organ systems: nasal and larynx

this lecture covered the bones, muscles, blood supply, and innervation of the nasal cavity and larynx. it started off with the nasal cavity structures: the nasal cavity is made up of the nasal, maxilla, ethnoid, palatine bones. the nasal septum divides the two nostrils and is made up of the ethmoid, vomer, and septal cartilage. the conchae are curved bones covered with a mucosal layer that serve to increase the surface area of the nasal cavity. the superior concha covers the superior meatus, which is the opening for the frontal sinus. the middle concha covers the middle meatus, which is the opening for the maxillary, ethmoid, and sphenoid sinuses. the inferior concha covers the inferior meatus, which is the site of the nasolacrimal opening.

the nasal cavity is innervated mainly by the mandibular and maxillary divisions of the trigeminal nerve [see diagram]. the anterior ethmoidal nerve branches off of V1 and enters the nasal cavity via the anterior ethmoidal foramen and innervates the anterior ethmoidal sinus, the anterior nasal cavity, and the frontal sinus. V1 also has an external branch that innervates the external nose. V2 comes through the foramen rotundum into the pterygopalatine fossa, and from there into the nasal cavity by way of the sphenopalatine foramina. at this point V2 has three branches that innervate the nasal cavity: 1) greater and lesser palatine branches travel through the palatine foramina and innervate the inferior palate. 2) posterior lateral nasal nerves innervate the concha. 3) nasopalatine branches go through the incisive canal and innervate the inferior aspect of the hard palate. V2 also has an external branch that innervates the exterior of the nasal cavity-- the infraorbital branch innervates the cheek and infraorbital canal and foramina, and the superior alveolar nerve innervates the top row of teeth.

the two major arteries in the nasal cavity are the sphenopalatine and the anterior/posterior ethmoidal arteries. the anterior/posterior ethmoidal branches off of the opthamalic branch of the internal carotid and the sphenopalatine artery branches off of the maxillary branch of the external carotid. it is due to the extensive anatamoses between the blood vessels in this area that nosebleeds are so difficult to stop.

olfactory receptors are bipolar neurons contained in the upper recesses of the nasal cavity that last 1-2 months before being replaced by undifferentiated basal cells. they have ciliated cells called sensory processes that project into the mucous layer which have receptors for specific "odorant" molecules from the environment, which trigger action potential in these neurons by g-proteins and second messenger cascades.

the last section dealt with the larynx muscles and cartilage. the larynx area is made up largely of the thryoid, arytenoid, and cricoid cartilage and also contains the epiglottis, which is attached to the inner surface of the thyroid cartilage. the quadrangular membrane is the connective tissue sheet from the arytenoid cartilage to the epiglottis, while the "conus elasticus" is the connective tissue sheet from the arytenoid/cricoid cartilage to the thyroid cartilage, the upper free edges of which forms the vocal cords.

there are several sets of muscles that control different types of movement in the larynx. the aryepiglottic, thryoepiglottic, and oblique arytenoid muscles close the laryngeal inlet. the posterior cricoarytenoid and lateral cricoarytenoid open the glottis (the space between the vocal cords) while the transverse and oblique arytenoid close it. finally, the cricothryoid lengthens the vocal cords (producing lower pitches) and the thyroarytenoid and vocalis shortens (higher pitches).

questions
nasal cavity and bones...
1. which bones is the nasal aperture made of?
2. what are the types of cartilages in the nose?
3. what is the fleshy part of the nose called and what is it made of?
4. which bones form the walls and the hard palate?
5. what part of the nasal cavity does the ethmoid form?
6. perpendicular plate of ethmoid forms...
7. what passes through the cribiform plate of the ethmoid bone?
8. besides the ethmoid, what else forms the nasal septum?

concha and meatuses...
9. describe the conchae bones.
10. inferior meatus is the site of...
11. middle meatus is the site of...
12. superior meatus is site of...
13. what is an important function of the conchae?
14. what does the respiratory epithelium do?

sinuses...
15. what are the paranasal sinuses?
16. where does the sphenoid sinus open?
17. where is the frontal sinus and where does it open?
18. where is the maxillary sinus and where does it open into?
19. proximity of sinus to maxillary teeth permits...
20. where does the ethmoid sinus open into?

innervation...
21. which nerves are the nasal cavity and hard palate innervated by?
22. describe the passage of the anterior ethmoidal branch of V1 into the nasal cavity.
23. what does the anterior ethmoidal nerve innervate?
24. what does the anterior ethmoidal nerve branch into?
25. describe the passage of the maxillary branch (V2) into the palatine area and the nasal cavity.
26. what does V2 branch into in the nasal cavity area?
27. where do the posterior lateral nerves project?
28. where do the greater and lesser palatine nerves project?
29. where do the nasopalatine nerves project?
30. what are the external branches of V2 and what do they innervate?
31. what is the hay fever ganglion? what nerves does it receive and what nerves does it project?
32. describe the parasympathetic innervation of the nasal cavity.

arteries...
33. what are two of the major arteries in the nasal cavity?
34. where does the anterior/posterior ethmoidal artery branch off of?
35. where does the sphenopalatine artery branch off of?
36. why are nosebleeds difficult to stop?

olfaction...
37. what are olfactory receptors? where are they?
38. what is the live span of a olfactory receptor? what happens when they die?
39. what are "sensory processes" and what do they do?
40. how do odorants trigger an action potential?

larynx and vocal cords...
41. what is the cartilage associated with the larynx?
42. what are some landmarks of the thyroid cartilage?
43. where is the epiglottis attached?
44. what does the thyrohyoid membrane do?
45. what are the vocal cords made of?
46. what is the conus elasticus?
47. what is the space between vocal cords called?
48. what is the quadrangular membrane?
49. what is the vestibular fold?
50. where is the ventricle of the larynx?

muscles and innervation of larynx...
51. what are the muscles that close the laryngeal inlet?
52. what are the muscles that open and close the vocal cords?
53. what are the muscles that lengthen and shorten vocal cords?
54. why do males have lower pitched voices than females?
55. what nerve innervates the larynx?
56. which branch supplies motor innervation to cricothyroid and sensory innervation to the mucosa?
57. which branch supplies motor innervation to all of the other intrinsic larynx muscles?

answers
1. nasal and maxilla
2. lateral, septal, alar
3. ala nasi, made of loose CT
4. maxilla and palate bones
5. the roof and part of the nasal septum.
6. part of nasal septum.
7. olfactory nerves.
8. vomer, septal cartilage.

9. curved bones covered with mucosa that overlie meatuses.
10. nasolacrimal opening (which is why crying produces a runny nose)
11. site of opening of the maxilla, ethmoid, frontal sinuses.
12. site of opening of the sphenoid sinus.
13. increasing surface area of nasal cavity.
14. warms, humidifies, dehumidifies air.

15. cavities within bones: sphenoid, ethmoid, frontal, maxillary.
16. above the superior concha.
17. within frontal bone, deep to the glabella and superior orbital fissure; opens into the middle meatus.
18. within maxilla bone, empties into middle meatus.
19. intercommunication of infections.
20. lateral nasal cavity.

21. V1 and V2.
22. anterior ethmoidal branch of V1 travels into the nasal cavity via the anterior ethmoidal foramen.
23. the frontal sinus, anterior ethmoidal sinuses, and anterior nasal cavity.
24. the external nasal branch which innervates the external nose.
25. enters the pterygopalatine fossa via the foramen rotundum and the nasal cavity via the sphenopalatine foramen.
26. posterior lateral nerves, greater/lesser palatine nerves, nasopalatine nerves.
27. the conchae
28. through the palatine foramina to the inferior palate.
29. into the anterior aspect of the hard palate via the incisive foramen.
30. the infraorbital branch innervates the cheek and infraorbital canal and foramen. the superior alveolar branches innervate the upper teeth.
31. the pterygopalatine ganglion; receives the facial nerve (CN VII) and projects nerves to the nasal, palatine, and lacrimal glands via V1 and V2.
32. preganglionics from the T1 level project to the superior cervical ganglion. postganglionics follow blood vessels to nasal cavity.

33. sphenopalatine and anterior/posterior ethmoidal.
34. from the opthamalic branch of the internal carotid.
35. from the maxillary branch of the external carotid.
36. because of the extensive anastamoses of arteries in the nasal cavity.

37. bipolar neurons within olfactory epithelium in upper recesses of nasal cavity.
38. 1-2 months, replaced by undifferentiated basal cells
39. ciliated cells that project into the mucus layer which have receptors for specific odorants.
40. via G proteins and second messengers.

41. thyroid, arytenoid, cricoid
42. lamina, thyroid notch. superior/inferior horns. laryngeal prominence (adam's apple).
43. inner surface of thyroid cartilage.
44. suspends larynx from hyoid bone.
45. upper free edges of the conus elasticus.
46. CT sheet from arytenoid/cricoid cartilage to thyroid cartilage.
47. rima glottidis.
48. CT sheet from arytenoid cartilage to epiglottis.
49. lower free edge of quadrangular membrane.
50. cavity between vocal and vestibular folds.

