PGY Exam 5 Review

alimentary canal

alimentary canal

30 ft long tube (mouth to anus)

five specialized sub-sections of the GI tract:

pharynx, esophagus, stomach, small intestine, large intestine

GI accessory glands

parotid salivary glands, sublingual salivary gland, submandibular salivary gland, liver, gallbladder, (exocrine) pancreas

primary function of the digestive system

transfer ingested nutrients, electrolytes, and water from the external environment into the body’s internal environment

digestion

chemical and mechanical breakdown of foods into small units to facilitate absorption

absorption

passive or active transfer of substances from the lumen of the GI tract to the circulatory system

secretion

release of substances (hydrochloric acid, bile, digestive enzymes) into the lumen of the GI tract to facilitate digestion

motility

mixing of luminal contents and movement of material along the GI tract by muscle contraction

structure of the GI tract wall

1. Mucosa: layer of luminal epithelial cells → connective tissue (lamina propria) → muscularis mucosa

2. Submucosa: connective tissue containing blood/lymphatic vessels and the submucosal plexus

3. Muscularis Externa: circular and longitudinal smooth muscle and the myenteric plexus

4. Serosa: connective tissue

total area of the luminal surface of the small intestine is increased by….

1. circular folds of the mucosa and submucosa

2. villi: projections of the mucosa into the lumen

3. microvilli: projections of the luminal membrane of the epithelial cells covering the villi (“brush-border”)

outer epithelial cell layer of each villus includes….

1. goblet cells that secrete

2. enteroendocrine cells that secrete hormones involved in the regulation of GI function

the interior of the villus contains

1. a capillary system…. takes up most of the materials absorbed from the lumen of the GI tract

2. a single blind-ended lymphatic vessel (lacteal) which is essential for fat absorption

3. immune cells…Peyers patches

venous drainage from the GI tract initially passes through the liver via the

hepatic portal vein

• allows absorbed material to potentially be processed by the liver prior to release into the general circulation

digestive actions of the stomach reduce ingested material to a solution called….

chyme

function of the salivary glands

1. secretes a hypotonic, alkaline fluid containing:

2. mucus, which lubricates the ingested material and facilitates swallowing

3. enzymes including alpha-amylase (ptyalin) and lingual lipase to initiate carbohydrate and lipid digestion

4. lysozyme, lactoferrin, and binding globulin for IgA….antibacterial action

function of the exocrine pancreas

1. secretes enzymes into the small intestine that digest fats, proteins, and nucleic acids

2. secretes bicarbonate into the small intestine to neutralize the acidic chyme coming from the stomach

function of the liver

1. secretes bile consisting of bicarbonate, cholesterol, phospholipids, and bile salts (required for fat digestion)

2. bile is stored in the gallbladder, concentrated between meals and injected into the duodenum via the common bile duct

input vs output in the GI tract (solids)

On average, we ingest up to 800 grams of solid material per day, but…

1. of this approximately 50 grams is excreted, thus 90-95% is absorbed (primarily by the small intestine)

input versus output in the GI tract (liquids)

on average, we ingest approximately 1200 mL of fluid per day but

1. an additional 7000 mL of fluid is added to the GI tract via salivary, gastric, liver, pancreatic, and intestinal secretions

2. of this 8.2 L total. 99% is absorbed

3. almost all salts in the secreted fluids are absorbed

GI tract epithelial cells consist of

1. a luminal membrane

2. basolateral membrane

   1. transcellular: through the cell across two membranes (luminal and basolateral)

   2. paracellular: between cells (across tight junctions by simple diffusion)

3. the (primary) transcellular route requires transport proteins on both membranes

carbohydratess are ingested primarily as…..

polysaccharides (starch) and disaccharides (sucrose and maltose)

only monosaccharides can be absorbed across the….

small intestine

what breaks down starch into maltose and glucose

salivary and pancreatic amylase

maltose are subsequently broken down to monosaccharides by ____ located on the luminal membrane of small intestine epithelial cells

enzymes

digestion and absorption of carbohydrates

1. Fructose: enters the cell across the luminal membrane by facilitated diffusion via a GLUT transporter

2. Glucose/Galactose: enter the cell via a Na+-glucose co-transporter

3. Most ingested carbohydrates are digested and absorbed within the first 20% of the small intestine

digestion and absorption of proteins

• typical US diet contains 60-90 grams of protein per day

  • Only di- and tripeptides and amino acids can be absorbed by the small intestine

stomach pepsin

initially breaks down proteins to peptide fragments

pancreatic proteases (trypsin and chymotrypsin)

further break down fragments to tri- and dipeptides in the small intestine

peptide fragments can be absorbed directly or can be….

digested to free amino-acids by pancreatic carboxypeptidases or one of twenty aminopeptidases located on the luminal membrane of small intestine epithelial cells

how to tri-dipeptides enter the cell?

across the luminal membrane via a H+-peptide co-transporter

• metabolized to amino acids within the cell

how do amino acids enter the cell?

via a Na+-amino acid specific co-transporter

how do tri-dipeptides exit the cell?

