Term
| What is the daily input/output balance of the GI tract on a daily basis (daily fluid load)? |
|
Definition
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|
Term
| What contributes to the influx of NaCl in the villus enterocytes? |
|
Definition
| NHE (Na/H antiport) and Cl/HCO3 exchange on the apical membrane; leads to net absorption of NaCl, and secretion of H + HCO3 |
|
|
Term
| On villus enterocytes, what ion channels/transporters are present on the apical membrane? |
|
Definition
| NHE (Na/H antiport); Cl/HCO3 exchange; SGLT1 (Na/glucose symport; 2:1 ratio) |
|
|
Term
| What are the ion channels/transporters on the basal membrane of villus enterocytes? |
|
Definition
Na/K-ATPase - creates Na gradient used for secondary active transport
GLUT2 - transports glucose into ECF from enterocyte |
|
|
Term
| Where does net Cl secretion occur in the small intestines/large intestines (from which "area")? |
|
Definition
It occurs mainly from the CRYPT cells via the CFTR channel on apical membrane
Cl is transported into the cell from the NKCC channel on the basal membrane -> Cl is secreted by CFTR channel |
|
|
Term
| What is used to drive glucose uptake in the small intestine? |
|
Definition
| The Na electrochemical gradient - glucose gets absorbed by SGLT1 2 Na/1 glucose symport |
|
|
Term
| How does "cholera toxin" stimulate excessive fluid loss from the body? |
|
Definition
It activates 2nd messenger pathways (increase cAMP)
cAMP increase functions to:
- Stimulate CFTR
- INHIBIT Na/H exchange, Cl/HCO3 exchange (apical)
Net function is to stimulate Cl secretion, while inhibiting NaCl absorption |
|
|
Term
| What is one membrane transporter not affected by cholera toxin? |
|
Definition
| SGLT1 on the apical membrane is not affected (makes treating with glucose ORS effective) |
|
|
Term
| How does the ORS stimulate less fluid loss? |
|
Definition
Contains a high concentration of glucose -> increases glucose reabsorption by SGLT1; in doing so thereby will also increase Na absorption (b/c Na/glucose symport)
This creates a stronger gradient for water to be reabsorbed, so less water is present in the feces. |
|
|
Term
|
Definition
| The maintenance of a relatively constant internal environment |
|
|
Term
|
Definition
Motility - muscular contractions to mix & move food
Secretion - enzymes, water, electrolytes released under neural & hormonal stimuli
Digestion - food breakdown into smaller, absorbable units
Absorption - small units absorbed via enterocytes, transported from GI lumen to circulation (blood/lymph) |
|
|
Term
| Types of Motility in GI tract |
|
Definition
Propulsive Movements - push contents forward
Mixing Movements - mix food w/ digestive juices and maximize SA exposure for absorption |
|
|
Term
| What are the reabsorbable monomer units of the macromolecules? |
|
Definition
Carbs = monosaccharides
Proteins = aa's, small peptides
Lipids = glycerol + fatty acids |
|
|
Term
|
Definition
Mucosa - epithelium, lamina propria, muscularis mucosa
Submucosa - submucosal plexus, CT, BVs
Musc. Externa - inner circular, outer longitudinal; in between layers have myenteric plexus
Serosa |
|
|
Term
| How does mucin become mucous? |
|
Definition
| By hydration (hydroxylation); mucin-OH = mucus |
|
|
Term
| What is the main structural unit which allows for Na/Cl and water reabsorption in the intestines? |
|
Definition
| The villus enterocytes function to account for the majority of NaCl and H2O absorption |
|
|
Term
| How much of an increase do the presence of villi and microvilli allow for the SA of the small intestine? |
|
Definition
|
|
Term
| Why is the Na/K ATPase necessary for nutrient absorption? |
|
Definition
| Because it creates the Na-gradient that is used to drive solute and water absorption in the intestines |
|
|
Term
| What exists in between adjacent enterocytes? |
|
Definition
Have leaky junctions which permit the paracellular movement of water and solutes
Junctions are composed of adherence junctions & desmosomes |
|
|
Term
| Where does the lymphoid tissue of the gut reside? |
|
Definition
| In the lamina propria (GALT) |
|
|
Term
| What is the main structural difference between the mucosae of the small and large intestines? |
|
Definition
| The large intestine contains NO villi |
|
|
Term
| 3 Methods of Communication in the GI tract |
|
Definition
Neural (Neurocrine) - sensory neurons release NT @ target cells
Endocrine - hormone effects
Paracrine - paracrine agents affect physically juxstaposed cells |
|
|
Term
| Parasympathetic Innervation to the GI tract |
|
Definition
Vagal Nerves (from medulla) - esophagus, stomach, small intestines
Pelvic Nerves (from SC) - descending colon |
|
|
Term
| Sympathetic Innervation to the GI tract? |
|
Definition
ALL act as prevertebral ganglia
Celiac - esophagus + stomach
S. Mesenteric - small intestine + ascending colon
I. Mesenteric - descending colon |
|
|
Term
| Where does all autonomic NS innervation act on in the gut? |
|
Definition
| Acts on submucosal and myenteric plexuses to affect the GUT tissue |
|
|
Term
| Difference between parasympathetic & sympathetic innervation in gut function? |
|
Definition
Parasympathetic = stimulate secretion/function
Sympathetic = inhibit secretion/function |
|
|
Term
|
Definition
Based on "cognitive stimuli" - sight/smell of food; hearing of conditioned stimulus
Activates GI tract to be ready for a meal |
|
|
Term
| What type of innervation does the cephalic phase trigger? |
|
Definition
Triggers activation of the dorsal motor nucleus in the MEDULLA OBLONGATA
Leads to increase in activity from vagal efferents from brainstem to GI tract - activates post-ganglionic motor neurons in GI tract |
|
|
Term
| Result of increased parasympathetic innervation in cephalic phase? |
|
Definition
Increased salivary secretion (****mediated by CN IX, NOT vagus nerve)
Gastric acid secretion from parietal cells (stomach)
Pancreatic enzyme secretion from acini
Gall bladder contraction & relaxation of sphincter of Oddi |
|
|
Term
| What nerve mediates salivary secretions? |
|
Definition
HYPOGLOSSAL nerve (CN IX)
ALL other reactions in cephalic phase are mediated by vagus efferents |
|
|
Term
| Two cell types in salivary glands: |
|
Definition
Acinar Cells - cells at back of glands; secrete proteins of the saliva (amylase, lipase, lysozyme, mucin)
Duct Cells - secrete K and HCO3 (alkaline solution) |
|
|
Term
| What is the relative composition of saliva? |
|
Definition
| 99.5% water, 0.5% electrolytes & proteins |
|
|
Term
| What are the proteins present in saliva, where are they secreted from, and what are their functions? |
|
Definition
All are secreted by the acini of the salivary glands.
