transcellular path → requires transport mechanisms in the apical (lumen-facing) and basolateral (interstitial space-facing) membranes --> Particularly important in carnivores and omnivores as most of the absorption is in the small intestine ** Almost complete absorption of most organic nutrients and monovalent ions in SI (H2o, Na+, Cl-) ** Divalent ions absorbed in SI is in accordance with the needs of the animal ** Absorption of bile salts & vit. B12 is limited to a specific part of the S.I. (the ileum) Mechanisms of Absorption 1. Paracellular, through tight junctions → inorganic ions & water (e.g., "leaky" tight junctions in parts of the small intestine) 2. Transcellular (most important) • Diffusion - passive movement down concentration/ electrochemical gradient (H2O via aquaporins, lipid soluble substances) • Endocytosis & exocytosis* --> In rare instances, the vesicle does not release content in the cytosol → transcytosis (shuttle through the cell, how food allergens and botulinum toxin enter blood w/o being destroyed) • Transport mediated by carrier proteins/selective channels - can be active or passive

Identify some distinguishing features b/w hindgut and forestomach fermenters

Digestion in the LI of simple-stomached herbivores is anaerobic, which facilitates microbial degradation in the absence of oxygen (fermentation). Fermentation of carbohydrates turns them into VFAs which then diffuse out of microorganisms and become available for absorption. VFAs are absorbed across the large intestinal epithelium and used as energy sources (including for the epithelial cells). Forestomach fermenters digest microbes as a source of protein; hindgut fermenters do not (microbes are excreted with the feces → proteins are wasted*). Some species (rabbits and rats) mitigate with coprophagy. This is when they eat fecal clumps derived from the cecum and have a high density of bacteria. This allows digestion of components of microorganisms (protein, vitamins such as vit. B) and occurs mainly at night ("night feces"). Ruminants (forestomach fermenters) obtain more energy for a given amount of cellulose than horses (hindgut fermenters) because: 1) Long retention time of feed particles in forestomachs 2) Location of the fermentation chamber prior to the small intestine → more complete absorption of VFA 3) Ability to digest microbial proteins (not done in hindgut fermenters)

Identify the various cell types and secretions of the gastric mucosa

Epithelial cells throughout the glandular gastric mucosa produce viscous, bicarbonate-rich mucus. This gives the characteristic "slimy", jelly-like feel on the inside of the stomach. It serves a protective function from mechanical injury and exposure to acidic contents. The epithelial cells are connected by tight junctions. There are also millions of pit shaped glands where gastric secretions are produced. These pits are most numerous in the fundus & corpus (most of the gastric juice is produced here). --> Mucin-producing cells make mucus for protection. The epithelial cells functioning as stem cells are scattered among the mucus-producing cells. These daughter cells differentiate into different types of mature cells and migrate up or down the gland• This means that damaged epithelial cells can be quickly replaced. --> Parietal cells secrete HCl and intrinsic factor (an essential component of stomach acid). They have their own invaginations with thin-like projections to increase SA for secretions. The low gastric pH converts inactive pepsinogen to its active form, pepsin (a protease that begins the process of protein digestion, stimulates HCl secretion, and has autocatalysis abilities to increase its own production) --> Chief cells produce pepsinogen (only secretory product of chief cells) and must be co-located with parietal cells as they need HCl to make pepsin --> Enterochromaffin-like cells (ECL lie slightly outside the glands but are closely related) and Endocrine cells • Pylorus: Gastrin-producing G cells, Somatostatin-producing D cells Gastrin → stimulates the secretion of HCl and Pepsinogen, promotes gastric motility (endocrine effect) Somatostatin → inhibitory effect on HCl production by inhibiting parietal cells (paracrine effect) • Acid-producing parts of stomach (esp. corpus): Histamine-producing ECL cells Histamine binds to neighboring parietal cells in paracrine fashion to stimulate HCl secretionstimulate

Review important concepts related to cellular transport

Facilitated diffusion is saturable because the passive movement still requires a channel. Na-K ATPase is the primary method of active transport in the GI tract creating the NA gradient.

Summarize the biochemistry of volatile fatty acid production along with the metabolic uses of volatile fatty acids for energy

Feed composition influences both the total amount and the relative proportions of VFAs. A high starch diet causes more propionate production (dual pathways [direct or indirect through lactate] to propionate). These VFAs are absorbed in the rumen (it is an important energy source for the microbes) and is almost entirely absorbed before the small intestine. They can be absorbed through two methods 1. Passive cotransport of VFA anions in exchange for bicarbonate ions (using a carrier protein) in the granulosa layer of the rumen epithelium (more metabolically active layer) --> HCO3- is made through carbonic anhydrase forming carbonic acid which then dissociates to HCO3- and H+ --> H+ combines with VFA anion in the epithelium to aid diffusion into the portal blood 2. Passive transport of undissociated VFA through the keratinized epithelium Pyruvate will either become acetic acid, propionic acid or butyric acid. --> Acetic acid is absorbed into circulation and is then a source of acetyl-CoA for synthesis of lipids (important for FA and triglyceride synthesis) --> Propionic acid goes to the liver through the circulation to be used in gluconeogenesis for glucose generation --> Butyric acid made from pyruvate through rumen fermentation. It is then metabolized to the ketone beta-hydroxybutyrate in the rumen epithelium (ketogenesis) so that it can be an energy source for rumen epithelial cells (once absorbed its used for cardiac and skeletal muscle) **During stressful conditions when energy demand is greater than energy supply, cows mobilize nonesterified fatty acids from adipose tissue for ketogenesis. The ketone bodies can overwhelm the metabolic pathway and accumulate, causing ketosis (lethargy, off feed)

Describe the organization of the esophagus

Functions include • Propulsion of ingesta - Enteric nervous system; peristalsis (contract and relax to move food down) • Protection of lumen wall from partially masticated ingesta - Stratified squamous epithelium (pretty thick and robust) • Lubrication of ingesta - Secretory gland secretions (serous and/or mucus) • Dilate to accommodate unchewed food - Longitudinal folds (gives the ability to stretch out) • Lamina epithelialis: Stratified squamous epithelium that varies in thickness and degree of keratinization • Lamina propria: Dense irregular CT, small vessels, small nerves, abundant elastic fibers (make esophagus stretchy), and diffuse lymphoid tissue; denser that that of the Tunica submucosa • Lamina muscularis: Longitudinally oriented smooth muscle bundles or confluent layer; forms the abluminal side of the mucosa (aka, muscularis mucosae) • Submucosa: contains submucosal glands (Mucous or Seromucous glands) that help lubricate ingesta --> Looser connective tissue (Contain large arteries, veins, lymphatics, and nerve trunks (submucosal plexus) --> Loose nature of the submucosa allows for longitudinal folding (rugae) of relaxed esophagus and expansion during ingestion of a food bolus • Muscularis: circular and longitudinal layers --> Lower esophageal sphincter is derived from inner circular layer • Adventitia proximally and Serosa caudally **The esophagus has significant species variation! --> Keratinized esophageal mucosa is diet dependent (ie cows have it from their tough food, but dogs do not) --> Lamina muscularis mucosae may or may not be present or can be a discontinuous layer (may be isolated bundles like in the distal canine esophagus) but will always be smooth muscle --> Submucosal glands may be present in greater densities in certain locations **in the mucosa in birds** --> Tunica muscularis starts striated and either stays striated or becomes smooth muscle in some species (point of change varies)

Discuss GI motility (added by me)

GI motility is the contraction and relaxation of the muscles of the walls of the G.I. tract and the sphincters. Most of the G.I. muscle is smooth muscle with cells coupled by gap junctions (exception is pharynx, proximal esophagus, and external anal sphincter). Unique to the smooth muscle of the G.I. tract are the cells with spontaneous, slow oscillations in membrane potential ("slow waves" of depolarization & repolarization). These are the "pacemakers" of the G.I. tract. The frequency of these cells is not influenced by neural or hormonal input as it is spontaneous. Frequency varies between different parts of the G.I. tract but is consistent within each individual region. G.I. tract pacemaker cells (where slow waves originate): --> Interstitial cells of Cajal → modified smooth muscle cells, abundant in the myenteric plexus --> Membrane potential moves towards the AP threshold during depolarization but doesn't spontaneously reach threshold (slow wave depolarization is necessary but insufficient by itself to result in an action potential & muscle contraction) --> Neural or hormonal input determines whether the cell will reach the AP threshold during the slow wave plateau ***Depolarization & plateau → due to inward Ca2+ current ***Repolarization → due to outward K+ current Acetylcholine or hormones released from nerve endings near gastric smooth muscle cells. Enough Ca2+ influx (from enough nerve signals of the myenteric plexus) to bring cell to the threshold and generate AP by opening voltage-gated Ca2+ channels. AP frequency depends on the degree of neural and hormonal input (high-frequency AP = more intracellular Ca2+ = greater contractile force). Elevated intracellular Ca2+ results in the generation of contractile force (proportional to intracellular Ca2+).

Describe the structure and function of the gallbladder and of its epithelium, and compare/contrast its histologic structure to that of the small intestine

Gallbladder does NOT have a muscularis mucosae and submucosa. The mucosa is thrown into large folds and the epithelial cells are supported by loose to mildly dense irregular CT. They are distinguishable from the small intestine as they have no crypts. The lamina epithelialis is made of simple columnar epithelium similar to enterocytes. There are apical tight junctions and lateral spaces for fluid absorption. Epithelial cells have microvilli and their transporters concentrate bile. Gallbladder has spiraled bundles of smooth muscle with interspersed CT forming a tunica muscularis. There is tunica serosa on the side of the gallbladder facing the world and a tunica adventitia on the side adhered to the liver.

Discuss gastric secretions (added by me)

Gastric Secretion 4 major components of gastric juice 1) Hydrochloric acid 2) Pepsinogen 3) Intrinsic Factor 4) Mucus Functions of hydrochloric acid in the stomach --> Proenzyme pepsinogen is converted to the enzyme pepsin at acidic pH --> Pepsin hydrolyzes proteins at acidic pH --> Denatures proteins to facilitate cleavage --> Kills microorganisms --> Degrades connective tissue and muscle into smaller pieces H+ ions that are secreted into the stomach lumen are formed inside the parietal cells in a reaction between CO2 and H2O (using carbonic anhydrase). CO2 comes from the capillary lumen and diffuses into parietal cells. There it combines with H2O to form H2CO3 which converts to HCO3- and H+. HCO3- goes into the interstitial fluid in exchange for Cl- into the parietal cell (then diffuses into gland lumen through channel). H+ is actively transported into the gland lumen in exchange for K+ into the parietal cell (H+-K+ antiporter = proton pump which is ATP dependent). H+ and Cl- combines to form HCl. Protein is a potent stimulant for HCl secretion into the stomach so after a high protein meal, the blood and urine pH will be elevated due to the alkaline tide.