across the basolateral membrane via amino acid transporter

how do amino acids exit the cell?

across the basolateral membrane via an amino-acid transporter

how do proteins enter the cell?

small amounts of protein can be absorbed via luminal endocytosis and basolateral exocytosis

triglycerides must be digested to promote absorption, this occurs primarily….

in the small intestine via pancreatic lipase

emulsification

large lipid droplets are divided into smaller droplets, thus increasing digestion rate

emulsification is due to:

1. mechanical disruption of droplets caused by motility of the lower stomach and small intestine

2. amphipathic emulsifying agents including ingested phospholipids and liver bile salts

problem: emulsifying agent coating could impair lipase accessibility to the lipid

solution: the pancreas secretes colipase which attaches to the droplet and binds lipase

how do monoglycerides and fatty acids cross the intestinal cell luminal membrane

diffusion

bile salts promote the formation of….

micelles (which contain released monoglyceride and fatty acid)

smooth endoplasmic reticulum

location within the cell where MG and FA are resynthesized into TG

vesicles containing the TG exit the cell across the basolateral membrane via…

exocytosis

chylomicrons

extracellular fat droplets (pass into the lacteals and ultimately the circulation)

what vitamins are fat-soluble

A, D, E, K

absorption of fat-soluble vitamins

essentially identical to that of fat

absorption of water-soluble vitamins

diffusion or mediated transport

vitamin B12

due to size/charge B12 must bind to intrinsic factor (secreted by stomach parietal cells)

vitamin b12/intrinsic factor complex

binds to receptors in the lower ileum (absorbed by endocytosis)

pernicious anemia

loss of intrinsic factor

heme

(derived from meat) important source of dietary iron

how is heme absorbed

across the luminal membrane of the small intestine by endocytosis → digested by lysosomal enzymes → released iron complexes with apoferritin to form ferritin within the epithelial cells

free lumen iron…

complexes with transferrin (secreted by the enterocytes) → binds to luminal receptors and is endocytosed → some iron is released across basolateral membrane; some binds to apoferritin to increase plasma iron concentration

decreased transferrin receptor expression

decreased iron uptake

increased ferritin transcription

decreased iron release, decreased plasma iron concentration

hematochromatosis

excess plasma iron

calcium absorption is dependent on….

Ca2+-binding protein (CaBP)

digestion and absorption of calcium

1. luminal content Ca2+ binds to a membrane CaBP and is transported intracellularly

2. intracellular CaBP's sequester released Ca2+ to prevent a rise in cytosolic Ca2+

3. Ca2+ transported across the basolateral membrane by Ca2+-ATPase and by Na+-Ca2+ exchanger

4. 1,25 (OH2) vitamin D stimulates absorption (likely by an increase CaBP expression)

Where is most of the ingested (and secreted) water absorped

small intestine

why are membranes of epithelial cells very water permeable

aquaporins (H2O channels)

digestion and absorption of water

1. primary → basolateral transporter os solute (Na+) creates osmotic gradient for

2. water movement both transcellulary and paracellularly

enteric nervous system

located within the GI tract and consists of:

1. myenteric plexus (smooth muscle activity)

2. submucosal plexus (exocrine gland secretory activity)

two types of neural reflex arc exist…

1. short reflex: change in luminal status is detected by receptors, triggers afferent signal, carried exclusively by enteric nervous system to either muscle or exocrine gland

2. long reflex: afferent signal is transmitted via enteric nervous system to central nervous system where it is processed and an efferent signal then returns to an effector in the GI tract

four primary GI hormones (all peptides)

1. secretin

2. cholecystokinin (CCK)

3. gastrin

4. glucose-dependent insulinotropic peptide (GIP)

cephalic phase of GI control

sight, smell, taste, chewing of food triggers primarily vagal parasympathetic efferents which, via the GI nerve plexus, affect secretory/contractile activity

gastric phase of GI control

reflexes triggered by stomach distension, acidity, amino acid and peptide content; mediated by short and long neural reflex responses and hormonally by gastrin

intestinal phase of GI control

reflexes triggered by small intestine distension, acidity, osmolarity, and solute content; mediated by short and long neural reflex responses and hormonally via secretin, CCK, and GIP

two primary regions of the stomach:

1. body

2. antrum

lower esophageal sphincter

controls input from the esophagus

pyloric phincter

controls transfer of chyme to the small intestine

the epithelial layer of the stomach invaginates into the mucosa to form tubular glands; secretions include….