Amylase - begin starch digestion
Mucin - glycoprotein for lubrication
Lysozyme - antibacterial agent
Lipase - fat digestion |
|
|
Term
| What is the tonicity of saliva in NON-stimulated conditions? |
|
Definition
| It is hypotonic; when the cephalic phase begins, CN IX innervation causes the change to nearly isotonic secretions in salivary fluid |
|
|
Term
| What are the secretions of the acini and duct cells of salivary glands, respectively? |
|
Definition
Acini - secretion of mucin, amylase, lipase, lysozyme which is isotonic
Duct Cells - secretion mainly of electrolytes, HCO3 (buffers), which is alkaline and hypotonic |
|
|
Term
| What mediates release of proteins from salivary acini? |
|
Definition
Neural/hormonal stimuli (e.g. Ach, VIP) cause an influx of extracellular Ca2+ -> leads to Ca depedent signalling in the cell
This signalling opens apical ion channels to allow secretion into lumen
Cl flows via Cl channels; Na, H2O take paracellular pathway via leaky junctions |
|
|
Term
| What is the function of duct cells in the salivary glands? |
|
Definition
Modify salivary secretions by reabsorbing NaCla nd secreting K and HCO3-
Secretion of DUCTS (only from duct cells) is hypotonic and alkaline |
|
|
Term
| What type of salivary solution is produced by mixing of ductal and acinar secretions? |
|
Definition
| An alkaline, isotonic saliva |
|
|
Term
| Two-Stage Model of Salivary Secretion |
|
Definition
Acinar cells secrete proteins; have basal receptors for Ach - parasympathetic innervation triggers protein release and ion release (isotonic solution)
Duct Cells - also have basal Ach receptors; primary ion secretion = K & HCO3; also function to reabsorb NaCl; creates a ductal secretion that is alkaline, hypotonic
Secretions mix to give net isotonic, alkaline salivary solution |
|
|
Term
| Which two NTs can stimulate an increase in flow of salivary secretion? |
|
Definition
|
|
Term
| How can a conditioned reflex elicit a salivary response? |
|
Definition
| Have pressure and chemoreceptors above the salivary center in the medulla (above dorsal motor nucleus); cognitive stimuli activate parasympathetic efferents to stimulate secretion |
|
|
Term
| What type of response/reflex is swallowing? |
|
Definition
| ALL or NONE; can be voluntarily initiated, but once initiated, cannot stop (will go to completion) |
|
|
Term
|
Definition
Tip of tongue presses back on soft palate - soft palate elevates to block off nasopharynx, palatopharyngeal arches move into one another
Epiglottis lowers and larynx moves up to block off trachea, also vocal folds close and UES relaxes (as UES relaxes, so does LES)
When bolus touches back of throat, pharyngeal muscles constrict to push bolus into pharynx and initiate peristaltic wave of contraction down to the esophagus... |
|
|
Term
| What is the relation between activation of the swallowing center in the medulla and its effects on the respiratory center? |
|
Definition
| When the swallowing center is initiated, the respiratory center is automatically inhibited |
|
|
Term
| Main functions of UES and LES |
|
Definition
UES - propel bolus away from mouth, into esophagus; protect airway during swallowing
LES - protect esophagus from acid reflux |
|
|
Term
| What stimulates the opening of the LES following opening of the UES? |
|
Definition
| The pressure change associated with the opening of the UES causes a neural reflex to relax LES |
|
|
Term
| 3 sections of the stomach |
|
Definition
Fundus - proximal to esophagus
Body - main portion
Antrum - distal portion containing the pylorus |
|
|
Term
| Where do the main gastric secretions occur? |
|
Definition
| Near the fundus (top); get HCl, intrinsic factor, mucus, pepsinogen, etc. mainly here |
|
|
Term
|
Definition
See non-permanent mucosal folds - RUGAE
Gastric mucosa is lined with Gastric Pits (parietal & chief cells) |
|
|
Term
|
Definition
Parietal cell - near neck of pits; secrete HCl and intrinsic factor
Chief Cells - secrete pepsinogen; at base of pit |
|
|
Term
| Two types of gastric mucosa |
|
Definition
Oxyntic Mucosa - lines body and fundus
Pyloric Gland Area - lines antrum of stomach |
|
|
Term
| Where are gastric pits located? |
|
Definition
| Located at the BASE of gastric glands; deep in mucosa of stomach |
|
|
Term
| What are the 3 types of gastric exocrine secretory cells? |
|
Definition
Mucus Neck Cells - secrete mucin (hydrated to mucus)
Parietal Cells - secrete HCl & intrinsic factor
Chief Cells - secrete pepsinogen |
|
|
Term
| Phases of Gastric Secretion |
|
Definition
Cephalic - autonomic (parasymp) stimuli cause increase in HCl and pepsinogen secretion BEFORE food reaches stomach
Gastric - when food reaches stomach; increases secretion further
Intestinal - inhibitory; shuts off flow of gastric juice as chyme enters the duodenum |
|
|
Term
| What stimulates the release of pepsinogen from Chief Cells? |
|
Definition
Ach - from ENS, vagal efferents
Gastrin - from G cells of antrum
Histamine - from ECL cells in body
ALL 3 secretions needed for pepsinogen secretion; same secretions mediate HCl secretion from parietal cells |
|
|
Term
| Functions of HCl in gastric lumen |
|
Definition
Activate pepsinogen -> pepsin; protein digestion & optimal pH for enzyme activity
Aid in CT and muscle breakdown of food
Kill microorganisms |
|
|
Term
| Steps of Gastric Acid Secretion |
|
Definition
Mediator = H/K ATPase on APICAL membrane to generate gradient for transport
CO2 diffuses from lumen into parietal cell; in cell CA creates carbonic acid <-> H + HCO3; H pumped into lumen by ATPase; on basal membrane Cl/HCO3 exchange pumps Cl in, HCO3 out to ECF
Cl channel on apical membrane secretes Cl into gastric lumen
NET SECRETION of Cl and H into the gastric lumen (dissociated HCl) |
|
|
Term
| Effects of Ach on parietal cells? |
|
Definition
Acts on muscarinic receptor on basal membrane -> GPCR -> increases in intracellular calcium; stimulate PKC
Protein kinase C (PKC) STIMULATES H/K ATPase to lead to more net HCl secretion |
|
|
Term
| Effects of Histamine on parietal cells? |
|
Definition
| Interacts at GPCR (H2 receptor) to stimulate increase in cAMP -> also stimulates activity of H/K ATPase |
|
|
Term
| What is secreted by Chief Cells in the stomach and what mediates their secretion? |
|
Definition
Stimulated by - Ach, secretin, HCl
Secrete - pepsinogen & lipase |
|
|
Term
| What is secreted by G cells in the stomach, and what mediates their secretion? |
|
Definition
Stimulated by - Ach, presence of proteins and lipids in gastric lumen
Secretes - gastrin (peptide hormone) |
|
|
Term
| What is secreted by ECL cells in the stomach, and what mediates their secretion? |
|
Definition
Stimulated by - Ach, gastrin
Secretes - histamine |
|
|
Term
| Overview of Gastric Acid Secretion: |
|
Definition
Cephalic reflex triggers vagal efferents to increase activity and Ach release to parietal, chief, G and ECL cells (direct stimulation)
G cells produce gastrin which acts directly on parietal cells, and on ECL cells (produce histamine, paracrine effect on parietal cells)
Presence of acid in lumen (HCl) stimulates pepsinogen secretion from the chief cells -> acid converts to pepsin
Eventually, excess luminal acid causes somatostatin release from D cells which negatively feeds back on parietal, G, and ECL cells (stop acid secretion) |
|
|
Term
| Types of responses involved in gastric secretion (neural, endocrine, paracrine) |
|
Definition
Neurocrine - effects of Ach directly on parietal cells
Endocrine - effects of gastrin from G cells on parietal cells
Paracrine - effects of histamine from ECL cells on parietal cells |
|
|
Term
| What stimulates somatostatin release from D cells in the stomach? |
|
Definition
| The presence of acid in the gastric lumen; functions to reduce activity of G cells to reduce acid secretion |
|
|
Term
| GI Vocab - Deglutition, Borborygmi, Chyme |
|
Definition
Deglutition - swallowing
Borborygmi - rumbling noises in GI tract from gas
Chyme - bolus mixed w/ gastric acid & pancreatic juice |
|
|
Term
| When does pepsinogen secretion begin? |
|
Definition
| In the CEPHALIC phase (due to vagovagal efferents activating chief cells by Ach release); also gastrin release from G cells (b/c of Ach) triggers pepsinogen release during cephalic phase |
|
|
Term
|
Definition
Apical gastric epithelium are IMPERMEABLE to H (HCl cannot enter); cells have impermeable junctions to prevent leakage of acid from stomach lumen
Surface epithelium are bathed with mucous secretions |
|
|
Term
| What prevents from acidic digestion of the stomach epithelium? |
|
Definition
| Gastric epithelium produce mucin & bicarbonate; mucus layer above epithelium is rich in bicarbonate |
|
|
Term
| pH difference between gastric mucus and gastric lumen |
|
Definition
pH of lumen = 2
pH of mucus = 7 |
|
|
Term
| How is H/Cl secreted by parietal cells despite the presence of the gastric-mucosal barrier? |
|
Definition
| By "fingering" - parietal cells produce a constant stream of acid so it does not diffuse into the mucus layer |
|
|
Term
| What functions to stimulate and inhibit the H/K ATPase that drives gastric acid secretion? |
|
Definition
Stimulate - PKC, PKA (both are protein kinases which increase ATPase activity)
Inhibit - omeprazole, H2 blockers (omeprazole inhibits ATPase; H2 blockers prevent histamine binding to its GPCR) |
|
|
Term
| Types of Gastric Motility |
|
Definition
Filling - receptive relaxation mediated by vagus nerve and triggered by eating
Storage - in body of stomach
Mixing - in antrum of stomach
Emptying - regulated by duodenal factors |
|
|
Term
| Interstitial Cells of Cajal |
|
Definition
Similar to fibroblasts & smooth muscle cells
Generate continuous, slow wave activity (can respond to vagal stimulation to alter rate)
Spontaneously depolarize to act as the pacemakers of the GUT |
|
|
Term
| How do cells of Cajal act on smooth muscle to initiate contraction? |
|
Definition
| Act on L-type Ca channel to cause Ca influx -> contraction |
|
|
Term
| When do cells of Cajal fire APs? |
|
Definition
If the threshold level is reached by the slow wave potentials
Force AND duration of contraction is directly related to amplitude and frequency of APs (graded potentials) |
|
|
Term
| Process of Gastric Mixing |
|
Definition
Bolus of food is pushed down to close pylorus - increases pressure in antrum of stomach -> causes contraction of the antrum (more increase in pressure)
Contraction pushes the bolus back upwards (retropulsion) - mixes & pulverizes bolus |
|
|
Term
| What is the force of gastric propulsion (retropulsion) related to? |
|
Definition
| The size of the meal; the larger the meal, the stronger the force of propulsion |
|
|
Term
| What duodenal factors regulate gastric emptying? |
|
Definition
