Study Notes Exam 3
Overview of Digestive System:
- alimentary canal (gastrointestinal (GI) tract): continuous muscular digestive tube that is open to the outside environment at both ends
o digests (breaks down) food & absorbs digested fragments into blood
o organs: mouth, pharynx, esophagus, stomach, small intestine, large intestine (leads to terminal opening or anus)
- accessory digestive organs: teeth, tongue, gall bladder
o large digestive glands in: salivary glands, liver & pancreas
§ produce secretions that help in breakdown of food
- Digestive Processes:
o Ingestion: taking food into digestive tract
o Propulsion: moves food along alimentary canal
§ swallowing
§ peristalsis: alternate waves of contraction & relaxation of muscles in organ (esophagus, stomach) walls
o mechanical digestion: physically prepares food for enzymatic (chemical) digestion
§ includes chewing, mixing with saliva, churning food in stomach & segmentation (rhythmic local constrictions of small intestine
o chemical digestion: complex food molecules broken down by enzymes released by glands of digestive organs
o absorption: passage of digested products from GI tract into blood or lymph
o defecation: elimination of indigestible substances in form of feces
- Basic Functional Concepts: regulation of digestive system
o Digestive activity is provoked by a range of chemical & mechanical stimuli (sensory receptors located in the walls of the GI tract organs)
o Controls of digestive activity are both intrinsic & extrinsic (local nerve plexuses & hormones as well as hormones released into blood)
- Digestive System Organs: Relationship & Structural Plan
o Relationship of the Digestive Organs to the Peritoneum:
§ Peritoneum: serous membrane of the abdominopelvic cavity
· visceral peritoneum: covers the external surfaces of most digestive organs
· parietal peritoneum: lines the wall of the abdominopelvic cavity
· peritoneal cavity: space between membranes containing serous fluid
· peritonitis: inflammation of peritoneum (can result from wounds, ulcers, burst appendix)
§ Mesentery: double-layered peritoneum that extends to the digestive organs from the body wall
· has routes for blood vessels, lymphatics & nerves; holds organs in place
· includes specialized membranes such as omentums
§ Retroperitoneal Organs: organs such as the pancreas & parts of the large intestine that lie posterior to the peritoneum (no mesentery)
· most organs of GI tract are intraperitoneal/peritoneal organs (have mesentery)
o Blood Supply: The Splanchnic Circulation
§ Splanchnic circulation includes arteries that branch off abdominal aorta & serve digestive organs & hepatic portal circulation
§ Branches of abdominal aorta that serve digestive organs:
· celiac trunk: branches to stomach (left gastric artery), spleen & pancreas (splenic artery; branches to pancreatic artery) and liver (common hepatic artery)
· superior mesenteric artery: branches serve all regions of the small intestine and ascending & transverse colon
· inferior mesenteric artery: branches serve transverse, descending & sigmoid colon, and rectum
§ hepatic portal vein recieves blood from the splenic vein & superior mesenteric vein & carries blood (containing absorbed nutrients as well as waste) to liver for storage & processing of nutrients & detoxification of waste
o Histology of Alimentary Canal
§ from the esophagus to rectum, the walls of the GI tract have the same 4 layers
· mucosa: moist epithelial membrane that lines the lumen
o functions: secretion (mucus, proteins); absorption of digested substances into blood; protection against infection
o 3 sublayers:
§ lining epithelium: mostly simple columnar epithelium with goblet cells (stratified squamous epithelium in esophagus)
§ lamina propria: loose areolar or reticular connective tissue
· capillaries that nourish epithelium; lymphoid tissue
§ muscularis mucosae: smooth muscle cells that twitch for local movements & folds mucosa in small intestine
· submucosa: dense connective tissue (with elastic fibers) containing blood & lymphatic vessels, lymph nodules & nerve fibers
· muscularis externa: inner circular layer & outer longitudinal layer of smooth muscle (stomach has additional innermost oblique layer)
o propels food along GI tract; circular layer has sphincters to prevent backflow
· serosa (visceral peritoneum): outermost layer of areolar connective tissue covered with mesothelium (simple squamous epithelium)
o in esophagus, replaced by adventitia (fibrous CT)
o retroperitoneal organs have both serosa & adventitia
o Enteric Nervous System of GI tract
§ enteric neurons of intrinsic nerve plexuses regulate digestive system activity
· submucosal nerve plexus controls glands & smooth muscle of mucosa
· myenteric nerve plexus (located between circular & longitudinal muscle layers of muscularis externa) control GI tract mobility (segmentation & peristalsis)
· enteric nervous system linked to CNS by afferent visceral fibers & ANS (extrinsic control, or control outside GI tract)
Functional Anatomy of Digestive System
Mouth & Associated Organs:
- Mouth (oral or buccal cavity): anterior opening is oral orifice; continuous with oropharynx posteriorly
o epithelium of mouth, hard palate & tongue is slightly keratinized stratified squamous epithelium
o oral mucosa produces antimicrobial peptides called defensins to prevent infection
- Lips & Cheeks:
o Lips (labia): formed by orbicularis oris muscle
§ red margin: reddish area visible externally; redness due to blood within blood vessels showing through (poor keratinization)
§ labial frenulum: median fold that joins lips to gums
o Cheeks: formed by buccinator muscles
o Vestibule: recess between cheeks & gums (& lips & gums)
o Oral cavity proper: cavity within teeth & gums
- Palate: forms roof of mouth