51. aryepiglottic, thyroepiglottic, oblique arytenoid
52. posterior cricoarytenoid, lateral cricoarytenoid open glottis, transverse and oblique arytenoid close glottis.
53. cricothyroid lengthens, thyroarytenoid and vocalis shortens.
54. higher testosterone levels elongate the thyroid cartilages and thus produce longer vocal cords and lower voices.
55. vagus
56. superior laryngeal
57. recurrent laryngeal

organ systems: oral and pharynx

this lecture talked about various aspects of the pharynx, including muscles, tonsils, and innervation. the first section covered structures of the mouth and teeth: philtrum is the median shallow groove in the upper lip, labia frenulum is the fold of mucosal membrane that attaches the lip to the gums, and lingual frenulum is the fold that connects the tongue to the base of the mouth. there are 32 teeth, 8 in each half of each jaw: 2 incisors, 1 canine, 2 pre-molar, and 3 molars. the crowns of the teeth are made up of dentine and enamel, and the pulp cavity inside contains nerves and blood vessels, which travel through the tooth in root canals and exit via the apical foramen. teeth are anchored to bone via the cementum and peridontium layers.

there are intrinsic muscles inside the tongue and extrinsic muscles of the tongue that attach to various structures in the pharynx and move the tongue in different directions. this includes the genioglossus, which attaches to the mental spine of the mandible and protrudes and depresses the tongue, the hyoglossus, which attaches to the hyoid bone and depresses the tongue, the styloglossus, which attaches to the styloid process of the mandible and retracts the tongue, and the palatoglossus, which attaches to the soft palate and raises the tongue. the first three tongue muscles are innervated by the hypoglossal nerve (CNXII), and the palatoglossus is innervated by the vagal nerve.

the tongue's sensory innervation can be divided into two aspects: somatosensory innervation delivers pain, touch, heat sensation from the filiform papillae of the tongue, while viscerosensory information delivers the taste information from the chemoreceptors from the valate and fungiform papillae on the tongue. on the top 1/3 of the tongue, both somatosensory and viscerosensory innervation is provided by the glossopharyngeal nerve (CNIX) while in the bottom 2/3 of the tongue, viscerosensory innervation is provided by the facial nerve (CNVII) and somatosensory by the lingual nerve (V3).

the next topic in the lecture was the pharyngeal and palatine muscles. there are several pharyngeal constrictor muscles which constrict the pharynx, all originate from the posterior pharyngeal raphe, and are all innervated by the vagus nerve. the superior constrictor attaches to the buccinator by way of the pteromandibular raphe, the middle constrictor attaches to the hyoid, and the inferior constrictor attaches to the cricoid and thyroid cartilage. the palatine muscles include the palatopharyngeus, which attaches the soft palate to the back of the throat and serves to lower the soft palate and the palatoglossus, which was covered above. the tensor veli palatini (innervated by CN V3), which originates on the base of the skull, hooks around the hamulus and tautens the palate while the levator veli palatini (innervated by the vagus nerve) lifts the palate.

tonsils are masses of lymphoid tissue which are present in 4 main places in the pharynx: the pharyngeal tonsils in the upper nasopharynx, the tubular tonsils near that auditory tube, the lingual tonsils on the posterior tongue, and the palatine tonsils, which are between the palatoglossus and the palatopharyngeus. lymph from these nodes ultimately drains into the deep cervical lymph nodes and into the venous system.

questions
lips and tongue...
1. what is the philtrum?
2. what is the labia frenulum?
3. what is the lingual frenulum?
4. what are sublingual veins used for?

teeth...
5. what are the crowns of teeth made up of?
6. what attaches the root of the teeth to the bone?
7. what is the pulp cavity made up of?
8. how many teeth are there? what are the different types?
9. which nerves innervates the teeth?

origins, insertions, actions, innervations:
10. genioglossus
11. hyoglossus
12. styloglossus
13. palatoglossus

tongue innervation...
14. which tongue muscles does the hypoglossal nerve innervate?
15. what are the two categories of sensory innervation of the tongue?
16. which nerves provide somatosensory and viscerosensory innervation to the lower 2/3 of the tongue?
17. which nerves provide somatosensory and viscerosensory innervation to the upper 1/3 of the tongue?
18. which nerves provide somatosensory and viscerosensory innervation to the palate and epiglottis?
19. what is the difference between the filiform, fungiform, and vallate papillae?

pharyngeal muscles...
20. where do the pharyngeal constrictor muscles all originate?
21. what are the pharyngeal constrictor muscles innervated by?
22. where does the superior constrictor insert?
23. where does the middle constrictor insert?
24. where does the inferior constrictor insert?

palate muscles...
25. how does the soft palate help regulate the passage of air and food?
26. how does the epiglottis help regulate the passage of air and food?
27. tensor veli palatini...
28. levator veli palatini...
29. palatopharyngeus...
30. salpingopharyngeus...
31. snoring is associated with...
32. palatopharyngeus and palatoglossus forms a ... space which contains the ...

tonsils...
33. what is waldeyer's ring?
34. what is unique about the nasopharyngeal tonsils?
35. where is the tubal tonsil located?
36. where is the palatine tonsil located?
37. where is the lingual tonsil located?

nerves and lymph nodes...
38. which nerve innervates the upper section of the oral and nasal cavities?
39. what part of the pharynx does the glossopharygeal nerve innervate?
40. what other sensations or reflexes in the pharynx does the glossopharyngeal nerve mediate?
41. which nerve innervates the lower pharynx and larynx?
42. superficial lymph nodes all drain into...

answers
1. the median shallow groove in the upper lip.
2. folds of mucous membrane that connects the lips to the gingiva.
3. folds of mucous membrane that connects tongue to the base of the mouth.
4. ingestion of medicine directly into the blood.

5. enamel and dentine.
6. cementum and peridontial membrane.
7. a root canal that exits through the apical foramen. also contains nerves and blood vessels.
8. 32 total; 8 in each half of each jaw. 2 incisors, 1 canine, 2 premolar, 3 molar.
9. upper teeth: superior alveolar (V2). lower teeth: inferior alveolar (V3).

10. O: mental spine of the mandible, I: body of tongue, N: hypoglossal (CNXII) A: depress and protrude tongue.
11. O: hyoid bone, I: body of tongue, N: hypoglossal nerve, A: depress tongue.
12. O: styloid process of mandible, I:body of tongue, N: hypoglossal nerve, A: retract tongue.
13. O: soft palate, I: body of tongue, N: vagal nerve, A: elevate tongue.

14. the extrinsic muscles of the tongue (except the palatoglossus) and the intrinsic muscles of the tongue.
15. somatosensory includes tactile, pain, temperature sensation and viscerosensory is the taste sensation.
16. SS: lingual nerve (V3), VS: facial nerve (VII)
17. glossopharyngeal (IX)
18. vagus (X)
19. filiform is pain, temperature, touch receptor; valate and fungiform are taste receptors.

20. the posterior pharyngeal raphe.
21. vagus nerve
22. buccinator via the pteromandibular raphe.
23. hyoid bone
24. thyroid and cricoid cartilage.

25. during breathing it lowers down against the tongue and during eating it raises against the pharyngeal wall.
26. ascends against the tongue during breathing and folds down over larynx during eating.
27. O: pterygoid plates, I: palatine aponeurosis, N: V3, A: tauten palate, open auditory tube.
28. O: base of skull I: pterygoid processes, N: vagus A: raise soft palate and open auditory tubes.
29. O: thyroid cartilage, I: soft palate, N: vagus, A: depress soft palate
30. O: auditory tube, I: pharynx, N: vagus, A: open auditory tubes.
31. obstructions in the soft palate region.
32. triangular space which contains the palatine tonsil.

33. the ring of lymphoid tissue that contains: pharyngeal, tubal, palatine, lingual tonsils.
34. they are the uppermost part of the nasopharynx and can commonly become inflamed (enlarged adenoids) and block the passage of air.
35. near the auditory tube.
36. between the "pillars of fauces".
37. on the posterior surface of the tongue.
38. trigeminal: V2,V3
39. upper pharynx, auditory tube, tonsils
40. gag reflex, sore throat pain.
41. vagus
42. deep cervical lymph nodes.

ms anatomy II: neurocranium pt III

this lecture looked at the ventricles inside the brain, the dural sinuses outside the brain, the production of CSF, the different types of barriers present in the brain, and the flow of CSF through the ventricles and sinuses. dural sinuses are spaces in between inner and outer dural layers, either at the junction of dural sheets or above the dura. sinuses convey venous blood and as such have a sequence for draining which eventually leads into the internal jugular vein. the superior sagittal sinus drains into the confluence sinus, which drains into the transverse sinus, which drains into the sigmoid sinus, which drains into the jugular foramen, which drains into the internal jugular vein. the internal sagittal sinus drains into the straight sinus and joins the main drainage pathway at the confluence sinus. the cavernous sinus drains into the petrosal sinuses, which joins the main pathway at the transverse sinuses.

along with venous blood, CSF also eventually drains into these sinuses (or goes into the spinal cord). CSF is produced by choroidal epithelial cells which line the choroidal plexus, which surround cerebral arteries on the lining of ventricles. CSF is produced by these choroidal cells and secreted into the ventricles. CSF then flows through the ventricles: lateral to 3rd, 3rd to 4th (by way of the cerebral aqueduct), and then either into the spinal cord or into the subarachnoid space by the foramina of luschka or magendie. from there CSF ascends to the level of the sagittal sinus and exits the subarachnoid space by way of the arachnoid villi, which contain a membranous layer that allows CSF to flow into the sinuses. from there the CSF follows the drainage pathway of the venous blood as described above.

there are 3 unique barriers in the brain relating to blood and CSF. first is the blood brain barrier (see neurocranium part 2 for more detail). second is the blood / CSF layer-- which consists of choroidal epithelial cells. these cells contain tight junctions which does not allow the passage of larger molecules. third is the brain / CSF layer-- essentially the lining of the ventricles, made up of ependymal cells which are not joined by tight junctions. as such, they allow the passage of larger molecules, such as the metabolites of neurotransmitters, which can thus be detected in spinal taps (parkinson disease shows decreased catecholamines in CSF)

one last note: emissary veins transmit blood from the dural sinuses to below the scalp layer. just like venae comitantes, they aid in thermoregulation, in this case by routing the colder outer blood closer to the brain to cool it, or the opposite direction to warm it.

questions
sinuses and veins...
1. cerebral veins drain blood into...
2. what are dural sinuses?
3. where are dural sinuses located?
4. trace the pathway of venous blood from the superior sagittal sinus to the internal jugular vein.
5. trace the pathway of venous blood from the inferior sagittal sinus to the internal jugular vein.
6. trace the pathway of venous blood from the cavernous sinus to the internal jugular vein.
7. what does the cavernous sinus contain?
8. what are emissary veins?
9. how are emissary veins used for thermoregulation?