Presence of lipids - if lipids are already present in duodenum, gastric emptying does not occur
Presence of acid - inhibits emptying
Hypertonicity of duodenal fluid inhibits emptying
Distension - excessive chyme in duodenum inhibits gastric emptying |
|
|
Term
| How can factors outside the GI tract mediate gastric emptying? |
|
Definition
Emotion - alter autonomic balance
Pain - increase in sympathetic activity, inhibits emptying |
|
|
Term
| Gastric emptying in saline vs. acid vs. oleate (protein) |
|
Definition
| Gastric emptying is FASTEST with saline solution, SLOWEST with protein & fat solution (because of more time needed for digestion) |
|
|
Term
| What is emptied faster from the stomach, glucose or protein? |
|
Definition
| Glucose is emptied faster |
|
|
Term
| Secretions of the exocrine pancreas? |
|
Definition
Pancreatic Proenzymes - actively secreted by ACINAR cells
Aqueous Alkaline Solution - actively secreted by DUCT cells |
|
|
Term
| What regulates pancreatic secretions? |
|
Definition
|
|
Term
| What is common to all enzymes released by the pancreas? |
|
Definition
| They are all stored in a zymogen form and not activated until within the duodenal lumen |
|
|
Term
| What is the 1st pancreatic enzyme to be converted to its active form? |
|
Definition
|
|
Term
| Pancreatic proenzyme activation in the duodenum: |
|
Definition
Trypsinogen is cleaved by enteropeptidase on the enterocyte brush border -> trypsin
Trypsin then activates all other pancreatic zymogens |
|
|
Term
| What stimulates acinar secretion and ductal secretion from the exocrine pancreas? |
|
Definition
CCK - stimulates ACINAR secretion of enzymes
Secretin - stimulates DUCTAL secretion of alkaline solution |
|
|
Term
| When does pancreatic secretion of enzymes NOT occur? |
|
Definition
| Does not occur in the fasting state -> only get zymogen release after eating has begun (after secretin release) |
|
|
Term
| Signal Transduction by Secretin vs. CCK in Exocrine Pancreas |
|
Definition
Secretin - binding causes increase cAMP -> protein phosphorylation and zymogen release
CCK - binding causes increase in intracellular Ca -> phosphorylation leads to exocytosis of zymogens |
|
|
Term
| Secretin Stimulation of Pancreatic Ductal Cells |
|
Definition
Leads to net secretion of HCO3 into lumen
On basal membrane - NBC-1 = 2 HCO3/1 Na symport into cells; NHE
On apical membrane - HCO3/Cl antiport (pumps all HCO3 into lumen); CFTR channel to regulate Cl balance
CO2 diffuses into the cell; converted by CA to H + HCO3 -> creates bicarbonate ions to be secreted into duct |
|
|
Term
| Negative feedback loop of secretin |
|
Definition
Chyme enters duodenum to decrease pH -> trigger for secretin release from S cells
Secretin acts on pancreatic duct cells to cause secretion of alkaline pancreatic juice to neutralize acid (rise in pH is the negative feedback to decrease secretin release from S cells) |
|
|
Term
| CCK release from duodenal I cells |
|
Definition
Trypsin activates binding of CCK-RP and monitor protein to I cells in duodenum (crypts)
CCK release is mediated by presence of fats & proteins in the duodenal lumen
Stimulates release of proenzymes from pancreatic acini (and contraction of gallbladder) |
|
|
Term
| Triggers for secretin & CCK release |
|
Definition
Secretin - presence of acid in duodenal lumen; causes alkaline pancreatic juice from duct cells in pancreas
CCK - caused by fat & proteins in duodenal lumen; causes proenzyme release from pancreatic ACINI |
|
|
Term
| Where does secretin act in the small intestines? |
|
Definition
| Acts to stimulate bicarbonate ion production from Brunner's submucosal glands |
|
|
Term
| Types of motility in the small intestine |
|
Definition
Segmentation
Migrating Motility Complex |
|
|
Term
| Where does the main absorption of carbs, proteins, and lipids occur? |
|
Definition
| In the duodenum (small amounts in jejunum & ileum) |
|
|
Term
| Where does the main absorption of bile salts occur? |
|
Definition
|
|
Term
| What are ways used by the small intestines to increase the surface area of reabsorption? |
|
Definition
| Microvilli, villi, plicae circulares (mucosal folds) |
|
|
Term
| How are monosaccharides absorbed in the small intestine? |
|
Definition
| By a transcellular pathway in their monomer form |
|
|
Term
| What is the secretion of the duodenal glands? |
|
Definition
An HCO3- rich secretion with isotonic saline solution; released from crypts
Duodenal secretion = "succus entericus"
Contains NO digestive enzymes |
|
|
Term
| What enzymes are located on the brush border of intestinal villi? |
|
Definition
Enterokinase - cleaves trypsinogen -> trypsin
Disaccharidases - cleave sugar dimers into monosaccharides
Aminopeptidases - exopeptidases which hydrolyze peptide bonds |
|
|
Term
| Where does most absorption occur in the small intestines? |
|
Definition
| In the duodenum and jejunum |
|
|
Term
| How often is the intestinal epithelium replaced/regeneratd? |
|
Definition
|
|
Term
| What faciliates the absorption of products of fat digestion? |
|
Definition
| Lymphatic capillaries = LACTEALS |
|
|
Term
| Monosaccharide Absorption in Small Intestine |
|
Definition
SGLT1 - functions for glucose and galactose uptake into enterocytes (w/ Na symport); GLUT2 can be used on basal membrane for glucose & galactose transport
GLUT5 - on apical membrane, used for fructose absorption; then fructose uses GLUT2 on basal membrane to enter ECF |
|
|
Term
| How can the intracellular glucose concentration be driven above its equilibrium value? |
|
Definition
| By use of the SGLT1 transporter - couples glucose absorption with the Na gradient to drive above equilibrium value |
|
|
Term
| Why did GLUT2 knockout mice not die? |
|
Definition
| When glucose is absorbed into cell by SGLT1, it can be phosphorylated to G6P -> can use exocytosis to allow for glucose to exit basal membrane (don't need GLUT2 transporter) |
|
|
Term
| In which two ways can glucose be absorbed to maximize its intestinal absorption? |
|
Definition
| Can be transcellular (SGLT1 -> GLUT2); can also be paracellular - SGLT1 makes junctions more leaky for paracellular transport |
|
|
Term
| What causes the pH change associated with absorption of glucose? |
|
Definition
SGLT1 activates the Na/H exchange to facilitate the Na gradient (balance) between the lumen & enterocyte
SGLT1 activates NHE -> causes an increase in pH (i think, don't quote me on this) |
|
|
Term
|
Definition
Endopeptidase - cleaves internal peptide bonds
Exopeptidase - cleaves terminal peptide bonds; can either be carboxy or amino (amino is more common) |
|
|
Term
| Different ways of protein absorption in the intestine? |
|
Definition
Free a.a.'s can be absorbed by Na-dependent transport
Di/tripeptides can be absorbed by PEPT1 (Na independent, H depdendent)
Small peptides can be transported through the cell via transcytosis
**Note that protein absorption can be Na-dependent OR Na-independent |
|
|
Term
| What occurs to the size of the villi during digestion? |
|
Definition
| They increase in volume -> increase in size; volume increase is regulated by Na cotransport |
|
|
Term
| Fat Absorption in Intestines |
|
Definition
Bile salts coat small fat droplets in the intestinal lumen to form an emulsion (micelle formation); makes fats soluble
Monoglycerides and fatty acids are taken into villi by diffusion; cholesterol is transported by membrane transporter
ALL combine in cells to form chylomicrons - released and absorbed by lacteals in lamina propria |
|
|
Term
| What is the primary method of motility in the small intestine? |
|
Definition
Segmentation - ring like contractions along the length of the small intestine; altering of contracted and relaxed segments leads to mixing of contents and more exposed area for absorption
No net forward movement |
|
|
Term
| What influences the responsiveness of circular smooth muscle in the intestines? |
|
Definition
| Distension (amount of contents), gastrin (from G cells in stomach), extrinsic nerve activity (vagal) |
|
|
Term
| Main Functions of Segmentation in S. Intestine |
|
Definition
Mix chyme with digestive juices (promote digestion)
Expose all chyme to absorptive surfaces of intestines |
|
|
Term
| Process of Segmentation in S. Intestine |
|
Definition
Simultaneous contraction & relaxation of alternating circular muscle areas in the intestines
No net forward movement, only facilitate digestion |
|
|
Term
| Migrating Motility Complex |
|
Definition
SWEEPS intestines clear in between meals
Initiated by interstitial cells of Cajal (same initiation as segmentation)
Occurs simultaneously w/ action of filling stomach and pancreatic secretions
Is NOT a physical entity, just migrating contractile activity in circular muscle |
|
|
Term
| What is relation to feeding and the electrical activity in the intestines? |
|
Definition
During feeding, electrical activity is CONSTANT (no migrating motility complex)
During fasting, electrical activity is NOT constant, activation of migrating motility complex |
|
|
Term
| How does SGLT1 lead to increased water absorption? |
|
Definition
| For every 2 Na/1 moc glucose transported by SGLT1, it causes 210-260 moc. of water to be simultaneously absorbed as well |
|
|
Term
| What is the driving force for most water reabsorption in the small intestine? |
|
Definition
| Electroneutral absorption of NaCl (by NHE and DRA transporters) which creates a stronger osmotic gradient for water reabsorption |
|
|
Term
| Methods of Na entering enterocytes from lumen |
|
Definition
SGLT1 - mainly in jejunum
NHE (Na/H antiport) - in jejunum and duodenum
Parallel transport by NHE and DRA - net absorption of NaCl |
|
|
Term
| What is the main method of NaCl absorption in the intestines? |
|
Definition
| Parallel transport by NHE (Na/H) and DRA (Cl/HCO3) exchangers; net absorption of NaCl, net secretion of H + HCO3 |
|
|
Term
| How does NaCl enter the ECF from the enterocytes? |
|
Definition
Na - by Na/K ATPase on basolateral membrane
Cl - by Cl channel on basolateral membrane |
|
|
Term
| Mechanism of Cl secretion in the Intestines |
|
Definition
NKCC transporter on basal membrane -> then Cl leaves into lumen by CFTR channel on apical membrane
Cl secreting cells are found mainly in intestinal crypts |
|
|
Term
| Mechanism of Na secretion in intestines |
|
Definition
| Mainly occurs via the paracellular pathway; due to gradient created by Cl secretion by the transcellular pathway |
|
|
Term
| Ion channels affected by cholera toxin |
|
Definition
Stimulates NKCC (basolateral), CFTR (apical)
Inhibits NHE (apical), DRA (apical)
Net Cl secretion; inhibition of NaCl absorption |
|
|
Term
| Acid Base Balance in the Stomach, Pancreas & Intestines |
|
Definition
Parietal Cells - extract Cl, H2O, CO2 from blood; secrete HCO3 into blood, HCl into lumen
