Final (Rachael's Contribution) Flashcards

Question

Intestinal Crypts

Answer 1

* Where cell division occurs * Some stem cells in the basement of the crypt * Travel up as they age * Cells in the crypt are secretory * Cells on villus are absorptive * Die at the villus * Whole epilthelium is renewed every 4-5 days.

Answer 2

* Release by salivary glands and pancreas * **Brush Border Enzyme** * Undigestable Carb: Fiber * Hold water, creates bulk, helps motility in the large GI * Poly and disaccharides need to be converted to monosaccharides for absorption * Start in **oral cavity** * Polysaccharide: acted on by salivary amylase * **Stomach** * salivary amylase inactivated by low pH * **Small intestine** * pancreatic amylase, break things down to be small polysaccharides * brush border enzymes break down to monosaccharide (sucrase, lactase, etc.)

Answer 3

* Lactose maldigestion, lactose ends up in large intestine * Large intestine: * Lactose digested by bacteria * Cause gas * More solute in large intestine (holds water and generates diarrhea) * Lots of symptoms, call lactose intolerance

Answer 4

* Co-transport coupled to Na+ * Absorption of monnosaccharide and amino acids

Answer 5

* Pepsin just in stomach * Works best at stomach pH * Good at taking apart collagen * Turns proteins into peptides

Answer 6

* trypsin, chymotrypsin, carboxypeptidase (pancreatic) and brush border enzymes * Pepsin inactivated (above pH 5) * Enzymes from pancreas * Digest down to very small peptides * Brush border enzymes * Down to the amino acid

Answer 7

* Co-transport coupled to Na+ * Co-transport may be couple with a specific amino acid

Answer 8

* Mechanism for passive immunity in infants * **Transcytosis** * To absorb intact polypeptides * Endocytosis at apical surface to bring in protein * Travel to basolateral membrane and exocytose * Ig-A secreted into breast milk and then absorbed by the infant via transcytosis * Also how antigens travel into the MALT

Answer 9

* Inactive enzyme precursor * Ex: Chief cell makes pepsinogen * Pepsinogen + Acid → change confirmation and open active site * Then cleaves pepsinogen to make pepsin * Activation of pancreatic zymogens * Gall stone * Enzymes get inappropriately activated in pancreas. * Results in inflammation of pancreas called pancreatitis

Answer 10

* Main fat is TAG * When fat digested, TAG goes to monoglyceride and 2 FA * Via lipase, this enzyme is water soluable * Fat want to associate with itself * Need to break up fat droplet into many little products * **Emulsification **

Answer 11

* Bile salts, phospholipids * Keeps fat from associating * Bile salt are made from cholesterol in the liver * Amphipathic molecules coat the small emulsion droplets

Answer 12

* ******Lipase** * Lipase bound to emulsion droplets via amphipathic protein called **co-lipase** * Co-lipase * amphipathic, secreted by pancreas, binds lipase, anchors lipase to the surface of emulsion droplets * Digestion occurs in emulsion droplets * Lipase digests TAG to monoglycerides and FA * Fat digestion products associate with bile salts and phospholipids to form micelles

Answer 13

* Micelles: fatty acids, monoglycerides, bile salts, phospholipids, cholesterol, fat-soluble vitamins * Fat digestion products * At the top are the amphipathic molecules that are in pancreas * 4-7 nm→1/200th the size of an emulsion droplet * Micelles ferry fat digestion products to the apical plasma membrane of enterocytes.

Answer 14

* Simple diffusion of freely dissolved monoglycerides and FA * Carrier proteins * Cholesterol absorption * Cholesterol in SI comes from cholesterol in bile and dietary cholesterol. * 50% cholesterol in SI is reabsorbed into body and 50% eliminated * Drug increases cholesterol elimination * **Ezetimibe:** blocks carrier protein for cholesterol (reduces absorption)

Answer 15

* Lipoproteins * TAG * Cholesterol * Fat soluble vitamins * Phospholipids * Apolipoproteins * Chylomicrons: lipoproteins produced by enterocytes * Way that fat is carried around in the circulation * Get into circulation by entering leaky lymphatic capillaries (lacteals), flow via lymphatic vessels and get into circulation * TAG in lipoprotein digested by lipoprotein lipase→monoglyceride and 2 FA that can go into cells

Answer 16

* Requires intrinsic factor * Water soluble * Important for cell division, affects RBC products, anemia occurs * Parietal cells in stomach produce intrinsic factor * IF bind to vitamin B12 to make complex * Complex travels to bottom of the SI * Ileum: absorption via receptor-mediated endocytosis * Lack of intrinsic factor (causes B12 deficiency)→**prenicious anemia** * Autoimmune cells destroys parietal cells * **Crohn’s disease** causing inflammation in ileum, causing decreased absorption of B12 (causes deficiency)

Answer 17

* Fat soluable vitamins→tag along with fat absorption * Water soluable vitamins→carriers, diffusion

Answer 18

* No efficient way to get rid of iron, so needs to be efficiently recycled. * Iron deficiency→anemia * Too much ion: free radical formation→tissue damage * Into enterocyte via DMT-1 * Then can go into 2 different pathways (ferritin or ferroportin) * **Ferritin** * not actually in the body because enterocytes overturn readily * Regulated iron absorption occurs in the duodenum * **Transferrin:** figure out how much iron in body by looking at saturation * \<25% saturated (normally)