CSF...
10. where does CSF in the lateral ventricles eventually end up? describe the two possible pathways.
11. what is the choroid plexus? what does it do?
12. what is the brain/CSF barrier composed of? what does it let through?
13. what is the total volume of CSF in the body at any given time?
14. what is the pressure of CSF?
15. what is the total volume of CSF produced per day?
16. how does CSF move from the subarachnoid space to the sagittal sinus?
17. how does CSF support the integrity of the brain?
18. describe the equilibrium that exists between the epidural space and the subarachnoid space.
19. describe the brain/CSF barrier.
20. blockage of the CSF flow causes...

answers
1. dural sinuses.
2. spaces between periosteal and meningeal dural layers that convey venous blood.
3. at the junction of dural sheets or above the dura.
4. superior sagittal sinus -> confluence sinus -> transverse sinus -> sigmoid sinus -> jugular foramen -> internal jugular vein.
5. inferior sagittal sinus -> straight sinus -> confluence sinus -> transverse sinus -> sigmoid sinus -> jugular foramen -> internal jugular vein.
6. cavernous sinus -> petrosal sinuses -> transverse sinus -> sigmoid sinus -> jugular foramen -> internal jugular vein.
7. cranial nerves: IV, V1,V2,V3, VI, and internal carotid artery
8. veins that allow for transport of venous blood between the scalp and the dural sinuses.
9. emissary veins help maintain the temperature of the brain by routing colder blood from the surface of the scalp closer to the brain during hyperthermia and the opposite motion during hypothermia.

10. travels from the lateral ventricle to the 3rd ventricle, through the cerebral aqueduct into the 4th ventricle. at this point it can flow downward into the spinal cord, or through the foramina of luschka and magendie into the subarachnoid space-- and from there into the superior sagittal sinus.
11. the choroid plexus surrounds cerebral arteries and secretes CSF into the ventricles.
12. made of choroid epithelial cells which are joined by tight junctions-- preventing the flow of large molecules.
13. 150mL
14. 10mm Hg
15. 450mL
16. through arachnoid villi, protrusions of the arachnoid layer that have a filtering membrane that allows CSF to pass into the sagittal sinus.
17. by being suspended in CSF, the brain is protected in three ways: the mass (~1400g) is effectively reduced to 40g due to buoyancy. the cranial nerves and veins are protected. lastly, arachnoid trabeculae serve to anchor the brain in place.
18. there is an equilibrium between the pressure of venous blood in the epidural space and the CSF in the subarachnoid space.
19. the brain CSF barrier is made up of ependymal cells which are not joined by tight junctions; hence fluid and larger molecules can flow readily-- this allows metabolites of neurotransmitters, for example, to be present in CSF in ventricles.
20. hydroencephaly

organ systems: glucose regulation

this lecture focused on glucose metabolism: specifically, the interplay of insulin and glucagon secretion and their effect of glucose metabolism and storage in different organs and tissues. the pancreatic islets of langerhans secrete glucagon from alpha cells, insulin from beta cells, and somatostatin from delta cells. glucagon is secreted in response to low blood sugar and has a variety of effects which ultimately serve to raise blood glucose levels. in the liver, glycogenolysis is initiated, freeing glucose units from storage (see the biochem chapter on glycogen for more detail), gluconeogenesis creates glucose from non-carbon precursors such as amino acids. additionally, triacylglyceride stores are converted into fatty acids, which can be cleaved into ketone bodies, which are used as an alternative fuel source. glucagon is released in response to hypoglycemic (low blood sugar) conditions. other mechanisms are in place to raise blood sugar: sympathetic stimulation, cortisol, growth hormone. the symptoms from severe hypoglycemia are caused by these mechanisms; hunger by the hypothalamus and anxiety/tremors/sweating by sympathetic stimulation.

on the other hand, insulin is released in hyperglycemic conditions (high blood sugar) and facilitates uptake of glucose into cells. it accomplishes this by binding to receptors that translocate glucose transport proteins to surface of cell membranes, thereby allowing glucose to enter. there are 5 categories of glucose transport proteins, with different affinities for glucose and found in different locations of the body (see the carb digestion biochem chapter for some more physiology of the GLUT transporters): GLUT1 are found everywhere in the body and also present in placenta. GLUT2 transporters are in the pancreas, liver, kidney, and intestine. GLUT3 transporters are everywhere in the body. GLUT4 transporters are in muscle and adipose tissue and are the only insulin dependent glucose transporters. GLUT5 transporters are in the jejunum.

insulin has a variety of actions on organs and tissues; in the liver it initiates glycogen storage, fatty acid synthesis and subsequent triacylglyceride synthesis. in adipose tissue it stimulates uptake of glucose, triacylglyceride synthesis, and triacylglyceride release (through VLDL's). in muscle it stimulates uptake of glucose and amino acids and promotes glycogen storage from the excess glucose. insulin release is stimulated by a variety of factors- primarily high blood glucose levels, but also via parasympathetic stimulation, amino acids, growth hormone, and various GI hormones. insulin release is inhibited by catecholamines, somatostatin, and glucagon. note: glucagon and insulin reciprocally regulate each other- the release of one inhibits the release of the other. in addition, the release of somatostatin inhibits the release of both insulin and glucagon- preventing "rapid nutrient exhaustion".

diabetes type I is caused by an autoimmune destruction of pancreatic beta cells, resulting in low insulin levels and therefore low glucose metabolism and therefore a shift to ketone body metabolism. this also results in increased glucose levels in the urine, which can cause polyuria (excess urine volume), polydipsia (excess thirst), and polyphagia (excess hunger). type II diabetes is a resistance to insulin that is associated with high visceral fat deposits with high lipolytic activity (releasing fatty acids into the bloodstream) that are resistant to the anti-lipolytic properties of insulin. this can be induced by high free fatty acid, cortisol, or testesterone levels.

questions
glucagon...
1. what are the three types of cells in the pancreatic islets of langerhans and what do they secrete?
2. describe glucagon's effect on the liver.
3. what are the specific processes that occur that release glucose and ketones from the liver?
4. what is glucagon release from alpha cells stimulated by?
5. what is glucagon release from alpha cells inhibited by?
6. how does somatostatin "prevent rapid nutrient exhaustion"?
7. glucagon corrects...
8. what are the other ways that the body corrects for hypoglycemia?
9. what are the symptoms of severe hypoglycemia and what are they caused by?
10. what is reactive hypoglycemia and what is it caused by?

insulin...
11. describe the general function of insulin.
12. how does insulin facilitate the uptake of glucose into cells?
13. where are GLUT1-GLUT5 found?
14. which glucose transporter protein requires insulin?
15. describe insulin's action on muscle.
16. describe insulin's action on the liver.
17. describe insulin's action on adipose tissue.
18. what are some factors that facilitate release of insulin from the pancreas?
19. what are inhibitors of insulin release?

hormonal regulation...
20. describe the "reciprocal regulation" of insulin and glucagon.
21. describe the concept of a "basin of attraction" in regards to glucose regulation.

diabetes...
22. what is IDDM? what is it caused by?
23. what do high glucose levels in urine cause?
24. what is type II diabetes? what is it caused by and what does it result in?

answers
1. alpha cells secrete glucagon, beta cells secrete insulin, delta cells secrete glucagon.
2. increases glucose and ketone production and secretion.
3. glycogenolysis, gluconeogenesis, lipolysis, ketogenesis.
4. amino acids, decreased bloods sugar, CCK, VIP, catecholamines.
5. insulin/glucose, somatostatin.
6. by inhibiting both alpha and beta cell secretion of glucagon and insulin secretion.

7. hypoglycemia.
8. sympathetic stimulation, cortisol, growth hormone.
9. anxiety, tremors, sweating are caused by sympathetic action and hunger is caused by hypothalamus.
10. low blood sugar levels after a meal that results from excess release of insulin triggered by high content of high glycemic index carbohydrates (or insufficient protein).

11. to store metabolic fuels.
12. by binding to receptors which translocate glucose transporter proteins into the cell membrane.
13. GLUT1- ubiquitous, placenta, GLUT2- beta cell, liver, kidney, intestine, GLUT3- ubiquitous, GLUT4- muscle,adipose, GLUT5-jejunum.
14. GLUT4.
15. causes uptake of amino acids and sugar (and therefore promotes glycogen storage).
16. glycogen synthesis, fatty acid synthesis.
17. uptake of glucose and converion into fatty acids and glycerols, triglyceride synthesis, and uptake of fatty acids from blood lipoproteins.
18. high glucose levels, amino acids, parasympathetic stimulation (cephalic phase of pancreatic secretion), growth hormone, cortisol, GI hormones such as gastrin, secretin, CCK, GIP.
19. somatostatin, catecholamines.

20. insulin and glucagon inhibit each other's release from islet cells via paracrine actions.
21. the basin of attraction is the set of homeostatic variables which the body settles into over time; long term changes in hormone levels or autonomic activity can shift this basin of attraction to a new equilibrium point.