Pancreatic Duct Cells - extract Na & HCO3 from blood; secrete NaHCO3 (ionic salt; buffer)
In duodenal lumen, have ion cycling of Na, Cl, CO2, and H2O from the lumen into the blood |
|
|
Term
|
Definition
| Measures NaCl absorption as a function of the ion rate of transport |
|
|
Term
| In an Ussing chamber what determines Na and Cl flux? |
|
Definition
Need to measure rate of transport from apical (mucosal) to basal (serosal) side
Flux = Net Absorption = (Apical to Basal) - (Basal to Apical) |
|
|
Term
|
Definition
| I = V/R; Conductance = 1/R |
|
|
Term
| What is I(Sc) in the usssing chamber? |
|
Definition
| It is the short circuit current; I(Sc) = I(Na) + I(K) + I(Cl) + I(HCO3) |
|
|
Term
| Relation of Cholera Toxin to flux measured by Ussing Chamber? |
|
Definition
Causes intracellular increase in cAMP to stimulate CFTR channel, inhibits NHE and DRA transporters
Causes an INCREASE in short-circuit current (increases the rate of Cl secretion) |
|
|
Term
| What are the two different anion exchangers in the small and large intestines |
|
Definition
DRA - Cl/HCO3 exchange
PAT-1 - Cl/HCO3 exchange
In the large intestine, DRA exchanger is the dominant one in functioning |
|
|
Term
| What is the method of HCO3 secretion in the duodenum? |
|
Definition
| DRA exchanger is the main method of bicarbonate exchange in the duodenum |
|
|
Term
| What was shown to be the most effective ORS for treating cholera, and why? |
|
Definition
| Rice ORS was most effective; the extract from the boiled rice inhibits the CFTR channel on the apical membrane to reduce secretion of Cl |
|
|
Term
|
Definition
| Saculations of large intestine; formed by contractions of the circular muscle of the large intestines; ACTIVELY changing (are not stationary; are movable) |
|
|
Term
| What is the primary determinant of motility in the colon? |
|
Definition
| Haustral contractions (contractions initiated by cells of Cajal) |
|
|
Term
| Methods of K absorption/secretion in colon |
|
Definition
Active secretion in PROXIMAL colon -> influx w/ basolateral NKCC, then K channel on apical membrane
Active absorption in the DISTAL colon -> K/H exchange on apical membrane; channels on basolateral |
|
|
Term
| Fatty acids generated by colonic bacteria |
|
Definition
| Na-propionate, Na-acetate, Na-butyrate |
|
|
Term
| What is the purpose of the fatty acids produced by colonic bacteria? |
|
Definition
| Fatty acids are transported into intestinal cells by SMCT1 transporter (Na-dependent); once in cells, fatty acids used as substrates for metabolism (used as energy by colonocytes) |
|
|
Term
| How does Na absorption occur in the large intestine? |
|
Definition
Via ENaC channel on apical membrane
Can increase ENaC function by presence of aldosterone (more sodium absorption); causes Cl to follow by paracellular pathway (net absorption of NaCl) |
|
|
Term
|
Definition
Mass Movements - contraction of circular smooth muscle; 3-4 times/day
Gastrocolic Reflex - mediated by gastrin from stomach & autonomic NS; primes the colon to be ready for food; most seen after 1st meal of day (need to defecate after)
Defecation Reflex - initaited by stretch receptors in rectal wall |
|
|
Term
|
Definition
Sensed by stretch receptors in rectal wall; stretch causes - internal anal sphincter to relax, colon and rectum to contract
To compensate, the EAS will normally contract (in reaction to IAS relaxation); need voluntary release of EAS to complete reflex |
|
|
Term
| What has been seen to occur in those with guts that are not filled with microbiota? |
|
Definition
| Decreased immune function and rate of colon development |
|
|
Term
| What is the "gut-brain axis"? |
|
Definition
Probiota in colon shown to reduce stress production; presence of bacteria in colon has an effect on the CNS
Also, lack of microbiota in colon have been shown to alter emotional responses and behavior |
|
|
Term
|
Definition
Metabolic processing of macromolecules
Detoxification of wastes & drugs (accomplished by portal system)
Synthesis of plasma proteins
Storage of glycogen, vitamins, etc.
Activates Vitamin D
Remove bacteria and old RBCs from blood
Excrete cholesterol & bilirubin -> BILE |
|
|
Term
| Cell Types w/in Hepatic Lobules |
|
Definition
Hepatocytes - epithelium of liver; unique membrane situation -> apical membrane is on the "lateral" portion; two apical membranes of adjacent hepatocytes are fused to form the bile caniculus
Endothelium of Sinusoid
Kuppffer Cells - line sinusoids; phagocytic cells
Stellate Cells - similar to fibroblasts; secrete growth factors to maintain viable hepatocytes |
|
|
Term
| Where does the bile duct join with the pancreatic duct? |
|
Definition
| At the hepatopancreatic sphincter of Oddi |
|
|
Term
| Difference between primary and secondary bile acids |
|
Definition
Primary Acids - formed in the liver (cholic acid or KDC acid)
Secondary Acids - formed by bacteria in the colon |
|
|
Term
| What is the rate-limiting step of bile acid production? |
|
Definition
| Hydroxylation of cholesterol in the liver to give primary bile acid |
|
|
Term
| What is bile composed mainly of? |
|
Definition
| Cholesterol & bile salts; cholesterol can exist as itself or as bile acids; also composed of lecithin (phospholipid), and billirubin (from Hb) |
|
|
Term
| What is the function of bile salts? |
|
Definition
| To emulsify the lipid droplets in the duodenum to make them soluble |
|
|
Term
| Micelle Structure w/ Bile Salts & Lecithin |
|
Definition
Bile Salts - polar (hydrophilic) tails, non-polar (hydrophobic) heads
Lecithin - polar head, non-polar tails
Combine to form a micelle with a non-polar (fat soluble) core, and a polar shell to interact with the aqueous environment |
|
|
Term
| In what form are bile salts secreted from the bladder? |
|
Definition
| As micelles (polar shell, non-polar core) |
|
|
Term
| What end of the bile salt is charged? |
|
Definition
| The tails have a NEGATIVE charge; bile salts break down fat droplets based on negative repulsion from nearby micelles |
|
|
Term
|
Definition
Types of modified "hepatocytes" lining the bile duct; columnar epithelium
Produce alkaline rich fluid (bicarbonate) |
|
|
Term
| Mechanism of fluid secretion from cholangicytes |
|
Definition
Produce alkaline (HCO3 rich) fluid
Apical - DRA exchanger to pump HCO3 into lumen
Basolateral - NKCC and Na/HCO3 symport to bring HCO3 into cholangicytes |
|
|
Term
| What mediates bile secretion from the gallbladder? |
|
Definition
Contraction of the gall bladder -> sitmulated by CCK release
Vagal efferents releasing AcH - causes contraction of GB
Vagal efferents releasing NO & VIP - relaxation of sphincter of Oddi |
|
|
Term
| Why does ammonia need to be detoxified by the urea cycle in the kidney? |
|
Definition
| Because it can freely diffuse across the BBB to kill neurons |
|
|
Term
| Where are releasing hormones from the hypothalamus released into? |
|
Definition
| The hypophyseal portal system to act on the anterior pituitary |
|
|
Term
| Hormones secreted by the anterior/posterior pituitary? |
|
Definition
Anterior - GH, FSH, LH, MSH, ACTH, TSH, PRL
Posterior - ADH & oxytocin |
|
|
Term
| What are tropic/trophic hormones? |
|
Definition
| Hormones that have effects on endocrine target tissues (cause release of additional hormones) |
|
|
Term
| Paracrine vs. Autocrine effects |
|
Definition
Paracrine - acts on adjacent/nearby cells
Autocrine - acts on cell that released hormone |
|
|
Term
| Mode of Synthesis & Release of Peptide hormones |
|
Definition
| Initially synthesized as preprohormones by translation of mRNA; preprohormones taken to ER to cleave signal sequence to create "prohormone"; prohormone packaged into vesicle in Golgi and modified to form active hormone -> exit cell via exocytosis |
|
|
Term
| Location of receptor of peptide hormones vs. steroid hormones? |
|
Definition
Peptide hormones = CM receptor
Steroid hormones = usually nuclear/cytoplasmic receptor; can have CM receptor for faster acting effects (uncommon) |
|
|
Term
| Of what clinical significance is C-peptide in insulin processing? |
|
Definition
| Can measure levels of C-peptide in the blood as a means of assessing the insulin production of the individual |
|
|
Term
| What is the general precursor for all steroid hormones? |
|
Definition
|
|
Term
| Main mode of action of steroid hormones? |
|
Definition
| Bind to cytoplasmic/nuclear receptor; receptor complex has a genomic effect which regulates gene transcription (can cause gene expression/inhibition) |
|
|
Term
| What are the two precursors for amine hormones? |
|
Definition
Tryptophan - melatonin
Tyrosine - thyroid hormones, catecholamines |
|
|
Term
| What class of hormones are thyroid hormones very similar to? |
|
Definition
| Similar to STEROID HORMONES; exert genomic effects by diffusing into cell to bind to receptor; long half-life; transported in blood by carrier proteins |
|
|
Term
| What class of hormones are catecholamines very similar to? |
|
Definition
| Similar to PEPTIDE HORMONES; released by exocytosis, dissolved in plasma; short half-life; bind to CM receptor |
|
|
Term
| What type of tissue comprises the infundibulum? |
|
Definition
| Made of neural (axons from cell bodies in hypothalamus) and non-neural tissue |
|
|
Term
| Where are the cell bodies of the axons which make up the posterior pituitary located? |
|
Definition
| Located in the supraoptic and paraventricular nuclei |
|
|
Term
| What type of tissue composes the anterior vs. posterior pituitary |
|
Definition
Anterior = non-neural tissue, true endocrine gland
Posterior = neural tissue (axons of hypothalamic nuclei) |
|
|
Term
| What is believed to be the PRL-inhibiting hormone released from the hypothalamus? |
|
Definition
|
|
Term
| What is the stimulus for oxytocin release? |
|
Definition
| Cervical stretch (brought on by contractions of the uterus during labor) |
|
|
Term
| When do oxytocin levels increase in relation to labor? |
|
Definition
| Increase AFTER onset of labor, DON'T cause the onset of labor |
|
|
Term
| Stimulus for vasopressin release? |
|
Definition
| Low blood pressure/low blood volume sensed by baroreceptors |
|
|
Term
| What neural stimuli can affect CRH secretion from the hypothalamus? |
|
Definition
Stress - causes CRH release
Day/Night Cycle - "cortisol rhythm"; low point at night, peaks during the morning |
|
|
Term
| Hormone Interactions - Synergism |
|
Definition
The combined effects of multiple hormones are more than additive
Example - glucagon, epinephrine, cortisol have a synergistic effect when all are combined (effects are stronger than sum of its parts) |
|
|
Term
| Hormone Interactions - Permissiveness |
|
Definition
| Need 2nd hormone to get full expression of the hormone's physiological effects (e.g. need estrogen for full effects of progesterone) |
|
|
Term
