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Glossary of IBS III Final

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What are the ovaries supported by?
Supported by
mesovarium & a pair
of supporting
ligaments; ovarian &
suspensory ligaments.
What are the ovaries attached to the uterus by?
The ovarian ligament.
What do the suspensory ligaments contain?
Major blood
vessels connected to
ovary at ovarian hilum.
What does the ovarian cortex contain?
– primordial follicles
– developing follicles
– corpus luteum
– stromal cells
What does the ovarian medulla contain?
– vascular elements
(branches of uterine &
ovarian arteries)
What are the steps in the process of oogenesis?
-Oogonia complete their mitotic divisions before birth.
-Primary oocytes prepare to undergo meiosis; proceed as far as prophase of meiosis I, then remain suspended until individual reaches puberty.
-Not all primary oocytes survive until puberty.
-Ovaries contain 2 million primordial follicles at birth.
-By puberty drops to 400.000.
-Atresia
-Primary oocyte cytoplasm unevenly distributed during 2 meiotic divisions.
-Ovary releases a secondary oocyte, suspended in metaphase of meiosis II until fertilization.
What is the first step in the maturation of follicles?
-Primordial follicle: Basic reproduction unit of ovary
–Primary oocytes are surround by granulosa cells.
-Primordial follicle becomes a primary follicle when oocyte enlarges and cells change and zona pellucida forms.
-Zona pellucida is a membrane that will eventually surround the oocyte.
What is the second step in the maturation of follicles?
– Only a few proceed to this step.
– Begins with proliferation of granulosa cells and forming multilayer.
– Granulosa secrets follicular fluids, accumulates in small pockets.
What is the third step in the maturation of follicles?
--Tertiary (mature/ graafian follicle
– Formation of a follicular cavity or antrum.
– As granulosa cells enlarge and multiply, adjacent cells form a layer of theca cells.
– Until this time, primary oocyte suspended in prophase of meiosis I.
– LH level begins rising & it promotes primary oocyte to complete meiosis I.
What is the fourth step in the maturation of follicles?
– Tertiary follicle reaches 2 - 2.5 cm.
– Follicle swells and wall ruptures.
– Ovary releases secondary oocytes.
--Usually only one is ovulated.
– Second meiotic division completed when secondary oocyte unites with sperm cell to form zygote.
What happens after the follicle matures?
-Mature follicle become corpus luteum
– Granulosa cells become luteinized & in conjunction
with stromal cell form corpus luteum (under LH).
– Produce progesterone & small amount of estrogen.
– If fertilization occurs, corpus luteum persists.
What happens to the corpus luteum if fertilization does not occur?
In absence of fertilization: corpus luteum is replaced by fibrous tissues, producing a scar tissue “corpus albicans”
What are the non-steriod ovarian hormones and where are they produced?
– Granulosa cells → Inhibin (decr. FSH)
– Granulosa cells → Activin (incr. FSH)
– Corpus luteum → Relaxin (softening of uterine cervix & relaxation of pelvic ligaments).
How is estrogen transported?
– Bind with high affinity to Sex Hormone Binding Globulin (SHBG) (38%), Albumin (60%), 2% Free.
– SHBG increased by estrogens, decreased by androgens .
-Female [SHBG] = 2x male [SHBG].
– May play a role in estrogen transport across cell membrane.
How is progesterone transported?
– Binds strongly to Corticosteroid Binding Globulin (CBG, 18%).
– Albumin (80%), 2% Free.
How is estradiol metabolized?
– Rapidly converted to estrone in liver.
– Most of estrone is further metabolized to 16 α-OH-estrone → estriol → conjugated to glucuronic acid and sulfate.
– Mostly is excreted in urine & 1/5 is excreted in
bile.
How is progesterone metabolized?
– Rapidly cleared from circulation (t1/2 = 5 min).
– Metabolized in liver & conjugated to glucuronic
acid and excreted in urine.
What physiological effects does estrogen have on the female reproductive system?
- Stimulate maturation of female reproductive system
– vagina, uterus and uterine tubes at puberty, increase uterine and genital size.
– increase endometrial proliferation, decrease
cervical mucus viscosity.
– a role in closing of the epiphyses of long bones occurs at puberty.
What physiological effects does estrogen have on secondary sex characteristics?
-breast/ pelvic development, alter the body fat distribution to hip & breasts.
What physiological effects does estrogen have on bone and muscle growth?
– increase osteoblastic activity.
– decrease the rate of resorption of bone.
(antagonize PTH on bone)
What physiological effect does estrogen have on CNS activity?
– in hypothalamus increase sexual activity (libido).
What physiological effects does estrogen have on the blood?
– increase coagulability factors.
– decrease anti-thrombin activity.
What is thrombin and anti-thrombin?
-Anti-thrombin: It inhibits blood clotting by inactivating thrombin.
-Thrombin: An enzyme that is formed from prothrombin
and facilitates the clotting of blood by catalyzing
conversion of fibrinogen to fibrin.
What are the physiological effects of estrogen on the cardiovascular system?
– increase HDL, decrease LDL.
– decrease platelet aggregation.
What is the mechanism of genomic action of estrogen?
- Plasma estrogen in blood are bound to SHBG & albumin, from which they dissociate to enter the cell (by passive diffusion).
- Upon entering cell, hormone binds to estrogen receptor (ER).
- In the absence of ligand, ER is present in the cytoplasm and nucleus in an inactive monomeric state.
- Binding of hormone to its receptor alters its conformation and results in dimmerization. This increase the affinity of its binding to DNA binding site (ERE).
- The ER/DNA complex recruits one or more coactivator proteins to the promoter region.
- Coactivators recruit other proteins to the complex and initiate the formation of transcription complex leading to the gene transcription.
How does progesterone aid in the preparation for pregnancy?
– Stimulates secretory activity of uterine glands.
– Prepares uterus for implantation of fertilized ovum.
– Decreases the frequency and intensity of uterine contractions.
– Increases viscosity of cervical mucus.
What are the effects of progesterone in the (female) body?
-preparation for pregnancy
-Breast development (high conc.).
-Increases basal body temperature.
-Increases insulin level leading to insulin resistance.
-Decreases in Na+ re-absorption (compete with aldosterone).
What are the effects of androgens in women?
-Ovary secrets potent androgens:
--Testosterone (<300 μg/day) &
--Dihydrotestosterone
– Hair growth at puberty.
– Some metabolic effects → acne
What occurs in the early follicular phase of the menstrual cycle?
– Low E2 & PG →GnRH → FSH & LH → development of follicle → follicles secrete E2.
– Negative feedback: Rising E2 → inhibits FSH & LH secretion.
What happens to the later part of the follicular phase in the menstrual cycle?
– At mid-cycle: sustain high level of E2 exert a positive feed back on pituitary.
– Initiates preovulatory surge of LH.
– LH Surge → initiate midcycle surge of FSH
– LH stimulates follicle rupture → corpus luteum → PG & E2
– In absence of pregnancy menstruation occurs.
What occurs during menopause?
– At 40-50, cycles become irregular & ovulation fails to occur during many
cycles. A few months later the cycles stops.