Be able to identify the layers of the brachydont tooth in a histologic section

General Tooth Structure Crown: above the gum line Root" below the gum line Three (nonvascularized) layers --> Enamel: a very hard, highly mineralized tissue made of crystals or prisms of calcium phosphate (~96%, more mineralized than bone), no collagen, made by ameloblasts (tall columnar cells that sit on top of the enamel layer), produced before the tooth erupts and once the tooth erupts through the gums, the ameloblasts die, outer layer of crown only in brachydont (classic tooth) --> Dentin: middle layer made of hydroxyapatite and type I collagen arranged in channels (dentinal tubules), less mineralized and less brittle than enamel (~70% mineral), produced by odonoblasts that sit on border next to pulp and extend processes into tubules (sensitive tissue), produced throughout life and in response to damage, entire tooth --> Cementum: covers root, made by cementocytes, histologically resembles bone (~65% mineral w/ cells), layer b/w periodontal ligament and dentin, root only in brachydont Pulp Cavity: center of tooth and contains nerves and blood vessels Gingiva: nonkeratinized, stratified squamous, prominent rete pegs and connective tissue papillae, divided into the attached gingiva and the marginal (unattached or "free") gingiva, produces a space next to the tooth known as the gingival sulcus (formed by marginal gingiva) Periodontal Ligament: connects tooth to alveolar bone to hold tooth in socket, made of collagen fibers

Describe important aspects related to motility in the large intestine (mass movement and defecation)

Goals of contractions of the large intestine a) Mixing contents → expose contents to epithelial surfaces for absorption of water, ions, and nutrients b) Retention (esp. in species that derive energy from fermentation in the lg. intestine) --> goal is to not let contents pass through or be secreted c) Propulsion of contents → excretion All digestion in the L.I. is carried out by microbial enzymes, not secreted enzymes. These microbes are a critically important source of energy for simple-stomached herbivores (hindgut fermenters-- Rabbits (cecum) and Horses (colon)). Glands produce HCO3- and mucin. HCO3- neutralizes organic acids formed by fermentation. Mucin is protective to epithelial cells. The mucosal surface area << small intestine (no villi, enterocytes have no microvilli). The size of the large intestine is relatively larger in hindgut fermentation as this is where the animal's energy supply is. Rodents and horses digest most carbohydrates in the hindgut (cecum + colon) and this has critical importance to their energy supply. Therefore the cecum + colon are very large. Motility Types of contractions in the large intestine 1. Segmentation → function to mix contents of large intestine --> Most common type of contractions in the lg. intestine --> Cause the contents to move back and forth, supporting the absorptive and storage functions (Contraction of longitudinal teniae coli muscles + contraction of circular muscles bulges into sacs (haustra)) 2. Peristalsis -- move in cranial/caudal direction for propulsion 3. Antiperistalsis facilitate the long transit time in the large intestine (important for those fermenting in the LI to provide sufficient time for fermentation and absorption) --> Ruminants & rodents move contents from colon back to cecum --> Horses move contents from colon back to ventral colon **only well digested fluid-like contents make it into the dorsal colon through the pelvic flexure, antiperistalsis move contents backward if needs further digestion** 4. Mass movements → move contents over large distances; expel contents of cecum into colon, move colon contents into rectum Regulation of Contractions Interstitial cells of cajal (pacemakers) generate spontaneous slow waves of depolarization that spread via gap junctions to adjacent smooth muscle cells. They generate action potentials when stimulated by neurotransmitters or hormones (won't reach AP threshold w/o these). These cells have a much stronger external influence from the autonomic nervous system (i.e., long reflexes) than the stomach and small intestine --> Parasympathetic: ↑ motility, ↑ frequency & strength of contraction, relaxation of sphincters (internal anal sphincter) ---> Sympathetic: ↓ motility (why stress or pain see symptoms of decreased motility)

Understand basic liver functions with regard to: a. The role of the liver in handling waste ammonia from amino acid catabolism b. Metabolic Functions c. Transformation and inactivation of substances such as hormones, toxins, and drugs d. Immune surveillance e. Repair & regeneration following damage

Handling Waste Nitrogen The liver converts ammonia, a byproduct of protein catabolism, to urea, (Urea cycle) which is then excreted in the urine. NH4+ is highly neurotoxic, and accumulates in the absence of a fully-functional liver. The urea cycle can be summed up as: 2 NH3 molecules are combined with CO2 to form urea Metabolic Functions Carbohydrate Metabolism: *Glucose control* Generation of glucose from non-carbohydrate substrates via gluconeogenesis in response to dropping blood glucose levels. Stores glucose as glycogen Protein Metabolism: Synthesis of nonessential amino acids, modification of amino acids so they can enter the synthetic pathway for carbohydrates (gluconeogenesis), synthesis of the vast majority of plasma proteins Lipid Metabolism: Synthesis of cholesterol, lipoproteins, and phospholipids, production of bile acids Transformation and Inactivation Toxic substances absorbed from the G.I. tract enter the liver via portal circulation. This helps ensure that little of the toxic substance enters the circulation. Enzymes found inside the hepatocytes modify endogenous and exogenous toxins to make them more water-soluble so they are excreted in bile or urine: 1. Phase I reaction: conversion reaction catalyzed by enzymes (e.g. cytochrome P450 enzymes) found in hepatocyte endoplasmic reticulum 2. Phase II reaction: conjugation of substances with glucuronide, sulfate, amino acids, or glutathione to facilitate excretion Modification of oral drugs by the liver is referred to as "First Pass Metabolism" as they are inactivated/eliminated from the systemic circulation.

Compare and contrast the tissues of the hard and soft palate

Hard Palate --> Stratified squamous and a lamina propria on the oral cavity side --> Pseudostratified columnar (ciliated) with goblet cells on the nasal cavity side --> Bony plate separates the oral cavity from the nasal cavity --> Palatine salivary glands (minor in soft palate) --> Transverse ridges: rugae --> Rostral thickening of mucosa in ruminants called dental pad Soft Palate --> Extends caudally from hard palate --> Valve function: can be elevated to separate the nasopharynx from the oropharynx --> Nasal cavity (dorsal surface) covered by PSCC --> Oral cavity (ventral surface) covered by stratified squamous epithelium

Describe the unique vascular supply to the liver and the route of blood flow through the liver, and how disruption of blood flow will manifest histologically

Hilum is the entry site for blood supply and the exit point for bile ducts & lymphatics. The liver has a dual blood supply from the portal vein (75% - nutrient and hormone-rich, O2-poor) and the hepatic artery (25% - highly oxygenated blood). Hepatocytes are organized into lobules (hexagonal arrangement with 6 portal triads), each with a bed of sinusoidal capillaries. Branches from the portal vein & hepatic artery lead to sinusoids that run between the hepatic cords (one portal triad can supply multiple lobules). The vessels run in CT known as the portal canal. The arterial and venous blood mixes in sinusoids. Sinusoids are lined by a discontinuous and fenestrated endothelium to facilitate the transfer of large complex molecules from the circulation into the liver but don't allow the passage of RBCs. Blood is then collected by a central vein (found alone) and drains into sublobular veins, which are tributaries of the hepatic vein. The efferent venous blood leaves thru the vena cava. There are hepatic parenchymal zones based on blood supply that divide hepatocytes in a lobule Periportal zone (Zone 1): closest to portal triads --> receive first dibs on the O2 and blood supply --> these hepatocytes are specialized for oxidative liver functions (gluconeogenesis, beta-oxidation of FAs, cholesterol synthesis) Midzonal area (Zone 2): region in between Centrilobular zone (Zone 3): closest to the central vein --> most vulnerable to the decreased blood supply, hypoxia, and anemia as it is the last to get O2 --> calls are important for glycolysis, lipogenesis, cytochrome P-450-based drug/toxin detoxification ***Portosystemic shunt (PSS) is an abnormal connection between the portal vascular system and systemic circulation. Blood from the abdominal organs which should be drained by the portal vein into the liver is instead shunted to the systemic circulation. This may show liver atrophy b/c they are not getting the hormones and factors necessary for liver development. There will not be necrosis b/c O2 comes from the hepatic artery. Congenital shunts are most common in small breed dogs, such as pugs, schnauzers, Maltese, Shih Tzus, and especially Yorkshire terriers.

Understand basic liver functions with regard to: a. Immune surveillance b. Repair & regeneration following damage

Immune Surveillance Kupffer cells and endothelial cells in the liver are important to innate immunity: --> Kupffer cells phagocytize large particles (microbes, cancer cells, cell fragments, damaged erythrocytes) --> Endothelial cells take up soluble molecules by receptor-mediated endocytosis (Macromolecules from extracellular matrix and Immune complexes) Phagocytosis leads to production of cytokines and acute phase proteins. This means there is a role in immune cell recruitment & activation. Repair and Regeneration Liver damage may result in scar tissue formation (fibrosis) due to activated stellate cells. This scar tissue is not functional liver tissue. Activated stellate cells proliferate and produce extracellular matrix. The liver is the only visceral organ with the capacity for compensatory hyperplasia, The mechanism of liver regeneration: 1. Activation of numerous gene pathways in remaining healthy hepatocytes 2. Production of cytokines & growth factors 3. Hepatocyte proliferation **fine line b/w liver regeneration and scar tissue formation**

Describe how the vomiting reflex occurs, recognize different causes of vomiting and note some species differences with respect to vomiting

In some species, vomiting is a normal means of emptying the stomach of indigestible food remnants. This reflex is regulated by the vomiting center in the medulla. The sensory arm originates in the pharynx. It can also be initiated by gastric irritation or distension. The effector arm creates forceful contractions of the abdominal muscles to increase abdominal pressure and open lower esophageal sphincter, while closing the glottis and moving the larynx upward. Species which close the esophageal sphincter in response to these stimuli cannot vomit (e.g. horses).