o hard palate: formed from palatine bone & palatine process of maxilla
o soft palate: formed mostly of skeletal muscle
§ uvula: projects downward from free edge of soft palate; closes off nasopharynx during swallowing
§ fauces: arched area (opening) of oropharynx that contains palatine tonsils
- Tongue: occupies floor of mouth & fills most of oral cavity
o composed of skeletal muscle that grips & mixes food with saliva to form a bolus
§ intrinsic muscles: change shape of tongue
§ extrinsic muscles: change position of tongue (protrude, retract, move side to side)
o lingual frenulum: mucosal fold that secures tongue to floor of mouth
o papillae: peglike projections of tongue mucosae, some of which contain taste buds
§ filiform papillae: small rough conical projections that provide friction for food manipulation
§ fungiform papillae: mushroom-shaped papillae scattered over tongue surface
§ circumvallate (vallate) papillae: in V-shaped row at back of tongue
o sulcus terminalis: groove that divides anterior 2/3 of tongue in oral cavity from posterior 1/3 of tongue in oropharynx
- Salivary Glands: glands inside & outside oral cavity that secrete saliva
o Intrinsic salivary glands or buccal glands: throughout oral mucosa
o Extrinsic salivary glands
§ Parotid glands: paired glands anterior to ear between masseter muscle & skin
· Mumps: inflammation of parotid glands; caused by mumps virus
§ Submandibular glands: walnut-sized glands that lie along medial aspect of mandible
§ Sublingual gland: anterior to submandibular gland under tongue
o salivary glands composed of mucous & serous cells
o saliva: mostly water; slightly acidic secretion containing electrolytes (sodium, chloride, bicarbonate ions), salivary amylase (digestive enzyme), mucin, lysozyme, IgA & metabolic wastes (urea & uric acid)
§ protection against infection provided by IgA, lysozyme, defensins & a cyanide compound
§ bacteria at back of tongue convert nitrites into nitric oxide, which acts as an antibiotic
o control of salivation: primarily controlled by parasympathetic division of ANS
§ salivatory nuclei in brain stem stimulated by sensory receptors in mouth, which trigger ANS
Teeth: lie in sockets (alveoli) in gum-covered margins of maxilla & mandible
- primary function is mastication (chewing)
- dentition: 2 sets of teeth
o primary dentition: deciduous (milk or baby) teeth; set of 20 teeth that first appear at about 6 months & generally last from 6 to 12 years
o permanent teeth: usually 32 teeth including wisdom teeth
- tooth structure:
o gingiva (gum): oral mucosa that surrounds tooth
o crown: exposed part of tooth above gingiva
o enamel: acellular brittle material composed of hydroxyapatite crystals (mostly calcium salts)
o root: portion of tooth embedded in jawbone (teeth can have from 1 to 3 roots)
o cementum: calcified connective tissue covering outer surface of root
o periodontal ligament: anchors the tooth to the bony alveolus of the jaw within joint (gomphosis)
o dentin: bonelike material under enamel forming bulk of tooth
o pulp cavity: central cavity containing pulp (connective tissue, blood vessels, nerves)
§ root canal: where pulp cavity extends into root
- tooth & gum disease
o dental caries (cavities): result from demineralization of enamel by bacteria in dental plaque
o gingivitis: inflammation of gingival caused by dental plaque & tartar accumulation
o periodontitis (periodontal disease): bacteria invade the bone surrounding a tooth, & immune system response further erodes bone & tooth
Pharynx: food passes from mouth into oropharynx & then laryngopharynx
- stratified squamous mucosa surrounded by 2 skeletal muscle layers to propel food into esophagus
Esophagus: food moving through laryngopharynx is routed into the esophagus as the epiglottis closes off the larynx
- esophagus extends about 25 cm from pharynx to stomach; route is through thoracic cavity posterior to trachea & then piercing diaphragm at esophageal hiatus to extend into abdominal cavity
- esophagus joins stomach at cardiac orifice
- cardiac (gastroesophageal) sphincter: smooth muscle valve preventing backflow of food from stomach into esophagus
- heartburn: symptom of gastroesophageal reflux disease (GERD); backflow of acidic gastric juice from stomach into esophagus
- histology:
o mucosa: nonkeratinized stratified squamous epithelium
o submucosa: contains mucus-secreting esophageal glands
o muscularis externa: shifts from skeletal muscle in superior region to mixed skeletal & smooth muscle to all smooth muscle in inferior region
o adventitia: fibrous connective tissue replaces serosa of stomach & intestines
Digestive Processes Occurring in Mouth, Pharynx & Esophagus:
- mastication (chewing)
- deglutition (swallowing)
o buccal phase: voluntary phase in mouth
o pharyngeal-esophageal phase: involuntary phase in pharynx & esophagus (controlled by medulla & pons)
Stomach: food entering stomach from esophagus is broken down by chemicals into a paste called chyme; major function is digestion (primarily proteolytic) of contents
- rugae: longitudinal folds of mucosa
- cardiac region: region near the heart; surrounds cardiac orifice
o cardiac sphincter
- fundus: dome-shaped region superolateral to cardiac region
- body: midportion
- pyloric region: funnel-shaped region inferolateral to body
o pylorus: continuous with duodenum through pyloric sphincter (valve-like smooth muscle that controls stomach emptying)
- greater curvature:
- lesser curvature:
- lesser omentum: mesentery that runs from the liver to lesser curvature of stomach
- greater omentum: mesentery that drapes inferiorly from greater curvature to cover small intestine
- Microscopic anatomy of stomach
o 3 layers of smooth muscle in muscularis externa (has innermost oblique layer)
o mucosa: simple columnar epithelium with goblet cells that secrete a protective alkaline mucus