| What is the most well known endocrine pathology? |
|
Definition
| Type I diabetes mellitus (autoimmune destruction of pancreatic B-cells) |
|
|
Term
| Abnormal Receptor Pathologies & Examples |
|
Definition
Downregulation of Receptors - seen in type II diabetes (insulin insensitivity)
Transduction Abnormalities - androgen insensitivity syndrome, leptin insensitivity (leads to morbid obesity) |
|
|
Term
| Androgen Insensitivity Syndrome |
|
Definition
Genetically male, phenotypically female
Lack proper androgen receptors so do not get proper genitalia development in utero (blind vagina; have testes but remain intra-abdominal) |
|
|
Term
| Leptin Gene/Receptor Mutation |
|
Definition
Normally, leptin functions to inhibit food intake (promotes satiety)
Lack of proper signaling leads to hyperphagia (overeating; leads to obesity) |
|
|
Term
| Primary vs. Secondary Endocrine Pathologies |
|
Definition
Primary - pathology is located in the FINAL endocrine organ of the axis
Secondary - pathology is somewhere upstream of final organ (pituitary or hypothalamus) |
|
|
Term
| How can you use the presence/absence of negative feedback to determine if it is a primary or secondary pathology? |
|
Definition
E.g. Hypercortisolemia
Primary if pathology is in adrenal gland; primary pathology if negative feedback IS present
Secondary if pathology is in hypothalamus or anterior pituitary; see a lack of negative feedback (secondary if there is NO negative feedback) |
|
|
Term
| Main hormones of HPA axis |
|
Definition
|
|
Term
|
Definition
Lipolysis (fat breakdown)
Protein breakdown/catabolism
Glucose synthesis in liver (gluconeogenesis)
Suppression of immune function |
|
|
Term
| What is cortisol bound to in the blood? |
|
Definition
| Bound to cortisol binding globulin (CBG), or albumin; needs to be bound to remain dissolved because it is a steroid hormone |
|
|
Term
| Glucocorticoids as Therapeutic Drugs |
|
Definition
Inhibit inflammation by inhibiting/suppressing the immune response
Can use as an immunosuppresant following an organ transplant |
|
|
Term
| What is another name for hypercortisolemia, and what does it lead to? |
|
Definition
Hypercortisolemia = Cushing's syndrome
Leads to:
Hyperglycemia (excess gluconeogenesis)
Loss of fat near peripheral regions; accumulation of fat in trunk, face, back
Protein catabolism |
|
|
Term
| Difference between Cushing's syndrome versus disease |
|
Definition
Syndrome = adrenal pathology leading to hypersecretion (primary)
Disease = pituitary pathology leading to hypersecretion (secondary) |
|
|
Term
| Causes of Cushing's (Hypercortisolemia) |
|
Definition
Adrenal tumor, or pituitary tumor
Iatrogenic effects (most common) - due to taking too many corticosteroids |
|
|
Term
| What is another name for hypocortisolemia? |
|
Definition
| Hypercortisolemia = Adrenal Insufficiency = Addison's |
|
|
Term
| Most common cause of Addison's? |
|
Definition
| Autoimmune destruction of adrenal cortex leading to hyposecretion of cortisol |
|
|
Term
|
Definition
Muscle weakness/fatigue; weight loss/decreased appetite
Hyperpigmentation of skin (stimulation of melanocytes)
Drop in BP (low aldosterone)
Salt craving (excess Na loss)
Hypoglycemia |
|
|
Term
| What causes hyperpigmentation in those with Addison's? |
|
Definition
Caused by ACTH and MSH having the same general precursor prohormone = POMC
POMC is cleaved to form ACTH, and other peptides; ACTH may then be cleaved to form MSH to cause hyperpigmentation and decreased food intake
Have higher levels of ACTH due to no negative feedback because of hyposecretion of cortisol |
|
|
Term
|
Definition
| Individual structural units of the thyroid gland; lined with follicular cells and have a central fluid filled space (antrum) filled with colloid |
|
|
Term
| Process of Thyroid Hormone Synthesis |
|
Definition
Enzymes and thyroglobulin from follicular cells diffuse into colloid; I is pumped into follicular cells from basal membrane by Na/I symport, and then into the colloid by "pendrin" transporter
In colloid, enzymes add I to tyrosine on the thyroglobulin backbone: MIT -> DIT -> T3 & T4
Then the entire thyroglobulin backbone structure is transported back into the follicular cells (need T3 and T4 to remain attached or they will diffuse away)
Upon TSH activation, T3 and T4 are cleaved and diffuse into the blood (carried by TBG) |
|
|
Term
| What are the relative amounts of T4 and T3 in the blood? |
|
Definition
80% T4, 20% T3
However, T3 is the more active form |
|
|
Term
| Thyroid Hormone Functions |
|
Definition
Provides substrates for oxidative metabolism
Important for ion transfer across CM and mitochondrial membrane
Thermogenic - maintains stable body temperature |
|
|
Term
| Inadequate thyroid function in children and newborns can cause (hypothyroidism).... |
|
Definition
| Growth defects, mental deficits, cretinism |
|
|
Term
| How is blood screening done to measure thyroid function in newborns? |
|
Definition
| Measure TSH secretion; if TSH levels are abnormally high, then have HYPOSECRETION of thyroid hormone (less negative feedback) |
|
|
Term
| What is more common, hypercortisolemia, or hypocortisolemia? |
|
Definition
| Hypercortisolemia (Cushing's) is more common |
|
|
Term
| What is more common, hypothyroidism or hyperthyroidism? |
|
Definition
|
|
Term
|
Definition
Hashimoto's (autoimmune destruction of thyroid)
Thyroiditis
Iodine deficiency
Congenital defect |
|
|
Term
| Clinical Symptoms of Hypothyroidism |
|
Definition
Reduced metabolism (because of reduced thyroid hormone)
Endemic goiter
Cold intolerant (always feel cold; due to lack fo thyroid hormones, slower metabolism, less thermogenic effects)
Slow HR
Decreased appetite w/ weight gain |
|
|
Term
| Treatment of Hypothyroidism |
|
Definition
| Thyroxine (T4) - taken orally or injected |
|
|
Term
| Causes of Hyperthyroidism |
|
Definition
Grave's (autoimmune stimulation of thyroid gland; stimulates TSH receptors)
Thyroid nodules (adenomas)
Iatrogenic (overmedication of thyroxine in treating hypothyroidism) |
|
|
Term
| Why can excess iodine NOT cause hyperthyroidism? |
|
Definition
| Cannot cause hyperthyroidism because the thyroid would become saturated with iodine before the pathology develops |
|
|
Term
| Clinical Symptoms of Hyperthyroidism |
|
Definition
Heat Intolerant
Increased appetite/weight loss
Goiter
Fatigue/weakness (increased metabolism leads to protein catabolism)
Exopthalamus (bulging eyes) |
|
|
Term
| Treatment of Hyperthyroidism |
|
Definition
Removal of thyroid
Treat w/ radioactive iodine (radiation destroys thyroid)
Drug Therapy - interfere with T4->T3 conversion, or the addition of iodine in the thyroid |
|
|
Term
| Goiter Caused by Hypothyroidism |
|
Definition
Could be caused by iodine deficiency -> hypothyroidism = low level production of thyroid hormone so no negative feedback leads to increased secretion of TRH and TSH
TRH and TSH stimulate development of the thyroid gland, but there is no I to make thyroid hormone with; gland enlarges, hypothyroidism persists as long as iodine deficiency continues |
|
|
Term
| Goiter caused by Hyperthyroidism |
|
Definition
| Caused by Grave's disease (autoimmune); autoimmune disease produces antibodies which stimulate TSH receptors on the thyroid gland to stimulate synthesis of excess thyroid hormone; get strong negative feedback to inhibit TSH and TRH, but thyroid is continually stimulated due to autoimmunity |
|
|
Term
| What factors does "growth" depend on? |
|
Definition
GH (& insulin, thyroid hormone, steroids) - need all hormones present for permissive/synergistic effects
Adequate diet - need all nutrients
Absence of chronic stress - cortisol production causes catabolism (BAD)
Genetic potential for growth |
|
|
Term
| Effects of GH on the body |
|
Definition
Hyperglycemic - stimulates gluconeogenesis by IGF production from the liver
Increases bone, muscle growth, and protein synthesis
IGF production from liver = gluconeogenesis, cartilage and bone growth |
|
|
Term
| What is the inhibiting hormone for GH from the hypothalamus? |
|
Definition
|
|
Term
| What has a stronger effect on GH secretion, GHRH or somatostatin? |
|
Definition
| GHRH; shown that GHRH is needed for GH secretion (when pituitary lost connection to hypothalamus, GH secretion decreased, so GHRH has a stronger effect than somatostatin) |
|
|
Term
| What is the primary reason that boys are taller than girls? |
|
Definition
| Due to a longer pubertal period (more time to grow) |
|
|
Term
| Nocturnal Secretion of GH, LH, and Testosterone |
|
Definition
Seen in early pubertal boys that when awake, there are low levels of LH and testosterone produced
However, when sleeping see a large spike in LH (causing testosterone to increase too); also see GH peak during sleep as well |
|
|
Term
| Difference between gigantism and acromegaly? |
|
Definition
Gigantism = excessive GH secretion BEFORE puberty
Acromegaly = excessive GH secretion AFTER puberty |
|
|
Term
| What is common pathology seen in those with acromegaly/gigantism? |
|
Definition
| Diabetes -> GH stimulates excessive IGF secretion from the liver (hyperglycemic) |
|
|
Term
| Compact bone vs. trabecular bone |
|
Definition
Compact bone = outer bone
Trabecular bone = inner, spongy bone |
|
|
Term
| What is the general composition of bone? |
|
Definition
| A collagen fiber lattice with calcium phosphate (hydroxyapetite) deposited onto it |
|
|
Term
|
Definition
Epiphysis = ends of long bone
Diaphysis = shaft of long bone |
|
|
Term
| What is the site of linear bone growth? |
|
Definition
|
|
Term
| Process of linear bone growth |
|
Definition
Growth occurs at the epiphyseal plate
Have continuous division of chondrocytes; new chondrocytes move towards the epiphysis, old chondrocytes form the collagen matrix onto which calcium phosphate is deposited onto |
|
|
Term
| What are the 3 locations of calcium in the body? |
|
Definition
Bone = 99%
ECF = 0.1%
ICF = 0.9% |
|
|
Term
|
Definition
| PTH is released by Chief Cells in the PT glands (posterior of thyroid) |
|
|
Term
| What is the main function of PTH and its stimulus for release? |
|
Definition
Stimulus = low [Ca] in blood
Function = increases [Ca] by stimulating osteoclast function, stimulating Ca reabsorption by kidney and absorption from small intestines (via Calcitriol) |
|
|
Term
| What is the function of Calcitonin, and its stimulus for release? |
|
Definition
Stimulus = high [Ca] in blood
Function = lowers [Ca] by decreasing bone resorption (decrease osteoclast function), increase Ca excretion from kidneys |
|
|
Term
| What cells release Calcitonin? |
|
Definition
| Calcitonin is released by C (parafollicular) cells of the thyroid gland; cells exist in between thyroid follicles |
|
|
Term
| How does PTH act on the kidney to modify calcium levels? |
|
Definition