Explain the general structure of the wall of the GI tract

Intestinal wall structure consistent throughout most of the G.I. tract (exception is in the oral cavity, esophagus, rectum and rumen) From lumen ⇢⇢ outward: 1. Mucosa (have folds and extensions to increase SA for absorption) --> Epithelial layer (single layer of columnar epithelial cells w/ tight junctions b/w adjacent cell membranes on the lumen (apical side) forming a continuous membrane) A) acts as a site for nutrient absorption and a barrier against the external environment (toxins ingested and keep bacteria in that are part of the digestive process) B) High turnover rate (every 2-3 days) contributes to their protective function (replaced before they sustain too much damage) C) Specialized functions as they produce digestive juices, mucus and hormones (stay in circulation or act in paracrine function) and are part of absorption --> Layer of connective tissue (thick) **lymphatics here pick up any bacteria that happen to penetrate the epithelial layer** --> Thin layer of smooth muscle (thin) 2. Submucosa --> Collagen & elastin (CT) --> Glands --> Blood vessels supplying intestinal wall --> contains submucosal plexus 3. Muscularis (important for peristalsis) --> Circular (inner) and longitudinal (outer) --> Intestinal motility --> contains myenteric plexus 4. Serosa: single layer of squamous epithelial cells and secrete fluid to provide lubrication for GI organs **outer layer of peritoneum**

Describe the mechanisms involved in and the location of the sites for the absorption/secretion of solutes

Jejunum Absorption Major site of Na+ absorption and nearly all dietary Na+ is absorbed. Homeostasis is then achieved via renal excretion of Na+. Absorption requires active transport mechanisms in the enterocyte. Na+-dependent coupled transporters (monosaccharides, amino acids) and Na+-H+ exchange on the apical surface. The source of H+ for the exchanger is from the reaction catalyzed by carbonic anhydrase. The HCO3- from this reaction is absorbed into capillaries. Ileum Absorption Same solute absorption mechanisms as the jejunum. There is also the additional HCO3-/Cl- exchanger in the apical membrane and Cl- channel in the basolateral membrane. This results in a net absorption of NaCl throughout the ileum and HCO3- to be secreted into the lumen. Colon Absorption The apical membrane contains aldosterone-sensitive Na+ (absorption) and K+ channels (secretion). These are the same as the ENaC in the kidney. Aldosterone promotes Na+ absorption (decreased BP results in aldosterone secretion from the adrenals causing Na+ reabsorption in the kidney and Na+ absorption from G.I. tract). Absorption of water and salt from the large intestine is vital in all species but has extra significance for herbivores that are "hindgut fermenters" (horses, rodents). These herbivores have a large expansion in the colon where they ferment and derive a lot of energy, this requires a lot of fluid. Secretion Solute and water secretion in the intestine are dependent on Cl- movement into the intestinal lumen. Secretion is more important in the small intestine. Cl- moves into the intestinal lumen through the apical membrane of the enterocyte and Na+ and water follow passively. Cl- channels open in response to the binding of various hormones and neurotransmitters on the basolateral membrane (Ach, VIP). The hormones bind and cause the production of cAMP which then opens the Cl- channels

Describe the sources, types and functions of the primary digestive enzymes

Luminal phase of chemical digestion - Enzymes acting in the lumen of the digestive tract from salivary glands, glands in the stomach, and pancreas Membranous phase of chemical digestion - Enzymes bound to the apical membrane of enterocytes in connection with absorption (brush border enzymes)

Describe the major anatomical structures of the digestive tract with emphasis on differences between species

Mammalian digestive tract anatomy: Digestive tract **food taken in, things are absorbed, waste is secreted** 1. Oral cavity 2. Pharynx 3. Esophagus 4. Fermentation chamber (ruminants only - breaking down carbohydrates from plants w/ enzymes that carnivores don't have) 5. Stomach (expandable in carnivores) 6. Small intestine --> Duodenum --> Jejunum --> Ileum 7. Large intestine --> Cecum --> Colon (ascending, transverse, descending) 8. Rectum Structures outside the digestive tract with secretory functions • Salivary glands • Pancreas • Liver & Gallbladder Most of the secretion occurs in the stomach and small intestine. These secretions are from glands outside the GI tract (salivary, pancreas, liver) and glands in the gastric mucosa and crypts of the small intestine. The primary location of absorption is the small intestine and some in the large intestine.

Understand basic liver functions with regard to: a. Metabolism of ingested lipids b. Excretion of bile pigments c. Protein Synthesis

Metabolism of ingested lipids Dietary lipids are insoluble in the aqueous environment of the intestinal lumen, so without emulsification, they would form "blobs" with little surface area available for digestion by lipases. The products of lipid digestion (monoglycerides, fatty acids) are also insoluble, so these need to be solubilized to be effectively absorbed into the circulation. In the lumen of the small intestine, bile salts emulsify lipids to prepare them for digestion, then solubilize the products of lipid digestion into packets called micelles. **Bile salts (amphipathic) are bile acids conjugated to glycine and taurine** Excretion of bile pigments Erythrocytes near the end of their lifespan become less flexible and are easily damaged passing through the vasculature: 1. Phagocytized by macrophages in the reticulo-endothelial system (RES; phagocytic cells in the lymphatics, bone marrow, liver, and spleen) 2. Hemoglobin is degraded, Fe2+ is recycled 3. Heme is converted in the macrophage to bilirubin (a pigment) **binds with albumin in blood to aid its transport** 4. Liver cells extract bilirubin from the blood, use UDG-glucuronyl transferase to conjugate it with glucuronic acid (= conjugated bilirubin), and secrete it into bile 5. Bile enters the small intestine, and bilirubin is converted to urobilinogen by intestinal bacteria 6. Urobilinogen is excreted in the urine Protein Synthesis --> Glutathione (GSH): Tripeptide, the most important cellular redox buffer, and defender against oxidative stress by scavenging reactive oxygen species; regulates apoptosis --> Albumin: Carrier protein, most abundant protein in plasma --> Clotting factors: All proteins involved in the clotting cascade are produced in the liver --> C-reactive protein: Acute phase protein which activates the complement system to initiate the immune response to dead/dying cells & some microbes --> Carrier proteins: Facilitate transfer of many hormones, vitamins, and minerals in the circulation --> Hormones and Prohormones: Angiotensinogen, IGF1, thrombopoietin --> Apolipoproteins: Amphipathic proteins that transport lipids in blood, CSF, and lymph

Discuss antibody transfer b/w mother and fetus/newborn

Most proteins are not absorbed intact as they would be recognized as foreign. A rare example of intestinal absorption of intact proteins is the passive transfer of maternal antibodies to neonates. Maternal-fetal transfer of antibodies occurs via the placental circulation in some species, but not all (oral absorption is critical for several species). Several unique features of neonatal G.I. tract allow passive transfer of antibodies through colostrum: 1. Membranes of intestinal epithelial cells are permeable to intact soluble proteins for ~24 hours after birth (close quickly after) 2. Production of HCl in the stomach is low for the first 1-2 days after birth, so protein-degrading pepsin is not produced (b/c pH is not low enough) 3. Pancreatic secretion of proteolytic enzymes is not fully developed in neonates 4. Colostrum contains substances that block the action of trypsin ****"Passive immunity" will last for first few months of life****

Describe the regulation of pancreatic secretion and the intestinal phase of pancreatic secretion

Pancreatic secretions are under long reflexes and hormonal control. There is no enteric or short reflexes. Cephalic & Gastric phase accounts for 20% of pancreatic secretion and are mediated via the vagal nerve. It produces mainly enzymatic secretion. Intestinal phase of pancreatic accounts for 80% of pancreatic secretion and produces both aqueous and enzymatic secretion. This involves hormonal and neural mechanisms. --> Acinar cells have receptors for CCK and Ach. The release of CCK by the I cells of the duodenal epithelium of acinar cells is stimulated by nutrients in the small intestinal lumen (AAs & small peptides, FAs) and stimulates the secretion of enzymes. Ach is released by vagal efferent nerve endings via vago-vagal reflexes. --> Ductal cells have receptors for CCK, Ach, and Secretin. The release of Secretin by the S cells of the duodenal epithelium is the major stimulant of HCO3- rich secretion. This is stimulated by acidic contents in the lumen of the small intestine. Pancreatic lipases are inactivated at low pH so the acidic gastric contents need to be neutralized by HCO3- for these lipases to be active. CCK and Ach potentiate the effects of secretin. ***Herbivores eat food and move it through the GI tract constantly so they need constant pancreatic secretion

Discuss rumen emptying and explain how differences in ruminant feed can affect it

Parasympathetic efferent nerves to the reticulo-omasal sphincter release VIP (vasoactive intestinal peptide) which relaxes the sphincter and promotes movement into the omasum. **Rate of emptying of the rumen is dependent of feed composition: 1) Finely ground feed & grain (fastest) 2) Hay and grass 3) Straw - high in lignin, a polymer that lies outside of plants giving them a tough external structure (slowest) Rumen osmolarity increases during fermentation which causes the volume to increase due to movement of water by osmosis.

Explain why digestive enzymes produced in the pancreas are inactive until they reach the duodenum and describe how these enzymes become activated

Proteolytic enzymes are released as inactive proenzymes (inactive protease = proenzyme). They are not activated until they reach the intestinal lumen. Trypsinogen and other proenzymes released into duodenum. Enteropeptidase released by duodenal epithelial cells and allows the conversion of trypsinogen to active trypsin. Trypsin then performs autocatalysis and activates other proenzymes so that they can breakdown nutrients. Active proteases would be dangerous to gland cells if they were secreted into the lumen of the duct in their active form. Pancreatic gland cells also produce trypsin inhibitor as a safeguard as it binds small amounts of active trypsin inside the gland.

Recognize that some messengers of the GI tract are also present in the brain and have roles in governing feelings of hunger and satiety

Regulation of appetite and food intake is controlled by the hypothalamus. Some of the regulating signals include degree of intestinal filling, concentration of energy-rich substances in the blood (glucose, AA's, VFA's), hormones released from GI tract and appearance/taste/smell of food. Ghrelin is released by gastric mucosa and is a pro-food hormone (increases feeding). Vagus nerves are from distension. Insulin is from pancreas. CCK is from the duodenum. Leptin is from adipose tissue. GLP-2 is from the small intestine.