o mucosa folds inward to form gastric pits & deeper gastric glands that secrete gastric juice
§ secretory cells of gastric glands:
· mucous neck cells: in upper ³neck² region; secrete acidic mucus
· parietal cells: in middle region; secrete hydrochloric acid (HCl) and intrinsic factor (necessary for vitamin B12 absorption in small intestine)
· chief cells: in basal region; produce pepsinogen (precursor of enzyme pepsin, a protease)
· enteroendocrine cells: a variety of cell types that secrete hormones & hormone-like molecules (including gastrin, histamine, endorphins & somatostatin)
o G cells: secrete gastrin
- mucosal barrier: protects stomach mucosa from acidic conditions inside stomach
o thick alkaline mucus
o epithelial cells of mucosa joined by tight junctions
o in deep regions of gastric glands, plasma membrane is impermeable to HCl
o stem cells in gastric pits replace damaged epithelial cells
- gastric ulcer: erosions of stomach wall due to persistent damage to mucosa & underlying tissues
o hypersecretion of HCl appears to be a predisposing factor, but the causative agent in most cases is the bacterium Helicobacter pylori, which destroys mucosal cells with enzymes, toxins & migration of inflammatory cells
§ treatment: course of antibiotics in combination with bismuth
- Digestive Processes occurring in stomach
o proteins digested with pepsin (children also have the enzyme rennin, which solidifies milk protein)
o alcohol & aspirin pass easily from stomach mucosa into blood
o intrinsic factor required for intestinal absorption of vitamin B12, which is necessary for red blood cell production
o regulation of gastric secretion:
§ phase 1: cephalic (reflex) phase: triggered by aroma, taste, sight, smell of food; inputs from sensory receptors relayed to hypothalamus & medulla oblongata, which in turn stimulates parasympathetic fibers & gastric glands
§ phase 2: gastric phase: initiated when food enters stomach; stomach distension activates stretch receptors & peptides & rising pH activate chemoreceptors
· stretch receptors feed back to medulla & vagus nerve to stimulate gastric juice secretion; chemical stimuli activate G cells to secrete gastrin, which in turn stimulates HCl secretion from parietal cells
§ phase 3: intestinal phase: low pH & partially digested foods in duodenum stimulate intestinal gastrin release to blood
· this is only brief as the enterogastric reflex following duodenal filling inhibits gastric secretion
· enteroendocrine cells in small intestine release 2 hormones:
o CCK (cholecystokinin) inhibits stomach emptying
o secretin decreases gastric secretions
Small Intestine: convoluted tube extending from the pyloric sphincter to ileocecal valve; major function is completion of digestion & absorption of nutrients
- 3 subdivisions: duodenum, jejunum & ileum
o duodenum: shortest region; continuous with pylorus of stomach
§ hepatopancreatic ampulla: union of bile duct (delivering bile from liver) & main pancreatic duct (carrying pancreatic juice)
§ hepatopancreatic sphincter (sphincter of Oddi): controls entry of bile & pancreatic juice
o jejunum: extends from duodenum to ileum
o ileum: continuous with large intestine through ileocecal valve
- mesentery: attaches jejunum & ileum to posterior abdominal wall
- Microscopic anatomy of small intestine
o plicae circulares (circular folds): deep folds of mucosa & submucosa slowing chyme movement for absorption
o villi: fingerlike projections of mucosa composed of absorptive columnar cells called enterocytes
§ in the core of each villus is a capillary bed & lymphatic lacteal for absorption
§ microvilli for increased surface area on epithelial cells give a ³brush border² appearance
o Histology of wall
§ mucosa: simple columnar absorptive cells with goblet cells & scattered enteroendocrine cells (as well as some T cells)
§ intestinal crypts (crypts of Lieberkuhn): tubular intestinal glands between villi
§ submucosa: areolar CT containing lymphoid follicles called Peyer¹s patches and mucus-secreting duodenal glands in duodenum
o intestinal glands secrete alkaline intestinal juice in response to distension of mucosa
Liver: largest gland in body; under diaphragm & mostly within rib cage; occupies most of right hypochondriac & epigastric regions
- 4 primary lobes: right (largest lobe), left, quadrate & caudate
- falciform ligament: separates left & right lobes & suspends liver from diaphragm & anterior abdominal wall
- round ligament (ligamentum teres): fibrous remnant of fetal umbilical vein (ductus venosus)
- hepatic artery & hepatic portal vein travel through lesser omentum & enter liver at porta hepatis & common hepatic duct
- bile travels through right & left hepatic ducts, which lead into common hepatic duct
o common hepatic duct fuses with cystic duct to form (common) bile duct
- Microscopic anatomy of Liver
o liver lobules: hexagonal structural & functional unit consisting of hepatocytes (liver cells) & a central vein
o portal triad: consists of a branch of the hepatic artery, a branch of the hepatic portal vein & a bile duct
§ blood from hepatic artery & portal vein percolates through sinusoids between hepatocyte plates & empties into central vein, which leads out of liver though hepatic veins
§ inside sinusoids are hepatic macrophages (Kupffer cells) which remove debris & bacteria from blood
§ bile flows through bile canaliculi to bile duct
- hepatitis: inflammation of liver, most often due to viral infection
- cirrhosis: chronic inflammation of liver often resulting from alcoholism or severe chronic hepatitis
- Composition of bile: bile is a yellow-green alkaline solution consisting of bile salts, bile pigments, cholesterol, neutral fats, phospholipids & a variety of electrolytes