22. autoimmune destruction of pancreatic beta cells which results in low levels of insulin, and thus a shift from glucose metabolism to ketone body metabolism.
23. polyuria (excess urine volume), polydipsia (excess thirst), polyphagia (excess hunger)
24. type II diabetes is an insulin resistance that is caused by excess fatty acids, cortisol, or testosterone, which blocks insulin's anti-lipolytic effect on adipose tissue. can not be compensated by excess insulin secretion.

biochem: vitamins

the information in our vitamin lecture...

immunology: class notes 3/10/09- psychoneuroimmunology

this lecture was about psychoneuroimmunology, the study of how the mindset can influence and be influenced by the interplay between the nervous and immune systems. contrast this with neuroimmunomodulation, which is the study of how the central nervous system can produce changes in the immune system. we looked mainly at the interplay between stress (actually defined as the perception of the inadequacy to cope to a situation that compromises one's physiological or psychological well being), the neuropeptides that it produces in the CNS, and the ultimate effect that it has on the immune system.

the HPA axis, hypothalamus / pituitary / adrenal cortex releases cortisol in response to stress: stress causes the hypothalmus to release cortitropin releaseing hormone and arginine vasopressin, which triggers the pituitary to make adrenocorticotropic hormone, which triggers the adrenal cortex to make cortisol. in addition, glucocorticoids are secreted by the adrenal cortex. both of these substances produce a wide variety of effects within the immune system, including mediation of cytokine production, chemokine production, adhesion molecules, cell trafficking, proliferation. in particular, glucocorticoids can bind to "transcription receptors" on cytokine producing cells, which are then endocytosed and bind to "response elements" which up or downregulate the transcription of cytokines.

the SAM axis is the sympathetic adrenal medullary axis, and produces norepinephrine and epinephrine (catecholamines) alongside the HPA's production of cortisol and glucocorticoids in response to stress. adrenergic receptors for catecholamines are present on macrophages in two forms; alpha adrenergic receptors have a high affinity for catecholamines and therefore are active during low stress levels. beta adrenergic receptors have a low affinity, and therefore are active during high stress levels. the alpha adrenergic receptors act to stimulate the immune response by increasing phagocytosis, TNF-alpha production, IL-6 production. in contrast, binding to the beta adrenergic receptors decreases phagocytosis, decreases antigen processing and presentation, and decreases IL-12 production.

questions
neuroimmunomodulation...
1. what is the difference between psychoneuroimmunology and neuroimmunomodulation?
2. what was a "historical" example of neuroimmunomodulation?
3. what is an example of evidence of how the immune system affects the brain?
4. what is an example of how the central nervous system affects the immune system?

stress and the HPA axis...
5. describe how stress can trigger events in the HPA axis.
6. what is adrenal fatigue?
7. what are glucocorticoids and what are their role in the immune system?
8. how do glucocorticoids affect cytokine levels?
9. what is the theory for how cortisol affects the immune system?

SAM axis and opiods...
10. what is the SAM axis and what is its role in the immune system?
11. what is the effect of catecholamines on the immune system?
12. what are the two types of adrenergic receptors on macrophage and how do they relate to stress levels?
13. what are the effects of binding to the alpha adrenergic receptor?
14. what are the effects of binding to the beta adrenergic receptor?
15. how do opioids affect the immune system?

answers
1. neuroimmunomodulation is based on the premise that the nervous system can affect the immune system and vice versa. psychoneuroimmunology is the study of how the nervous and immune system interact with mood as well.
2. injecting LPS into someone can cause a fever- this implies that the immune response activates the HPA axis to secrete cortisol. we now know that the mechanism is related to macrophage's secretion of IL-1 that crosses the blood brain barrier.
3. the presence of IL-1 receptors in the brain; IL-1 makes you sleepy.
4. the innervation of lymph nodes, receptors on lymph nodes for certain neurotransmitters.

5. stress causes hypothalamus to release corticotropin releasing hormone and arginine vasopressin, which triggers the pituitary to make adrenocoricotropic hormone, which triggers adrenal cortex to make cortisol.
6. adrenal fatigue is the idea that chronic stress can eventually deplete cortisol levels, after an initial increase. the idea also states that cortisol and DHEA are similar hormones made from the same precursor, and that as cortisol levels increase, DHEA decreases; but that DHEA levels are maintained while cortisol levels eventually fall.
7. a hormone produced by the adrenal cortex that has diverse effects in the immune system, including mediation of cytokines, chemokines, adhesion molecules, cell trafficking, proliferation.
8. glucocorticoids bind to transcription receptors which are endocytosed upon binding and attach to "response elements" in front of cytokine genes, allowing it to upregulate or downregulate transcription of cytokine genes.
9. cortisol might play a role in preventing the immune system from being overstimulated. this has been evidenced in some rheumatoid arthritis patients who had increased disease activity when cortisol levels were blocked.

10. the sympathetic adrenal medullary axis; works in concert with the HPA axis by producing catecholamines.
11. similar to glucocorticoids produced by the HPA axis; cell proliferation, cytokine production, antibody production, cell trafficking. in general, catecholamines mediate the "fight or flight" response.
12. alpha adrenergic has a high affinity for catecholamines and therefore is active during low stress levels; beta adrenergic has a low affinity for catecholamines and therefore is active during high stress levels.
13. increases phagocytosis, increases TNF-alpha, increases IL-6.
14. decreases phagocytosis, decreases antigen processing and presentation, decreases production of IL-12.
15. decreases IL-12 production by macrophages, favoring a Th2 response.

immunology: class notes 3/8/9- cancer

this lecture focused on cancer from an immunological perspective. tumors appear in the body on a somewhat regular basis due to viral infection. because these tumors are virally induced, the APC's that bind to tumor cells will also express co-stimulatory molecules (viral elements will bind to toll like receptors). however, in cancerous tumors, this is not necessarily the case, and tumors can subvert the surveillance of the immune system by the absence of these co-stimulatory molecules. in this case, macrophages can go so far as to eat the dead tumor cells (cells on the center of the tumor die because of the lack of blood supply) and present them in MHC class II; but since there is no CD86, an immune response will not be mounted.

there are several approaches to cancer treatment. first is a historical approach with "coley's toxin", which is basically ground up, heat killed gram negative bacteria that is injected at the tumor site. the bacteria signals an infection and the APC's that are presenting the tumor peptide are able to express the co-stimulatory molecules required to mount an immune response (note- this method also induces a high fever in its patients). a more modern approach is the dendritic cell treatment, which isolates dendritic cells outside of the body, stimulates them to differentiate with GMCSF and IL-4, exposes them to heat killed tumor, and injects them back into the body to mount an immune response. this method is effective but as it is completely individualized, is prohibitively expensive and hard to access.

some ways that the presence of a tumor can be identified: the abnormal or over expression of proteins, high telomerase activity (telomerase is an enzyme that adds base pairs to the end telomeres of genes during DNA replication), and other tumor specific antigens. some of these include MAGE and MART in melanoma, BRCA 1-5, MUC 1-3 in breast cancer, prostate specific antigen in prostate cancer.

questions
treatment strategies...
1. describe the studies performed in mice that lead to the conclusion that injecting dead tumors can confer protectivity.
2. how does protectivity of the dead tumor cells depend on the method used to kill the tumor?
3. how are non-cancerous tumors normally destroyed by the body?
4. what is the idea behind IL-2 treatment and what are its pitfalls?
5. what is the dendritic cell cancer treatment and what are its pitfalls?
6. what is "coley's toxin"?

tumor specific antigens...
7. what is the relationship of tumors and telomeres?
8. what is the problem with mounting an immune response against cells with high levels of telomerase?
9. what are three ways that protein expression can indicate presence of tumors?
10. what are the tumor specific antigens in melanoma?
11. what are the tumor specific antigens in breast cancer?
12. what are the tumor specific antigens in prostate cancer?
13. how do most tumors escape immunosurveillance?

14. what are the different ways that cells of the immune system could potentially kill tumor cells?
15. what is the relationship between severe burns and cancer treatment?

answers
1. in one study, two mice were injected with dead tumor A, and then one mouse with live tumor A and the other with live tumor B. the mouse injected with tumor A survived and the other died. in another study, two mice were injected with dead tumor A, then had their t cells depleted. one mouse was then injected with tumor A and the other with tumor B; both of them died. these studies showed that injecting a dead tumor can confer protectivity against its live counterpart as long as t cells are in healthy supply.
2. the tumor cells must be killed via necrotic cell death (generally by freeze-thawing twice)- necrosis causes CD86 expression which mimics infection and can provoke an immune response.
3. most of these tumors are virally caused and therefore express CD86; the immune system can mount a response to them immediately.
4. IL-2 is the cytokine involved in t cell proliferation and thus might be able to intensify the t cell population's response to the tumor. however, it can cause t cells not specific for the tumor to divide, and also cause systemic shock simply because of the presence of high cytokines levels in the blood.
5. similar to the HIV DC treatment; removing DC cells, putting them in a dish with GMCSF and IL-4 to induce differentiation, then adding necrotically killed tumor cells- this causes DC's to secrete IL-12, CD86. DC's are them put back into the host and migrate to the lymph nodes where they mount an immune response agains the live tumor; the downside is that this is a completely individualized treatment and prohibitively expensive. also, treatment depends on the individual having a functioning immune system and thus chemotherapy patients must wait 2-6 years before receiving the treatment.
6. ground up, heat killed, gram negative bacteria that is injected in cancer patients at tumor sites; binds to TLR's and induces expression of co-stimulatory molecules so that CD8 t cells can be activated. treatment also causes high fever.

7. most tumor cells have overactive telomerase activity, which normally add base pairs to the end of genes during DNA replication.
8. stem cells also have high levels of telomerase.
9. presence of mutant proteins, abnormal expression of protein (foot protein being expressed in head), over-expression of proteins.
10. MAGE, MART
11. BRCA 1-5, MUC-1,3
12. prostate specific antigen
13. the absence of CD86 expression, the fact that the cells originate from the self, the expression of low levels of MHC (sometimes the tumor cells make their own MHC molecules), and cytokine production such as TGF-beta which can inhibit t cell activity.