Describe rumination and the physiological processes that comprise it

Regurgitation = transport of reticulorumen contents back to the oral cavity (occurs during rest periods b/w feeding) Rumination = movement of swallowed ingesta back to the oral cavity for additional chewing & mixing with saliva Reflexes involved in rumination are initiated by coarse feed fibers stimulating sensory nerve endings in the digestive tract 1. Extra reticular contraction replaces newly ingested food with partially-fermented ingesta 2. Inspiratory muscles contract to reduce intrathoracic pressure → reticular content gets "sucked" into the esophagus due to the pressure difference 3. Antiperistaltic contraction in the esophagus → moves bolus of ingesta into the oral cavity 4. Fluid fraction gets swallowed 5. Solid fraction gets chewed and mixed with more saliva

Describe the histologic features that distinguish the different compartments of the ruminant forestomach (i.e. reticulum, rumen, omasum, and abomasum)

Rumen The rumen papillae are like the villi in the intestine but larger. There is a mix of long and short papillae which increase the SA for absorption and make the mucosa appear as a plush carpet. The role of these papillae is to aid with fermentation (mechanical and chemical action facilitated by rumen bacteria and protozoa). The papillae have an outer keratinized stratified squamous epithelium, a lamina propria, and no muscularis mucosae. There is no muscle within the papillae. The rumen mucosa is made of the outermost epithelial layers for protection and deep layers for absorption of VFAs. There is no lamina muscularis mucosae so there is no official tunica submucosa. Reticulum The mucosal surface has interconnecting folds (creating a "honeycomb" appearance) for mechanical grinding and stratified squamous epithelium. The reticulum collects smaller digesta particles and moves them into the omasum (larger particles remain in the rumen for further digestion). It also traps and collects heavy/dense objects the animal consumes. The Interconnecting folds are called the reticular crests, which create reticular cells. Primary crests create the walls of the reticular cells, secondary crests subdivide the cells and the floor is made of reticular papillae. There is no lamina muscularis mucosae except at the tips of the primary crests (which comes from a continuation of the esophageal muscularis mucosae). This muscle at the tip allows for a "squeezing" action of the tops of the primary crests of the "reticular cells" for grinding. Omasum The lumen is filled with numerous interdigitating, folds called the laminae which allow for the squeezing out of the liquid so small particles can move to the abomasum. The contents are pressed into interlaminar recesses and ground by omasal papillae. The laminae are super long while the papillae are like little knubs (w/ a fair amount of ground substance and elastin) and both are covered with stratified squamous epithelium. This also means there is additional surface area for absorption of water & VFAs. The laminae have 3 layers of smooth muscle. There are two outer layers, which are extensions of muscularis mucosae, and one inner layer, which is an extension of muscularis external (tunica muscularis). Abomasum Histology is similar to other glandular stomachs (ie fundus of dog). Abomasal glands contain chief cells and parietal cells.

Compare and contrast microbial or fermentative digestion with glandular or constitutive digestion

Rumen microbes are essential for ruminants to turn feed into energy Fermentation = microbial degradation in the absence of oxygen --> Oxygen in the rumen would cause nutrients to be degraded all the way to CO2 and water BUT instead metabolites that the ruminant can use for energy or building blocks are generated --> Small # of microbes are facultative anaerobes meaning they use up what little O2 is in the rumen --> Most of the microbes are obligatory anaerobes Rumen bacteria is classified based on the nutrients they metabolize 1. Primary rumen bacteria: break down nutrients found in feed Amylotic --> Metabolize starch and soluble carbohydrates --> Unable to break down cellulose --> Tolerant of acidic conditions (more amylotic activity means ↑ ↑ VFA produced causing the pH to drop) Cellulotic --> Degrade carbohydrates that are part of plant cell walls (e.g., cellulose, hemicellulose, pectins) & linked by b-glycosidic bonds --> Bind to plant fibers and have extracellular enzymes that start the breakdown process --> Slow process, pH sensitive (slows down at low pH - greatly reduced at pH < 6) Proteolytic 2. Secondary rumen bacteria: break down products produced by the primary bacteria Rumen protozoa (ciliates) and fungi Protozoa --> Obligate anaerobes --> Thrive on small feed particles & starch --> Deposit glucose as glycogen in the cytoplasm → helps curb production of VFAs when starch intake is high Fungi --> Important for digestion of plant fibers, hyphae help to break apart lignin → increases the surface area available for cellulotic attack (which then breaks down cellulose) --> Fungal biomass is highest in animals fed high-lignin feed (e.g. straw) --> Reproduction process is slow (sporulation), so they adhere to food particles with a long retention time in the rumen

Describe the basic anatomy of the ruminant stomach

Ruminant forestomachs contain 4-chambered enlargement of the G.I. tract after the esophagus (camelids have 3 and other differences) 1. Rumen: (largest) --> The cranial sac shares a large opening with the reticulum 2. Reticulum: --> Ingesta moves back and forth between the rumen and reticulum ("reticulorumen" - takes up a very large portion of animal) --> Reticulum tends to collect inedible objects for removal --> Muscular walls help mechanically process grasses --> Empties into the omasum through the reticuloomasal orifice 3. Omasum: --> Muscular, leaf-like wall projections into lumen help "filter" ingesta and squeeze out liquid --> Additional mechanical processing of grass (leaves are covered with papillae) 4. Abomasum: --> Analogous to the "true stomach" of a monogastric so it looks very similar to them **Epithelium does not produce digestive enzymes, but microbial enzymes cause extensive anaerobic degradation of organic nutrients (carbohydrates, lipids, & proteins). This fermentation is time-consuming, so long retention time is necessary (total time depends on diet). Postnatal Development Considerations A) Reticulorumen and omasum are not useful until grass consumption begins B) Abomasum is well developed at birth, but reticulorumen and omasum are bypassed and smaller before grass consumption --> Abrasive effect of forage stimulates the development --> Milk passes directly from the esophagus into the abomasum due to reflex closure of the reticular groove & omasal canal (continuations of the esophagus) --- Reflex stimulated by suckling & chemoreceptors in the oral cavity and pharynx then integrated in the medulla and mediated by vagal nerve, the reflex is lost after weaning

Describe the neural regulation of salivary secretion

Salivary secretion is entirely under neural control (unlike other digestive secretions). Both SNS and PNS stimulation induce salivary secretion. --> SNS stimulation → small volume, highly viscous --> PNS stimulation → high volume, watery consistency **dominates during meals as it is involved in reflexes caused by food in the mouth** There are two types of reflexes influencing the rate of salivary secretion. 1) Unconditional (inborn): Afferent arm in the G.I. tract (oral cavity, etc.) --> Integrated in the salivary center of the medulla --> Efferent arm = SNS and PNS nerve fibers to salivary glands (SNS= small contribution to salivary production through the release of NE which binds to adrenergic receptors to increase production, PNS= predominant secretion during meals through the release of ACh that binds to muscarinic receptors) 2) Conditioned (acquired): Afferent arm = sensory stimuli that are not associated with salivation until they are repeatedly combined with feeding --> Initiated in the cerebral cortex --> Activates the salivary center of the medulla

Describe the functions of the major GI hormones (secretin, gastrin, GIP and CCK) of the digestive tract

Short and long reflexes and the composition of lumen contents stimulate the release of hormones for hormonal regulation. Classical hormones are released by cells in the wall of the GI tract and then travel to their target cells (in another region of the GI tract) via the bloodstream. These secretory cells look similar to one another but secrete distinct hormones. They do not form glands but are simply groups of cells. Their secretion then travels into portal circulation to the liver which brings them into the systemic circulation and then to the target cell. Neurohormones are released from nerve endings into a synapse with their target cell. --> ACh (released from cholinergic neurons) will cause contraction of smooth muscle in wall, relaxation of sphincters and increase salivary, gastric and pancreatic secretion --> NE (released from adrenergic neurons) will cause relaxation of smooth muscle in wall, contraction of sphincters and increase salivary secretion (meaning both PNS and SNS do this) --> Vasoactive intestinal peptide (VIP - released by enteric nervous system) will cause relaxation of smooth muscle (anti-motility) and increase intestinal and pancreatic secretion --> NO (released by enteric nervous system) will cause relaxation of smooth muscle of sphincters (pro-digestion) --> Gastrin-releasing peptide (GRP) or bombesin (released by vagal neurons of gastric mucosa) will cause increased gastrin secretion Paracrine hormones are also involved in hormonal regulation and reach their target cell through local diffusion in the interstitium.

Discuss the contribution of signals leading to gastric emptying

Stomach Signals to Stimulate Gastric Emptying (increase contractility) 1. Expansion of the stomach after a meal (activate mechanoreceptors) • Short reflexes • Long reflexes via the Vagus N. ** both cause Ach release and gastric muscle contraction ** 2. Gastrin secreted by the endocrine epithelial cells (G cells) of the pylorus (sensed by chemoreceptors, functions through classic endocrine mechanism) • Stimulates gastric contraction and pyloric sphincter relaxation Duodenum Signals to Slow Gastric Emptying (inhibit contractions) 1. High-fat content in the duodenum causes the release of CCK which acts in an endocrine fashion --> Absorption begins in the duodenum so needs more time with fat to absorb everything it needs to --> Strongest signal for hormonal inhibition of gastric emptying 2. Low pH contents in duodenum result in short reflexes --> Receptors in duodenal mucosa detect high H+ conc --> Enzymes in the small intestine do not function at low pH (could not degrade ingested nutrients if a large volume of acidic gastric contents passed into the duodenum at once before it could be neutralized by alkaline small intestinal secretions) 3. Mechanoreceptors: distension of the duodenum → short & long reflexes --> Efferent arm = sympathetic fibers inhibit smooth muscle contraction, vagal fibers release NO (inhibitory for sm. musc. Contraction) 4. Chemoreceptors: elevated osmolarity and increased concentration of peptides in the duodenum

Describe taste buds. Describe the structure b/w the different types of gustatory lingual papillae and be able to ID them (and their taste buds) in a histologic section

Taste Buds ---> Found in fungiform, vallate, and foliate papillae• --> Three cell types !) Sensory cells 2) Sustentacular cells (supportive) 3) Basal (stem) cells - regenerate other cells every 10 days --> Saliva carries molecules through taste pore to sensory cells --> Changes in ion flow or a secondary messenger cascade causes release of neurotransmitters that stimulates afferent neuron (Sweet, salty, bitter, sour, umanmi) --> Info sent through cranial nerves VII, IX, & X Gustatory Papillae Fungiform --> Small number on apex and body of tongue --> Project above surface with its mushroom shaped (smooth with a rounded surface). --> Nonkeratinized epithelium (don't want to block taste bud), core of connective tissue --> Taste buds on surface but sparse --> Taste molecules carried by saliva in oral cavity --> No associated gustatory glands Vallate (circumvallate) --> Body and root of tongue --> Large, flat topped, level with surface (slightly sunken down), surrounded by a deep sulcus (filled w/ saliva) --> Nonkeratinized epithelium --> Taste buds in the side of the papillae --> Associated with Gustatory (serous = watery, pink color) salivary glands that fill the sulcus **each vallate has its own glands** Foliate --> Parallel folds on lateral margin of tongue covered by nonkeratinized epithelium --> Taste buds on the sides facing the "gustatory furrows" --> Gustatory glands in connective tissue, fill the furrows --> Absent in ruminants