Answer 19

* 1. **Is there a need for iron** (w/ regard to bone marrow) * Needed because making RBC * Don’t know what that signal is * 2. **Body iron stores** (mostly liver, some spleen)→signal (hormone: **hepcidin**)→act of enterocytes to allow iron absorption * When body iron stores full * increased hepicidin by liver, travels to duodenum, bind ferroportin, ferroportin internalized and degraded

Answer 20

* Disorder of iron overload * Mutation in HFE gene * most common cause * Unregulated iron absorption * Accumulation of iron in tissue * form free radicals * tissue damage * Liver, pancreas, heart, joint * Symptoms arise in middle age * Treatment: * Bleeding to remove iron, **phlebotomy** * HFE protein thought to be involved in sensing the amount of iron * When defective * iron isn’t sensed properly * deficient secretion of hepcidin

Answer 21

* Inappropriate immune response to gluten * Involves CD4+ helper T Cells * Not an allergy b/c not atopic disorder * Duodenal biopsy to diagnose celiac disease * Flattened mucosa (no villi) * Inflammation * Increased lymphocytes * Normal small intestine mucosa * Decreased iron absorption * Decreased folate * Anemia will occur * In lamina propia MALT engulf those peptides and display them on their surface * Consequences: * Malabsorption * Diarrhea * Anemia (iron deficiency)

Answer 22

* Weight loss surgery * The two most common bariatric surgery procedures are **Roux-en-Y gastric bypass** and **adjustable gastric banding **

Answer 23

* Small pouch created so person feels full more quickly * Restricted procedure

Answer 24

* Combine restrictive and malabsorptive * Small pouch at fundus is created; piece of SI is brought up and joined to the pouch. Creates a tiny stomach and channel that food flows down. * Stomach left there so that secretions from liver, stomach and pancreas still go SI * **Duodenum is powerhouse of absorption**, so food bypasses this. * can cause micronutrient deficiency (like anemia) * **Alimentary channel** is where the food is. The **biliopancreatic channel** is where the secretions are. * **Length of common channel** determines the degree of absorption/malabsorption * For reasons not well understood endocrine changes occur that can achieve **remission from Type 2 diabetes** * 75-80% who have DM2 achieve remission

Answer 25

* Start to have changes in responsiveness and occur even before the profound weight loss * Hypothesis #1: * There might be an **upper GI hormone** that is involved in glucose homeostasis * Hypothesis #2: * Food quicker to lower small intestine * Stimulates **endocrine L cells ** * Release **GLP1 and PYY** * GLP1 increases insulin secretion, decreases glucagon secretion, increasing satiety

Answer 26

* Branch of autonomic nervous system * Neurons in wall of GI tract controlling behavior * Can work in isolation from the CNS * Afferent neurons responding to changes in GI tract * Chemical sensors * Stretch sensitive sensors * Efferent neurons→projecting to secretory cells, smooth muscle * Interneurons: connecting and coordinating neurons * Vagus nerve inputs (parasympathetic part of ANS) * submucous plexus * deeper than the myenteric plexus * myenteric plexus * Between muscle layers regulating motility * More neurons

Answer 27

* Cells are spontaneously active in smooth muscle * Cells are electrically coupled into groups so that they work in concert. * Via gap junctions * Spontaneous activity in specialized smooth muscle cells (**pacemaker cells**) produces the **basic electrical rhythm** * Spontaneous activity makes the **slow waves** (“basic electrical rhythm”) * Electrical coupling causes region to have the oscillating membrane potential * Slow waves with spikes of action potentials * In the stomach there are 3 waves/min * Duodenum: 12/min * Ileum: 9/min * Action potential lets calcium in that regulates muscle contractions (More calcium, stronger contraction) * Slow wave frequency: contraction frequency * **Number of action potentials (@ peak): contraction strength** * Excitatory input makes the cell more depolarized so that when slow wave reaches the peak, there will be more action potentials * Skeletal muscle only input is somatic efferent * Smooth muscle can have a variety of inputs (more complex): * Neurons * Hormones * Excitatory or inhibitory * Spontaneous activity

Answer 28

* Endocrine cells are generally in the epithelium * Internal secretion, hormone going to the blood stream * Important hormones: gastrin, cholecystokinin (CCK), secretin, incretins (GLP-1, GIP) * Important paracrines: histamine, somatostatin, serotonin * Change in lumen→triggers secretion * Causes feedback regulation of lumen of GI tract * Often act as growth factors

Answer 29

* phase=location of stimulus 1. cephalic phase (cephalic=head) * stimuli: sight, smell, taste, chewing 2. gastric phase (gastric=stomach) * food in stomach * stimuli: stomach distension, acidity, peptides 3. intestinal phase * stimuli: distension, acidity, osmolarity, digestive products

Answer 30

* Release saliva in response to food in the mouth * Amylase to digest carbohydrate (from serous acinus) * Also antibacterials * Mucus from mucus acinus

Answer 31

1. Oral (buccal) Phase 2. Pharyngeal Phase 3. Esophageal Phase

Answer 32

* Food in mouth * Swallowing is voluntarily initiated * Retracted tongue: push food to the pharynx * Food in pharynx triggers pharyngeal sensory neurons that project to brainstem nuclei that coordinate the other two phases * Elevation of soft palate so no food up the nose

Answer 33

* Area common to breathing and eating * Inhibit respiration * Glottis muscles close breathing * Larynx elevated to tip the epiglottis down so the trachea is covered

Answer 34

* Esophageal sphincters relax to allow food to pass * One at top and one at bottom * Smooth muscle engages in propulsive movement * peristalsis

Answer 35

* Technical term is emesis * Nausea not well understood (can’t use animal models and ask how they feel) * Strong contractions of abdominal muscle to increase abdominal pressure * Relaxation of esophageal muscle * Reverse peristalsis * automatic behavior controlled by nuclei in the brainstem, referred to as the **vomiting center** * During retching, the lower esophageal sphincter relaxes, abdominal skeletal muscles contract, and strong peristaltic contractions of the muscularis externa operate in reverse of the normal pattern, forcing the contents of the stomach and even the small intestine upward into the esophagus * Emesis occurs when these contractions are strong enough to expel the contents of the GI tract past the upper esophageal sphincter.