14. CD8 t cell mediated immunity, macrophage production of reactive oxygen species, NK cell response (?).
15. burn victims express high levels of TNF-alpha, which aids in the protection against cancer.

organ systems: GI embryology and vascular structures

this lecture describes the development of the gut tube starting from the infolding of the yolk sac in the development and positioning of the different sections of the intestines and stomach. early development: the epithelium and mucosa are derived from the endoderm layer while the muscularis is derived from the mesoderm layer. the gut tube is surrounded by two peritoneal sacs that form the visceral and parietal peritoneum. the dorsal mesogastrium is the section of the peritoneum early in development that connects the gut tube to the posterior abdominal wall. the greater omentum is part of the peritoneal layer that folds down over the intestines and serves as a repository for visceral fat (as well as having an active role in the immune system). the mesentary is the portion of the dorsal mesogastrium that attaches to the posterior gut tube and contains neurovascular bundles within its layers.

the gut tube itself undergoes several revolutions and many convolutions during its development, starting with a 90 degree rotation that positions the stomach to the left and the liver to the right of the abdominal cavity. the midgut then herniates and forms a U shaped loop in the 6th week, within which the small intestine develops. the formation of this long section of gut tube causes a bulging of the tube into the vitelline duct (?) and a subsequent entry into the abdominal cavity. the order of re-entry determines whether the section of the gut tube is classified as retroperitoneal or intraperitoneal-- retroperitoneal sections are affixed to the posterior abdominal wall and includes the duodenum, ascending, and descending colons. intraperitoneal are loosely suspended by mesentary and includes the small intestine and transverse colon. if the abdominal cavity closes before reentry of the gut tube is complete, this can result in a persistent vitelline duct, which might lead to such pathologies as vitelline cyst, vitelline fistula, or diverticulosis.

the gut tube is divided into three sections: foregut, midgut, hindgut. each section corresponds to multiple sections of the GI tract as we know it and also corresponds to a different major artery. for example, the foregut includes the stomach and duodenum and has blood supplied by the celiac artery. the midgut includes the jejunum, ileum, and ascending/transverse large intestine, and has blood supplied by the superior mesenteric artery. the hindgut includes the transverse and descending large intestine, rectum, and anal canal. as mentioned before, the mesentery that suspends the small intestine contains neurovascular bundles within its folds; there are two types of arteries that supply blood to the gut- vasa recta and arcade arteries. vasa recta arteries are more prevalent in the jejunum, arcades in the ileum.

sympathetic activity can constrict arteries, either in response to stress or a drop in blood pressure and activation of the RAAS system, decreasing blood and oxygen flow to the intestinal mucosa. eventually, the autoregulatory escape mechanism kicks in and brings the blood pressure in the intestines back to normal even with continued sympathetic activity. the sympathetic response to stress can ultimately result in toxemia due to the weakened epithelial wall (because of reduced oxygen flow) allowing in more microorganisms and toxins. this same result can come about due to ischemia caused by decreased cardiac output or decreased blood pressure as well.

questions
basic structures...
1. what is the gut tube made from? when does it start to develop?
2. the epithelium and mucosa of the gut tube are derived from...
3. smooth muscle is derived from...
4. describe the origin of the peritoneum.
5. what is the dorsal mesogastrium? what does it form?
6. what is the greater omentum? what are some of its properties?
7. spleen splits the greater omentum into...
8. describe the formation of the mesentery.
9. what travels between the layers of mesentery?

rotation and differentiation...
10. describe what happens in peritoneal rotation.
11. how does the large intestine come to surround the small intestine?
12. what does it mean for a section of the gut tube to be retroperitoneal and what is an example?
13. what does it mean for a section of the gut tube to be intraperitoneal and what is an example?
14. what determines whether a section of the gut tube will be retroperitoneal vs. intraperitoneal?
15. what is a persistent vitelline duct and what pathologies can it result in?
16. what is omphalocoele?

gut divisions and blood supply...
17. which arteries define the three sections of the GI tract?
18. what does the foregut form?
19. what does the midgut form?
20. what does the hindgut form?
21. which branches of the superior mesenteric artery supply the jejunum and ileum?
22. which branches of the superior mesenteric artery supply the ascending and transverse colon?
23. what are the two types of arteries that branch off and anastamose in the jejunum and ileum?
24. sympathetics constrict arteries in response to...
25. what is autoregulatory escape?
26. what are the two ways in which ischemia of the gut can occur?
27. how can toxemia result from ischemia of the gut?

answers
1. from the yolk sac during the 4th week.
2. endoderm
3. mesoderm
4. during the 5th and 6th weeks, two peritoneal sacs press against either side of the liver and stomach and form the visceral and parietal peritoneum.
5. the dorsal section of the peritoneal fold- forms the greater omentum and mesentery.
6. part of the dorsal mesogastrium that folds down over the intestine and is a repository for visceral fat. also has strong immune stimulating properties.
7. gastrolienal and lienorenal ligaments.
8. mesentary is formed from the portion of the dorsal mesogastrium that is attached to the posterior wall of the stomach.
9. neurovascular bundles to the visceral organs.

10. due to the 90 degree rotation of the peritoneal cavity, the stomach ends up to the left and the liver to the right (whereas they were both in the center before)
11. the midgut "herniates" and forms a U shaped loop during the 6th week, rotating 270 degrees around the superior mesenteric artery.
12. the portions that are affixed to the posterior wall of the abdominal wall and partially covered by peritoneum: examples are the ascending and descending large instestine and the duodenum.
13. the portion that is surrounded by the visceral peritoneum and is relatively mobile, suspended by mesentary. example is the small intestine and transverse colon.
14. the order of "reentry" into the abdominal cavity.
15. the vestiges of the vitelline duct which can result in a connection between the ileum and abdominal wall- potentially causing meckel's diverticulum, vitelline cyst, or a vitelline fistula.
16. a section of intestine trapped by early closing of the abdominal cavity before full retraction.

17. celiac artery: foregut, superior mesenteric: midgut, inferior mesenteric: hindgut.
18. stomach, duodenum
19. jejunum, ileum, proximal large intestine (ascending and transverse)
20. transverse, descending, sigmoid large intestine, rectum, anal canal.
21. sequential branches
22. ileocolic, right and middle colic arteries.
23. vasa recta in jejunum, arcades in ileum.
24. exercise or a drop in blood pressure
25. a compensatory mechanism which will allow vasodilation to offset excess sympathetic activity.
26. either by occlusion of the mesenteric arteries or decreased cardiac output/continuous vasoconstriction.
27. toxemia can develop by bacterial / toxin entry into intestinal epithelium which might occur when oxygen flow to the mucosa is decreased because blood flow is decreased (oxygen diffuses from arterioles to venules rather than to mucosa)

ms anatomy II: neurocranium part II

[picture courtesy of erica zelfand]
this is the second lecture in the series on the "neurocranium" and dealt with a variety of topics such as structure of the brain, functions of each lobe, blood supply, spinal cord, meninges, glial cells, and the blood brain barrier.

the cerebral portion of the brain is divided up into different lobes, which have been shown to have distinct cognitive and emotional correlates. for example, the frontal lobe is the primary motor area, and is also involved in speech and behavior. the parietal lobes are involved in somatosensory input, prioprioception, sense of self. the temporal lobes are involved in audition, olfaction, and memory. the occipital lobes are involved in vision. cerebellum, midbrain, medulla, are underneath the cerebral portion and are involved more in basic physiological processes. for example, the medulla is involved in autonomic regulation of the cardiovascular system and respiration. the hypothalamus is involved in autonomic, affective, and hormonal activity. the midbrain is involved in motor control. the cerebellum is involved in motor coordination and timing.

the blood supply to the brain comes ultimately from the brachiocephalic branch of the aorta, which branches into the common carotid and the subclavian. the vertebral arteries branch off of the subclavian, travel in the transverse foramen of C1-C6, and penetrate the atlanto-occipital membrane. from there they ascend on the ventral surface of the brainstem and combine to form the basilar artery, from which other arteries branch out (see diagram) such as the pontine and cerebellar arteries. the common carotid artery, on the other hand, branches into the internal and external common carotid; the internal common carotid branches into the anterior and middle cerebral arteries, which supply blood to the lateral and medial cerebral cortex, internal capsule, basal ganglia, and cingulate gyrus. the occlusions in each of these small branches can produce different effects (see diagram).

a few details about the spinal cord: it extends down to L1, beyond which the dura extends until S2. the spinal cord ends at the conus medullaris, a tapering down of the cord which ends in the caudus equinus, which is a splaying out of a horse tail-like arrangement of nerve rootlets. around the spinal cord, there are the three meninge layers: pia, arachnoid, dura mater. denticulate ligaments are pial "projections" into the arachnoid and dura mater which serve to anchor the spinal cord. the filum terminale is the pial strand that connects from the end of the spinal cord (L1) to the end of the dural sac (S2).

a few notes about glial cells and the blood brain barrier. glial cells were covered briefly in histology as the cells that "support" the neurons. in the central nervous system these cells are astrocytes, oligodendrocytes. oligodendrocytes are the cells that produce the myelin sheath that increases the rate of neuronal conduction. whereas schwann cells can only wrap around 1 axon, a single oligodendrocytes can wrap up to 50 different axons. astrocytes provide electrical insulation between neurons, secrete neuronal growth factors and cytokines, and absorb neurotransmitters. they can be further divided into protoplasmic and fibrous- fibrous astrocytes are involved in repairing damaged neuronal tissue. astrocytes also aid in the maintenance of the blood brain barrier, which is made up of astrocyte foot processes, basal lamina, pericytes, and endothelium.

questions
general anatomy and fissures...
1. cerebral hemispheres include...
2. the cerebral cortex is the site for...
3. what are gyri and sulci/fissures?
4. what are the three main fissures in the brain?
5. what does the longitudinal fissure separate?
6. what does the lateral fissure separate?
7. what does the central fissure separate?

functions of...
8. frontal lobe
9. parietal lobe
10. occipital lobe
11. temporal lobe
12. medulla
13. cerebellum
14. pons
15. midbrain
16. thalamus
17. hypothalamus

cerebral arteries...
18. where does the common carotid artery branch off from?
19. where does the common carotid artery split?
20. what does the internal carotid artery split into?
21. what does the internal carotid artery supply blood to?
22. what is the difference between an ischemic and hemorrhagic stroke?
23. where does the middle cerebral artery run?
24. what do the cortical branches supply blood to and what occurs during a stroke of these arteries?
25. what do the lateral striate branches supply blood to and what occurs during a stroke of these arteries?
26. what does the anterior cerebral artery supply blood to?
27. what happens after stroke in the anterior cerebral artery?

basivertebral arteries...
28. describe the passage of the vertebral artery.
29. vertebral arteries unite to form...
30. where is the path of the basilar artery? what does it branch into?
31. what does occlusion in the anterior and posterior spinal branch lead to?
32. what does occlusion in the posterior inferior cerebellar branch lead to?
33. what does occlusion in the anterior inferior and superior cerebellar branch lead to?
34. what does occlusion in the pontine arteries lead to?
35. what does occlusion in the labyrinthine branch lead to?
36. how do occlusions of the vertebral basilar arteries result in deficits in vision?
37. how do occlusions of the vertebral basilar arteries result in problems with balance?

posterior cerebral and circle of willis...
38. where does the posterior cerebral artery project to?
39. what happens when the posterior cerebral artery is occluded?
40. what is the circle of willis?
41. what does the anterior communicating artery connect?
42. what does the posterior communicating artery connect?