– The cause is “burning out” of the ovaries.
– During reproductive life, ~400 primordial follicles grow & ovulate.
– At 45, only a few remain to be stimulated by FSH/LH → E2 decreases.
What are the characteristics of hypogonadism in women?
– Lack of ovaries, abnormal ovaries, poorly formed ovaries
– Prolonged growth of long bones (E2 in epiphyses)
– Smaller uterus and vagina, breast atrophy
– Amenorrhea: Absence or suppression of menses
What are the characteristics of hyper-secretion of the ovaries?
– Occurs in rare granulosa cell tumor in ovary (esp..after menopause)
-bleeding
-hypertrophy of uterine endometrium
What concentration of sperm in the semen is considered to be sterile?
– <20 million sperms/ml: Sterile
Of all of the sperm that is released into the vagina, how many make it to the ampulla?
– From 200 million sperms, only 200 reach ampulla.
What structures promote the movement of sperm in the uterine tube?
Uterine myometrium and ciliary current in uterine tube help sperm transport.
What are the steps of fertilization?
1. Ovulation releases a secondary oocyte and a first polar body; both are surrounded by corona radiata. At first, many sperms attach to the corona radiata.
2. Sperm cells bind to ZP3 receptors on the zona pellucida.
3. Acrosomal enzymes digest zona pellucida and helps sperm penetration. Fusion of secondary oocyte with sperm
causes zona pellucida to prevent second fertilization.
4. In response to sperm head entry, oocyte nucleus moves to one side of oocyte where it completes the second
meiotic division and gives off a second polar body. The oocyte nucleus now called female pronucleus.
5. Sperm head enlarges and becomes male pronucleus.
6. Two pronuclei fuse to form a single nucleus. Fertilization is complete and zygote results.
What are the characteristics of implantation?
-Attachment of the blastocyst to endometrium.
-Trophoblast invades maternal tissue.
-Syncytial trophoblasts erode a path through endometrium.
-Inner cell mass separated from trophoblasts by amniotic cavity.
-Trophoblast separated from
amniotic cavity by a layer named amnion.
-Developing villi helps to form placenta.
-Takes places in the fundus or in the body of uterus.
-In ectopic pregnancy, gestation occurs somewhere other than within uterus (e.g. fallopian tubes).
What are the four general processes that occur in the first trimester of pregnancy?
-Cleavage
-Implantation
-Placentation
-Embryogenesis
What are the characteristics of cleavage?
-Occurs in the 1st trimester
-A series of cell division which subdivides the cytoplasm of zygote.
-First cleavage produces 2 identical cells “ balstomer”.
-It finally develops to multicellular complex known as blastocyst.
What is a morula?
Morula: A globular solid mass of blastomers (12 or more cells).
What does the trophoblast become?
becomes placenta, chorion & amnion
When is an embryo considered a fetus?
after 60 days
What is languo?
-fine soft hair covering the fetus
What is the vernix caseosa?
Waxy coat of epithelial cells protects fetus from
toxic nature of amniotic fluids formed by accumulation of waste products from the fetus.
What are the characteristics of the fetal-placental unit?
-By the end of first trimester, fetal endocrine
system is developed to influence placenta function.
– A source secretion of protein & steroid hormones
into maternal circulation.
– Controls the fetal endocrine function/growth and
development.
– Works as a selective barrier between fetus & mother.
What are the placental protiens?
- Human chorionic gonadotropin (hCG)
- Human placental lactogen (hPL)
-Other chorionic peptide hormones:
–Similar to TSH, FGF, EGF, PDGF, IGF
What are the characteristics of hCG?
-First measurable product of placenta, synthesized by trophoblast.
-hCG is detectable in maternal serum within 1
day after implantation or 3 gestational weeks.
-Glycoprotein with 237 aa, two subunits (α & β).
• α subunit is identical to TSH, LH, FSH.
• β subunit is similar to LH (67%), +24 aa.
-Long half-life (24 - 30 h); relative ease of obtaining → used therapeutically.
What is the action of hCG?
-Maintain corpus luteum until placenta can secrete progesterone; under hCG, corpus luteum secretes progesterone.
-In early pregnancy, hCG concentration doubles every 2 days; pregnancy diagnose.
What are the characteristics of hPL?
-human placental lactogen
-Second placental hormone; synthesized by trophoblasts and later by placenta.
-Reaches to detectable serum conc. in 4-5 gestational weeks.
-Protein with 190 aa, similar in structure to GH, PRL.
-An indicator of health of placenta.
What is the action of hPL?
-Weak growth-promoting and lactogenic activity.
-Insulin resistance of pregnancy can be induced by hPL:
–-contributes to altered maternal glucose metabolism.
–-causes hyperinsulinemic response to glucose load.
–-directly stimulates β cells in pancreatic islets.
What is the relationship between the placenta and the corpus luteum?
-Corpus luteum can be removed after 7th gestational
wks, placenta becomes source of PG.
-Placenta doesn’t produce 17-OH-PG; a marker of corpus luteum function.
What are the basic hormone changes during pregnancy?
- HCG reaches a max near the end of 1st trimester and then decr.
- PG continues to incr. until its level off near the end of pregnancy
- E2 incr. slowly throughout pregnancy, but they incr. rapidly as the end of pregnancy approaches.
What are the changes in site of secretion of progesterone and estrogen through pregnancy?
-Early in pregnancy, E2 & PG are secreted by ovary.
-During midpregnancy, there is a shift toward secretion by placenta.
-Late in pregnanacy, they are secreted by placenta.
What are the changes in the blood during pregnancy?
-volume: 50% increase by 2nd trimester
-hematocrit: decreases slightly
-fibrinogen: increases
-electrolytes: no change
What are the physiological changes in the cardiovascular system during pregnancy?
-heart rate: gradually increases by 20%
-blood pressure: gradually decreases 10% by 34 weeks, then increases to prepregnancy values
-cardiac output: rises rapidly by 20%, then gradually increases 10% by 28 weeks.
How does the pituitary gland change during pregnancy?
– Pituitary enlarges (by 1/3)
– Lactotrophs hyperplasia: PRL is increased (peaks at delivery).
How does the thyroid gland change during pregnancy?
– Thyroid enlarges.
– Iodide renal clearance is increased.
– Maternal total serum thyroxin (T4) and TBG are elevated.
How does the parathyroid gland change during pregnancy?
– The fetus Ca2+ need (≈ 30 g/term) is met by maternal parathyroid hyperplasia & maternal bone reserve.
– Maternal serum PTH is elevated.
– Maternal serum Ca2+ is decreased.
How does the pancreas change during pregnancy?
– Size of pancreatic islet is increased, β cell hyperplasia.
– Basal insulin is increased in the second trimester (elevated insulin secretion).
– Altered glucose tolerance test.
– Pregnancy is a hyperinsulinemic state with peripheral resistance to insulin.
How do glucocorticoids change in pregnancy?
Maternal plasma cortisol and CBG is increased in third trimester (high production and low catabolism in liver leads to increase in half life).
How do mineralocorticoids change in pregnancy?