PTH acts on the kidney to stimulate Ca reabsorption from the filtrate within the nephron
PTH also acts on the kidney to stimulate the release of Calcitriol -> increases Ca absorption in the intestines |
|
|
Term
| What is the main means of prevention of osteoporosis? |
|
Definition
| Accumulate as much bone as possible before the age of 35 |
|
|
Term
| Osteoporosis Treatment Methods |
|
Definition
Hormone Replacement Therapy - used in post menopausal women; most effective but no longer used b/c of increased risk of breast cancer and heart disease
Bisphosphonates - improve bone deposition by osteoclast apoptosis
Teriparatide - derivative of PTH; prevents loss of bone |
|
|
Term
| Hormones released by the endocrine pancreas |
|
Definition
a-cells - glucagon
B-cells - insulin & amylin
D cells - somatostatin |
|
|
Term
| What does insulin promote and when does it predominate? |
|
Definition
| Insulin promotes ANABOLISM; dominates in the FED state |
|
|
Term
| Mechanisms of Insulin Anabolism |
|
Definition
Increased glucose transport into liver, muscle, fat
Enhance cellular utilization of glucose; enhance glycogen synthesis
Enhance utilization of a.a.'s, enhance lipid synthesis |
|
|
Term
| What is the stimulus for insulin release? |
|
Definition
| Insulin release from pancreatic B-cells is caused by elevated blood glucose and aa levels |
|
|
Term
| What are the 3 main target tissues of insulin? |
|
Definition
| Liver, skeletal muscle, adipose tissue |
|
|
Term
| What are the effects of insulin in the liver? |
|
Definition
| Glycolysis (glucose breakdown), glycogenesis (glycogen synthesis), lipogenesis |
|
|
Term
| What functions to stimulate insulin release from the pancreas? |
|
Definition
High plasma glucose and aa concentrations
Feed-forward effects of GI hormones (GLP1)
Parasympathetic activation |
|
|
Term
| What inhibits insulin release? |
|
Definition
|
|
Term
| What type of effects does glucagon have and when does it dominate? |
|
Definition
| Glucagon is a catabolic hormone, and it dominates in the FASTING state |
|
|
Term
| What are the 3 main functions/effects of glucagon? |
|
Definition
| Glycogenolysis (glycogen breakdown), gluconeogenesis, ketogenesis |
|
|
Term
| Why is ketogenesis important in the fasted state? |
|
Definition
| Leads to the production of ketones which are used as energy sources for neural tissue |
|
|
Term
| Body Response to Prolonged Fasting |
|
Definition
Liver - glycogenolysis; ketogenesis
Fat - lipolysis -> leads to fatty acids and glycerol (substrates for glcuoneogenesis and ketogenesis)
Muscle - protein catabolism to give aa's |
|
|
Term
| What is the target cell response pathway for insulin? |
|
Definition
Insulin (peptide hormone) binds to tyrosine kinase receptor on CM -> phosphorylates IRS (2nd messengers)
IRS's act to modify CM to create insertion of GLUT4/GLUT2 channel in CM |
|
|
Term
| Difference between GLUT4 and GLUT2 channels; functions and locations? |
|
Definition
GLUT4 - found in resting skeletal muscle and adipose tissue; insulin dependent (needs insulin present for glucose uptake)
GLUT2 - present in liver, pancreatic B-cells, small intestines, brain; insulin independent (can get glucose uptake even when there is no insulin) |
|
|
Term
| Insulin DEPENDENT Glucose Uptake |
|
Definition
Seen in adipose tissue and resting skeletal muscle - need insulin bound for glucose uptake
Insulin binding causes insertion of GLUT4 in CM - glucose uptake |
|
|
Term
| Insulin INDEPENDENT Glucose Uptake |
|
Definition
Seen in hepatocytes (liver), brain, small intestine, pancreatic B-cells
GLUT2 is present in the CM in both the fed and fasted states; glucose entry into cell -> phosphorylation to G6P to maintain low intracellular concentration of glucose |
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|
Term
| What are the two types of diabetes mellitus? |
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Definition
Type 1 - autoimmune destruction of pancreatic B-cells (insulin deficiency)
Type 2 - insulin resistant; target cells are non-responsive to insulin, despite its production |
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Term
| What is the method of treatment for type 1 diabetes? |
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Definition
| Treatment with insulin (treat with insulin because of deficiency present) |
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Term
| What is the method of treatment for type 2 diabetes? |
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Definition
Can treat with insulin (may not be as effective if insulin receptors are inactive)
Modify lifestyle -> increase exercise (improve glucose uptake because exercising muscle is insulin INDEPENDENT) |
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Term
| Pathophysiology of Diabetes (General) |
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Definition
No insulin = catabolic state = protein & fat breakdown
Fat breakdown leads to ketogenesis -> diabetes can lead to ketoacidosis (metabolic acidosis) |
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Term
| What type of state is the body believed to be in in the case of type I diabetes? |
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Definition
| Despite the high levels of blood glucose, the body cannot uptake glucose (mainly) so it sees itself to be in the FASTED state -> switches to a catabolic state |
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Term
| Pathophysiology of Type I Diabetes |
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Definition
Body cells cannot uptake glucose -> believe they are in FASTED state, switch to catabolism
Fasted state promotes glycogenolysis & gluconeogenesis (b/c body believes it has no glucose because non can be reabsorbed)
Increase in glucose causes polyphagia, polyuria, polydipsia (eating, urination, drinking)
Hyperglycemia eventually results in glucose being expelled in the urine -> glucose brings water in to also increase urine production
Eventually develop metabolic acidosis (ketoacidosis)
If you haven't been treated by this point, then you're pretty fucked. |
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Term
| Clinical Signs of Type I Diabetes |
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Definition
3 P's - polyuria, polyphagia, polydipsia
Fatigue & weight loss (increased metabolism) |
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Term
| How can you clinically test for type I diabetes? |
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Definition
Use glucose tolerance test (oral glucose challenge)
Collect "fasting" sample of blood in the morning; patient then drinks glucose solution, and take blood tests at time periods afterwards
If there is NO compensation to the elevated glucose levels -> then person has diabetes |
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Term
| What is the more common form of diabetes mellitus? |
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Definition
| Type 2 (insulin resistant) |
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Term
| Therapy for Type 2 Diabetes |
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Definition
Change diet (consume less simple sugars, more complex carbohydrates)
Increase exercise (glucose uptake is insulin independent in exercising skeletal muscle)
Oral hypoglycemic drugs
Gastric bypass surgery |
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Term
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Definition
Sulfonylureas - close B-cell K(ATP) channels to depolarize B cell; depolarization causes exocytosis of insulin & release
Biguanidines (Metformin) - reduce plasma glucose (decrease gluconeogenesis in liver); most common
Amylin Analogs (Pramlintide) - delay gastric emptying; suppress glucagon, promote satiety (overall decrease plasma glucose)
Incretin (GLP-1) - stimulate insulin secretion, decrease glucagon secretion; similar affects to amylin |
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Term
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Definition
| Hypoglycemic drug; depolarizes B-cells in pancreas by binding to K(ATP) channels -> depolarization causes Ca influx and exocytosis of insulin (insulin release) |
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Term
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Definition
| Reduce plasma glucose by decreasing the rate of gluconeogenesis in the liver; most commonly prescribed hypoglycemic drug |
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Term
| What cells do LH and FSH act on in males? |
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Definition
LH = Leydig cells
FSH = Sertoli cells |
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Term
| Functions of Sertoli Cells? |
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Definition
Paracrine signals for sperm development
Production of ABP (binds testosterone in lumen) and inhibin (negative feedback to decrease FSH release)
Form blood-testis barrier |
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Term
| What is unique about GnRH release? |
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Definition
| Released in PULSES; receptors for GnRH on anterior pituitary can be downregulated by constant exposure to GnRH; need release to be pulsatile to have desired effect |
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Term
| LH action on Leydig cells |
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Definition
LH binding to Leydig cells triggers testosterone production
Testosterone has paracrine effects on Sertoli cells; also testosterone negatively feeds back to inhibit LH secretion & GnRH secretion |
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Term
| What keeps testosterone dissolved in the general circulation? |
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Definition
| Sex hormone binding globulin (SHBG) |
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Term
| Why is it necessary that the testes need to be suspended in the scrotum? |
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Definition
| For heat regulation; testes need to remain 2-3 degrees cooler than core body temperature for spermatogenesis (**Note: steroidogenesis in testes is not temperature dependent) |
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Term
| What can a lack of the descent of testes cause? |
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Definition
| Descent of the testes can cause infertility and an increased risk of testicular cancer |
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Term
| Where do Sertoli cells and Leydig cells exist, respectively? |
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Definition