Answer 36

* Irritant in GI tract affects cells that release serotonin * **Serotonin** acts as paracrine * Excites afferents in vagus nerve * Up to the vomiting center in brain * Toxin in circulation * Act of **area postrema** in the brain * project to and activate vomiting center * Also the chemoreceptor trigger zone * At the posterior end of the 4th ventricle * Outside the BBB * CNS * Blow to head can trigger vomiting * Vestibular mismatch

Answer 37

* Post operative nausea and vomiting * opiods and anethestics * activate opiod receptors in area postrema * Chemotherapy induced nausea and vomiting * serotonin release of intestinal epithelium * Free radical formation release serotonin * Treated prophylactically with antiemetic

Answer 38

* Serotonin antagonist: Zofran and palonosetron (Aloxi®) * Bind to serotonin receptors 5HT3 antagonists * Substance P antagonists: Aprepitant (Emend) * P involved in inflammatory pain pathways * Very effective in limiting vomiting * Antagonists for dopamine, histamine and acetylcholine * dopamine antagonists promethazine (Phenergan®) and prochlorperazine (Compazine®) * histamine anatagonist dimenhydrinate (Dramamine®) * muscarinic anatagonist scopolamine * Cannabinoid agonists such as tetrahydrocannabinol (THC; the principal psychoactive ingredient in marijuana) are also used to reduce nausea and vomiting

Answer 39

* Upper sphincter limits air into the GI tract (if gets in there, belching) * Factors that increase risk of gastroesophageal reflux: * decreased tone in lower esophageal sphincter * increased abdominal pressure (pregnancy, obesity, overeating ) * hiatal hernia * When a piece of the stomach fundus goes through the “hiatus” (the hole in the diaphragm) * Diaphragm normally reinforces lower esophageal sphincter * GERD Treatments: * Suppression of acid secretion

Answer 40

* The mucosa changes with continual exposure to acid * Columnar epithelium appears reddish (abnormal appearance) * Confirmation: * Biopsy to look for **intestinal metaplasia**: mucosal change where you see columnar epithelium where it should be stratified squamous. Will see goblet cells * Increased risk for esophageal adenocarcinoma * May need increased surveillance if known Barrett’s esophagus

Answer 41

* Functions: * Solubilizes food * Pepsin activity * Kills bacteria * Parietal cells secrete HCl acid * H+/K+ ATPase-“proton pump” * Apical plasma membrane * Stimulation of acid secretion: translocation of proton pumps to apical plasma membrane

Answer 42

* Stimulation of acid secretion: translocation of proton pumps to the apical plasma membrane * Regulators: * Neurotransmitter: **acetylcholine** * ****Released from enteric neurons * Paracrine: **histamine** * Released from ECL cells * Hormone: **gastrin** * ****Released by G cells in gastic epithelium * Stimulates ECL cells to increase histamine (indirect effect) * Stimulates proliferation of parietal cells (direct effect) * Negative Regulator:** Somatostatin** * ****secreted by endocrine cells of the gastric epithelium * Acts as both a paracrine and a hormone

Answer 43

* taste, small, sight * stimulate parasympathetic preganglionic neuron (in vagus nerve) to eneteric neurons to stimulate parietal cell, ECL and G cell. * Only a little acid secretion

Answer 44

* With food in the stomach, get the most acid secretion * Distends stomach, activates neural reflex to stimulate acid secretion * Peptides in food stimulate acid secretion from G cells * Food acts as a buffer to bind hydrogen ions. Lots of hydrogen ions, somatostatin turned on. * Relieves inhibition

Answer 45

* Want to limit acid * As food reaches duodenum stimulates factors to feed back inhibits enteric neurons and stimulate enterogastrones * **Enterogastrones**: hormones that inhibit stomach processes

Answer 46

* Acetylcholine and histamine directly stimulate parietal cells to increase acid secretion * Gastrin stimulates acid secretion by stimulating histamine release from ECL cells

Answer 47

* Gastric ulcers (stomach) * Duodenal ulcers * Mucus in the stomach is protective * Use of NSAIDs can block prostaglandin production * Prostaglandins: promote mucus formation and inhibit acid secretion

Answer 48

* Causes peptic ulcer disease * Bacteria colonize by burrowing into the mucus and have enzymes that neutralize stomach acid near the bacteria * Causes gastritis (inflammation in the stomach) * Only certain individuals that have H. pylori will have ulcer

Answer 49

* Gastritis setting up in pylorus * Causes endocrine deregulation * Decreased somatostatin, increase in gastrin * Acid hyper-secretion and no inhibits from somatostain * Overwhelms protective mechanisms in the duodenum * Gastritis setting up in body * Atrophy in the glands, decreased parietal cells * Decreased acid secretion: hypochlorhydria * Get change in mucosa: intestinal metaplasia: pre-malignant lesion

Answer 50

* Goal is to eradicate bacteria * Give a couple of antibiotics to really make sure bacteria gone as well as giving drugs to decrease acid secretion * Histamine antagonists: H-2 receptors, Cimetidine, Ranitidine * Proton Pump Inhibitors: Omeprazole, Lansoprazole