-Maternal serum aldosterone is elevated (high production), reaches to peak by mid pregnancy and maintained until delivery.
-Renin and renin substrate are increased.
How does the cervix change near the end of pregnancy?
– Softening of cervix; lower uterine segment & cervix become softer and thinner.
– Relaxin produced by corpus luteum & placenta
What does relaxin do?
-ripens the cervix
-act with progesterone to inhibit uterine contraction.
In the fetus, what gland is enlarged prior to parturition?
Adrenal glands.
What is the role of progesterone in maintaining pregnancy?
– PG hyperpolarizes myometrium → decreases Ca2+
entry →prevents contraction.
– PG decreases α receptors.
– PG inhibits estrogen receptor synthesis.
How does the estrogen/progesterone ratio change immediately prior to labor?
– Estrogen antagonizes PG → ripening of uterine cervix.
– Increases maternal oxytocin release at posterior
pituitary gland.
What are some factors used to induce labor?
-Oxytocin infusion; increases the force of uterine contraction; Caution must be taken.
-PGF2α
-Catecholamine
-Nitric oxide synthase (NOS) inhibitors
-Fetal growth/ size: activate myometrium/neuroendocrine reflex
What stimulates the neuroendocrine reflex?
Fetus size.
What are the characteristics of preeclampsia?
A toxic condition developing in late pregnancy:
-Sudden rise in blood pressure, weight gain, edema, albuminuria, headache, and visual disturbances
What causes hyperthyroidism during pregnancy?
– Thyroid enlargement, increased cardiac output, peripheral vasodilation.
When in pregnancy does gestational diabetes mellitus typically occur?
-Usually occurs in the second or third trimester (by week 24 to 28) (4%).
What are the contents of breast milk?
-Breast milk: water, protein, amino acids, lipids, sugar, salt, and enzymes with antibiotic properties.
What is the sequence of the initiation of lactation?
-there is a decrease in the levels of progesterone and estrogen
-prolactin inhibitory factor (PIF) is inhibited
-prolactin release from the anterior pituitary leads to lactation
What are the characteristics of A cells in the pancreas?
-Make up 10% of the pancreas mass
-produce glucagon and proglucagon
What are the characteristics of B cells in the pancreas?
-Make up 75% of pancreas mass
-produce C-peptide/ proinsulin/islet amyloid polypeptide (IAPP)
-insulin
What are the characteristics of D cells in the pancreas?
-Make up 3-5% of the pancreas mass
-produce somatostatin
What are the characteristics of F cells in the pancreas?
-Make up less than 2% of pancreas cells
-produce pancreatic polypeptide
What are the characteristics of basal insulin secretion?
Basal insulin secretion:
– Insulin secreted in fasting state (in the absence of exogenous stimuli) (5-15 μu/ml; 30-90 Pmol/l).
- Insulin is released from pancreas at a rate of 1-2
U/h.
- Human pancreas secrets ≈ 40-50 U of insulin /day.
- Unit: Hypoglycemic activity of insulin in rabbits; on the basis of weight (28 unit = 1 mg).
– The entire pancreas contains up to 8 mg (about
200 units).
What are the actions of insulin on the liver?
--Promotes storage of glucose as glycogen.
- Inhibits glycogenolysis.
- Inhibits conversion of fatty acids (FA) to ketoacids (ketogenesis).
- Inhibits conversion of amino acids (AA) to glucose (gluconeogenesis).
- Reduces FA influx to the liver.
– An indirect effect to decrease hepatic ketogenesis and gluconeogenesis.
What are the actions of insulin on muscle?
-- Increased protein synthesis.
– increases amino acid (AA) transport.
– promotes incorporation of AA to protein.
– increases ribosomal protein synthesis.
– decreases protein catabolism.
-- Increased glycogen synthesis.
– increases glucose transporter (GLUT-4) in
membranes of muscle.
What are the actions of insulin on adipose tissue?
-- Reduced circulating FA.
-- Increased triglyceride (TG) storage or fat synthesis.
- by inducing lipoprotein lipase, hydrolyzes TG from lipoproteins.
- by inhibiting intracellular lipase, decreases lipolysis of stored TG.
- by increasing Glut-4 in membrane of adipose, increases G transport into cell provides glycerol phosphate to permit esterification of FA to TG.
What are the characteristics of glucagon?
-A large polypeptide contains 29 aa arranged in 1 chain.
--Human proglucagon
- Produced by alpha cells of islet of Langerhans from pro-glucagon.
- Other peptides within proglucagon: glicentin-related peptide, glucagon-like peptides (GLP)
- Short half-life (3-6 min); mainly removed by liver & kidney.
What is truncated GLP-1?
- an endogenous truncated derivative of GLP-1, with the first 6 of its 37 aa absent.
- extremely potent stimulator of pancreatic B cells.
- a major gut factor that potentiates glucose-induced insulin secretion after meals.
- released by small intestine.
What is the action of glucagon?
- Glucagon makes energy available to the tissues & induces hyperglycemic effects within minutes.
- Stimulates breakdown of glycogen in liver, glycogenolysis.
- Increases hepatic glucose output from amino acids, gluconeogenesis.
- Promotes hepatic ketone bodies output, ketogenesis.
- Increases protein catabolism & conversion to ketone bodies. Glucagon infusion for 4 h causes intensive liver glycogenolysis.
--Continued infusion causes continued hyperglycemia:
–by increasing the rate of amino acid uptake by liver and then conversion to glucose (gluconeogenesis).
-Increases lipolysis.
-Inhibits TG storage in liver.
-It works primarily on liver.
-In very high concentration has (+) inotropic effects on heart.
What is the secretion of glucagon activated by?
– Amino acids (arginine, alanine, leucine)
– Exercise
– Catecholamines, glucocorticoids
– GI Hormones (gastrin, CCK, gastric inhibitory polypeptide)
What is the secretion of glucagon inhibited by?
– Blood glucose concentration
– Insulin
– Somatostatin
– High levels of free fatty acids
What are the characteristics of somatostatin?
-In pancreas, produced by Delta cells of islet of Langerhans from preprosomatostatin.
-Single chain polypeptide with 14 AA.
-Some circulating hormone is 28-AA peptide; somatostatin-28 is more potent in inhibiting growth hormone & insulin.
-Very short half-life (< 3 min).
What activates the secretion of somatostatin?
– Increased blood glucose
– Increased amino acids
– Increased fatty acids
– Increased GI hormones in response to food intake.
What are the inhibitory effects of somatostatin?
– Acts locally within islets to depress insulin & glucagon secretion.
– Decreases the motility of stomach, duodenum and bladder.
– Decreases gastric emptying, gastric acid production.
– Reduces nutrient absorption in GI tract.
– Inhibits GH and TSH secretion from ant. pituitary.
What calorie distribution should come from carbohydrates, protein, and fats based on a 2500 cal/day diet?
-1400 carbs
-750 fat
-250 protein
What are the effects of short-term fasting (3-7 days)?
– Gluconeogenesis, lipolysis, ketogenesis all stimulated.
– Increased protein catabolism.
What are the effects of long-term fasting (more than 7 days)?