o bile salts: cholesterol derivates that emulsify fats (suspend in water), aiding in digestion & absorption of fats
o bilirubin: bile pigment produced as a waste product of heme of hemoglobin during red blood cell breakdown
Gallbladder: thin-walled green muscular sac in a shallow fossa on the ventral surface of liver
- stores (& concentrates) bile that is not immediately needed; when needed, it is expelled through cystic duct into bile duct
- bile release is stimulated by the intestinal hormone cholecystokinin (CCK) following chyme entry into duodenum
- gallstones: crystallization of cholesterol in gallbladder due to too much cholesterol or too few bile salts
Pancreas: extends across abdomen under stomach; most is retroperitoneal
- releases pancreatic juice through main pancreatic duct to duodenum
o contains digestive enzymes: proteases trypsin, chymotrypsin, carboxypeptidase; amylase, lipases & nucleases
- digestive hormones released by enteroendocrine glands in duodenum (CCK & secretin) regulate secretion of pancreatic juice & bile
o secretin stimulates bicarbonate ion secretion from liver cells & pancreas
o CCK stimulates gallbladder contraction to release bile & secretion of pancreatic enzymes
- requirement for optimal intestinal digestive activity: requires import of enzymes from liver & pancreas & slow delivery of chyme from stomach
- motility of small intestine: chyme mixed with bile & pancreatic & intestinal juices & propelled forward by segmentation
o gastroileal reflex: enhances force of segmentation due to enhances stomach activity
Large Intestine: major function is to absorb water from indigestible foods & eliminate them from body as feces
- teniae coli: smooth muscle line along colon formed from longitudinal muscle layer
- haustra: sacs formed in large intestine wall due to muscle tone of tenia coli
- subdivisions: cecum, appendix, colon, rectum, & anal canal
o colon: ascending, transverse, descending & sigmoid subdivisions
o appendicitis: inflammation of appendix caused by blockage (fecal) & bacteria
o anal canal has 2 sphincters (internal & external anal sphincters) that open & close the anus during defecation
- microscopic anatomy:
o most of large intestine mucosae is simple columnar epithelium with goblet cells; anal canal mucosa is stratified squamous epithelium
- bacterial flora: bacteria remaining in material from food & entering through anus
Digestive Processes occurring in Large Intestine:
- motility of large intestine: haustral contractions propel material into next haustrum & aid in water absorption, while mass movements propel material toward rectum
- defecation: defecation reflex initiated by stretching of rectal wall & mediated by spinal cord & parasympathetic fibers
o muscles of rectal wall contract to expel feces
o diarrhea: insufficient water absorbed from waste
o constipation: over-absorption of water from waste
o food poisoning: caused by Salmonella bacteria
- nutrient: substance in food that is used by the body to promote normal growth, maintenance & repair
o major nutrients: carbohydrates, lipids, proteins, vitamins, minerals & water
o essential nutrients: nutrients that cannot be synthesized by chemical reactions in the body, & must be obtained from the diet
- Carbohydrates
o Dietary sources: sugars from fruits, sugar (cane), honey, milk; starch from grains, vegetables; cellulose from most plants (cellulose is indigestible = fiber)
o Uses in the body: glucose is major body fuel; used to make ATP (other sugars such as fructose & galactose are converted to glucose by liver)
o Dietary requirements: 200-300 grams/day recommended (40% of total calories)
- Lipids
o Dietary sources: saturated fats in meats & dairy products (& some plants); unsaturated fats in seeds, nuts & vegetable oils; cholesterol in egg yolks, milk products, meats
o Uses in the body: fats help the body absorb fat-soluble vitamins; triglycerides are major source of energy for hepatocytes & skeletal muscle; phospholipids used to synthesize cellular membranes; fats used as cushioning & insulation in adipose tissue; cholesterol used in plasma membrane, steroid hormone synthesis & bile salts
o Dietary requirements: fats should represent 30% or less of total calories; saturated fats should be 10% or less of total fats; less than 200 mg/day cholesterol
- Proteins
o Dietary sources: eggs, milk & most meats are complete proteins (contain all essential amino acids); vegetables must be used in combination to obtain all essential amino acids (cereal grains and legumes)
o Uses in the body: functional proteins regulate most chemical reactions in cells; structural proteins important for skin, connective tissue fiber & muscle contraction; nitrogen balance (nitrogen in protein intake = nitrogen in urine & feces); energy source only if in excess or insufficient carbs or fats
o Dietary requirements: 0.8 g/kg body weight recommended (~ 55 g/day for a 150 lb. Individual)
- Vitamins: organic compounds needed in small amounts for growth & metabolism
o Vitamins not used for energy, but are critical in energy-producing reactions
o most vitamins function as coenzymes (assist enzyme in its activity)
§ B vitamins niacin & riboflavin act as coenzymes NAD+ & FAD) in oxidative phosphorylation
o most vitamins must be obtained from diet; exceptions are vitamin D made in the skin, vitamin K & some B vitamins synthesized by intestinal bacteria, & vitamin A which can be synthesized from beta-carotene (orange-yellow pigment in some vegetables)
o water-soluble vitamins: absorbed along with water from GI tract
§ includes vitamin C & the B vitamins
o fat-soluble vitamins: bind to ingested lipids & absorbed along with their digestion products
§ includes vitamins A, D, E & K
o vitamin A can be synthesized from beta-carotene (antioxidant in orange vegetables) required for synthesis of visual pigments, normal development of bones, teeth & maintenance of epithelia