Answer 51

* During eating * Expand during ingestion * Neural reflex response to eating

Answer 52

* Basic propulsive movement * Inside is circular muscle, outside is longitudinal muscle * In segment, two parts: propulsive segment and receptive segment * Squeeze in propulsive segment and open in receptive segment * Contraction in circular muscle and relaxation of longitudinal muscle in propulsive segment * Reverse in receptive segment * Stronger peristalsis in pylorus * Once in food pylorus * Rate determined by BER (basic electrical rhythm) (3/min) * Gastric phase stimuli (stomach distension and/or gastrin) increase strength of contractions * Intestinal phase stimuli decrease strength of contractions; slow stomach emptying

Answer 53

* Rate determined by BER (basic electrical rhythm) (3/min) * Gastric phase stimuli (stomach distension and/or gastrin) increase strength of contractions * Intestinal phase stimuli decrease strength of contractions; slow stomach emptying * Strong contraction in stomach smooth muscle, increase stomach emptying * Weak contraction in stomach smooth muscle, decrease stomach emptying * Enterogastrones: inhibit acid secretion and inhibit smooth muscle * Neural and hormone inputs to GI smooth muscle change the strength, but not the timing of contractions.

Answer 54

* Providing digestion enzymes and bicarbonate * Exocrine secretion in the pancreas: acinar cells and duct cells * Acinar cells secreting digestive enzymes * Duct cells secreting bicarbonate and fluid * Regulated by hormones * Chyme in duodenum stimulate hormones * Low pH stimulate secretin release * Acts on duct cells to stimulate bicarbonate and fluid release * Fats and peptides stimulate CCK release * Travels in circulation to stimulate secretion from acinar cells * Some stimulation during cephalic and gastric phase via vagus nerve to cause secretions

Answer 55

* Bile salts, phospholipids, bicarbonate, cholesterol, bile pigments, trace metals. Last three are targeted for excretion * Smooth muscle closing outlet: Sphincter of Oddi * Basically at the duodenal papilla * Regulates whether or not bile will enter duodenum * No meal: interdigestive period. * No need to for bile in duodenum, sphincter contracts * Pressure builds up and bile flow to gallbladder for storage * Digestive period. About 2 hours * Sphincter relaxed and bile flows into duodenum * Secretin stimulated by H ions * CCK stimulated by digestive products * Cholecystokinin * Cholescyst: gallbladder, kinin: to move * Triggers smooth muscle contraction in gallbladder * In SOO relaxes smooth muscle * Enables bile to flow out * Amount of bile not sufficient to digest all meal so bile salts need to be recycled…enteroheaptic circulation

Answer 56

Transporters take up bile salts in ileum and back to intestinal capillaries

Answer 57

* Too much cholesterol in gallbladder precipitates to gallstones * Need enough bile salts to keep it soluable * Female (estrogen promotes cholesterol into bile), age (enzymes producing bile salts less active * Can be completely asymptomatic

Answer 58

* When problem is gallstone moved into bile duct. * Cystic bile duct: painful gallbladder contractions * Common bile duct: pain and nausea, lack of bile release, failure to excrete bilirubin leads to **jaundice** * Duodenal papilla: block pancreatic enzymes leading to inappropriate activation of pancreatic zymogens, **acute pancreatitis**

Answer 59

* **Cholecystectomy**→Removal of gallbladder * Endoscopic removal * Nonsurgical: give oral bile salts * Delivered to bile ducts via enterohepatic circulation * Shockwaves to break up stones

Answer 60

* Villus: absorptive * Crypt: secretory enterocytes * Depends upon activity of CFTR * Sodium follows chloride passively * Digestive pathologies of cystic fibrosis * Can cause intestinal blockage * Pancreatic insufficiency (digestive enzymes not produced/getting to duodenum) * Chronic pancreatitis * Excessive activation * Excessive secretion of fluid * Secretory diarrhea (cholera)

Answer 61

* Occurs during the digestive period * Turned on by cephalic phase stimuli * Alternating contractions and relaxations of smooth muscle * Helps mix things up * Cephalic phase stimuli switches on segmentationàcontinues during digestive period * Bi-directional movement: things going back and forth * Thing goes forward with gradual propulsion (net movement towards cecum) because BER has gradient: faster in duodenum (12/min) and slower in ileum (9/min)

Answer 62

* During inter-digestive period * Get segment of pertalsis that travel down upper GI and then stops * Migrating segment of peristaltic activity * Like sweeping floor. Go forward and then backwards, etc. * Clears out what is left in the small intestine * Indigestible, un-absorbable, bacteria * Stomach growling: disrupts bubbles * Turns off when eat, because switches to segmentation

Answer 63

* absorption of fluid * secretion of mucus * bacterial digestion * storage of feces * defecation

Answer 64

* Slow mixing movement * Slow irregular contractions of circular muscle * Mass movement * Propulsive movement * **Sustained contraction** of circular muscle (squeeze and hold) * Provides stimulus for defecation

Answer 65

* External anal sphincter to maintain continence * Anorectal angle during rest and defection. Contraction of puborectalis establishes more acute anorectal angle that keeps feces from leaking out * When defecation occur, conscious relaxation to allow feces passage * Mass movement puts feces in sigmoid colon and rectum and causes stretch * Triggers responses that causes more pressure inside the rectum (see course website) * The urge to defecate * If spinal injury or infants, pressure increases to a point where there is reflective defecation * **Valsalva maneuver** is pushing to increase abdominal pressure and push feces out * Contraction of abdominal muscles