spinal cord...
43. how far down does the spinal cord extend?
44. how far down does the spinal dura extend?
45. what is the conus medullaris?
46. what is the cauda equina?
47. where is the junctional zone between the central and peripheral nervous systems?
48. what does the dura turn into at this point?

meninges and spinal veins...
49. how far down does the dura mater extend?
50. what is in the epidural space?
51. what is arachnoid mater?
52. what are denticulate ligaments?
53. what is the filum terminale?
54. where would one extract CSF from the spinal cord?
55. what are the two ways of administering anesthetic to the spinal cord?
56. what does the basivertebral vein do?
57. what is the connection between the basivertebral veins and prostate cancer?
58. describe the vertebral vein's use as a shunt.

glial cells and blood brain barrier...
59. what are oligodendrocytes and what do they do?
60. "unlike schwann cells, oligodendrocytes do not..."
61. what do astrocytes do?
62. what is the difference between protoplasmic and fibrous astrocytes?
63. what are microglia and what do they do?
64. what cell types line the ventricles?
65. what makes up the blood brain barrier?
66. what is the blood brain barrier maintained and induced by?
67. describe the transport of glucose, amino acids, and gases through the blood brain barrier.
68. which brain regions is there no blood brain barrier?

answers
1. white matter, basal ganglia, cerebral cortex.
2. sensorimotor integration, perceptive quality of our experiences
3. gyri are convolutions of the cortex and sulci are divisions or gaps between the gyri.
4. longitudinal, lateral, central.
5. the left and right hemispheres.
6. the frontal and temporal lobes.
7. the frontal and parietal lobes.

8. primary motor area, speech, behavior
9. sensorimotor, prioprioception, association of sensorimotor-audition-vision, formation of egocentric space, sense of self
10. vision
11. audition, olfaction, memory
12. autonomic control over respiration, cardiovascular systems
13. motor coordination and timing
14. cerebellar connection
15. motor control
16. sensorimotor information to cerebral cortex
17. autonomic, hormonal, affective activity

18. the brachiocephalic branch of the aortic arch.
19. at the carotid sinus into the internal and external carotid arteries.
20. anterior and middle cerebral arteries
21. most of the cerebral hemispheres.
22. ischemic is blockage of the cerebral artery via a thrombus or embolus which leads to necrosis. hemorrhagic is rupture of the artery which causes a hematoma, which leads to necrosis.
23. in the lateral fissure; along the lateral surface of the cerebral cortex.
24. lateral surface of cortex. stroke causes sensory, motor, language deficits.
25. internal capsule and basal ganglia. stroke causes hemiplegia.
26. medial surface of cerebral cortex, including cingulated gyrus.
27. sensory, motor, emotional deficits.

28. branches off the subclavian artery, passes through transverse foramina of C1-C6, and penetrates the atlanto occipital membrane.
29. basilar artery on ventral medulla.
30. the ventral surface of the brainstem; branches into cerebellar, pontine, posterior cerebral arteries.
31. loss of spinal cord function
32. Wallenberg syndrome: loss of sensation of pain, heat, muscle coordination.
33. loss of muscle coordination.
34. cranial nerve dysfunction.
35. deafness and vertigo.
36. torsion/compression of vertebral basilar arteries can reduce blood flow to brain stem, cerebellum, occipital lobe- anoxia in the occipital lobe causes loss of vision.
37. anoxia in cerebellum or inner ear can cause problems with balance.

38. temporal and occipital lobes.
39. visual deficits.
40. the anterior and posterior communicating arteries.
41. anterior cerebral arteries.
42. middle and posterior cerebral arteries.

43. down to L1.
44. down to S2.
45. tapered end of the spinal cord.
46. the “horse’s tail”, the end of the spinal cord which branches into nerve roots that extend to lumbar and sacral foramina.
47. the intervertebral foramina
48. the epineurium that covers the dorsal and ventral rami and ganglia.

49. S2
50. veins and fat.
51. the meninge layer in between the dura and pia mater, with trabeculae inside the subarachnoid space.
52. pial connective tissue that suspends spinal cord to the inside of arachnoid / dura mater.
53. a pial strand that connects down to the end of the dural sac.
54. from the subarachnoid space.
55. to the epidural and subdural spaces.
56. drains vertebral bodies.
57. prostate cancer can metastasize into vertebrae through the basivertebral veins.
58. blood shunts from caval veins into vertebral veins if IVC constricted (while coughing, for example)

59. cells in the CNS that myelinate up to 50 axons.
60. "cover unmyelinated axons, which lay bare in the CNS"
61. electrically insulate neurons from each other, uptake neurotransmitters and ions, and secrete neuronal growth factors and cytokines.
62. protoplasmic interconnect neurons, induce early growth and development of the blood/brain barrier, whereas fibrous form astrocytic scars after brain tissue destruction.
63. phagocytic cells related to monocyte/macrophages which consume debris and secrete cytokines during inflammation.
64. ependymal cells.
65. endothelium, pericytes, basal lamina, astrocyte foot processes.
66. maintained by astrocytes.
67. glucose and amino acids pass through BBB via transport proteins, and gases diffuse through lipid membrane.
68. hypothalamus, area postrema, other periventricular regions.

immunology: class notes 3/2-3/3- autoimmunity

autoimmunity is the phenomenon of the immune system attacking host cells, including immune system cells. it arises either from "spontaneous" factors, or from infection, or from various environmental triggers. autoimmunity can be viewed in the same framework as the four types of hypersensitivity in that the mechanisms are the same. the exception is type I hypersensitivity, which involves a class switch to IgE- this mechanism is not seen in autoimmunity. type II autoimmunity involves a class switch to IgG, which binds to different self-antigens.

the first example of type II autoimmunity is autoimmune hemolytic anemia, in which b cells specific for red blood cells start proliferating and producing antibodies, which bind to red blood cells. in this case, the b cells can proliferate using a "antibody crosslinking" mechanism, bypassing the need for IFN-gamma. the antibodies opsinize red blood cells and leave them primed for phagocytosis and destruction by macrophages and natural killer cells. myesthenia gravis is another example of type II autoimmunity, in which antibodies bind to acetylcholine receptors at the neuromuscular junction and thus prevent neural conduction. grave's disease is the third example, where antibody binds to thyroid stimulating hormone receptors, this time stimulating the receptor, resulting in hyperthyroidism.

type III autoimmunity involves a class switch to IgA. this often induces formation of antibody/antigen complexes which block blood vessels or nephritic tubules and cause macrophages to come and secrete reactive oxygen species and damage surrounding tissue. lupus is an example of type III autoimmunity- where the self antigens are all contained within the nucleus of cells: histones, nucleosomes, spliceosomes, transcription factors. these self antigens are thus attacked only in places of high cell turnover or division; such as the skin and joints.

type IV autoimmunity involves a t cell mediated response against self antigens. the first main example is type I diabetes, where pancreatic beta cells are attacked by CD8 t cells specific for insulin, which are activated by dendritic cells which express co-stimulatory molecules by means of a simulaneous infection (or other "spontaneous" means). in multiple sclerosis, the self antigen is the myelin basic protein which coats neurons-- in this case CD4 t cells are activated to produce antibody which opsinize the myelin sheath and cause macrophages to attack. at this point the myelin sheath can be regenerated from oligodendrocytes, but eventually CD8 t cells are activated to attack the oligodendrocytes as well. finally, rheumatoid arthritis is an autoimmune disease in which the antigen is not clearly defined; either collagen or heat shock proteins, which end up with macrophages being recruited to joints and causing damage by reactive oxygen species, etc. rheumatoid factor is also present in the disease, which acts as an antibody to antibodies and can form antibody complexes which can exacerbate disease by damage by macrophages.

questions
1. what is autoimmunity?
2. how does autoimmunity arise?
3. what are some factors involved in development of autoimmune disease?
4. what percentage of monozygotic twins and dizygotic twins show autoimmune disease concordance?
5. what disease occurs when an autoimmune response to myelin basic protein is mounted?
6. what disease occurs when an autoimmune response to insulin is mounted?

7. what is type I hypersensitivity and how is it related to autoimmunity?
8. what is type II hypersensitivity and how is it related to autoimmunity?
9. what are the two ways in which IgM normally class switches to IgG?
10. describe the mechanism of autoimmune hemolytic anemia.
11. describe the mechanism of myesthenia gravis.
12. describe the mechanism of grave's disease.
13. how would one test for the presence of an autoimmune disease in which host cells are being killed (as in question 10)?
14. how would one test for the presence of an autoimmune disease in which host cell receptors are being blocked? (question 11)?
15. how would one test for the presence of an autoimmune disease in which host cell receptors are being overstimulated (as in question 12)?

16. what is the class switching that occurs in type III autoimmunity?
17. how is damage caused by self-specific IgA in type III autoimmunity?
18. what are the self antigens in lupus?
19. why does lupus cause joint pain and skin problems?
20. what is the difference in the autoimmune response to apoptosis vs. necrosis?

21. what is type IV autoimmunity? what are some examples?
22. why does type I diabetes result in hyperglycemia?
23. what is the hereditary component to type I diabetes?
24. which immune system cells "escape tolerance" in type I diabetes?
25. describe the mechanism of autoimmunity in type I diabetes.
26. how are CD8 t cells activated in type I diabetes?
27. what is glutamine acid decarboxylase and how is it related to type I diabetes?

28. what is MS?
29. what is the relative prevalance of MS in males compared to females?
30. what is the average age of onset in MS?
31. what are some epidemiological trends of MS?
32. what is the mechanism to the autoimmune response in MS?
33. what is the role of oligodendricytes in MS?