– Protein catabolism ↓
– Blood ketone ↑
– Brain utilization of ketones ↑ (reduces
dependence on glucose).
What are the classifications of weight and bmi?
Underweight: <18.5
Normal: 18.5-24.9
Overweight: 25.0-29.9
Obesity-
Class I: 30.0-34.9
Class II: 35-39.9
Class III: >40
What are some of the diseases associated with obesity?
– Type 2 Diabetes
– Hypertension
– Atherosclerotic Heart Disease & Stroke
– Hyperlipidemia & dyslipidemia
– Gallbladder Disease
– Osteoarthritis
– Cancer (e.g. endometrial, breast, prostate, and colon cancer)
What is ascites?
-Def: abdominal swelling created by accumulation of fluid in peritoneal cavity
-Increase rate of fluid movement into the peritoneal cavity
-Causes:
--Liver disease
--Kidney disease
--Heart failure
What is peritonitis?
-Def: inflammation of the peritoneal membrane
-Causes:
--Physical damage
--Chemical irritation
--Bacterial invasion
--Untreated appendicitis
-Complication of surgery when peritoneal cavity is opened
What is mesentery?
-A double layer of peritoneum that provides:
--Vascular and nerve supplies to the viscera
--A means to hold digestive organs in place and store fat
What organs are retroperitoneal?
pancreas, duodenum, ascending and descending colons, rectum, urinary bladder, aorta, inferior vena cava, kidneys, suprarenal glands
What are some peritoneal organs?
stomach, small intestine (jejunum and ileum), transverse colon, liver and gallbladder
What are the 4 tunics of the walls of the GI tract?
From the lumen outward they are the mucosa, submucosa, muscularis externa, and serosa.
What are the characteristics of the mucosa of the GI tract?
Mucosa – innermost layer of GI tract
-Def: moist epithelial layer that lines the lumen of the alimentary canal
--**epithelium (mucous membrane) – varies from one part of the tract to the next, provides important protective and absorptive functions
-stratified squamous epithelium
--lamina propria – contains mucous glands, lymph nodules,
and capillaries, helps with nourishment
--muscularis mucosa – innermost layer of smooth muscle, produce local movement of mucosa.
What are the characteristics of the submucosa of the GI tract?
Submucosa – consists of connective tissue (collagen, elastin) and also contains nerves and blood vessels
-areolar connective tissue
What are the characteristics of the muscularis externa of the GI tract?
-Muscularis externa – contractions of these
muscles mix and propel contents of intestinal
lumen
-- circular, longitudinal muscle
-- Segmentation, peristalsis
What are the characteristics of the enteric plexus?
-myenteric (located between circular and longitudinal
muscle)
--major nerve supply that controls GI tract motility
--parasympathetic ganglionic neurons
--sympathetic postganglionic fibers
-submucosal (located in submucosa)
--regulates glands and smooth muscle in the mucosa and submucosa
--parasympathetic ganglionic neurons
--sympathetic postganglionic fibers
What are some parts of the GI tract that have adventitia?
oral cavity, pharynx, esophagus, rectum
What are the differences in cell types within the mucosa?
-simple (stomach, small intestine, most of large
intestine)
-or stratified (areas with mechanical stress) columnar
epithelium and mucus-secreting cells
What do the stomach and small intestine mucosa contain?
-Enzyme-secreting cells
-Hormone-secreting cells (making them endocrine and
digestive organs) – enteroendocrine cells
What is the general life span of GI mucosal epithelium?
-Life span 2-3 days (esophagus) or 6 days (large
intestine)
-Related to rate of cell destruction and loss
What protects the GI mucosal epithelium from precancerous lesions?
Phytochemicals such as: Vit. C, Vit. E, carotenoids, retinoids, isothiocyanates,
polyphenols
What are the 3 pairs of extrinsic salivary glands?
-parotid: parotid duct opens into the vestibule next to the second upper molar
-Submandibular: Its ducts open at the base of the lingual frenulum
-sublingual: It opens via 10-12 ducts into the floor of the mouth
What are the characteristics of the esophagus?
-Esophageal mucosa – nonkeratinized stratified squamous epithelium
-The empty esophagus is folded longitudinally and flattens when food is present
-Glands secrete mucus as a bolus moves through the esophagus
-Muscularis changes from skeletal (superiorly) to smooth muscle (inferiorly)
What is Esophageal Varices?
-Def: dilated blood vessels within the wall of the esophagus
-Cause: portal hypertension –venous pressure in the hepatic portal vein becomes abnormally high
-blood flow through liver diminished
-venous drainage of esophagus
-hepatic portal vein to liver
-cirrhosis & other liver diseases
--Problem:
-distended veins in esophagus may bulge and constrict esophageal passageway
-veins susceptible to rupture- emergency situation
What are the components of gastric juice?
-Hydrogen ions (acid)
-intrinsic factor (required to absorb B12)
-Pepsin
-Mucin
What are the muscles of the stomach?
-Muscularis mucosa
--Innermost layer of smooth muscle
-Muscularis externa
--Circular and longitudinal muscle
-Oblique muscle layer (unique to stomach)
--deep to muscularis externa layer
--overlies mucosa
--Enhances gastric motility and mixing of food
-Rugae (temporary folds)
-Pyloric sphincter
What are the types of glands in the stomach?
-Oxyntic gland – fundus and body
-Pyloric gland – antrum
-Cardiac gland – cardia
What is the location and product of surface mucus cells in the stomach?
-all glands and mucosa
-produce mucins, bicarbonate
What is the location and product of neck mucus cells in the stomach?
-all glands
-produce mucins
What is the location and product of parietal cells in the stomach?
-Oxyntic glands
-produce HCl, intrinsic factor
What is the location and product of chief cells in the stomach?
-oxyntic glands
-produce pepsinogen
What is the location and product of G cells in the stomach?
-Antrum
-Gastrin
-Histamine
What is the location and product of D cells in the stomach?
-Antrum
-Somatostatin
What are the actions of parietal cells in the stomach?
-Secrete intrinsic factor (B12 absorption)
-Create acid environment within stomach
--kills microorganisms
--denature proteins
--destroys plant cell walls
--breaks down animal connective tissues
--activates pepsinogen (pepsin)
What are the actions of chief cells in the stomach?
-Secrete pepsinogen (proenzyme)
-Acidic environment activates pepsinogen
--pepsin activated within stomach
--proteolytic enzyme
--begins digestion of proteins
What does gastrin stimulate in the stomach?
-parietal cells secretion of acid
-chief cells secretion of pepsinogen
-gastric contractions
What does histamine stimulate in the stomach?
-parietal cell secretion of acid
--H2 (histamine receptor)
What are the basic characteristics of the small intestine?
- primary site for digestion
- primary site for absorption
--90% of absorption
- ~20 feet in length (6m)
-3 sections
-- Duodenum
-- Jejunum
-- Ileum
What are the characteristics of the duodenum?
-first section after stomach
-~10 inches in length (25cm)
-“mixing bowl” function
--chyme from the stomach
--bile from the liver
--pancreatic exocrine secretion
-alkaline pH (7-8)
What are the characteristics of the jejunum?