Sertoli cells - exist in the seminiferous tubules, near their basal lamina
Leydig cells - exist in interstitial space IN BETWEEN tubules |
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Term
| Where are the most mature sperm located relative to spermatogonium in seminiferous tubules? |
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Definition
Most mature -> near the lumen of the tubule
Least mature -> near the basal lamina |
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Term
| Steps from spermatogonium to spermatozoa development |
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Definition
| Spermatogonium -> Primary Spermatocyte (undergoes meiosis I...) -> Secondary Spermatocyte (undergos meiosis II...) -> Spermatid -> Spermatozoa |
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Term
| How do interstitial tissues in the testes support spermatogenesis? |
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Definition
Leydig cells produce testosterone (paracrine effects)
Have BVs located in tissues for blood supply |
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Term
| Contributions to semen from seminal vesicles: |
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Definition
Prostaglandins, fructose, vitamin C; makes sperm motile
Prostaglandins cause smooth muscle contraction in vagina (help sperm move) |
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Term
| Symptoms caused by abuse of anabolic steroids |
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Definition
| Testicular atrophy (infertility), back acne, loss of hair, roid rage |
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Term
| Definition of "Infertility" |
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Definition
| No conception after 1 year of regular, unprotected intercourse |
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Term
| Infertility in males is typically associated with... |
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Definition
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Term
|
Definition
Concentration = 100 million/mL
Motility = > or equal to 40% motile
Morphology = > or equal to 40% normale
Volume = 2-4 mL |
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Term
| Intrauterine Insemination of Concentrated Sperm |
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Definition
Take sperm sample from male & remove all seminal fluid (removal of prostaglandins) to concentrate
Directly inject sample into the uterine artery |
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Term
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Definition
| Take sperm sample & also collect oocyte from ovary; inject sperm into ovary in vitro and implant embryo into endometrium |
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Term
| What infertility treatment can be used in azeospermic men (men with no sperm production)? |
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Definition
| Can use intracytoplasmic sperm injection in vitro - collect immature sperm from male, and inject into oocyte |
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Term
| What is the name of the structure that develops during the ovarian cycle? |
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Definition
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Term
| Cell types within the ovarian follicle and general functions |
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Definition
Granulosa Cells - primary source of estrogen, but dependent on theca cells for estrogen production; acted on by FSH; directly surround oocyte
Theca Cells - external to follicles; produce testosterone from LH stimulation |
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Term
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Definition
| The mixing of granulosa and theca cells following ovulation which creates the corpus luteum |
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Term
| What is needed for a primary follicle to develop into a secondary follicle? |
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Definition
| Need FSH release from the anterior pituitary |
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Term
| What cells are analogous to Sertoli cells and Leydig cells in females? |
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Definition
Sertoli = Granulosa
Leydig = Theca |
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Term
| What is the primary stimulus for ovulation? |
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Definition
| The LH surge from the anterior pituitary; due to switiching of estrogen from negative to positive feedback (actually stimulates LH release) |
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Term
| What is the primary hormone secreted during the "follicular phase"? |
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Definition
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Term
| What is the primary hormone secreted during the "luteal phase"? |
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Definition
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Term
| How do the hormonal stimuli for the ovarian and uterine cycles differ? |
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Definition
Ovarian - dependent on gonadotropin stimulation from pituitary and steroid stimulation
Uterine - only dependent on steroid stimulation from the ovaries |
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Term
| What phase of the ovarian cycle does menses correspond to? |
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Definition
| It corresponds to the early follicular phase |
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Term
| What is the signal for the beginning of menses? |
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Definition
| The decrease in progesterone that is caused by the degeneration of the corpus luteum |
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Term
| What phase of the ovarian cycle does the proliferative phase coincide with? |
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Definition
| Coincides with the mid-late follicular phase (increased estrogen production from developing follicles stimulates proliferation of endometrium) |
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Term
| What phase of the ovarian cycle does the secretory phase correspond to? |
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Definition
| Corresponds to the luteal phase (increased progesterone production leads to secretions from the endometrium in preparation for implantation) |
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Term
| What hormonal changes mark the beginning of the menstrual cycle? |
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Definition
| Decrease in estrogen/progesterone due to loss of corpus luteum; less negative feedback causes increased secretion of GnRH and FSH/LH |
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Term
| How are granulosa cells dependent on theca cells for production of estrogen? |
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Definition
Under stimulation of LH, theca cells secrete testosterone -> this testosterone is converted to estrogen by the enzyme aromatase
Estrogen then exerts paracrine effects on granulosa cells to stimulate follicular development |
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Term
| When does estrogen change from negative to positive feedback during the ovarian cycle? |
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Definition
| Changes to positive feedback during the late follicular phase to stimulate the LH surge from the pituitary which signals ovulation |
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Term
| Effects of progesterone during the luteal phase |
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Definition
Causes development of the endometrium into a secretory structure (secretory phase)
Causes thickening of the cervical mucus |
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Term
| What is hypothalamic amenorrhea? |
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Definition
| Cessation of the menstrual cycles due to a lack of ovulation (considered secondary amenorrhea because menstruation had occurred before, then stops) |
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Term
| Causes of hypothalamic amenorrhea |
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Definition
Chronic stress
Improper diet - anorexia nervosa, excessive exercise |
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Term
| What is the neural mechanism for hypothalamic amenorrhea? |
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Definition
| Believed to be caused by inhibition of GnRH (so no LH/FSH secretion); may be due to increased cortisol levels which inhibit GnRH production |
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Term
| What is the mechanism of action of oral contraceptives? |
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Definition
| Function to inhibit ovulation from occurring; typically do so by increasing the negative feedback on the hypothalamus and pituitary (less GnRH, LH, FSH secretion) |
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Term
| Where does sperm capacitation occur and what does it involve? |
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Definition
Occurs in the vagina/uterus
Involves the destabilization of the acrosomal membrane by removal of epididymal and seminal glycoproteins |
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Term
| Why is capacitation of sperm needed before fertilization? |
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Definition
| Because it weakens the acrosomal membrane so that the acrosomal reaction can occur; essentially, makes sperm fully active and motile |
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Term
| What type of cells make up the corona radiata surrounding the oocyte? |
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Definition
| Made of granulosa cells from the follicle |
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Term
| What is the cortical reaction? |
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Definition
| Occurs when the sperm fuses to the CM of the oocyte; causes depolarization of the membrane and prevents polyspermy from occurring (fertilization of egg by multiple sperm) |
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Term
| Difference between embryo, morula, and blastocyst |
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Definition
Embryo - mass of 2-4 cells
Morula - solid mass of approximately 30 cells
Blastocyst - hollow ball of approximately 100 cells |
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Term