Answer 66

* Hepatic portal vein, deoxygenated put nutrient rich * If water soluble in the diet, then first goes to the liver * Role in nutrient homeostasis * Makes lots of plasma proteins * Good reason to take amino acids there

Answer 67

* Cells arranged in rows with sinusoids inbetween * Place where blood flows through * Look at sinusoid via EM * In sinusoid are some other cells * Enothelial cells * Hepatocytes making bile to go into own distinct secretory pathway * Green guys are canaliculi that hook up to bile ductule to let things flow out of the liver

Answer 68

* No basement membrane and not tightly linked * Liver secretion and taking things out of blood in sinusoids * Need lipoproteins to get in and out so need gaps

Answer 69

* (reticuloendothelial cells) * macrophages; consume aged RBC’s * iron recycling and storage

Answer 70

* AKA Ito cells * Connective tissue cells * Involved in situation with disorders causing injury to liver cells * Liver can regenerate (with limited capacity) * Chronic Liver injury: * Stimulates stellate cells * Can get too much connective tissue…**fibrosis** * Can reach terminal stage of fibrosis called **cirrhosis** * Connective tissue making islands of isolated hepatocytes that no longer function properly

Answer 71

* **Bile synthesis and secretion** * **Nutrient homeostasis** * Absorptive state: synthesis of glycogen, TAG * Post absorptive state: glycogenolysis, gluconeogenesis, ketogenesis * **Biotransformation** * Metabolism of drugs, hormones, etc. to promote excretion via the urine * Convert to more soluble forms * **Synthesis of plasma proteins** * albumin, binding proteins, clotting factors, complement * Albumin is making sure that there is enough osmotic pressure to keep fluid in circulatory system * When not enough plasma proteins, can get edema * **Cholesterol homeostasis**

Answer 72

Apolipoprotein is also a label for cells to read

Answer 73

* Are synthesizes in enterocytes from absorbed lipids * Synthesis of TAG in ER

Answer 74

* TAG rich * Liver makes with extra glucose * Deliver TAG to cells * TAG extracted by lipoprotein lipase, on the surface of endothelial cells and acting of lipoprotein so FA and glycerol can be taken up by cells * When stripped of TAG, becomes more dense and then get taken up by liver and remodeled and sent out as LDL

Answer 75

* Cholesterol delivery * LDL uptake into cells is via receptor mediated endocytosis * LDL receptor is really important in cell using cholesterol and in liver * Liver using LDL receptor to see how much LDL is out in circulation

Answer 76

* Cleanup, reverse cholesterol transport * Empty bag that scavenges and picks up extra cholesterol to take back to liver * When high levels of LDL and low HDL cholesterol, increases risk of atherosclerosis * Fatty plaques inside blood vessels that lead to clots and blockage of blood * Lipid panel measure cholesterol but really we carry about the particles. * Familial hypercholestolemia * VERY high levels of LDL and have heart attacks at young ages * Major cause is mutation in gene for LDL receptor * Defective LDL reecptors means that liver can’t take up LDL and see how much is out there * Keeps pumping out LDL

Answer 77

* **synthesis of cholesterol** * HMG-CoA reductase: rate limiting enzyme for cholesterol synthesis; increases cholesterol in the hepatocyte decreases HMG-CoA reductase activity * **synthesis of HDL** * **LDL uptake** * Regulates levels of cholesterol in the circulation * **synthesis of bile salts** * **secretion of cholesterol in bile (some in feces)** * Cholesterol elimination from the body

Answer 78

* Altered levels of lipids that predispose to atherosclerosis * **statins: ** inhibit HMG-CoA reductase * Reduce LDL cholesterol * Shown in clinical trials to reduce cardiovascular events * May have anti-inflammatory effect * **ezetimibe: **inhibits GI cholesterol uptake * Blocks cholesterol transporter in the small intestine * **Fibrates** * **Niacin**

Answer 79

* Digestive enzymes released in inactive form * to prevent digesting the cells that create them * Peptide blocks active site of enzyme * Cleave the peptide to activate the enzyme

Answer 80

* Peptidase in the stomach is **pepsin** * Active at pH 2-3 and inactive at pH 5 * **Chief cells **at the base of gastric glands secrete the zymogen * called **pepsinogen** * Partially activation by **HCl** secreted by **parietal cells** * Then cleaves the peptide in other pepsinogens to activate them

Answer 81

* Brushborder enzyme **enterokinase** cleaves **trypsinogen **forming the active enzyme **trypsin** * **Trypsin **then activates other enzymes * Pancreatitis * inapropriate activation * Acinar cell secrete **trypin inhibitor** within the pancreas * Trypsin also has **autolysis **(self-digestion) * Fluid by duct cells flushes zymogens out * can get blocked by gallstone * Fluid secretion in pancreas depends upon chloride channel **CFTR** * Increased Risk for pancreatitis * Mutation in trypsin inhibitor * Cystic Fibrosis * Alchol consumption * hyperlipidemia

Answer 82

* Most dietary fat is TAG * hydrolyzed by **lipase** to release FFA and glycerol

Answer 83

* Key issue in digestion and absorption of fats is their solubility * **lipase **is water soluable and only work at surface of fat droplet * Digestion aided by **emulsifaction **of fat into **emulsion droplets** * **Bile salts **and **cholesterol** are **ampipathic** and are present in the **bile** * SI motility breaks up fats and then coats them with bile salts and phospholipids to prevent them from sticking together * Digestion occurs in emulsion droplets * Increases surface area for lipase * **Colipase** is ampipathic and anchors lipase to surface of emuslion droplet