1. mucus (and bicarbonate) from cells at the opening of the glands

2. HCl (and intrinsic factor) from parietal cells

3. pepsinogen from chief cells

4. histamine (paracrine) from enterochromaffin-like (ECL) cells

5. gastrin from antral enteroendocrine G-cells

6. somatostatin (endocrine) from D cells

parietal cells

possess luminal invaginations (canaliculi) which increases total surface area

HCl is primarily generated in the ____ of the stomach

body

how is HCl generated

intracellularly from CO2-H2O interaction

• reaction catalyzed by carbonic anhydrase

carbonic anhydrase catalyzed reaction

1. hydrogen generated is actively secreted into the lumen by H+-K+-ATPase

2. bicarbonate generated is transported across the basolateral membrane into the bloodstream via bicarbonate/chloride exchanger

3. chloride that enters the cell on this exchanger is secreted into the lumen via a chloride selective channel

regulation of HCl secretion by the parietal cells

1. acid secretion is increased by insertion of more H-K-ATPase units into the luminal membrane. vesicles containing ATPase units translocated from the cytosol and fuse with the luminal membrane

2. four factors regulate this insertion (and thus H+ secretory capacity)

   • three stimulate: acetylcholine, gastrin, histamine

   • one inhibits: somatostatin

3. histamine potentiates the response to acetylcholine and to gastrin

cephalic parasympathetic activity leads to:

1. acetylcholine release from the enteric nervous system

2. gastrin and histamine secretion

gastric phase stimuli (distension, peptides)…

1. vagovagal reflex: sensory nerve endings in the stomach wall detect stretch/distension

   • long/short neural reflexes increase vagal efferent activity → acetylcholine, gastrin, histamine → increase HCl

2. luminal contents can directly stimulate gastrin release (G cells)

neural, endocrine, and paracrine factors that regulate HCl secretion

1. neural: direct stimulation of the parietal cell

2. hormonal: gastrin release from G cells

   1. parasympathetic efferent fibers (note: release unique neurotransmitter gastrin releasing peptide (GRP))

   2. stomach contents

3. paracrine: histamine release from ECL cells

   1. parasympathetic efferent nerve activity

   2. gastrin

luminal HCl also regulates HCl secretion…

1. increase HCl secretion=inhibits gastrin secretion

2. increase HCl secretion=stimulates somatostatin

   1. directly inhibits HCl secretion by parietal cells

   2. inhibits the release of gastrin and histamine

intestinal phase regulation of acid secretion

1. digestive activity of enzymes and bile salts in the small intestine is reduced by acidic solutions

2. high acidity in the duodenum reflexly inhibits gastric acid secretion

   1. via short and long neural reflexes

   2. via the intestinal hormones secretin and CCK…enterogastrones

regulation of pepsin secretion

1. pepsin secreted by chief cells as an inactive precursor, pepsinogen (zymogen)

2. acidity of the stomach lumen initiates autocatalysis (pepsinogen → pepsin) & then released pepsin can then cleave additional pepsinogen as well as cleave ingested proteins

3. pepsin is optimally active at low pH, passage through to the small intestine results in inactivation since secreted bicarbonate neutralizes the chyme pH

4. most of the factors that regulate HCl secretion elicit parallel effects on pepsin secretion

what is the functional unit of the salivary duct system?

salivon

four primary elements of the salivon

1. terminal (blind-ended) acinus: epithelial cells secrete the initial saliva

2. myoepithelial cells: surround the acinar cells, contractile

3. intercalated duct: channels saliva to striated duct

4. striated duct: bidirectional ion transport that modifies the composition of the saliva

   1. chloride exchanged for bicarbonate, sodium exchanged for potassium

saliva composition is _______ dependent

flow-rate

at essentially all flow rates, when compared to plasma composition…

1. salivary bicarbonate and potassium levels are higher

2. salivary sodium and calcium are lower

both parasympathetic and sympathetic fibers innervate the salivary glands….

1. unique in that both stimulate salivary secretion (parasympathetic to a much greater extent)

2. xerostomia: absence of saliva

the exocrine portion of the pancreas seretes:

1. bicarbonate: to neutralize the acidic chyme coming from the stomach

2. digestive enzymes: to breakdown proteins, fats, carbohydrates, and nucleic acids

   1. secreted into the pancreatic duct, joins the common bile, enters the duodenum

bicarbonate synthesis and secretion:

1. generated intracellularly from CO2 and H2O, catalyzed by carbonic anhydrase

2. crosses the lumenal membrane via a chloride-bicarbonate exchanger

3. chloride ions recycle to the lumen via cystic fibrosis transmembrane regulator (CFTR)

4. hydrogen ions are transported across the basolateral membrane via Na-H exchanger, interacts with bicarbonate produced by stomach parietal cells

5. sodium transported into the lumen paracellularly, driven by lumen-negative potential due to CFTR-dependents chloride transport across the basolateral membrane

6. accumulation of sodium and chloride in the lumen creates osmotic gradient for paracellular flux of water

what substrate does trypsin, chymotrypsin, and elastase work on

proteins

what is the action of trypsin, chymotrypsin, or elastase on proteins

break peptide bonds in proteins to form peptide fragments

what substrate does carboxypeptidase work on

proteins

what does carboxypeptidase do to proteins

splits off terminal amino acid from carboxyl end of proteins

what substrate does lipase act on

fats

what does lipase do to fats

splits off two fatty acids from triglycerides, forming free fatty acids and monoglycerides

what substrate does amylase act on

polysaccharides

what does amylase do to polysaccharides

splits polysaccharides into glucose and maltose

all proteolytic enzymes are secreted as:

inactive zymogens (prevents autolysis of producing cells)

what cleaves trypsinogen to trypsin

enterokinase