- middle section of Small Intestine
- ~8 feet in length (2.5m)
- supported by mesentery
- bulk of digestion
- majority of absorption
What are the characteristics of the ileum?
- last section of Small Intestine
- ~12 feet in length (3.5m)
- supported by mesentery
- ends at ileocecal valve (sphincter)
- controls entry into large intestine
- cecum contains vermiform appendix
- lower right quadrant
What are plicae? (small intestine)
- permanent transverse folds
- increased surface area
- Each plica is covered with millions of villi
What are the functions of villi in the small intestine?
- finger-like projections
- columnar epithelium covering
- Goblet cells – produce mucus
- Absorptive cells
-- microvilli (brush border)
What are the cell types that make up the histology of the small intestine?
1) absorptive cells
- brush border enzymes
- integral membrane proteins
- digestion of materials contacting brush border
2) goblet cells (mucus)
3) enteroendocrine cells
- secrete several hormones
4) grandular cells (Paneth’s cells)
- may help protect the intestinal epithelium from bacteria
What are the regional variations in histology among the duodenum, jejunum, and ileum?
-Duodenum
--few plicae
--many submucosal glands
-Jejunum
--many plicae, villi & microvilli
--diminish in size & number as approach ileum
-Ileum
--lacks plicae & few villi/microvilli
What makes up the lamina propria of the small intestine?
-extensive capillary network
--blood vessels originate in
submucosa
--transports gases, nutrients, etc. (water soluble)
-“Lacteal”
--lymph channel
--transports lipid soluble
materials
--chylomicrons
-Muscularis mucosa (wiggling)
How long is the large intestine?
About 5 feet (1.5 m)
What are the characteristics of the cecum?
-expanded pouch with ileocecal valve
-lower right abdominal quadrant
-vermiform appendix
-begins process of compaction
What are the distinctive features of the colon?
-Haustra (pouches)
-Taenia coli (longitudinal muscle)
-Epiploic appendages (fatty sacs)
What are the major characteristics of the large intestine?
- lack of villi
- abundance of goblet cells
-- mucus secretion
-- lubrication
- glands
-- no enzyme secretion
How many deciduous teeth do humans usually have?
20, they usually erupt at intervals between 6 and 24 months
What are the characteristics of H. Pylori?
-Helicobacter pylori
-Resides primarily in the mucin layer of the antrum
-Thick layer of mucus protects stomach lining
-H. pylori takes advantage of
this protection by living in the mucus lining.
- Protects itself by producing urease NH4+ and HCO3- which neutralizes acid
- Inflammatory response to the infection leads to gastritis and then an ulcer
What are the characteristics of GI smooth muscle?
-Capable of stretch
-Capable of prolonged contraction without fatigue
-Capable of tonic contraction or tone
--Sphincters remain tonically constricted
---Sphincter – thickening of the smooth muscle
-Low energy requirements
How is smooth muscle innervated?
- Smooth muscle lacks neuromuscular junctions
- Innervating nerves have bulbous swellings called varicosities
- Varicosities release neurotransmitters into wide synaptic clefts called diffuse junctions
What are the microscopic anatomical characteristics of smooth muscle?
- SR is less developed than in skeletal muscle and lacks a specific pattern
- T tubules are absent
- Plasma membranes have pouchlike infoldings called caveoli
- Ca2+ is sequestered in the extracellular space near
the caveoli, allowing rapid influx when channels are opened
- There are no visible striations and no sarcomeres
- Thin and thick filaments are present
What is the involvement of actin and myosin in smooth muscle?
- Actin and myosin contractile elements are not arranged in sarcomeres
- Loosely arranged in long bundles extending obliquely as lattice across the periphery of the cell
- Myosin filaments (thick filaments) have numerous heads along their length
- Myofilaments are longer than in skeletal muscles allowing them to be stretched further and still maintain tension
How does stimulus-contraction coupling work in smooth muscle?
Stimulus-contraction coupling:
- Stimulus
- → inc. cytoplasmic [Ca2+]
- → Ca2+ binds calmodulin
- → activates MLCK
- → myosin light chain (MLC) phosphorylation
- → cross-bridge formation between actin and myosin
- → contraction
What is the role of calcium in the contraction of smooth muscle?
- Ca2+ binds to calmodulin and activates it
- Activated calmodulin activates the kinase enzyme
- Activated kinase transfers phosphate from ATP to myosin cross bridges
- Phosphorylated cross bridges interact with actin to produce shortening
- Smooth muscle relaxes when intracellular Ca2+ levels drop
What are the characteristics of myofilaments in smooth muscle?
- Ratio of thick to thin filaments is much lower
than in skeletal muscle
- Thick filaments have heads along their entire length
- There is no troponin complex
- Thick and thin filaments are arranged diagonally, causing smooth muscle to contract in a corkscrew manner
- Noncontractile intermediate filament bundles
attach to dense bodies (analogous to Z discs) at
regular intervals
What are the interstitial cells of Cajal?
Interstitial cells of Cajal (myenteric plexus) are
the pacemaker cells that:
- Generate slow waves
- Oscillations of RMP in visceral smooth muscle
- Communicate with smooth muscle cells via gap junctions
- The slow wave provides intrinsic control over the timing and pattern
of smooth muscle contractions in the GI tract
- Resting membrane potential varies in time
- Low frequency oscillations vary from 3/min – stomach to 12/min duodenum
What are the control systems of smooth muscle?
1. Intrinsic activity of the pacemaker cells
2. Neurally released transmitters
3. Circulating hormones
What are the different gastrointestinal peptides?
- Neurotransmitters (or “neurocrines”)(ANS or ENS)
-- released by action potentials and act on cells at the synapse.
- Endocrine hormones (or “endocrines”)
-- released from mucosal endocrine cells and are transported by the blood back to the GI tract
-Local factors (“paracrines”) – short distance
-- mucosal endocrine cells act on other cells near their sites of release
- Have many different actions depending on which cells contain receptors or are in proximity to the sites of release.
- May inhibit or augment the effects of each other.
What is the regulation of the digestive system from the ANS?
-Sympathetic
-- Motor neuron cell bodies are in ganglia organized in
vertical chains near the spinal cord and in ganglia within the abdomen
-- Norepinephrine is the major NT
- Parasympathetic
-- Motor neuron cell bodies are located in ganglia that lie close to target organs
-- Acetycholine is the major NT
What are the roles of the neural plexuses in digestive system regulation?
-Myenteric plexus
-- Lies in between the circular and longitudinal layers of smooth muscle
-- primarily regulates motility
- Submucosal plexus
-- Located in the submucosa
-- primarily controls secretion, blood flow, and absorption
What is the action of acetylcholine in the digestive system?
Stimulates contractions of smooth muscle; stimulates
secretion of salivary glands (the watery secreted fluid), stomach, and pancreas
What is the action of norepinephrine in the digestive system?
Inhibits contractions of smooth muscle, stimulates
contractions of some sphincters, stimulates secretion of salivary glands (low volume & protein-rich) (only transient)
What is the action of Vasoactive intestinal peptide
(VIP) in the digestive system?