Answer 84

* Monoglycerides and glycerol associate with bile salts and phospholipids to form micelles * 200 times smaller than emulsion droplets * small enough to fall between the microvilli * Transport to surface of enterocyte for absorption * Micelle contains **fat soluable vitamins **and **cholesterol** * Constant forming and breaking down * Only freely dissolved monoglycerides and FFA can be absorbed by diffusion across membrane * Some have facillitate transport proteins

Answer 85

* Monoglycerides and FA resynthesized back into TAG inside the cell * TAG, cholesterol, fat solubale vitamin packaged into **chylomicrons** * are **lipoproteins** * Released from basal membrane of enterocytes * Enter **lacteals** and then drained into blood in chest * TAG in chylomicrons is hydrolyzed by **lipoprotein lipase, **found in capillary endothelial cells

Answer 86

* Some cholesterol in SI is dietary and other is put there by the liver via bile * Only half of cholesterol is absorbed and rest eliminated in the feces * **Ezetimibe**: blocks transport of cholesterol across apical membrane. Reduced LDL levels, especially when combined with **statins **that inhibit cholesterol synthesis in liver * Lowers MI and stroke risk as well

Answer 87

* Iron absorption matches iron loss (1-2 mg) * Iron is necessary component for many enzymes but plays important role in binding oxygen in Hb * anemia: reduced oxygen carrying capacity of blood * Too much iron can lead to **free radical formation** * Most iron in RBC, rest in **liver's hepatoctyes **and **Kupffer cells** (aka **reticuloendothelial cells)** * Macrophage that ingest RBC to release iron * Iron brought into cell by active transporter **DMT-1 (divalent metal transporter 1)** * in duodenum * zinc, copper, cobalt, manganese, cadmium or lead * also absorb heme iron * Two fates of iron once inside cell: * leave the enterocyte and enter the body via the **basolateral transporter** known as **ferroportin** * bound to** ferritin**, an** intracellular iron-binding protein** * ****iron lost when enterocyte dies * Iron in the internal environement is rapidly bound by **transferrin** * delivered to RBC precursors and taken up by **receptor-mediated endocytosis** * Generally more transferrin than iron but, **transferrin saturation **determines if too much iron in the blood (normal 20-45%)

Answer 88

* One signal reflects the need for iron due to **erythropoiesis** * hormone **erythropoietin** stimulates red blood cell production (another signal for iron absorption) * second signal depends upon the amount of iron in **body stores** * Regulate iron absorption in the proximal duodenum * ** Hepcidin** is produced by hepatocytes when iron stores are full. Inflammation can also stimulate hepcidin production. * causes ferroportin to be internalized and degraded * more iron in enterocyte, stimulating ferratin synthesis, more iron loss

Answer 89

* severe juvenile form of hemochromatosis is due to a homozygous deletion of the gene for hepcidin * HFE functions in the process of sensing body iron levels and regulating hepcidin secretion * deficient secretion of hepcidin, iron absorption by duodenal enterocytes continues even when body iron stores are full * Half a liter of blood contains approximately 200-250 mg of iron

Answer 90

* also known as** gluten enteropathy** or **celiac sprue** * malabsorption because of inappropriate immune response to gluten * not atopic becuase not involve IgE * immune response in celiac disease is mediated by **CD4+ helper T-cells** * All individuals who develop celiac disease express particular alleles of one type of **MHC molecule**

Answer 91

* Peptides derived from gluten contain many proline and glutamine residues, making them **resistant to digestion **by pancreatic and brush border enzymes. * peptides gain access to the **lamina propria** (where MALT is located) either by **transcytosis** or by a **paracellular route** * paracellular by breakdown of tight junctions and increase intestinal permeability * in the lamina propria, an enzyme modifies these peptides, making them even more antigenic * displayed on the surface of **antigen presenting cells** (APC's) by **MHC II molecules** * stimulate **CD4+ helper T-cells**, which secrete **cytokines** that orchestrate the inflammatory response that leads to tissue damage * One cytokine in particular (**IL-15**) stimulates **intraepithelial lymphocytes**, promoting their recruitment, survival, and cell-killing properties

Answer 92

* observed in a **duodenal biopsy,** which is a key test in the diagnosis of celiac disease * **flattened mucosa** * greatly decreases the surface area of the small intestine, causing** malabsorption of nutrients**, which can cause **diarrhea** and **malnutrition** * Duodenal tissue also shows increased numbers of **lymphocytes** * In adults, primary symptom is **iron deficiency anemia ** * get a skin rash, which is termed **dermatitis herpetiformis**

Answer 93

* Avoidance * bacterial and plant enzymes capable of digesting the immunostimulatory peptides that resist digestion by human digestive enzymes * block the breakdown in the epithelial barrier of the intestine * Peptides derived from gluten stimulate the release of** zonulin**, a regulatory molecule that causes tight junctions to open up * A drug that is in development blocks zonulin receptors

Answer 94

* often performed** laparascopically** * adjustable gastric banding * band around **fundus** * **restrictive procedure** because weight loss from limited intake * More gradual weight loss * RYGB * both restrictive and malabsorpative

Answer 95

CCK, secretin, GLP-1, and GIPact as enterogastrones.

Answer 96

* Bleeding in the lower GI, left colon * Bleeding from upper GI would cause black, tarry stools * Passage of recognizable blood is called **hematochezia** * Passage of tarry stools is called **melena**

Answer 97

Descending and sigmoid colon.