Discuss the three phases of regulation

The 3 phases of the regulation of digestive processes refer to where the regulatory signals originate (not a sequence of events). 1. Cephalic phase --> Processes which occur in anticipation of food (results in pro-digestion processes) --> Occur via long reflexes Excitatory signals → via vagus nerve Inhibitory signals → via sympathetic efferent fibers (fight or flight situation) 2. Gastric phase --> Initiated by stomach distension --> Occurs via short and long reflexes --> Gastrin secretion occurs during this phase 3. Intestinal phase --> Initiated by intestinal volume (distension) and composition (concentration of carbs : protein : fat) (mainly duodenum) --> Secretions from pancreas and gall bladder occur during this phase

Describe the mechanisms involved in and the location of the sites for the absorption of Fe and Ca

The G.I. tract contains a large amount of fluid and electrolytes and absorption of these from the G.I. tract is a critical homeostatic mechanism. The fluid source in the G.I. tract is from dietary intake and secretions. The intestinal mucosa is freely permeable to water and it moves across an osmotic gradient following the transport of solutes. The fluid absorbed is always isosmotic (absorption of solute and water in proportion). S.I. absorbs ~ 90% of the water it receives and the L.I. absorbs ~90% of the water it receives. Water and electrolytes move across via the transcellular or paracellular route. Some tight junctions are "leaky" (small intestine) so more paracellular while some tight junctions are "tight" (colon) so transcellular. Iron The bioavailability of oral iron varies according to the form and the source. Iron ingested as part of a heme molecule has excellent bioavailability (found in hemoglobin and myoglobin). Non-heme iron is less bioavailable due to factors that interfere with absorption (phosphates & oxalates for insoluble salts with Fe2+). Vitamin C increases the absorption of iron as it reduces Fe3+ to Fe2+ which is more easily absorbed. Heme iron is digested by lysosomal enzymes inside the enterocyte and free Fe2+ is released. Free iron binds to ferritin (intracellular storage form of iron). It won't be stored here long as it will be lost when the enterocytes turn over. Iron can be transported across the basolateral membrane via ferroportin and absorbed into capillaries. It is then bound to transferrin in capillaries and transported to storage sites. Low plasma iron content results in this absorption while high plasma iron does not see iron absorption as the transferrin is saturated. Calcium Intracellular Ca2+ concentrations must remain very low to ensure proper intracellular signaling mechanisms. it is absorbed from the intestinal lumen via paracellular (through TJs) and transcellular routes. The transcellular route involves the transfer of Ca2+ across the apical membrane through channels and across the basolateral membrane via Ca2+-ATPase pump & Ca2+/Na+ exchanger. Regulatory mechanism --> Increased Ca2+ absorption in the presence of the biologically active form of Vitamin D (1,25 dihydroxycholecalciferol) as it Increases calcium-binding protein and increases # of calcium channels and pumps in the basolateral membrane

Describe the basics of GI histology

The GI tract follows the basic histology of tubular organs. If the tunica submucosa is present then the lamina muscularis mucosae will be present. the lamina propria is often loose CT (not always) and the lamina muscularis mucosae can have multiple layers. G.I. Tract has an intrinsic nervous system made of two distinct plexuses (enteric nervous system) --> Submucosal (FYI: Meissner) - within submucosa (cluster of cell bodies with processes being sent out) --> Myenteric (FYI: Auerbach) - between smooth muscle layers The organs are distinguished by the type of epithelium in the Tunica Mucosa. The thickness of muscularis mucosae varies as well. The intestine has the least histologic variation across the different species while the stomach has the most variation. All of the organs within the body cavity have tunica serosa as the body wants to ensure they don't stick together. The esophagus has tunica adventitia cranially where it is embedded in CT and does not want to be moving around. Once the esophagus is in the thorax, it has tunica serosa so it does not get stuck to other organs.

Describe the ultrastructure of bile canaliculus, hepatic sinusoid, and the space of Disse

The Space of Disse is found b/w hepatocytes and sinusoids. This space creates bi-directional, free movement b/w the liver and capillaries. It contains blood plasma (no cells) and microvilli of hepatocytes that extend into this space. Proteins and other plasma components from the sinusoids are absorbed by the hepatocytes while plasma that collects in the space of Disse flows back toward the portal tracts, collecting in lymphatic vessels. The space also contains stellate cells (a.k.a. Ito cells) found under endothelium. They secrete cytokines (inflammatory mediators) important in the normal maintenance, growth, & repair of the liver. These are the main cell type involved in the production of extracellular matrix components of the space of Disse and activation of stellate cells can lead to fibrosis. With continuing fibrosis, the liver is subdivided into nodules of proliferating hepatocytes surrounded by scar tissue. Their major function when quiescent is Vitamin A storage and storage of other lipid-soluble vitamins. They can also play a role in angiogenesis and stem cell proliferation. The hepatic sinusoid is made of endothelial cells with open fenestrations seen in the cell cytoplasm. You can find Kupffer cells in the sinusoidal capillaries. These are resident liver macrophages responsible for phagocytosis of bacteria & particulate matter as well as degrading bacterial endotoxin. They also aid in removing damaged RBCs. Some kupffer cells contain iron from phagocytized RBCs & lipofuscin/ceroid from lipid metabolism. Kupffer cells secrete cytokines that can activate stellate cells, they have an antigen-presenting function, and are involved in tumor cell surveillance. The bile canaliculi are found along the lateral side of hepatocytes. Hepatocytes absorb bilirubin from the blood, conjugate, and secrete into bile canaliculi• Canaliculi (C) are minute spaces between apposed hepatocytes formed by tight junctions. Canaliculi transport bile out of the hepatic cords and from canaliculi bile flows to bile ductules. Note that the direction of bile flow is opposite that of the blood flow. Bile ductules are lined by a low, simple cuboidal epithelium (cholangiocytes = name for the epithelial cells). Ductules connect to the interlobular bile ducts of the portal tracks and they are lined by simple cuboidal to columnar epithelium. Interlobular bile ducts connect to the larger hepatic ducts which coalesce to form the common bile duct.

Compare the compartments of the camelid stomach to those of the ruminant stomach

The camelid forestomach has three chambers. C1 & C2 - mix of glandular and nonglandular areas --> C1 is larger but they are very similar --> Nonglandular: keratinized stratified squamous epithelium --> Glandular: has saccules containing tubular mucous glands --> Glands may be involved in fluid & bicarbonate secretion (also make mucus) C3 --> Proximal 2/3: somewhat analogous to ruminant omasum - longitudinal pleats (grinding, squeezing, fluid out) --> Distal 1/3: similar to ruminant abomasum (Glandular Stomach)

Describe the basic anatomy of the avian GI system and be able to recognize the proventriculus and ventriculum, and their components, in a histologic section.

The crop is an aglandular caudal diverticulum situated 2/3 of the way down the esophagus. It is lined by a stratified squamous nonkeratinized epithelium and stores food. The stomach of avians is made of the proventriculus and the ventriculus (gizzard). --> Proventriculus (Glandular stomach) is a cylindrical organ located b/w the crop and the gizzard. It produces and secretes both HCl and pepsinogen (both made by cuboidal oxynticopeptic cells). The proventriculus (submucosal) glands are grouped into lobules, each with a central lumen (duct). The tubular glands in each lobule share a common opening into a papilla with a central duct. The mucosal surface has plicae (folds) much like villi and is lined by columnar mucous cells (the core of the fold is lamina propria). This organ has lamina muscularis and tunica submucosa. The tunica muscularis has 3 layers of smooth muscle. The outside is lined by tunica serosa. --> Ventriculus (Gizzard) is a grinding organ used to macerate ingesta after it is softened by chemical digestion in the proventriculus. It is best developed in seed-eating birds which eat rough food. It is made of two asymmetrical thick masses of muscle that insert on tendinous surfaces. There is no muscularis mucosae. Some birds swallow grit/ stones that act as "teeth" in the gizzard. The mucosal surface has cuticle composed of koilin (polysaccharide-protein complex, hardened by HCl). Koilin is a secretory product of mucosal glands and is NOT keratin. This works together with the grit to grind seed. Koilin solidifies and wears unevenly (b/w soft koilin [pink] and hard rodlets [bluer]) forming sharp points. It is replenished as it is worn down.**Cuticle thicker in birds on seed, grain, or insect diet** Ventricular glands are simple columnar epithelium. The muscular wall is made of smooth muscle and has thick and thin muscle.

Describe important aspects of motility with regard to the oropharynx/esophagus (prehension, mastication, swallowing)

The digestive process starts in the oral cavity (stratified squamous w/ keratinization in some places). The oral cavity has sensory neurons w/ receptors detecting touch, pain, temp and taste. The oral cavity is involved in the mechanical processing of food (breaking it down into smaller pieces), lubricating food with saliva (to facilitate passage into the esophagus), and initiating the swallowing reflex. Within the oral cavity, animals chew their food for three reasons. This mixes food with saliva to lubricate it, reduces the particle size to facilitate swallowing & provides a larger surface area for digestive enzymes to work on, and mixes carbohydrates w/ salivary amylase to begin the digestive process. **The muscles of mastication (striated) are one of the few muscles in the GI system under voluntary control (the other is the external anal sphincter). They are also controlled by reflexes through mechanoreceptors in the oral cavity that are integrated in the brainstem.** The swallowing reflex is stimulated through pressure against the pharynx. • Sensory receptors → located in the walls of the pharynx • Afferent arm → vagus and glossopharyngeal nerves • Integration → medullary swallowing center • Efferent arm → motor nerves to the striated muscles of the pharynx and upper esophagus (20-30 muscles involved in swallowing) There are three phases of swallowing. 1. Oral: voluntarily moving food back toward the pharynx (ie tongue moves the food bolus back into mouth toward the oropharynx) 2. Pharyngeal: food goes from the oral cavity, through the pharynx, into the esophagus --> Soft palate moves into position to block the nasopharynx --> Esophageal sphincter relaxes to open the esophagus --> Epiglottis moves to block the trachea 3. Esophageal• --> Reflex closure of upper esophageal sphincter once food bolus has passed (avoid refluxing) --> Primary peristaltic wave moves food down the esophagus (starts as striated muscle then transitions to smooth muscle [proportions vary by species]) --> Starts at the pharynx and moves all the way down the esophagus --> Secondary peristaltic wave occurs if there is continued distension --> Starts at the site of distension (mediated by local reflexes of the enteric nervous system only, responding to distension) and moves downward in order to clear the esophagus of any food left behind from the primary wave

Describe the functional roles of microvilli and crypts in the small intestine and crypts in the large intestine.