o vitamin D required for calcium & phosphorus absorption during digestion
o vitamin E is antioxidant (prevents oxidation of vitamin A & polyunsaturated fatty acids)
o vitamin K required for blood clotting
o B vitamins (B1-B12) required for cellular metabolism
o vitamin C (ascorbic acid) required for collagen production, storage of folic acid, & metabolism of some amino acids; promotes iron absorption & synthesis of steroid hormones
o vitamins A, C, & E are antioxidants that neutralize harmful free radicals in body
o balanced diet necessary to obtain all required vitamins
- Minerals: also not used for energy, but used by other nutrients to carry out necessary cellular reactions
o 7 minerals required in moderate amounts: calcium, phosphorus, potassium, sulfur, sodium, chloride & magnesium
o several minerals also required in trace amounts (e.g.: fluorine, iodine, iron, zinc)
- metabolism: all chemical reactions occurring in the body & necessary to maintain life
o anabolism: reactions that build up molecules (larger molecules are built from smaller molecules)
§ example: bonding of amino acids to make a protein
o catabolism: reactions that break down molecules (complex structures are broken down into simpler ones)
§ example: cellular respiration (food fuels broken down in cells & energy released is captured to make ATP)
- phosphorylation: addition of a phosphate molecule to another molecule (usually a protein or nucleotide (ADP))
o often used to activate a protein or chemical (sometimes used to inactivate)
- oxidation: the gain of oxygen or the loss of hydrogen (or electrons)
- reduction: the loss of oxygen or the gain of hydrogen (or electrons)
- oxidation-reduction (redox) reactions: one molecule is oxidized (loses electrons & energy) while another molecule is reduced (gains electrons & energy)
o dehydrogenases: enzymes that catalyze transfer of hydrogen
o oxidases: enzymes that catalyze transfer of oxygen
o use coenzymes NAD+ & FAD
- Mechanisms of ATP synthesis
o Substrate-level phosphorylation: high-energy phosphate transferred directly from a substrate molecule to ADP
o Oxidative phosphorylation: a chemiosmotic process where hydrogen ion transport across the mitochondrial membrane (chemiosmosis) provides the energy required for the enzyme ATP synthase to synthesize ATP from ADP and phosphate
- Carbohydrate metabolism
o Oxidation of glucose: glucose + oxygen -> water + carbon dioxide + 36 ATP + heat
§ Glycolysis: glucose broken down to 2 molecules of pyruvic acid
· occurs in the cytoplasm of cells
· net gain of 2 ATP
· following glycolysis, if oxygen is available pyruvic acid is converted to acetyl coA on the way into the mitochondrion (transition reaction) to go into the Krebs cycle
o pyruvic acid is converted to acetic acid, which is then combined with coenzyme A (a pantothenic acid derivative)
o carbon dioxide is released in the conversion
· if oxygen is in short supply, pyruvic acid is reduced to lactic acid (anaerobic respiration or fermentation)
o some lactic acid is transported to liver & can be converted back to pyruvic acid when oxygen becomes available; lactic acid remaining in cells impairs cellular activity (muscle cell fatigue during exercise)
§ Krebs Cycle: an 8-step cycle that shuffles carbon atoms while oxidizing sugars to reduce NAD+ & FAD
· occurs in the mitochondrial matrix
· the resulting 3 NADH molecules and 1 FADH2 molecule per acetyl coA will enter the electron transport chain
· net gain of 1 ATP per acetyl coA
§ Electron Transport Chain & Oxidative Phosphorylation: NADH & FADH2 are oxidized, & the hydrogen ions removed are sent across the inner mitochondrial membrane while electrons are transported from protein to protein on the inner mitochondrial membrane
· the hydrogen ions are sent back across the mitochondrial membrane through an ATP synthase enzyme, releasing energy that is used by the enzyme to produce ATP from ADP & phosphate
· occurs on the inner mitochondrial membrane
· oxygen acts as an electron acceptor, & uses the transported electrons with available hydrogen atoms to form water
§ 36-38 ATP yield from the complete breakdown of 1 glucose molecule
§ Glycolysis: 2 ATP (net yield) & 2 NADH
§ Formation of Acetyl Coenzyme A: 2 NADH
§ Krebs Cycle: 2 ATP, 6 NADH & 2 FADH2
§ So far: 4 ATP, 10 NADH & 2 FADH2
§ Electron Transport Chain: yields 3 ATP per NADH & 2 ATP per FADH2
· this would typically result in 30 ATP from the 10 NADH & 4 ATP from the 2 FDH2, or 34 ATP
· 34 ATP from electron transport, added to the 4 ATPs produced previously yields a total of 38 ATP from aerobic respiration
· however, the 2 NADH from glycolysis were produced in the cytoplasm. These NADH molecules cannot enter the mitochondrion, but transfer their electrons to shuttle molecules, which then transfer the electrons to NAD+ or FAD molecules inside the mitochondrion. Most cell types use the glycerol phosphate shuttle, which transfers its electrons to FAD to form FADH2 & only yields 2 ATP per NADH; in heart, liver & kidney cells, the malate-aspartate shuttle transfers its electrons to NAD+ to form NADH & yields 3 ATP per NADH – hence the 36-38 ATP yield, depending on the cell type
o Glycogenesis: when more glucose is available than is needed for energy, glucose molecules are combined in long chains to form glycogen
§ occurs in liver & skeletal muscle cells
o Glycogenolysis: when blood glucose levels drop, glycogen lysis occurs, releasing glucose molecules from glycogen
o Gluconeogenesis: when too little glucose is available, glycerol & amino acids are converted to glucose
§ occurs in liver
- Lipid metabolism: fats are concentrated energy source; about twice as much energy can be gained from fats as from glucose (most cell types can use fats as an energy source, but some cell types (neurons & red blood cells) rely almost exclusively on glucose for energy