Answer 98

Infection with Clostridium difficile. Treatment with broad-spectrum antibiotics kills off many bacteria, allowing overgrowth with C. difficile, which causes pseudomembranous colitis.

Answer 99

Increased ESR is indicative of inflammation.

Answer 100

Ulcerative colitis. Shallow ulcerations that are limited to the mucosa are indicative of ulcerative colitis. Another characteristic feature is the uniform granular appearance seen with colonoscopy.

Answer 101

* standard treatment to achieve remission is with drugs containing **5-aminosalicylate** (5-ASA)

Answer 102

Bacteria in the large intestine.

Answer 103

If a patient does not achieve remission with a 5-ASA drug, then he might be treated with **glucocorticoids**. A newer drug for ulcerative colitis treatment is a sort of topical glucocorticoid treatment for the colon. The glucocorticoid drug is contained in a matrix designed to allow steady release once it reaches the colon. This avoids the side effects associated with systemic use of glucocorticoids. More serious cases of inflammatory bowel disease are treated with biologic therapies such as **infliximab**, a monoclonal antibody drug that inhibits the action of TNF-alpha.

Answer 104

Stratified squamous epithelium.

Answer 105

The H+/K+-ATPase, or proton pump. Proton pump inhibitors are the most potent antisecretory drugs (drugs that decrease acid secretion).

Answer 106

The intestinal epithelium is a **simple columnar epithelium**. A characteristic feature of intestinal metaplasia is the presence of **goblet cells**, the mucus-secreting cells that are found in the intestines.

Answer 107

cellular abnormalities that indicate the beginnings of malignant transformation leading to cancer.

Answer 108

* Acid in the stomach kills many bacteria, but H. pylori can evade destruction by burrowing into the protective mucus layer. H. pylori also expresses **urease**, an enzyme that hydrolyzes urea to produce ammonia, which is used to buffer acid in the immediate environment of the bacterium. * Infection with H. pylori causes chronic** gastritis**, which is inflammation of the stomach lining * Inflammation causes the recruitment of white blood cells and the production of **cytokines**, which have effects on the physiology of cells in the stomach epithelium

Answer 109

* excessive quantities of acid * gastritis is localized in the pyloric region * cytokines released in response to inflammation disrupt the regulation of the endocrine cells located in the pylorus * **G cells** are stimulated to secrete more **gastrin**, while **somatostatin** secretion is inhibited * Gastrin stimulates **parietal cell proliferation **and increased parietal cells along with decreased somatostatin leads to **acid hypersecretion** * acid-neutralizing mechanisms become overwhelmed, and the duodenal tissue becomes damaged.

Answer 110

* gastritis is located predominantly in the body of the stomach * inflammation induces apoptosis of parietal cells, and there is eventual atrophy of the gastric glands * hyposecretion of acid, or** hypochlorhydria** * Continued tissue damage may lead to development of a **gastric ulcer** * H. pylori is classified as a carcinogen because infection increases the risk of developing certain types of **gastric cancer** * atrophic gastric glands undergo a further change known as** intestinal metaplasia** * begins to resemble an intestinal epithelium, with villi and goblet cells

Answer 111

* Reducing the acidity in the stomach lumen promotes healing, and it also increases the effectiveness of the antibiotics (for treating H. pylori) * **Histamine blockers**: these drugs are **histamine antagonists** that block the stimulatory effect of histamine released by **ECL cells** * **Proton pump inhibitors**: these drugs bind to and inactivate the **H+/K+-ATPase** on the apical membrane of the **parietal cell**

Answer 112

* **Acinar cells** produce digestive enzymes: amylase, lipase, and peptidases * Pancreatic peptidases are produced as inactive **zymogens** that are only activated after they reach the duodenum * other major secretion is **bicarbonate (HCO3-)**, which is produced by the** duct cells** * neutralize acidic chyme coming from the stomach * fluid that is produced by duct cells flushes enzymes and zymogens out into the large pancreatic duct. * intercalated duct * receive the acinar cell secretions, and secrete bicarbonate and fluid * connect to larger ducts that eventually lead to the large pancreatic duct that has its outlet at the duodenal papilla

Answer 113

* small amount of pancreatic secretion occurs due to neural inputs that are triggered by cephalic phase and gastric phase stimuli * majority of pancreatic secretion arises from **intestinal phase stimuli **(when chyme reaches the duodenum) * hormones **secretin** and **cholecystokinin (CCK)** are released by endocrine cells that are located in the duodenal epithelium. * secretin release is triggered by H+ ions * Secretin then travels via the circulation to stimulate bicarbonate secretion by duct cells * CCK release is triggered by digestive products (fats and peptides) * CCK then travels via the circulation to stimulate secretion by acinar cells.

Answer 114

* Secretion of bicarbonate by duct cells depends upon the protein** CFTR** * CFTR protein is also a bicarbonate channel * When the CFTR protein is defective, as it is in patients with cystic fibrosis, duct cell secretion is disrupted * causes a lack of fluid secretion to flush out pancreatic zymogens, blockage of pancreatic ducts, and inappropriate activation of trypsin in the pancreas * damage to acinar and duct cells, which may be replaced by connective tissue * Patients with severe mutations of CFTR (little or no CFTR function) are often born with **pancreatic insufficiency**, meaning their pancreas does not release sufficient quantities of digestive enzymes * failure to thrive, and need to be treated with digestive enzyme supplements * Less severe mutations in CFTR (with some channel function) still increase the risk for **pancreatitis. **

Answer 115

* produced in the liver by **hepatocytes** * ** **contains **phospholipids** and **bile salts**, **emulsifying agents** that are necessary for fat absorption and digestion * bile is also a route for excretion of **cholesterol **and **bile pigments** * Bile pigments are metabolic breakdown products of hemoglobin and cytochromes that give bile its yellow-green color * Bile pigments are further metabolized by bacteria in the colon, causing feces to have a characteristic brown color * bile contains water and **bicarbonate ions** that are secreted by **duct cells** that line the bile ducts within the liver.