The enterocytes of the GI epithelium are the "workhorse" site of fluid and electrolyte transport. The small and large intestines are lined with simple columnar epithelium ("enterocytes"). There is functional variation throughout the G.I. tract.. Enterocytes are constantly being renewed as stem cells found in crypts & migrate upward as they differentiate. **Absorption takes place in the villi and secretion takes place in the crypts** The crypts also contain Paneth cells (secrete antimicrobial peptides), goblet cells (secrete mucus), and then enteroendocrine cells.

Describe the two components of pancreatic exocrine secretion, their cells of origin, and their functions

The exocrine pancreas comprises ~90-98% of the pancreatic mass. Its secretion contains HCO3- and enzymes. The secretions are always isotonic but ion compositions can change. There are 2 functions of pancreatic secretions --> HCO3- neutralizes H+ delivered to the duodenum from the stomach --> Enzymes digest carbohydrates, proteins, and lipids to absorbable molecules Pancreatic secretions enter the duodenum through the pancreatic duct, close to the bile duct. Innervated by sympathetic and parasympathetic nerves, which synapse directly on the exocrine pancreas --> Sympathetic → inhibits pancreatic secretion --> Parasympathetic → stimulates pancreatic secretion Pancreatic exocrine glands are organized into acini, similar to salivary glands. The enzymes and aqueous components are secreted separately --> Aqueous component by centroacinar (transition b/w acinar and ductal cells) and ductal cells --> Enzymes secreted by acinar cells (sac-like part) Functions of pancreatic juice 1) High concentration of HCO3-, alkaline pH → prevents injury to duodenal mucosa by acidic gastric contents & provides optimal pH for pancreatic enzymes 2) Enzymes degrade all digestible molecules • Carnivores & omnivores → pancreatic enzymes digest food nutrients almost completely

Explain the major functions of the gastrointestinal (GI) tract

The function of the GI tract is digestion!! Macromolecules in food cannot be directly absorbed from the G.I. tract so they must be degraded into monomers to be absorbed. Once absorbed, they are synthesized back into macromolecules to be used as an energy source. This process of breakdown and resynthesis is so that it avoids the immune system from recognizing the ingested proteins as foreign. There are 4 main processes of digestion (not necessarily sequentially) 1. Mechanical processing Chewing → increase surface area of particles available for enzymatic degradation **the chewing muscles and the external anal sphincter are the only muscles under voluntary control in the GI tract, the rest are passive** Alternating contraction/relaxation of stomach & small intestine → mix content to enhance the efficiency of enzymatic degradation 2. Secretion of enzyme-containing digestive juices: Produced by epithelial cells in the gastric & intestinal mucosa and glands/organs outside the digestive tract (the composition and pH are adapted to the enzymes present) --> this includes the production of endocrine factors that will also be secreted somewhere else in the GI tract --> Goblet cells in epithelial cells also produce mucus to protect intestinal epithelial cells from injury and lubricate the intestinal contents --> Water, ions, and proteins are secreted and then absorbed and recirculated 3. Enzymatic breakdown of organic nutrients: enzymes catalyze the breakdown of polymers (carbohydrates, lipids and proteins) into monomers by hydrolysis --> happens in a step-wise function where different regions of GI tract secrete different enzymes to keep breaking it down further and further 4. Absorption --> Small molecules (monomers), water, ions, and vitamins are transported from the digestive tract lumen to the blood or lymph capillaries --> Nutrients cross the epithelial cells of the intestinal mucosa by active transport and diffusion

Describe the organization of the small intestine

The function of the small intestine is for digestion, absorption, and the transport of ingesta to the cecum and colon. There is not much species variation. The gastro-duodenal junction can be identified from the change from flat-topped gastric mucosa and pyloric glands to duodenal mucosa with "shaggy villi and crypts. The layers include --> Villus are only in the small intestine (not in the large) and vary between intestine locations (Tallest in the jejunum) --> Crypt is similar to gastric pits and are present in the small and large intestine, cells appear denser b/c there is not as much cytoplasm ** Villi and crypts have microvilli which increase the SA for absorption and goblet cells for protection --> Muscularis mucosae --> Tunica submucosa with plexus (submucosal) and submucosal glands (in duodenum +/- jejunum, species variation in secretion [usually mucus and HCO3-], protect mucosa + neutralize HCl) --> Tunica muscularis with plexus (myenteric) b/w muscle layers --> Tunica serosa The jejunum and ileum contain peyer's patches (GALT) which is usually secondary as we are looking at adult patients. There are also mucosal cells that secrete digestive enzymes to split disaccharides (lactase, maltase and sucrase) into glucose. The cell types of the intestine include --> Enterocytes - Absorption & secretion of enzymes, water, electrolytes --> Goblet cells --> Paneth cells - Innate immunity (make defensins, lysozyme, and tumor necrosis factor) of the mucosal surface at the base of crypts, brightly eosinophilic granules --> Enteroendocrine cells - Paracrine & endocrine function, more than 20 peptide hormones --> Stem Cells - in the crypt to replicate and replace the cells at the tip of the microvilli (experience normal wear and tear)

Describe the organization of the cecum and colon

The functions include absorption of water, vitamins and electrolytes and the secretion of mucus. These look the same in all species. --> Contain crypts --> Straight tubular glands (Crypts of Liberkühn) --> No Villi (flat top) --> Abundant goblet cells for lubrication of ingesta --> Prominent diffuse lymphoid tissue

Describe the difference b/w the oral and pharyngeal mucosa from integument, including specializations present at the transition at the mucocutaneous zone

The functions of the oral cavity are prehension (Lips, teeth, limbs, tongue), reception (oral cavity is the "food holder" - Buccinator muscles of cheeks keep food between teeth), insalivation (enzymatic breakdown of food, moistening aids swallowing), mastication (voluntary or reflex (rumination), breaking down food into small pieces, mixing with saliva - the result is a soft, moist bolus of macerated food), and deglutition (swallowing, coordinated voluntary movements of lips, cheeks, tongue to move bolus into the pharynx and esophagus, root of tongue pushes epiglottis over larynx to prevent entrance into the trachea). Lip --> Mucocutaneous junction: transition from the skin (haired) to mucous membrane (non-haired) with numerous interdigitations --> Mucus membrane has stratified squamous (somewhat keratinized in ruminants & equids) and a lamina propria (dense CT & minor salivary glands) ***no submucosa*** --> Skeletal muscle within the lip as prehension requires voluntary control (skeletal muscle is in the cheek as well) --> Similar mucosal histology is found: Lip, buccal mucosa, tongue (ventral surface), hard & soft palate, pharynx --> sheep, goats, and horses have soft flexible lips to help pick up food while the lips of cattle and pigs are stiff and do little more than close the mouth

Describe the basic histologic structure of the gastric glands, the functional differences between cardiac, fundic, and pyloric glands, as well as the structure and function of the various gastric epithelial cells

The glands differ but they all start with surface mucous cells, gastric pits lined by mucous-neck cells, and an isthmus. It is only the deeper glands that vary. --> Cardiac glands -- Band in cardiac region surrounding opening of esophagus, short glands with wide lumen, simple cuboidal epithelium, protects esophagus against gastric reflux and overall protection through mucus production and bicarb buffering --> Pyloric glands -- Localized to pyloric region, not much difference to cardiac glands, short coiled glands; deeper gastric pits, simple cuboidal epithelium, overall protection through mucus production and bicarb buffering --> Fundic glands -- Present in fundus & body, base of the neck divides into 2-3 long coiled tubular glands, simple cuboidal epithelium with two colors (Pink Parietal cells (HCl) and blue Chief cells (pepsinogen)) ~ Mucus cells - surface & neck region; lesser numbers in gland ~ Parietal cells (large, pink, triangular) - HCl secretion; pH <1.0 - 2.0; neck and deeper regions of fundic glands, apex faces lumen, round nuclei (often binucleated), lots of cytoplasm ~ Chief cells - Apical zymogen granules contain pepsinogen and other enzymes, deeper regions of the fundic glands, abundant rough ER give the cytoplasm a blue colr ~ Enteroendocrine Cells - Gastrin, histamine, somatostatin all levels, but especially near base of glands ~ Stem cells in isthmus

Discuss basic regulation and neural regulation basics of the GI system

The goal of regulation is to obtain complete absorption of ingested organic nutrients and restore homeostasis via negative feedback mechanisms. The G.I. functions are coordinated by neural regulation and hormonal regulation. The relative importance of different regulator mechanisms varies throughout the digestive tract. For example, salivary secretion is almost exclusively through ANS, The stomach has a good mix of ANS, hormones, and local reflexes. The pancreas is ANS and hormones. The small intestine is mostly local reflexes with some ANS. The large intestine is mostly PNS with some local reflexes. Neural reflex regulation is responsible for motility and secretion. There are sensors (for osmoloairty, pH, chemical contents, mechanical for distention of food) in the walls of the intestinal tracts. The effectors are then the smooth muscle cells, secretory epithelial cells and endocrine cells which produce either muscle contraction or secretion. Innervation to the GI tract is through the autonomic nervous system (extrinsic) and through the enteric nervous system (intrinsic) made of the myenteric and submucosal plexuses. Parasympathetic fibers are carried via the vagus nerve to the upper GI tract or the pelvic nerve to the lower GI tract. They have long preganglionic fibers that synapse (release ACh) in the myenteric or submucosal plexus. PNS tends to be stimulatory with increased secretion and motility resulting. The sympathetic postganglionic fibers originate in the celiac, sup. mesenteric, inf. mesenteric and hypogastric ganglia. They then go to the plexuses or directly to smooth muscle, secretory cells or endocrine cells (release Norepi). SNS tends to be inhibitory with decreased secretion and motility (except in the sphincters that contract). Neurons of the intrinsic system synapse with each other, smooth muscle and glandular cells or with the autonomic nervous system.