Inhibits contractions of smooth muscle, stimulates
intestinal and pancreatic secretion.
What is the action of gastrin-releasing peptide in the digestive system?
Stimulates secretion of gastrin.
What is the action of enkephalins in the digestive system?
Inhibit smooth muscle contraction, inhibit intestinal secretion
What is the action of neuropeptide Y in the digestive system?
Inhibits intestinal secretion of water and electrolytes, inhibits smooth muscle contraction
What is the action of Substance P in the digestive system?
Stimulates the contraction of smooth muscle.
What is the action of nitric oxide in the digestive system?
Inhibits smooth muscle contraction, vasodilator.
What is the action of seratonin (5-HT) in the digestive system?
Excitatory in neuroneuronal transmission.
What is the action of GABA in the digestive system?
Receptors modulate release of ACh, gastrin, somatostatin, histamine, and prostaglandins.
What are the characteristics of gastrin?
-From the stomach mucosa
-Stimulated by gastric distension, amino acids
-Stimulates gastric acid and motility
What are the characteristics of Cholecystokinin (CCK)?
-From the duodenal mucosa
-Stimulated by fatty chyme, partially digested proteins
-Inhibits gastric emptying, stimulates gallbladder and pancreatic functions
What are the characteristics of secretin?
-From the duodenal mucosa
-Stimulated by a pH of lower than 4.5 in the duodenum
-Stimulates pancreatic and liver bicarbonate secretion, inhibits gastric acid secretion and motility
What are the characteristics of gastric inhibitory peptide (GIP)?
-From the duodenum and jejunum
-Stimulated by Fatty acids,
amino acids, glucose
-Stimulates secretion of insulin, inhibits gastric emptying and gastric secretion of HCl
What are the characteristics of motilin?
-from the duodenum and jejunum
-stimulated by fasting
-Stimulates motility of the stomach and small intestines
What are the characteristics of the lower esophageal sphincter (LES)?
- Important barrier between the esophagus and the stomach
- A tonically constricted 3 – 4 cm ring of smooth muscle
- Not fully developed in infants - regurgitations or “spit-ups”
- During pregnancy, hormones (i.e. progesterone) reduce LES tension
-- Excessive reflux of gastric acid (about 0.1N HCl) lead to burning sensation, pyrosis (heartburn)
What are the steps of the pharyngeal phase of swallowing?
- Pressure by food in the back of the mouth activates sensory receptors that send impulses to a swallowing center in the medulla
- Programmed sequence of events in swallowing center
- Reflex: Upper esophageal sphincter (UES) relaxes, elevated pharynx opens the esophagus, food pushed into esophagus
- Events prevent bolus from entering respiratory passages
- During this period, the respiratory centers are inhibited and breathing stops
- UES pressure > atmospheric between swallows
- UES relaxes during swallows
- Swallowing initiates esophageal peristalsis
What are the steps of the esophageal phase of swallowing?
- Reflex: Epiglottis is tipped posteriorly, larynx
elevated to prevent food from passing into larynx
- Traveling pressure wave moves downward (primary peristalsis)
- Contraction initiated by the swallowing center and
mediated by the vagus nerve
- Begins at UES and moves until reaching LES
- The lower esophageal sphincter (LES) relaxes well in advance of the traveling bolus
What are some factors that decrease pressure of the LES?
- High fat meals
- Alcohol
- Chocolate
- Peppermint, spearmint
- Cigarette smoking
- Caffeine (coffee, cola, tea, citrus juices)
What is the secondary peristaltic wave?
- Distension of esophagus by large particles that remain in esophagus after the primary wave
- Do not involve swallowing center
- Involve local reflex centers
What role do the pacemaker cells have in gastric motor activity?
- basic electrical rhythm (BER) – determines the rate of slow wave
- Spike potentials – trigger contractions and occur at the peak of the depolarization phase
- After a meal, larger sustained contractions are superimposed on the BER
What is the role of gastrin in gastric motor activity?
Increases frequency and velocity of the gastric slow wave, stimulates antrum motility, constricts the pyloric sphincter, raises LES pressure
What are the effects of the sympathetic and parasympathetic nervous systems on motility?
- Motility stimulated by parasympathetic
- Motility inhibited by sympathetic
What are the major factors that contribute to greater gastric emptying and motility?
- Volume and chemical composition of chyme in the duodenum
-- Enterogastric reflex – inhibits gastric motility
-- Hormonal response
--- Enterogastrones (secretin, CCK, GIP) – inhibit gastric contractions
--- Fatty acids in the duodenum stimulate release of CCK stimulating constriction of the pyloric sphincter
--- CCK is the dominant regulator of gastric emptying
- Volume → distention mechanoreceptors stimulated → inhibition of gastric motility via intrinsic nerves
- Emptying:
-- pH (lower slower)
-- osmolality (isotonic faster)
-- particle size (larger slower)
-- caloric load of contents (high slower)
What are the problems associated with accelerated and delayed emptying of the stomach?
- Accelerated – delivery to duodenum may exceed the capability of the intestine to digest it
- Delayed – can lead to loss of appetite, nausea, and vomiting
What is the mechanical sequence of emesis?
􀂄 Hypersalivation
- A deep breath
- Closing of glottis to temporarily inhibit breathing
- LES, esophagus, UES relax
- Abdominal wall muscles and diaphragm contract
- Intra-abdominal pressure pushes the stomach against the diaphragm, forcing gastric contents to be expelled
*Vomiting reflex mainly under parasympathetic
control by a vomiting center in medulla
What inhibits bacterial overgrowth in the small intestine in periods of fasting?
Migrating motor complexes (MMCs).
What are the movements of the colon?
1. haustral churning – segmentation movements to
mix contents of adjacent haustra
2. mass movements – powerful peristaltic contractions
3. distension of rectum reflexively causes
evacuation of bowel
What makes up saliva?
- ~ 99.5% water
- Electrolytes – Na+, K+, Cl-, PO4 2–, HCO3–
- Digestive enzyme – salivary amylase
- Proteins – most protect against microorganisms
-Mucin – lubrication
-Lactoferrin, lysozyme, muramidase – inhibits bacterial growth in the mouth, tooth decay
- Defensins – local antibiotic, call defensive cells into mouth
- IgA antibodies
- Buffers – keep pH near 7.0
What do acinar cells in salavary glands do?
- Secrete primary saliva, iso-osmotic with plasma
- Secretions are mediated by second messengers (cAMP and
Ca2+)
- Secrete all proteins in saliva
-- Packaged in zymogen granules
-- Released into sac by exocytosis
- Secrete ions
-- Cl- - major secreted ion
-- Other ions: HCO3- and K+
- Secrete all of the water in saliva
What do ductal cells in salavary glands do?
- Modify saliva via ion transport systems
-- Na+ reabsorbed, HCO3- secreted (buffers for caries & reflux)
-- Cl- reabsorbed, K+ secreted
- pH and HCO3- increase with flow rate
What are the autonomic controls on salavation?