Answer 116

* Whether or not bile is released into the small intestine depends upon the activity of the **sphincter of Oddi** * interdigestive period, the sphincter of Oddi is contracted, preventing bile from flowing out into the duodenum * pressure increases in the** common bile duct**, and bile flows into the **gallbladder** * gallbladder, epithelial cells reabsorb water and electrolytes, causing the bile to become more concentrated.

Answer 117

* During the digestive period, **intestinal phase **signals stimulate the release of bile into the small intestine. * Fatty acids in the lumen of the duodenum stimulate endocrine cells to release the hormone **cholecystokinin** (**CCK**) * stimulates contractions in the smooth muscle of the gallbladder * causes relaxation of the sphincter of Oddi, allowing bile release into the duodenum. * Acidic chyme in the lumen of the duodenum stimulates other endocrine cells to release the hormone **secretin** * Secretin stimulates **duct cells** in the liver to release bicarbonate into the bile.

Answer 118

* bile salts present in the body are not sufficient to fully process the fats in a typical meal, thus they need to be recycled * Specific transporters in the **terminal ileum** move bile salts from the lumen of the digestive tract to the intestinal capillaries * transported directly to the liver via the **hepatic portal vein** * Hepatocytes take up bile salts from the blood, and increase the secretion of bile salts into the **bile canaliculi** * 95% of the bile that is released to the small intestine is recycled via the enterohepatic circulation,while 5% of the bile salts are lost in the feces

Answer 119

* maintained by two sphincters that surround the anal canal * **internal anal sphincter** * ****extension of the muscularis externa, and thus is smooth muscle innervated by enteric neurons found in the myenteric plexus * **external anal sphincter** * skeletal muscle that can be consciously controlled, and is innervated by somatic efferent neurons * **puborectalis muscle** * loops around the rectum like a sling, pulling it forward to create a more acute angle between the rectum and the anal canal * **anorectal angle** * During defecation, there is conscious relaxation of the puborectalis muscle, which creates a more open anorectal angle and allows for a straigther passage through the anal canal

Answer 120

* mass movement triggers a **defecation reflex** * mass movement is a maintained, high-intensity contraction of the circular muscle in the colon, which will propel feces toward the rectum * sufficient volume is deposited in the rectum, the increased pressure will stimulate a reflexive contraction in the sigmoid colon and rectum, **relaxation of the internal anal sphincter** and **contraction of the external anal sphincter** * With delay, continued contraction of the external anal sphincter and high pressure eventually trigger reverse peristalsis in the rectum * Defecation involves the **relaxation of the external anal sphincter** (as well as **relaxation of the puborectalis muscle**, to create a broader anorectal angle) * Expulsion of Feces * **Valsalva maneuver** * closure of the glottis along with **contraction of abdominal muscles **to increase abdominal pressure

Answer 121

* in hepatocytes * under** negative feedback regulation** * increased cholesterol in the cell decreases the activity of HMG-CoA reductase * rate-limiting enzyme in cholesterol synthesis.

Answer 122

* Two types of lipoproteins are triglyceride-rich: the chylomicrons and VLDL * Chylomicrons are synthesized by enterocytes from lipids absorbed in the small intestine * VLDL is synthesized in the liver * deliver energy-rich triacylglycerol (TAG) to cells in the body * TAG is stripped from chylomicrons and VLDL through the action of lipoprotein lipase * TAG to fatty acids and monoglycerides, which can then diffuse into the cell to be oxidized, or in the case of an adipose cell, to be re-synthesized into TAG and stored in the cell

Answer 123

* As VLDL particles are stripped of triacylglycerol, they become more dense * deliver cholesterol to cells, where it is used in membranes, or for the synthesis of steroid hormones * Cells take up cholesterol by r**eceptor-mediated endocytosis**. LDL binds to a specific** LDL receptor** and is internalized in an endocytic vesicle * Receptors are recycled to the cell surface, while hydrolysis in an endolysosome releases cholesterol for use in the cell

Answer 124

* Excess cholesterol is eliminated from the body via the liver, which secretes cholesterol in bile or converts it to bile salts * liver removes LDL and other lipoproteins from the circulation by receptor-mediated endocytosis * excess cholesterol from cells is brought back to the liver by HDL in a process known as **reverse cholesterol transport** * HDL is synthesized and secreted by the liver and small intestine * travels in the circulation where it gathers cholesterol to form mature HDL, which then returns the cholesterol to the liver via various pathways

Answer 125

* essential nutrient of the vitamin B complex * niacin increases HDL levels and decreases triglyceride and LDL levels * inhibit an enzyme in the liver that is involved in triacylglycerol synthesis, causing a decrease in VLDL production * prolong the half-life of HDL particles by preventing HDL breakdown * Niacin is indicated when HDL is low, as it is the most effective drug for raising HDL levels.

Answer 126

* bind to the nuclear receptor PPAR-alpha * receptor works as a transcription factor to alter gene expression in target cells * increase HDL levels and decrease triglyceride levels * primarily used when the primary problem is high levels of triglycerides.