| When does the blastocyst arrive in the uterus? |
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Definition
| 4-5 days following pregnancy |
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Term
| What do the inner cell mass and trophoblast of the blastocyst develop into, respectively? |
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Definition
Inner cell mass = stem cells; develops into fetus
Trophoblast = develops into the placenta |
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Term
| Placental Endometrial Interface |
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Definition
Site of all fetal-maternal gas exchange
Chorionic villi contain embryonic BV's and are bathed in maternal blood
Umbilical Artery - DEOXYGENATED blood to villi
Umbilical Vein - OXYGENATED blood from villi to baby |
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Term
| Human Chorionic Gonadotropin |
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Definition
Similar in function to LH - acts on the corpus luteum to "rescue" it; hCG secretion prevents degradation of the corpus luteum so it continues production of progesterone & estrogen
Bases for pregnancy test |
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Term
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Definition
| Stimulates breast development in the mother; similar in function to PRL |
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Term
| What is the primary endocrine organ during pregnancy? |
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Definition
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Term
| When does the placenta begin to produce estrogen and progesterone? |
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Definition
| During the 20th week of pregnancy; at this point, the corpus luteum degenerates and the placenta takes over all endocrine function |
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Term
| What causes sex determination in the developing embryo? |
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Definition
| The presence or absence of the SRY protein |
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Term
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Definition
SRY gene is present on the Y chromosome; SRY protein determines the sexual development of the fetus
Presence of SRY protein = male
Absence of SRY protein = female |
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Term
| Female Development of Fetus |
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Definition
At 6 weeks, still have bipotential gonads -> ABSENCE of SRY protein causes gonadal cortex to develop into ovarian tissue
Absence of aMH - development of Mullerian ducts into uterus, oviducts, an upper vagina
Absence of testosterone causes degeneration of Wolffian ducts |
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Term
| Male Development of Fetus |
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Definition
Presence of SRY protein @ 6 weeks -> male directed development; gonadal medulla develops into testes
Presence of aMH causes degeneration of Mullerian ducts
Presence of testosterone causes Wolffian ducts to develop into epididymis, vas deferens, seminal veiscles
DHT causes development of external genitalia and prostate |
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Term
| Development of Male External Genitalia |
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Definition
Testosterone is converted to DHT; DHT acts to:
Genital Tubercle - glans penis
Urethral Folds - body of penis
Labioscrotal Swellings - scrotum |
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Term
| Development of Female External Genitalia |
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Definition
Absence of androgens causes:
Genital Tubercle - clitoris
Labioscrotal Folds - labia majora
Urethral Folds - labia minora & vagina |
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Term
| What are the effects of the SRY protein on Leydig and Sertoli cells in the developing fetus? |
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Definition
Leydig - causes testosterone production
Sertoli - causes production of aMH |
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Term
| What are the developmental effects of androgen insensitivity syndrome? |
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Definition
SRY protein causes bipotential gonad medulla to develop into testes; however, they remain intraabdominal
Lack of androgen effects = degeneration of Wolffian ducts
Production of aMH = degeneration of Mullerian ducts
Absence of DHT = external genitalia develop into clitoris, vagina, labia (blind vagina because of NO development of uterus) |
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Term
| What is the role of oxytocin during labor? |
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Definition
| Oxytocin release is stimulated by cervical stretch; acts at the level of the smooth muscle of the myometrium and endometrium; myometrium = contraction; endometrium = prostaglandin release (to cause more contraction) |
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Term
| Hormones and Mammary Gland Development at Different Stages of Life |
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Definition
Puberty -> increase in estrogen causes growth of ducts and fat deposition
Early Pregnancy -> increased estrogen (also GH and cortisol) stimulates further development
Late Pregnancy -> progesterone converts epithelium to "secretory epithelium" |
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Term
| What are the two main hormones that act on mammary tissue, and on what cells do they act? |
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Definition
PRL - acts on the secretory epithelium to stimulate milk production
Oxytocin - acts on myoepithelial contractile cells; contraction of ducts causes milk let down |
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Term
| Why does lactation not occur during pregnancy? |
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Definition
Due to the presence of PRL inhibiting hormone (dopamine) released by the hypothalamus
Also, high levels of estrogen/progesterone stimulate breast development, but also inhibit lactation |
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Term
| What are the main benefits of breast feeding to the newborn? |
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Definition
| Nutrients & immunity (maternal antibodies) |
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Term
| What is the stimulus for oxytocin release in relation to the breast? |
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Definition
| The suckling of the newborn on the nipple - allows PRL secretion and oxytocin secretion as well |
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Term
| How does continued breast feeding help inhibit ovulation? |
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Definition
PRL acts to negatively feedback and inhibit GnRH from the hypothalamus - no LH/FSH release (no ovulation)
Also, suckling can physically inhibit GnRH release as well |
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Term
| When is breast feeding most effective in inhibiting ovulation? |
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Definition
| When it is done on an "on demand" basis |
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Term
| What is typically the first sign of pubertal development in males and females? |
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Definition
| Typically the development of pubic hair due to presence of sex steroids (DO NOT need to be gonadal steroids; can be adrenal steroids as well) |
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Term
| Role of leptin & kisspeptin in pubertal onset |
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Definition
Leptin - produced by fat cells; acts on KISS neurons of the hypothalamus
Kisspeptin - produced by KISS neurons, acts on GnRH neurons to promote GnRH release |
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Term
| Causes for decreasing age of onset of puberty? |
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Definition
More leptin production in youth due to everyone being fat now.
Previously, people were undernourished so pubertal onset was inhibited due to inadequate leptin release -> now with better nutrition, we have reached the "true" age of puberty |
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Term
| What is the main clinical aspect of precocious puberty (main physiological change)? |
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Definition
| See increased secretion of sex steroids (can be either gonadal or adrenal sex steroids) |
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Term
| How can precocious puberty be brought on by an adrenal deficit? |
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Definition
Can have a defect in an enzyme which converts a precursor into cortisol; leads to low cortisol so increased ACTH secretion; leads to more of precursor made
Because of high level, precursor is instead made into sex steroid which causes "non-true" precocious puberty |
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Term
| Difference between true and non-true precocious puberty? |
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Definition
True = activation of HP-gonadal axis which causes increased GnRH secretion at an early age
Non-true = steroid production by some other endogenous means |
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Term
| How can true precocious puberty be treated? |
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Definition
| Treat with GnRH AGONIST -> becuase GnRH is released in pulses, treating with an agonist causes down regulation of its receptors and it prevents the effects of endogenous GnRH activity |
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Term
| What is the main cause of menopause? |
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Definition
| The depletion of follicles in the ovary; also is met by decreased responsiveness of the ovaries to FSH and LH (no estrogen production, subsequent increase in LH and FSH levels because of no negative feedback) |
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Term
| How does male and female gametogenesis differ? |
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Definition
Male - mitosis of gametes begins in utero and continues throughout life; constantly produce new spermatogonia
Female - mitosis of gametes only occurs in utero and then stops; born with finite number of gametes |
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