Recognize liver and the structures of the hepatic lobule in a histologic section

The liver is surrounded by a hepatic capsule (Glisson's Capsule) made of an underlying dense irregular CT layer containing small blood vessels, nerves and lymphatics. The CT of Glisson's capsule invaginates at the hilum of the liver but does not really divided the liver into lobules. The outside layer of the capsule is made of mesothelial cells. Dense irregular CT forms portal tracts/portal canals which encase small-caliber branches of the hepatic artery and portal vein, bile ducts, nerves, and lymph channels. This group of structures is called portal triads. --> Portal vein: thin wall, wide lumen with just endothelium --> Hepatic artery: a thin layer of smooth muscle and lining of endothelium --> Bile duct: simple cuboidal epithelium The rest of the liver has reticular CT found throughout most of it. Hepatocytes make up 80% of the cells and is arranged in hepatic cords or plates separated by sinusoidal capillaries. They are large polyhedral cells, with round euchromatic centrally located nuclei (frequently polyploidy (>1 nucleus)). They are the chief functional cells of the liver and have metabolic, endocrine, and secretory functions. They are active in the synthesis of protein and lipids for export. There is bountiful quantities of both rough (RER) and smooth (SER) endoplasmic reticulum (for detox). EM will show many stacks of Golgi membranes, especially near bile canaliculi. Hepatocytes also store lipid droplets (LD) and synthesize very low density lipoproteins (abnormal accumulation of lipid can be triggered by metabolic disease [diabetes mellitus] or as a consequence of anorexia in cats or ferrets). Glycogen (polymer of glucose) can be stored in hepatocytes and more can be seen after a meal or with metabolic disease (e.g. Cushings disease). The surface of hepatocytes is specialized depending on their orientation. --> Apical: Microvillous surface faces the perisinusoidal space --> Lateral: Contact surfaces between hepatocytes with tight junctions and desmosomes so cells are tightly adhered (form surfaces that border bile canaliculi b/w cells)

Describe the basic architecture of the hepatic acinus and the anatomy of the liver circulatory system

The liver receives 75% of its blood supply from the hepatic portal vein (deoxygenated blood that contains everything absorbed in the GI tract such as nutrients and toxins). The other 25% of blood comes from the hepatic artery because the liver still needs some oxygenated blood. These two blood supplies mix in the liver sinusoids (liver capillary bed) and all the blood from the liver drains into the caudal vena cava. The sinusoid capillaries have incomplete walls of their endothelial cells which then provide direct contact between the hepatocytes and the blood. This also means that large molecules (like proteins) can easily move between the blood and the hepatocytes. The hepatic acinus is the functional unit of the liver. Within it, there is the portal triad made of the arteriole of the hepatic artery, the venule of the portal vein and the bile duct. The arteriole and venule mix in the sinusoid capillaries (mix of oxygenated and deoxygenated blood) and these capillaries all drain into the central vein. Within the hepatic acinus are --> Kupffer cells: derived from macrophages and play an important role in innate immunity (immuno-surveillance in the liver, "clean-up" cells) --> Stellate cells ("Perisinusoidal cells"): pericytes that store vitamin A in its quiescent state and produce extracellular matrix when activated by liver damage (role in liver regeneration and fibrosis).

Explain the functions of saliva

The lubrication of food protects epithelial cells as it allows food to slide over the epithelial cells without damaging them. There needs to be an antibacterial effect as food is not initial sterile and brings in bacteria with it. Tannins are a protection mechanism of plants so the saliva will bind them to reduce that protective ability so that the food is more digestible.

Describe the structure and function of pancreatic exocrine and endocrine tissue

The pancreas has a septae of fine, dense-ish irregular and loose CT which divide the pancreatic parenchyma into lobules. Endocrine islets of Langerhans are pale patches scattered throughout the exocrine tissue (most of the pancreas is exocrine). The acinar cells of the exocrine pancreas have a deeply basophilic basal region (where the making of protein and hormones occurs) and an eosinophilic apical area (distinct, big, and easy-to-see pink zymogen granules that contain inactive precursor forms of digestive enzymes). The acinar cell in EM has condensing vacuoles in the Golgi region and mature secretory granules at the cell apex. These protein-dense vesicles (zymogen granules) contain inactive digestive enzymes which will be exocytosed into the intercalated ducts. The first portion of the duct system extends into the center of the acinus, which is lined by small centroacinar cells (unique to the pancreas). Their nuclei are visible in the lumen of the acinus while the nuclei of the secretory cells are basilar. Acinus centroacinar cell duct (simple squamous) continues as intercalated duct (low cuboidal). Intercalated ducts then connect to the intralobular duct which then connects to the interlobular duct. *****missing the striated duct found only in the salivary gland duct system*****

Describe the fundamental architecture of salivary glands and be able to identify the different types of secretory units (serous, mucous and mixed seromucous) and the different types of ducts in a histologic section

The secretory product of salivary glands is saliva (People: 1 L / day, Sheep: 6- 10 L/day, Cattle: 100 - 200 L/day) There can be serous (pink, granular), mucus (pale w/ nuclei pushed to the side, no granules) and mixed (serous-mucous) secretions (serous demilune w/ serous on outside and mucus on the inside is an artifact of standard fixation). Myoepithelial cells are the functional cells of the salivary gland that wrap around the acinar cells. They are modified epithelial cells beneath the luminal cells that can contract and expel the secretions of exocrine glands. Major salivary glands are those that can be identified surgically as distinct areas of tissue in specific locations. These include the parotid, zygomatic, mandibular, and sublingual salivary glands. These glands see the active secretion of Na+ & Cl- (water follows), amylase (starch digestion in cows, horses, and rodents), lingual lipase (lipid breakdown in some species), mucus (protection & lubrication) and antimicrobial substances. Minor salivary glands are scattered throughout the oral cavity and are located in the lamina propria. they are not grossly visible and are named by their location. --> Labial glands - Lips --> Lingual glands - Tongue --> Gustatory glands - with Foliate & Vallate papillae (all are serous) --> Buccal glands - Buccal mucosa (cheeks) --> Palatine glands - Hard & Soft palate --> Pharyngeal Salivary Gland Ducts --> Acinus: berry-like --> Intercalated ducts: the first part of the duct system, simple squamous to low cuboidal cells, small (nothing but a straw-like structure) --> Striated ducts: largest structure within lobule, unique to major salivary glands, infoldings of the cell membrane (striation appearance) in the basal region with numerous mitochondria between infoldings, metabolically active ducts as it modifies saliva ([HCO3] secretion, reabsorption of Na+ & Cl- (concentrate saliva), kallikrein (protease) secretion and IgA secretion) --> Intralobular duct: slightly larger but less impressive (not as much cytoplasm), within lobule, taller cuboidal cells, passive conducting duct --> Interlobular duct: larger duct w/ more of a wall, between lobules, simple cuboidal to stratified cuboidal (sometimes) **Ranula: a term that means a cyst under the tongue; block or rupture of sublingual salivary gland duct not the gland

Describe the functions and the basic anatomy of the stomach

The stomach is a location of secretions but no absorption occurs here. There is also some enzymatic degradation of starch (salivary amylase moving with it from the oral cavity) and protein (proteolytic enzyme pepsin produced and released in the stomach). The stomach provides a temporary storage location for ingested food (once mixed with stomach secretions and converted to a semi-liquid mixture, referred to as chyme). The stomach's storage capacity maximizes the digestion of each meal, which is particularly important in animals that consume energy-dense meals that take a long time to completely digest (carnivores). It also passes partially-processed ingesta into the intestines at a rate that optimizes digestion. The stomach plays a role in the mechanical processing of ingesta. The coordination of peristaltic contractions and pyloric sphincter closure facilitates the mixing of stomach contents to churn food inside the stomach (when the sphincter opens, only a little bit leaves and the rest undergoes retropulsion). HCl secreted into the stomach helps kill bacteria ingested with food and has a role in food breakdown. The parietal cells in the gastric mucosa also secrete intrinsic factor, a glycoprotein that is required for the absorption of vitamin B12. Vitamin B12 is not absorbed until the ileum, but the Intrinsic factor binds to it in the stomach and "carries" it to the ileum (considered an essential component of gastric secretion). The stomach is divided into glandular and non-glandular portions. The esophageal (non-glandular portion of the stomach) is lined with stratified squamous epithelium which is why it's also called squamous mucosa. There are no secretions produced here and it is visible to the naked eye (looks bright shiny white). This part is usually a pretty small proportion but is particularly large in horses (likely for storage) and rats. All parts of the glandular stomach are lined with simple columnar epithelium. All the important secretions of the stomach occur here. In the pig, the largest part is the cardia (right after the esophageal part) and is likely for storage. In dogs and humans, the storage part is most likely the fundus and corpus. The distal corpus and transition into the pylorus is a mixing chamber for ingested food and stomach secretions. The final part of the stomach is the pylorus which has the thickest muscle layers (the stomach is made of 3 layers of smooth muscle: outer longitudinal, middle circular, and inner oblique). The gastric mucosa on the inside of the stomach is slimy and shiny as it serves as protection. **Carnivores have a large, distensible stomach (thin muscular wall b/c need to be able to expand). The hindgut fermenter herbivores have a proportionally smaller stomach than the rest of the GI tract (ie cecum).

Discuss the two neural reflexes in GI regulation

The two types of neural reflexes are the long and short reflexes. Most of the time the stimuli is in the wall of the GI tract but there are cases where it comes from outside the GI tract (sight/smell of food). Short reflex arc: Adjust to local conditions, while being modulated by the ANS --> Stretch/volume (mechanoreceptors) or Composition (chemoreceptors) --> Can involve different segments of the G.I. tract (E.g., sensory cells in the upper G.I. tract affecting secretion and motility in the lower G.I. tract = "entero-enteric reflexes") --> do not induce CNS output as signals travel through interneurons and remain in the wall of the GI tract --> Most effector arms are stimulatory/excitatory (pro-digestion) and use Ach as a neurotransmitter --> Some effector neurons release inhibitory neurotransmitters, e.g. NO, to relax muscles (sphincters) Long reflex arc: Central nervous system influences digestive functions --> Afferent (sensory) arm usually originates in the G.I. tract, but they can also originate from sensations associated with food (smell, taste, sight, sound) --> Most of the effect is mediated through the enteric motor nerve fibers --> Sympathetic efferent fibers also reduce the blood supply to the G.I. tract (e.g., during exercise) **Most neurons in the enteric nervous system secrete more than one chemical.

Describe the general anatomy of the salivary glands, the structure of the salivon, and the composition of saliva.