o Oxidation of glycerol & fatty acids: triglycerides are broken down into fatty acids and glycerol; glycerol enters glycolytic pathway while fatty acids are oxidized to acetic acid
§ Beta oxidation: fatty acids oxidized to acetic acid, to which coenzyme A is added & the acetyl coA enters the Krebs cycle
o Lipogenesis: triglyceride synthesis from acetyl coA & glycerol
§ occurs when cellular ATP & glucose levels are high (one of the problems with diets very high in sugars/carbohydrates)
o Lipolysis: breaking of stored fats into fatty acids & glycerol
- Protein metabolism: when more protein is ingested than needed for protein replacement, amino acids can be oxidized for energy or converted to fat
o Oxidation of amino acids: amino acids are converted to keto acids, which can then be converted to pyruvic acid & acetyl coA; occurs in liver & requires 3 steps:
§ Transamination: transfer of amine group from amino acid to a-ketoglutaric (keto) acid to form glutamic acid
§ Oxidative deamination: amine group of glutamic acid is removed as ammonia (which is combined with carbon dioxide & excreted as urea in urine) & keto acid
§ Keto acid modification: keto acid modified as necessary (to form pyruvic acid, acetyl coA) to enter energy pathways
o Synthesis of Proteins: protein synthesis is first priority for amino acids absorbed
§ 8 essential amino acids must be absorbed through digestive system from food
§ nonessential amino acids can be synthesized from other molecules in liver
- Catabolic-Anabolic Steady State of Body: organic molecules (proteins, carbohydrates, lipids) are continuously broken down & rebuilt
o Nutrient pools: the body¹s total supply of nutrients; most nutrients are interconvertible
§ amino acid pool: the body¹s total supply of free amino acids; must be converted to carbohydrate to be used for energy
§ carbohydrate pool: can be used directly for energy or stored
§ fat pool: can be used directly for energy or stored
- Absorptive State: the time during & shortly after eating when nutrients are actively being absorbed from GI tract
o Carbohydrates: absorbed monosaccharides are delivered to liver; fructose & galactose are converted to glucose; glucose is used for energy if necessary & excess is stored in liver as glycogen or converted to fat & stored in adipose tissue
o Triglycerides: collected in lymph & converted to fatty acids & glycerol; fatty acids & glycerol are used for energy if necessary or converted back to triglycerides & stored in adipose tissue
o Amino Acids: delivered to liver; remain in blood if needed for protein synthesis; otherwise, amino acids are deaminated to keto acids for use as energy
o Hormonal control: insulin released by pancreatic islets directs events of absorptive state
§ Insulin is primarily a hypoglycemic hormone; it removes glucose from blood into tissue cells, lowering blood sugar levels
§ Deficiency in insulin or malfunctional insulin receptors can lead to diabetes mellitus
- Postabsorptive state: between meals when blood sugar levels are falling
o Goal is to maintain blood glucose levels within normal limits (80-100 mg/100 ml)
§ Sources of glucose: glycogenolysis in liver & skeletal muscle cells; lipolysis in adipose tissue & liver (released glycerol is converted to glucose); catabolism of cellular protein (deamination of amino acids to keto acids & conversion of keto acids to glucose)
§ Glucose sparing: use of noncarbohydrate molecules for fuel to conserve glucose
o Hormonal control: glucagon released by pancreatic islets is a hyperglycemic hormone; it raises blood glucose levels
o Neural control: epinephrine released by sympathetic fibers mobilizes fat stores for energy & promotes glycogenolysis
- Role of Liver in Metabolism:
o Hepatocytes carry out many ( 500) metabolic functions
o Cholesterol metabolism & regulation of plasma cholesterol levels
§ cholesterol is used in synthesis of bile salts, steroid hormones, vitamin D & plasma membrane in all cells; also part of embryonic hedgehog protein
· ~ 15% of cholesterol comes from diet; rest is synthesized from acetyl coA
§ Lipoproteins & cholesterol transport:
· very low density lipoproteins (VLDLs): transport triglycerides from liver to tissues (primarily adipose tissue)
· low-density lipoproteins (LDLs): transport cholesterol to tissues (bad cholesterol)
· high-density lipoproteins (HDLs): transports excess cholesterol from tissues to liver for use in bile salts
- Regulation of Food Intake:
o neural signals: vagal nerve fibers communicate between gut & brain
o nutrient signals: increases in plasma levels of glucose, amino acids, fatty acids & leptin (satiety-related hormone released by adipose tissue) depress eating
o also, insulin appears to be an important satiety signal, & body temperature & psychological factors affect eating habits
- Regulation of Body Temperature:
o Hypothalamus is main integrating center for thermoregulation
§ Thermoregulatory centers include heat-loss center & heat-promoting center
- heat-promoting mechanisms: hypothalamic heat-promoting center activated
o vasoconstriction of cutaneous blood vessels (blood rerouted to internal organs)
o increase in metabolic rate
o shivering (contraction of skeletal muscle)
o enhanced thyroxine release (increases metabolism & heat)
- heat-loss mechanisms: hypothalamic heat-loss center activated
o vasodilation of cutaneous blood vessels (heat lost through skin)
o enhanced sweating
Chapter 25: The Urinary System
- kidneys lie in a retroperitoneal position in superior lumbar region
- renal hilus: cleft in concave medial surface of kidneys
o the ureters, renal blood vessels, lymphatics & nerves enter & exit kidneys at hilus & occupy renal sinus