- Parasympathetic stimulation, saliva is secreted continuously at a basal rate
- Parasympathetic inhibition inhibits salivation and results in dry mouth
What is the gastric mucosal barrier?
- Maintains protective buffered layer of pH 7 mucus
along surface of epithelial cells
- Function: prevents damage to the gastric mucosa from
corrosive HCl and pepsin
What do mucosal neck and surface epithelial cells secrete?
Secrete specific products such as mucins (glycoproteins form protective flexible gel) and
bicarbonate
What damages the gastric mucosal barrier?
bile salts, ethanol, corticosteroids, and NSAIDS
What are the detrimental effects of NSAIDs involving drug-induced gastric disease?
- Cause breaks in gastric mucosal barrier
- H+ ion leaks into mucosa → epithelial cell injury & death
- Overwhelms mucosa ability to protect itself
- Local capillaries are also damaged → bleeding
- Inhibit activity of cyclo-oxygenase – enzyme important in synthesis of gastroprotective prostaglandins
What does H. Pylori do?
Bacteria protects itself by producing large amounts of urease → hydrolyzes the urea → ammonia → damage to mucous layer and epithelial cells
What is used to treat H. Pylori infections?
- Two antibiotics (i.e. metronidazole and tetracycline)
- Bismuth-containing compound (i.e. Pepto-Bismol)
- H2-receptor blocker (i.e. cimetidine or ranitidine) or PPI
What do parietal cells do in relation to GI secretion?
- Possess ion transport mechanisms, proton pumps
- Produce HCl– causes pH of stomach lumen to average 1-3
- CO2 from bloodstream (interstitial space) results in H+ and HCO3- via carbonic anhydrase (parietal cell)
- HCO3- is transported to the blood side (interstitial space) of the cell
- H+ is actively transported to stomach lumen, exchanged
for K+
- Acid activates pepsinogen
- Acid kills most bacteria and inactivates salivary
amylase
How is HCl secretion in parietal cells inhibited?
-HCl secretion is regulated through membrane receptors
- Parietal cell agonists
-- ACh – from vagal parasympathetic/enteric synaptic pathway bind with M3-muscarinic receptors → IP3 increase →
Ca2+ release → protein kinases → H+/K+ ATPase
-- Gastrin – from G cells after parasympathetic
stimulation bind with gastrin/CCK-B receptors → IP3
increase → Ca2+ release → protein kinases → H+/K+ ATPase
--Histamine- paracrine from enterochromaffin-like (ECL) mast cells in gastric mucosa bind with H2 receptors to increase cAMP → activates protein kinases → H+/K+ ATPase
How is HCl secretion in parietal cells stimulated?
- Parietal cell antagonists
-- Prostaglandins
-- EGF
-- SST
How do proton pump inhibitors work?
-Treat ulcers and GERD
- Act on H+/K+- ATPase on parietal cells
- Cause permanent inhibition of enzyme activity, leads to inhibition of H+ ions into the lumen of the stomach
- Secretion of acid only resumes after new molecules of H+/K+- ATPase are inserted into the gastric mucosa
What are a few of the anticholinergic drugs used to decrease HCl production?
•atropine
•dicyclomine (Bentyl)
What is intrinsic factor?
-produced by parietal cells
- *only indispensable constituent of gastric fluid
- Within the stomach, intrinsic factor combines with B12 to form complex necessary for absorption of B12 in the ileum of the small intestine
- Vitamin B12 – essential factor in formation of RBCs
-- Deficiency in bone marrow - Pernicious anemia
What is pepsinogen?
-Chief cells produce pepsinogen (stored and secreted form) in response to the presence of gastric acid
- Optimally active at pH=2
- Activated by H+, gives pepsin (active form)
- Activated pepsin begins the process of protein digestion
What is gastric lipase?
-Chief cells secrete gastric lipase (active at pH=3)
- Digest triglycerides
What do pyloric glands -enteroendocrine cells- secrete?
-Gastrin (G-cells)
-SST (D-cells)
What does gastrin do?
- Stimulates acid release by parietal cells
- Stimulates pepsinogen release by chief cells
- Stimulates stomach mucosal growth
- Stimulates contractions of the gastric wall that mix and stir the gastric contents
What does SST do?
- secreted by D-cells
- Inhibits gastrin release (G cells)
- Inhibits histamine release (mast cells)
- Inhibits acid secretion (parietal cells)
What are the functions of the cephalic phase of gastric secretion?
- **20-30% of gastric secretory response to a meal
- Proceeds food entering stomach
- Thoughts of food (smell, sight, or taste)
- Chewing or swallowing
- Mediated by vagus nerve and gastrin
- Promote HCl and pepsinogen secretion
-duration: minutes
What are the functions of the gastric phase of gastric secretion?
- **60-70% of gastric secretory response to a meal
- Elicited by the presence of food in the stomach
-- Distension → stretch receptors
-- Elevated pH → chemoreceptors
-- Protein
-- Caffeine
-- Alcohol
- Mediated by the intrinsic nerves, the vagus nerve, gastrin
-- Promote HCl and pepsinogen secretion
-duration: 3-4 hours
What are the functions of the intestinal phase of gastric secretion?
- About 10% of gastric secretory response to a meal
- Excitatory component
-- release of intestinal gastrin in response to the products of protein digestion in the duodenum
→ HCl and pepsinogen secretion
- Inhibitory component
-- Distension, lipids, acids, hyperosmotic chyme at duodenum inhibits gastric secretion by
--- Enterogastric reflex
--- Release of enterogastrones
----Secretin, CCK, GIP (all inhibit gastric secretion)
-duration: hours
What is the general funciton of the pancreas?
-Exocrine glands account for 98% of its mass
- Function:
1. Provide essential enzymes required for digestion
2. Neutralize stomach acid in the duodenum
Where is pancreatic juice transported from the pancreas to the duodenum?
The pancreatic duct.
What does pancreatic juice do?
-Alkaline and contains a high concentration of bicarbonate ion
-- Neutralizes the acidic chyme entering the duodenum
from stomach
What do epithelial duct cells do in the pancreas?
- sites of electrolyte and water secretion
- **secrete bicarbonate that will neutralize excess stomach acid in the duodenum
What regulates release of pancreatic secretions?
- CCK (acinar cell activity)
- Secretin (bicarbonate secretion by epithelial duct cells)
What are acinar cells?
-They produce enzymes in the pancreas.
-The enzymes are stored as zymogen granules.
How are starch and disaccharides broken down?
1. by salivary amylase
2. by pancreatic amylase
-broken into ogliosaccharides and disaccharides- lactose, maltose, sucrose
3. brush border enzymes in small intestine (dextrinase, glucoamylase, lactase, maltase, sucrase) break down to galactose, glucose, and fructose
4. galactose and glucose are involved in Na+ cotransport, fructose in facilitated diffusion
5. Enter the blood through villi and are transported to the liver by the hepatic portal vein
How are unemulsified fats broken down?
1. unelmusified fats are emulsified by detergent action of bile salts ducted in from the liver
2. pancreatic lipase action to give monoglycerides, glycerol, and fatty acids
3. diffusion into intestinal cells + protein = chylomicrons
4. Enter the lacteals (lymphatic capillaries of small intestine)through villi and are transported to systemic circulation via the lymph
Where does blood flow to the liver come from?