There are 3 large paired sets of salivary glands. 1. Parotid (50% of total salivary volume, serous) 2. Sublingual (mixed serous & mucous) 3. Mandibular (mixed serous & mucous) There are also other smaller salivary glands such as the various buccal glands in different species (viscous, mucus-rich saliva). All of these glands empty into the oral cavity through ducts (parotid duct) in order to mix with the food for lubrication. Saliva is 98% water and the remainder is ions and organic compounds. The structure of a salivary gland resembles a "bunch of grapes". The acinus plus the collecting duct is called the salivon, the functioning unit of the salivary gland. The acinar cells secrete the initial saliva (aka primary secretion) which is comprised of water, ions, enzymes, and mucus. This initial saliva is an isotonic plasma-like solution as it has the same osmolarity and the same concentration of Na+, K+, Cl-, and HCO3- as plasma. Ions are transported from the extracellular fluid by active transport and then water follows by osmosis. The ductal cells modify the initial saliva by altering the electrolyte concentrations. Na+ and Cl- are absorbed back into the blood while K+ and HCO3- are secreted into the saliva. This creates a net absorption of Na+ and Cl- but the ductal cells are water impermeable so the saliva becomes hypotonic. There will also be some alpha-amylase and lingual lipase within the saliva. **Ruminants are the exception as their saliva is always isosmotic due to increased HCO3- and phosphate secretion into saliva** Finally, the myoepithelial cells contract with neural input to eject the saliva. The flow rate has an effect on the saliva composition. Saliva composition is dependent on the contact time with ductal cells. If there is more contact time, more solute reabsorption will occur (water stays in ducts due to impermeability). Less contact time with ductal cells means less time to modify the solute concentration of saliva. So... --> Rate of saliva production is LOW → saliva has lower osmolarity than blood --> Rate of saliva production in acini is HIGH → flows through ducts so quickly that osmolarity is the same as blood

Discuss the gallbladder

There are three functions of the gall bladder. --> Stores bile → hepatocytes continuously produce bile --> Concentrates bile → epithelial cells of the gallbladder absorb water & ions --> Ejection of bile → contracts in response to CCK release There are also many species differences with the gallbladder. Species with continuous digestion have bile flowing into the small intestine continuously so they don't need a bile-concentrating mechanism. --> Horses and rats - no gallbladder (secrete bile into small intestine continuously) --> Ruminants - Gallbladder has a short retention time (usually pretty empty)

Describe the organization of the glandular (monogastric) stomach

This type of stomach is present in dogs, cats, part of the horse and the abomasum of ruminants. The functions include storage, chemical & enzymatic digestion, grinding of ingesta and delivery of ingesta to intestine. The transition from the esophagus to stomach can be seen from the change from stratified squamous to simple columnar. There is a flat surface in the stomach covered by "surface mucous cells" (simple columnar epithelium and mucus-producing). The flat surface has downward invaginations called gastric pits which continue into gastric glands in lamina propria. These gastric pits contain specialized secretory cells doing the enzymatic work of the stomach. --> Mucous neck cells line gastric pits [Mucin (glycoprotein), HCO3-] make a thick, slimy layer traps bicarb & protects against acid --> Isthmus (neck), at base of pit, contains stem cells (replace glandular cells above and mucus-producing cells below) --> The base of the neck (isthmus) divides into 2-3 coiled tubular glands The stomach contains stomach rugae (gastric folds) at the level of the submucosa and does not include the muscular layer. This provides stretch to the stomach. The subglandular layer of carnivores are between the base of the glands and the lamina muscularis. It contains the stratum granulosum (inner layer containing many fibroblasts) and the stratum compactum (an outer dense sheet of collagen fibers so no nuclei). **The non-glandular stomach has no glands and stratified squamous epithelium** In the horse, the margo plicatus is the distinct border b/w the glandular and non-glandular stomach.

Describe the tongue. Describe the structure b/w the different types of mechanical lingual papillae and be able to ID them (and their taste buds) in a histologic section

Tongue --> highly muscular organ used to manipulate food in the mouth and is important for sense of taste --> intrinsic muscles of the tongue are arranged in 3 perpendicularly oriented planes which helps with prehension and swallowing (skeletal muscle) --> covered with stratified squamous epithelium (dorsal surface: keratinized vs ventral surface: nonkeratinized) --> Dorsal epithelium forms specialized structures: lingual papillae (mechanical vs gustatory function) --> Species variation in types, numbers, and distribution of papillae Mechanical Papillae (for holding onto food) Filiform: dorsal apex of tongue --> sharply pointed caudally to help push food backwards to esophagus (manipulation of food) --> highly keratinized and come in pairs (one tall, one short) --> Cats have a particularly large, heavily keratinized filiform papillae called their grooming patch (helps them pull meat off the bone) --> Cow and Horse have a velvet like tongue b/c they have tiny filiform papilale Conical: caudal 1/3 of dorsal tongue (dogs, cats, pigs, ruminants) -- none in horses --> Large, project above other papillae --> Thick, keratinized epithelium (cone shaped) --> No taste buds --> Ruminants have conical papillae on the inside of their cheeks as well (buccal papillae). Lenticular (only in ruminants) --> flattened, lentil-shaped papillae found on the torus linguae of ruminants (swelling across tongue that pushes food against hard palate) --> Covered by stratified squamous epithelium with core of dense irregular connective tissue --> very keratinized

Describe important aspects related to motility in the small intestine (segmentation and peristalsis)

Two types of small intestinal contractions: 1. Mixing (segmentation contractions of circular smooth muscle) --> Mix the intestinal contents with digestive enzymes and pancreatic secretions (continue food breakdown) --> Ensure that the luminal content comes in contact with the apical membrane of mucosal epithelial cells (where digestion and absorption occur) 2. Propulsion of contents (peristalsis) --> Stimulated by expansion of the intestine due to entry of chyme (reflex process in response to chyme in intestine) --> Contraction of the circular muscle "behind" the stimulated segment, relaxation of the circular muscle "in front of" the stimulated segment -- receptive relaxation Step 1 - Expansion of intestine stimulates release of serotonin (5-HT) from ECL cells of small intestinal mucosal epithelium → binds to afferent neurons of the intrinsic nervous system Step 2 - Excitatory neurotransmitters are released "behind" the expanded segment (e.g. Ach) to contract it Step 3 - Inhibitory neurotransmitters are released "in front of" the expanded segment (e.g., VIP & NO) to relax it **Local reflexes play a prominent role in small intestinal motility, but ANS still has some effect** --> Slow wave oscillations in membrane potential of pacemaker cells (cells of Cajal) -- neural/hormonal influence on pacemaker cells needed to reach AP frequency and AP frequency depends on the degree of input ( ⇢ and therefore contractile strength) --> PNS via the Vagus N. = increased contractile strength from ACh causing more intracellular Ca2+ --> SNS via postganglionic fibers from celiac & cranial mesenteric ganglia = decreased contractile strength -- anything causing widespread SNS activation will affect GI motility (pain, stress) Carnivores and omnivores: --> When digestive processes are occurring, mixing contractions predominate & peristaltic contractions are weak --> Slow movement of small intestinal contents allows time for chemical digestion & absorption b/c an energy-rich diet --> During the "interdigestive state", when most of the nutrients have been absorbed from the small intestine, there is a pattern of electrical activity (migrating motility complex = electrical oscillations b/w cells) which clears the intestine of residual, often indigestible, substances (housekeeping function) **Pyloric sphincter remains open during MMC contractions to allow for some removal through vomiting** Ruminants and simple-stomached herbivores: --> No distinction between the digestive and interdigestive periods --> Stomach and small intestine are never truly empty

Explain the difference b/w osmotic (malabsorptive) and secretory diarrhea and discuss disorders that may lead to each

Types of diarrhea 1. Decreased surface area for absorption --> inflammation in G.I. tract causes damage to epithelium so there is less SA for H2O and solute absorption, this means fluid builds up in the lumen 2. Osmotic (presence of nonabsorbable solutes causes osmotic retention of water in G.I. tract)_ --> lactase deficiency means there is no breakdown of polysaccharides into monosaccharides so they cannot be absorbed 3. Secretory (e.g. cholera, enteropathogenic E. coli → many enterotoxins of clinical significance in animals ) --> Cholera toxin stimulates adenylyl cyclase causing excess fluid secretion which overwhelms the absorptive mechanisms and causes secretory diarrhea Diarrhea causes an increased speed of flow of intestinal contents (from increased fluid) which influences the resulting electrolyte disturbances. --> Flow-dependent K+ channels open, resulting in more K+ loss into the G.I. tract -- hypokalemia --> Inadequate time for HCO3- absorption, resulting in loss of HCO3- in the feces -- metabolic acidosis --> Inadequate time for Cl- secretion resulting in high levels of Cl in the blood -- hyperchloremic --> Treatment should include oral rehydration with glucose and electrolytes, as Na+-glucose cotransport will stimulate intestinal reabsorption of fluid

Define the basic motility patterns of the ruminant stomach (mixing, rumination and erucation)

What is the purpose of rumen contractions? 1. Mix reticulorumen contents in a circular fashion before moving to omasum (mixing or "primary" contractions) 2. Enable regurgitation of rumen contents back to the mouth as part of the rumination process (rumination contractions) 3. Enable removal of fermentation gasses by eructation back-up esophagus (eructation or "secondary" contractions) ~ 1-2 coordinated rumen contractions per minute, move caudally in a peristaltic wave Contraction Sequence 1. 1st reticulum contraction empties most into the cranial sac of the rumen 2. 2nd reticulum contraction finishes the emptying to the cranial sac of the rumen (there is a brief opening of reticulo-omasal sphincter for a small volume of fluid, well-fermented content to move into the omasum) 3. Reticulum relaxes and dorsal rumen contraction begins (starts cranially, spreads causally) --> Atrium contents move into the reticulum 4. Ventral rumen contraction begins 5. Secondary mixing contraction begins → initiates eructation at dorsal caudal sac and pushes content toward the esophagus **Factors influencing rumen contractility: --> Hypocalcemia (decreased strength & frequency of contractions) --> Reflex control of reticulorumen contractions (Short (well-developed enteric nervous system) and Long (mediated by the vagus nerve, vago-vagal reflexes, integrated in the medulla)) --> Sensory receptors (Stretch/mechanoreceptors [increased motility through vago-vagal reflexes] and Chemoreceptors in the rumen epithelium [decreased motility in response to elevated concentration of VFA's which need more time for absorption, pH < 5]) --> Reflex decrease in motility (Distension of abomasum, external factors influencing the autonomic nervous system [stress, pain], fever) Eructation Similar sequence to rumination, but initiated by secondary rumen contraction 1. Contraction of the rumen wall 2. Contraction of the respiratory muscles (dropping intrathoracic pressure so the esophagus can expand) 3. Antiperistaltic contraction of the esophagus