- 3 layers of supportive tissue around kidney:
o renal capsule: fibrous CT on surface of kidney
o adipose capsule: attaches kidney to posterior abdominal wall
o renal fascia: dense fibrous CT surrounds kidney, other membranes & adrenal glands & anchors them to surrounding structures
- 3 regions to kidney interior:
o renal cortex: most superficial region
o renal medulla: deep to cortex; composed of medullary or renal pyramids
§ renal columns: inward extensions of cortex that separate pyramids
§ lobe: pyramid with its surrounding cortical tissue capsule
o renal pelvis: lateral to hilus within renal sinus & continuous with ureter leaving hilus
§ major calyces: branching extensions of pelvis; subdivide to form minor calyces
- Blood & Nerve Supply:
o Pathway of Blood: aorta®renal artery®segmental artery®lobar artery®interlobar artery®arcuate artery®interlobular artery®afferent arteriole®glomerulus (capillary bed)®efferent arteriole®peritubular capillaries & vasa recta®interlobular vein®arcuate vein®interlobar vein®renal vein®inferior vena cava
o Nerve Supply: renal plexus (network of ANS fibers & ganglia; largely supplied by sympathetic fibers)
- Nephrons: blood-processing units that form urine; consists of glomerulus associated with a renal tubule
o Glomerulus: tuft of capillaries associated with renal tubule
§ fenestrated capillaries allows fluid (filtrate) to pass from blood into glomerular capsule
o Glomerular (Bowman¹s) capsule: end of renal tubule; encloses glomerulus
§ parietal layer: simple squamous epithelium
§ visceral layer: highly modified branching epithelial cells called podocytes
· podocyte extensions terminate in foot processes
· filtration slits (slit pores): openings between foot processes that allow filtrate to pass into capsular space inside glomerular capsule
§ Renal corpuscle: glomerulus & glomerular capsule
o 3 parts to remainder of renal tubule:
§ proximal convoluted tubule (PCT)
· walls of simple cuboidal epithelial cells with microvilli; actively reabsorbs substances from filtrate & secretes substances into it
§ loop of Henle
· descending limb: cuboidal cells give way to simple squamous cells (thin segment)
· ascending limb: cells of wall again become cuboidal to low columnar (thick segment)
§ distal convoluted tubule (DCT): empties filtrate (urine) into collecting duct
· cuboidal cells mostly lacking microvilli (secretion rather than absorption)
· late in DCT (in connecting tubule) before collecting ducts, 2 cell types appear:
o intercalated cells: cuboidal cells with microvilli; maintain acid-base balance in blood
o principal cells: lack microvilli; help maintain water & sodium balance
o collecting ducts: receive urine from many nephrons; run through medullary pyramids & fuse to form papillary ducts at renal pelvis, which deliver urine to calyces
o cortical nephrons: ~ 85% of nephrons; almost entirely located within cortex
o juxtamedullary nephrons: remaining nephrons; near cortex-medulla junction; loops of Henle run deep into medulla
§ play role in production of concentrated urine
- Capillary beds (Microvasculature) of Nephron
o Glomerulus fed by afferent arterioles & drained by efferent arterioles
§ Peritubular capillaries: arise from most efferent arterioles draining glomeruli
§ Vasa recta: in deepest part of cortex, efferent arterioles form bundles of long straight vessels (rather than emptying into peritubular capillaries) serving juxtamedullary nephrons
o vascular resistance in microcirculation protects glomeruli from fluctuations in systemic blood pressure
- Juxtaglomerular apparatus: region in nephron where initial portion of DCT lies against arteriole feeding glomerulus
o Juxtaglomerular (JG) cells: smooth muscle cells with secretory granules containing renin
§ Act as mechanoreceptors to sense blood pressure in afferent arteriole
o macula densa: group of tall, closely packed DCT cells that lies adjacent to JG cells
§ act as chemoreceptors (or osmoreceptors) that respond to changes in solute content
o mesangial cells: appear to play a role in controlling rate of filtration
- Filtration membrane: filter that lies between blood & interior of glomerular capsule; consists of:
o fenestrated endothelium of glomerular capillaries: allows all plasma components but not blood cells to pass
o visceral membrane of glomerular capsule (made of podocytes)
o Intervening basement membrane composed of fused basal laminas of other layers: restricts large proteins but allow small proteins & solutes to pass
- ~1000-2000 ml blood pass through glomeruli each minute; ~650 ml of this is plasma; ~120-125 ml of plasma is forced into renal tubules
- filtrate: everything in blood plasma except proteins
- urine: mostly metabolic wastes & unneeded substances (filtrate without most water, nutrients & essential ions)
- Glomerular filtration: mostly a passive, nonselective process in which fluids & solutes are forced through a membrane by hydrostatic pressure
o glomerulus is a much more efficient filter than tissue capillary beds because:
§ filtration membrane is thousands of times more permeable to water than other capillary membranes
§ glomerular blood pressure is much higher than other capillary beds (~55 mm Hg vs. ~18 mm Hg), resulting in a much higher net filtration pressure
o Net filtration pressure (NFP): NFP = Hpg – (Opg + Hpc)
§ normally ~ 10 mm Hg
§ glomerular hydrostatic pressure (Hpg): chief force pushing water & solutes out of blood across filtration membrane; normally ~ 55 mm Hg
§ colloid osmotic pressure of glomerular blood (Opg): normally ~ 30 mm Hg
§ capsular hydrostatic pressure (Hpc): exerted by fluids in glomerular capsule; normally ~ 15 mm Hg
o Glomerular filtration rate (GFR): total amount of filtrate formed per minute by kidneys
§ Directly proportional to NFP; normally ~ 120-125 ml/min.