- About 1350 ml/min (27% of CO)
-Hepatic artery
-- Brings 300 ml/min of oxygenated blood from aorta
- Hepatic portal vein
-- Brings about 1050 ml/min of blood from digestive tract
-- Low in oxygen
-- High in nutrients absorbed from the intestines
What are the different cell types in the liver?
- Hepatocytes
-- liver cells
-- predominant cell type
- Endothelial cells
-- line passage ways (sinusoids)
- Kupffer cells
-- phagocytes
What are sinusoids in the liver and where do they drain?
sinusoids:
- spaces between plates
- empty into central vein
What are the portal areas (triads) of liver lobules?
- hepatic artery branch
-- delivers oxygenated blood
- portal vein branch
-- delivers absorbed & secreted materials
- bile duct branch
-- removes bile
How does the liver act as a blood reservoir?
-Liver is a large distensible organ
- 10% of blood volume
- As needed, blood may be mobilized to increase VR then increase CO
How, in general, does the liver filter blood?
- Protective function
- Kupffer cells, large phagocytic macrophages, line
hepatic venous sinuses
-- Take in and digest bacteria
-- Efficiently removes 99% of the bacteria from hepatic
portal blood
What are IGFs?
-Synthesis of IGFs (somatomedins) done by the liver
- Responsible for many of GH’s growth-promoting
effects
What vitamins does the liver store?
- Vitamin A – up to 10 months
- Vitamin D – 3-4 months
- Vitamin B12 – at least 1 year
- Iron (in form of ferritin) is released when circulating iron blood levels low
What blood clotting factors does the liver produce?
- Blood clotting factors (II, VII, IX, X)
What hormones does the liver metabolize?
- Thyroid hormone
- All steroid hormones (estrogen, cortisol, aldosterone…)
What is bile?
- Def: aqueous, yellow-green, alkaline fluid
consisting of a complex mixture
- Bile salts, bile pigments, cholesterol, neutral fats,
phospholipids, variety of electrolytes
- Bile salts are synthesized from cholesterol
- Bile salts are amphipathic (hydrophilic and hydrophobic regions) and arrange themselves around lipid droplets
What are the functions of the gallbladder?
-bile storage
-- 1 liter of bile produced/day
-- bile made continuously
-- enters gallbladder if sphincter closed
- bile modification
-- water reabsorbed
-- increased concentration (up to 20X)
What stimulates the gallbladder to empty?
The presence of dietary fat and protein.
What are the hepatic and gallbladder ducts?
- Cystic duct
-- leads in/out of gallbladder
- Common hepatic duct
-- Common drainage for all the lobes
- Bile duct
-- union of cystic and common hepatic ducts
-- joins pancreatic duct
-- opens into duodenum
How do bile acids regulate bile release?
-Target: hepatocytes
-Action: increases bile flow, inhibits bile acid synthesis
How does secretin regulate bile release?
-Target: bile ducts in the liver
-Action: stimulates secretion of water and bicarbonate into the bile
How does CCK regulate bile release?
Targets: gallbladder, Oddi's sphincter
Action: Stimulates contractions of the gallbladder and relaxes Oddi's sphincter
How does the vagus nerve regulate bile release?
Targets: gallbladder
Action: stimulates contractions (minor effect)
What are the steps in the regulation of bile release?
1. Acidic, fatty chyme entering duodenum causes release of CCK and secretin from duodenal wall enteroendocrine cells
2. CCK and secretin enter bloodstream.
3. Bile salts and secretin transported via bloodstream stimulate liver to produce bile more rapidly.
4. Vagal stimulation causes weak contractions of gallbladder
5. CCK (via bloodstream) causes gallbladder to contract and hepatopancreatic sphincter to relax, bile enters duodenum
6. Bile salts reabsorbed into blood
What are the cell types in the small intestine?
1) absorptive cells
- brush border enzymes
- integral membrane proteins
- digestion of materials contacting brush border
2) goblet cells (mucus)
3) enteroendocrine cells
- secrete enterogastrones (gastrin, secretin, CCK)
What stimulates mucus stimulation of the goblet cells in the lg. intestine?
- tactile stimuli and irritation
- parasympathetic stimulation
What does the liver do to proteins?
- Deamination of amino acids
- Formation of urea (for removal of ammonia from body fluids)
- Formation of plasma proteins (albumins, fibrinogen, globulins)
- Conversion of amino acids into other compounds
What does the liver do to lipids?
- Oxidation of fatty acids to supply energy for other functions
- Synthesis of cholesterol, phopholipids, and lipoproteins
- Synthesis of fat from proteins and carbohydrates
What are the steps of protein digestion?
1) Proteins are broken down by pepsin (in the presence of HCl) in the stomach leading to
2) Lg. polypeptides, broken down by pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) in the small intestine
3) makes sm. polypeptides and peptides that are broken down by brush border enzymes (carboxypeptidase, aminopeptidases, dipeptidase) in the sm. intestine.
4) Leads to amino acids (and some di-and tri-peptides) that pair with cotransport Na+ to enter the blood through villi and are transported to the liver by the hepatic portal vein
How are nucleic acids digested?
1) nucleic acids are broken down in the sm. intestine by deoxyribonuclease and ribonuclease
2) Then broken down by brush border enzymes (nucleosidases and phosphatases) in sm. intestine
3) gives pentose sugars, N-containing bases, phosphate ions which enter the blood through villi and are transported to the liver by the hepatic portal vein
What do bile salts do?
They facilitate the action of pancreatic lipase and formation of micelles (small lipid-bile salt complexes).
What is the relationship between water and the colon?
- About 1.5 L of fluid passes the ileocecal valve each day
- Only 150 mL of water is lost in stools
- Maximum absorptive capacity is about 4.5 L and
when this is exceeded, diarrhea will occur
- Water moves by transcellular (through cell) and paracellular (between cell) mechanisms
What are the relative volumes of fluids in the different body compartments?
- 2/3 – intracellular fluid (ICF)
-- fluid within cells or cytosol
-- ICF = 0.4 x (body weight) = 28 L
- 1/3 – extracellular (ECF)
-- fluid found outside of cells
-- ECF = 0.2 x (body weight) = 14 L
-- 3/4 – interstitial fluid (0.15 x body weight = 10.5 L)
-- 1/4 – blood plasma (0.05 x body weight = 3.5 L)
What are the concentrations of solutes in the ICF?
- low sodium, chloride & bicarbonate
- high potassium & protein
- 50% of osmolality due to potassium
What are the concentrations of solutes in the ECF?
- high sodium, chloride & bicarbonate
- 50% of osmolality due to sodium & chloride
- low potassium
In general, what are the different excretory systems of the body?
-Respiratory system removes the metabolic waste product
-- CO2
- Digestive system removes:
-- Undigested materials
-- Bacteria
- Urinary System removes:
--Waste products
--- Urea, uric acid, creatinine, ammonia salts
-- Water
-- Toxic molecules
-- Excess ions

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