34. what is rheumatoid arthritis?
35. what is the relative prevalance of rheumatoid arhritis in women vs. men? why?
36. what is the self antigen in rheumatoid arthritis?
37. what are heat shock proteins and what do they do?
38. what are gamma delta t cells and how might they be involved in rheumatoid arthritis?
39. how are joints damaged in rheumatoid arthiritis?
40. what is it that recruits macrophages and neutrophils to the joint areas?
41. what is rheumatoid factor? how does it exacerbate disease?


answers
1. an immune response to self-tissue.
2. either by spontaneous/unknown causes, or in response to extreme childhood stress or trauma, or by infection.
3. environmental (including nutrition), hereditary, the tissues involved, the mechanism of the autoimmune response.
4. mono: 20%, di: 5%
5. multiple sclerosis.
6. diabetes.

7. an allergic response which involves a class switch to IgE. this type of mechanism is not found in autoimmunity.
8. a cytotoxic/antibody dependent response which involves a class switch to IgG. this type of mechanism is the main response used against self tissues in autoimmunity.
9. via IFN-gamma or CD40/CD40L.
10. b cells which are specific to host blood cells are not destroyed during development as they should be and begin proliferating and class switching to IgG (subverting the normal mechanism in question 9 by "cross linking antibodies"). IgG binds to red blood cells and are either opsinized by macrophages or destroyed by NK cells.
11. b cells secrete antibodies which are specific for the host's nicotinic acetylcholine receptors- which blocks acetyl choline binding and results in muscle weakness.
12. b cells secrete antibodies which are specific for thyroid stimulating hormone receptors- which stimulate the receptors, resulting in hyperthyroidism and a downregulation of the TSH receptors on the affected cells.
13. in the case of autoimmune hemolytic anemia, one could look for an abnormally low red blood cell count or an abnormally high b/t cell count in a blood sample.
14. one could test for elevated amounts of the ligand which can no longer bind to the receptor.
15. one could test for elevated levels of the product of the stimulation of the particular host cell, or test for presence of phosphorylated proteins (indicating that the receptor has been bound to and endocytosed).

16. a class switching of IgG or IgM to IgA.
17. IgA can form large complexes with self antigen in vessels or nephritic tubules and block them. additionally, macrophages will bind to the antibodies using Fc receptors and produce reactive oxygen species, which will damage nearby tissues.
18. histone, nucleosome, spliceosome, transcription factors: Ro, La.
19. the self antigens are contained in the nucleus of cells; thus they are primarily exposed to the autoimmune response at places of high apoptosis and necrosis, which would expose nuclear contents during degradation. the joints and skin are two such places.
20. apoptosis is considered "silent" compared to necrosis because only necrosis initiates the inflammatory response.

21. t-cell mediated autoimmunity: multiple sclerosis, type I diabetes, rheumatoid arthritis.
22. because the insulin producing beta-islet cells in the pancreas are destroyed and thus cells can not take in glucose from the blood.
23. the passing down of HLA molecules which are predisposed for diabetes: HLA DR3, DR4, DQ, DQB1*0302.
24. CD8 t cells, CD4 t cells, b cells.
25. a dendritic cell phagocytoses and presents insulin on its surface in both MHC classes. normally, this does not provoke a response from the immune system; however, if this occurs simultaneously with an infection, co-stimulatory molecules will be expressed and t cells specific to insulin will be stimulated to destroy pancreatic beta cells.
26. APC's will stimulate CD4 t cells, which will differentiate into Th1 cells, which will produce IFN-gamma, which will activate CD8 t cells.
27. another antigen that can invoke a similar autoimmune response against the pancreas.

28. an autoimmune disorder which results in multiple sites of demyelination in the brain, spinal cord without axonal degeneration.
29. 7:1 more common in females.
30. 25-35
31. high prevalence in far northern and far southern locales: might be vitamin D related. also very dependent on residence during the first 15 years of life. higher prevalance in high socioeconomic groups and among caucasians.
32. dendritic cells ingest and present myelin basic protein in both MHC classes, causing CD4 t cells to differentiate into Th1 cells, which secrete IFN-gamma, which cause a class switch in MBP specific b cells to produce IgG. IgG binds to myelin and opsinizes, priming myelin for opsinization by macrophages (by way of Fc receptors).
33. oligodendrocytes produce MBP and as such can counter the effects of MS-- until the CD8 t cells are stimulated to attack the oligodendrocytes.

34. an autoimmune disease that leads to destruction of cartilage, bone, and joint deformities.
35. 3:1 prevalence in women as compared to men-- estrogen triggers higher TNF-production via macrophages.
36. unknown; possibly collagen, or heat shock
37. bind to denatured proteins and prevent them from being degraded; activated by excess heat or cold.
38. a special type of t cell that makes high levels of IFN-gamma, causing a class switch to IgG, and also is involved in the production of RF factor.
39. by macrophages which produce reactive oxygen species, IL-1, TNF-alpha.
40. Th17 cells, cytokines such as IL-1, TNF-alpha, IL-6, IL-17.
41. antibody for antibodies which can bind to all antibodies within one isotype. they exacerbate disease when forming antibody "complexes", the accumulation of antibody and RF factor, which blocks vessels and causes macrophages to come and produce ROS, etc.

biochem: mark's medical biochem chapter 41- purines and pyrimidines

note: i smashed my laptop last week so some of these entries won't have the question/answer section.

purines and pyrimidines are two categories of bases from which nucleosides (base plus ribose sugar) and thus nucleotides (base plus ribose plus phosphate) are made. they are not obtained easily from the diet and as such need to be synthesized de novo. purine synthesis begins with ribosyl-5 phosphate and ATP:

1. ribosyl 5-phosphate and ATP combine to form 5-phosphoribosyl pyrophosphate (PRPP) via PRPP synthetase.
2. the pyrophosphate in PRPP is exchanged for an amine group from glutamine via amido phosphoribosyl transferase, forming 5-phospho ribosylamine.
3. a glycine molecule is added, forming glycinamide ribosyl 5-phosphate.
4. a series of C and N donations: N10 formyl FH4 donates carbon 8.
5. glutamine donates nitrogen 3.
6. N10 formyl FH4 donates carbon 2.
7. aspartate donates carbon 1.
8. CO2 donates carbon 6, forming the purine nucleotide inosine monophosphate (IMP)

IMP can be converted to the nucleotides GMP or AMP as well. the conversion to AMP involves the addition of an aspartate molecule to form adenylosuccinate, using one GTP (in a reaction similar to adding aspartate to citrulline in the urea cycle). adenylosuccinate then loses a fumarate in the subsequent reaction to form AMP. to form GMP, IMP is oxidized by IMP dehydrogenase to xanothine, which is then decarboxylated to GMP with the help of ATP.

regulation of purine synthesis occurs at four places: PRPP synthetase (step 1) is inhibited by ADP and GDP, while amidophosphoribosyl transferase (step 2) is inhibited by AMP and GMP. IMP dehydrogenase and adenylosuccinate synthetase are inhibited by the products they eventually form, GMP and AMP, respectively.

the purine nucleotide cycle occurs in the brain: IMP is converted to AMP by the process described above, and AMP is converted back to IMP by a deaminase reaction, the net result being the conversion of aspartate to fumarate and the production of ammonia (recall from the urea cycle chapter).

the purine salvage cycle (see diagram) is a system of enzymes that are designed to rebuild the purine nucleotides in the peripheral tissues from the free bases or nucleoside components that are delivered to them. except for adenosine, the general strategy is to convert nucleosides to free bases, and then to nucleotides. there are several types of enzymes involved which interconvert nucleosides, nucleotides, and free bases. 5'nucleotidases convert nucleotides to nucleosides by dephosphorylating the ribose. purine nucleotide phosphorylases cleave the nucleoside into a free base and a phosphorylated ribose. hypoxanthine guanine phosphoribosyl transferase enzymes add an phosphoribosyl unit from PRPP to the base, creating a nucleotide. deaminases can convert AMP to IMP. finally, adenosine kinase can directly phosphorylate adenosine into the nucleotide AMP (it is the only nucleoside that can be converted to a nucleotide directly via salvage enzymes)

purines can be degraded by salvage enzymes as well: AMP is deaminated to form IMP. the nucleotides IMP and GMP are then converted into nucleosides inosine and guanosine, which are then converted to the bases adenine and guanine. adenine and guanine are converted to xanthosine, which is converted to uric acid and excreted in the urine.


pyrimidine synthesis begins by building the ring structure and adding the phosphoribose later (as opposed to purines, which start with the phosphoribose):

1. glutamine, CO2, and 2ATP combine via carbamoyl phosphate synthetase II to form carbamoyl phosphate.
2. an aspartate is added, forming carbamoyl aspartate, via aspartate transcarbamoylase.
3. dihydroorotase adds an OH, forming dihydroorotate.
4. dihydroorotate is oxidized by dihydroorotate dehydrogenase into orotate, forming the ring structure.
5. a phosphoribosyl unit is added to orotate by orotate phosphoribosyl transferase, forming the nucleotide orotate monophosphate.
6. orotate monophosphate is decarboxylated by OMP decarboxylase to form the nucleotide UMP.
7. UMP can be phosphorylated to UTP.
8. UTP can be converted to the nucleotide CTP.

synthesis of pyrimidines is mainly regulated at the CPS II enzyme level (recall that CPS I is involved in the first step of the urea cycle, in the mitochondria as opposed to the cytosol in pyrimidine synthesis). this enzyme is activated by ATP and inhibited by UTP. pyrimidines are degraded similarly to purines; nucleotides converted to nucleosides converted to free bases cytosine, thiamine, and uracil. cytosine is deaminated to uracil, which is degraded further into CO2, ammonium, and beta-alanine, while thiamine is degraded into CO2, ammonium, and beta-aminoisobutyrate.

purines and pyrimidines can be converted to the deoxygenated form for use in DNA synthesis. the enzyme that catalyzes this reaction is ribonucleotide reductase, and the electron donor is thioredoxin (which is regenerated by the enzyme thioredoxin reductase and NADPH from the pentose phosphate pathway). ribonucleotide reductase regulation is complex in that it can be activated and inhibited towards specific molecules depending on what binds to it (see diagram).