o Regulation of Glomerular Filtration:
§ Renal autoregulation (intrinsic controls): kidney adjusts its own resistance to blood flow to maintain a nearly constant GFR despite fluctuations in systemic blood pressure
· myogenic mechanism: increase or decrease in systemic blood pressure causes afferent arterioles to constrict or relax, restricting or enhancing blood flow to glomerulus
· tubuloglomerular mechanism: macula densa cells of juxtaglomerular apparatus in walls of distal tubules respond to filtrate flow by releasing or inhibiting release of chemicals that produce vasoconstriction of afferent arterioles
o also activates the renin-angiotensin mechanism
§ Sympathetic nervous system controls: when sympathetic division of ANS is activated, norepinephrine & epinephrine cause constriction of afferent arterioles
· also activates the renin-angiotensin mechanism by stimulating macula densa cells
§ Renin-angiotensin mechanism: renin released by JG cells converts angiotensinogen in plasma (made by liver) to angiotensin I, which is in turn converted to angiotensin II by angiotensin-converting enzyme (ACE)
· Angiotensin II is a potent vasoconstrictor that raises mean arterial blood pressure
· Angiotensin II also stimulates adrenal cortex to release aldosterone, which causes renal tubules to reabsorb more sodium ions from filtrate
o Since water follows sodium, blood volume & blood pressure rise
· renin release is triggered by reduced stretch of JG cells, stimulation of JG cells by macula densa cells, direct stimulation of JG cells by epinephrine or norepinephrine, & direct stimulation of JG cells by angiotensin II
o Tubular reabsorption: transepithelial process that reclaims most of tubule contents & returns them to blood
§ Sodium reabsorption: primary active transport
· Sodium enters the tubule cell from the filtrate at the luminal membrane
· Sodium is actively transported out of the tubule cell by a sodium-potassium ion ATPase pump in the basolateral membrane
· Sodium moves passively by diffusion into the peritubular capillaries
§ Reabsorption of water, ions & nutrients: passive & secondary active transport
· Passive tubular reabsorption: anions (chloride & bicarbonate)
· Secondary active transport: glucose, amino acids, lactate, vitamins & most cations are transported along with sodium
§ Nonreabsorbed substances: some substances are not reabsorbed because they lack carriers, are not lipid soluble, or are too large
· Most important are urea, creatinine & uric acid
§ Absorptive capabilities of different regions of renal tubules
· PCT cells are most active reabsorbers
· Loop of Henle: reabsorbs water, sodium, chloride & potassium ions
o water can leave descending limb but not ascending limb
· DCT cells can reclaim some water, sodium & chloride ions
o Reabsorption of sodium regulated by aldosterone
o Tubular secretion: reverse reabsorption; substances such as hydrogen & potassium ions, creatinine, ammonium ion, & some organic acids can move from blood of the peritubular capillaries through tubule cells into filtrate
§ Urine excreted would contain both filtered & secreted substances
§ PCT is main site of secretion
§ Secretion important for: disposing of substances not already in filtrate (drugs), eliminating unwanted substances (urea & uric acid), elimination of excess potassium ions & controlling blood pH
- Formation of dilute urine: normal course of filtration; low antidiuretic hormone (ADH) levels & collecting ducts remain impermeable to water
- Formation of concentrated urine: increased release of ADH from posterior pituitary inhibits diuresis (urine output) by increasing reabsorption of water from collecting ducts (by creating water channels - aquaporins)
Diuretics: chemicals that enhance urinary output through inhibition of water or sodium ion reabsorption or increased osmotic pressure in kidney tubules
- alcohol inhibits ADH release, while caffeine & drugs such as Lasix & Diuril inhibit sodium ion reabsorption
Renal clearance (RC): volume of plasma that is cleared of a particular substance in a given time (1 minute)
- used to determine GFR (glomerular filtration rate) & assess renal function
- uses a molecule such as inulin that is not reabsorbed, stored or secreted as a standard (RC = 125 ml/min)
Ureters: tubes that convey urine from kidneys to bladder
- pressure increases in bladder during filling normally compress & close the distal ends of the ureters, preventing backflow
- mucosa lined with transitional epithelium; muscularis with inner longitudinal & outer circular smooth muscle sheets; adventitia of fibrous CT
- contraction of smooth muscle propels urine to bladder
- renal calculi (kidney stones): form from crystallization of salts in urine in renal pelvis; can obstruct ureters
o surgical removal has generally been replaced by shock wave lithotripsy (ultrasonic shock breaks up stones)
Urinary Bladder: collapsible muscular sac that stores urine temporarily
- trigone: triagonal region encompassing openings for both ureters & opening for urethra
- mucosa lined with transitional epithelium; muscularis (detrusor muscle) with inner longitudinal, middle circular & outer longitudinal smooth muscle sheets; adventitia of fibrous CT
- very distensible; collapses when no or little urine present & expands to accommodate urine
Urethra: muscular tube that drains urine from bladder & conveys it out of body
- epithelium of mucosa changes from transitional to pseudostratified columnar to stratified squamous near external urethral orifice
- internal urethral sphincter: near bladder; smooth muscle (involuntary control)
- external urethral sphincter: near urogenital diaphragm; skeletal muscle (voluntary control)
- in males: prostatic urethra, membranous urethra & spongy (penile) urethra lead to external urethral orifice
Micturition (voiding or urination): act of emptying bladder
- when ~ 200 ml or urine has accumulated in bladder, contractions of bladder due to activation of stretch receptors & spinal reflexes in turn activates voiding reflexes
- the micturition center of the pons signals parasympathetic neurons that stimulate contraction of the detrusor muscle & relaxation of the internal & external sphincters, allowing urine expulsion
- voluntary control of the external sphincter allows urine retention
- incontinence: inability to control micturition (normal in infants)
- urinary retention: bladder unable to expel urine (can occur following anesthesia or in males with prostate hypertrophy)