organ systems: the liver and lipid digestion

this unit reviewed some basic concepts about fat digestion and went into some more depth about the anatomy and physiology of the liver and gall bladder. the liver is located in the upper right quadrant of the abdomen, deep to the 5-10th ribs. it is suspended by the lesser omentum ligament, which attaches it to the intestine and the stomach, and the falciform ligament, which attaches it to the anterior of the abdominal wall. it has four lobes- left, right, quadrate, and caudate. the ligamentum teres (round ligament) is the vestigial remains of the umbilical vein that brought blood from the placenta. finally, the porta hepatis is the "hilum" or root of the liver (similar to the hilum of the lung) and contains the bile duct, hepatic portal vein and hepatic artery.

the liver receives nutrient rich and oxygen poor blood from the GI tract- specifically the gastric, splenic, and mesenteric arteries, which comes into the liver via the hepatic portal vein. it receives nutrient poor, oxygenated blood from the hepatic artery which branches off of the celiac artery. the liver cells, hepatocytes, are in hexagonal arrangements which have portal "triads" in each corner which contain bile ducts, hepatic portal veins, and hepatic arteries. in the center of the hexagons is the central vein, which leads to the hepatic vein, which leads to the inferior vena cava back to the heart. running from the edges of the hexagonal "lobule" are the sinuosoids where most of the functional activity of the liver takes place. the liver acinus theory describes the functional unit of the liver as the triangle between two portal triad corners and a central vein-- which is divided into three zones: zone 1 is closest to the central vein and although has lowest oxygen / nutrient content, is the site of most detoxification and chemical activity.

portal hypertension can occur from blockages in liver blood flow, resulting in a backpressure in portal circulation. this can cause a number of pathologies such as caput medusa, esophageal varicosities, and hemorrhoids. additionally, excess lymph can be drained from the liver (lymph drains into the space of disse, the tiny canals between the hepatocytes and sinusoids) and can collect in the peritoneal cavity, resulting in ascites. in this condition, the loss of fluid in the circulatory system must be compensated by renal devices which increase fluid retention such as aldosterone and renin secretion.

bile is secreted by hepatocytes and flows to the periphery of the hexogonal lobule, draining into the bile ducts, which drain into the right and left hepatic ducts. these combine to form the common hepatic duct, which combines with the bile duct from the gall bladder, called the cystic duct, to form the common bile duct. the common bile duct intersects with the main pancreatic duct at the hepatopancreatic ampulla and exits into the duodenum at the major duodenal papilla. the tissue around this point forms a sphincter called the sphincter of odie which contracts between meals or during fasting, which causes bile to stored in the gall bladder instead of being released into the duodenum.

bile stored in the gall bladder is made of bile salts, cholesterol, phospholipids, water, and can be concentrated over time via water reabsorption, or secretion of bile salts and cholesterol. if the bile becomes too concentrated in the gall bladder, over long periods of time with no contraction, then gall stones can precipitate out. in normal function, CCK and secretin are released from duodenal I and S cells, respectively, in response to protein, fat, or acid in the intestine (see "intestinal phase" in last lecture), causing an increase in pancreatic secretion, decrease in gastric secretion/motility, and bile release from gall bladder via contraction of the gall bladder and relaxation of the sphincter of odie. vagal stimulation can have the same effect. once in the intestine, bile surrounds fat molecules and aids in their absorption. the chapter in biochem covers this in much greater detail than what was presented in this lecture.

questions
location and anatomy...
1. where is the liver located?
2. what are the two ligaments that suspend the liver and where are they?
3. what are the lobes of the liver?
4. what is the ligamentum teres of the liver?
5. what is the porta hepatis?

physiology...
6. what are some of the functions of the liver?
7. how much blood does the liver receive (in terms of percentage of cardiac output)?
8. how does the liver get its oxygenated blood?
9. what does the portal vein bring to the liver? where does it bring it from?
10. what are sinusoids lined with?
11. what do the hepatic veins do?

lobules...
12. what is the classical lobule model of the liver?
13. what are the portal triads and what do they contain?
14. what is in the middle of the classical lobule?
15. what is the liver acinus model of the liver?
16. what are the three zones in the liver acinus model?
17. which zone is most susceptible to hypoxia and toxic damage?

hypertension and other pathologies...
18. where are the spaces of disse? what flows in them?
19. what is meant by "portal hypertension"?
20. what are some pathologies that portal hypertension can contribute to?
21. what is ascites?
22. how does ascites affect blood pressure?

bile secretion...
23. describe bile secretion by hepatocytes.
24. what are bile secretions made of?
25. what do the right and left hepatic ducts do?
26. ...common hepatic duct?
27. ...cystic duct
28. ...common bile duct
29. ...hepatopancreatic ampulla
30. ...main pancreatic duct
31. ...major duodenal papilla

gall bladder...
32. what are the three parts to the gall bladder?
33. what are three functions of the gall bladder?
34. how does the sphincter of oddi help store bile in the gall bladder?
35. describe two ways in which bile can be released by the gall bladder.
36. besides gall bladder emptying, what else does CCK mediate?
37. what effect does secretin have on the gall bladder and pancreas?
38. how are gallstones created?
39. what are two functions of bile?

micelles...
40. what is the general scheme for fat digestion?
41. about how big are micelles?
42. what pH is optimal for the action of pancreatic lipase?
43. which enzyme hydrolyzes cholesterol?
44. what are micelles made of?
45. how are bile salts formed?
46. what happens to the micelle contents at the enterocyte?
47. where does most of the reabsorption of bile acids and salts occur in the intestine?

chylomicrons and lipoproteins...
48. what are chylomicrons composed of?
49. 80-90% of chylomicrons are transported into...
50. how is the processing of short and medium chain fatty acids different?
51. what are the roles of: chylomicrons, VLDL, LDL, and HDL?
52. what makes feces brown and urine yellow?
53. jaundice is caused by...

answers
1. upper right abdomen between ribs 5-10.
2. lesser omentum between liver and stomach/intestine, falciform ligament between liver and anterior abdominal wall.
3. left, right, quadrate, caudate.
4. the round ligament, which is a vestigal remains of the umbilical vein carrying blood from the placenta to the fetus.
5. the "hilum" of the liver that contains bile ducts, hepatic arteries, and portal vein.

6. glycogen storage, gluconeogenesis, synthesis of TG's, cholesterol, phospholipids, fatty acid oxidation, protein synthesis, urea cycle, storage of vitamins and iron, detoxification, bile secretion.
7. 29%
8. via the celiac artery which branches off of the aorta
9. nutrient filled, deoxygenated blood from the gastric, splenic, and mesenteric veins.
10. hepatocytes
11. bring blood out of the superior aspect of the liver into the inferior vena cava.

12. divides hepatocytes into hexagonal "lobule" arrangements.
13. the corners of the hexagon in the classical lobule which contain the bile duct, hepatic artery and portal vein.
14. the central vein, which leads to the hepatic vein.
15. a model which has a functional "acinus" unit which is the triangle between two portal triads and a central vein.
16. zone 1 is closest to the portal triads and has the highest concentration of oxygen and nutrients. zone 2 is in the middle, zone 3 is closest to central vein and receives least nutrients but is primary site of alcohol and drug detoxification.
17. zone 3.

18. between hepatocytes and endothelium of sinusoids. lymph flows from sinusoids into space of disse, and sent to thoracic duct or inferior vena cava.
19. when a blockage of blood flow in the liver leads to backpressure in the portal circulation.
20. hemorrhoids, caput medusae, esophageal varicosities.
21. when portal hypertension causes excess lymph to flow in the space of disse, causing buildup of fluid in the peritoneal cavity.
22. since blood volume is lost to the lymph fluid that is trapped in the peritoneal cavity, blood pressure drops and the kidneys compensate by increasing salt and fluid retention until pressure is restored.

23. bile is secreted by hepatocytes and flows to the periphery of the portal lobules.
24. bile acids, phospholipids, cholesterol, along with bicarbonate and bile pigments (bilirubin)
25. bile outflow from the liver
26. junction between right and left hepatic ducts.
27. outflow from gall bladder.
28. outflow of bile from both gall bladder and liver.
29. junction of bile and pancreatic ducts.
30. outflow from pancreas.
31. bile and pancreatic secretion into duodenum.

32. body, neck, fundus.
33. store bile, concentrate bile, release bile into duodenum.
34. by contracting between meals, it allows backflow of bile from common bile duct into cystic duct into gall bladder.
35. CCK release triggered by fat or protein reach chyme entering the duodenum causes the sphincter of oddi to relax and the gall bladder to contract. vagus nerve stimulation has the same effect.
36. inhibits gastric mixing and secretion, stimulates intestinal mixing, stimulates pancreatic secretion.
37. increased water and bicarbonate secretion from duct cells.
38. either too much absorption of water (can be due to inflammation of epithelium), or high cholesterol content in stored bile (from too much absorption of bile salts, or too much secretion of cholesterol into bile)
39. to aid in fat digestion, and also elimination of various endogenous and exogenous substances such as cholesterol, bilirubin, drugs, heavy metals.

40. pancreatic lipase hydrolyzes triacylglycerides into free fatty acids, which are packaged into micelles via bile droplets. fatty acids are absorbed into enterocytes and bile is reabsorbed. fatty acids are reconverted to triacylglycerides, packaged into chylomicrons and transported in the blood.
41. ~1um
42. pH 8.
43. cholesterol esterase.
44. bile acids, phospholipids, cholesterol, and the fat that is trapped in the lipophilic core
45. bile acids are conjugated in the liver to form bile salts.
46. fatty acids are repackaged into triacylglycerol and cholesterol is esterified in the enterocyte, then packaged into a chylomicron in the ER.
47. the ileum.
48. cholesterol and triglycerides in a phospholipid shell with apoproteins.
49. lacteals and thoracic duct.
50. they are not packaged into chylomicrons and instead are transported directly into the venous system and stored in the liver and adipose.
51. chylomicrons transport fat from intestine into the blood. VLDL's transport triacylglycerides from the liver into the blood. LDL's are produced in plasma and trasnport cholesterol esters from liver to organs and tissues. HDL's are produced in plasma and transport cholesterol from peripheral tissues to the liver.
52. bilirubin is converted by colonic bacteria into urobilinogen, which can be excreted in the urine or converted to stercobilin and excreted in feces.
53. excess bilirubin