Physiology - GI & Endocrine

Question 1

Achalasia

Answer 1

One of the most important functions of Nitric Oxide (the neurocrine, as opposed to the neurotransmitter) is relaxation of the Lower Esophageal Sphincter (LES) during deglutition (swallowing). When the NO-mediated relaxation is not function, results in Achalasia.

Question 2

List 7 GI Endocrine hormones

Answer 2

Gastrin, CCK, Secretin, GIP (Gastric Inhibitory Peptide OR Glucose-dependent Insulinotropic Peptide), Motilin, Pancreatic Polypeptide, and Enteroglucagon

Question 3

What does Gastrin stimulate and inhibit?

Answer 3

Stimulates: Gastric acid secretion and growth of the gastric Oxyntic gland mucosa

Inhibits gastric emptying

Question 4

Site of release and releasing stimuli of CCK

Answer 4

Stimulated by peptides, amino acids, and fatty acids. Released from I-cells of the Duod and Jejunum

Question 5

Who is the MAJOR stimulator of pancreatic enzyme secretion?

Answer 5

CCK

Question 6

Site of release and releasing stimuli for Secretin

Answer 6

Stimulated by peptides and acids. Released from S-cells of the Duod

Question 7

Secretin action (stimulates and inhibits)

Answer 7

Stimulates: Water and bicarb secretion from pancreas, liver, and intestine. Also stimulates pepsinogen secretion by gastric chief cells.

Inhibits gastric acid secretion by parietal cells

Question 8

Action of GIP

Answer 8

GIP = Gastric Inhibitory Peptide OR Glucose-dependent Insulinotropic Peptide

Stimulates: Pancreatic beta-cell release of Insulin

Inhibits (at pharmacologic levels) gastric acid secretion and emptying

Question 9

Releasing stimuli and site of release of GIP

Answer 9

Oral glucose, as well as acid, amino acids, and hydrolyzed fat. K-cells of the Duod and proximal Jejunum.

Question 10

Site of release and action (stimulate/inhibit) of Motilin

Answer 10

M-cells of the duod and proximal jejunum.
In ALKALINE pH, stimulates Gastric/Duod Motor Function (starts the Migrating Motility Complex)

In ACID pH, inhibits the gastric motor function

Question 11

Site of release and action of Pancreatic Polypeptide

Answer 11

PP-cells of the endocrine pancreas.

Inhibits: Pancreatic enzyme release AND pancreatic water/bicarb secretion

Question 12

Releasing stimuli and site of release of Enteroglucagon

Answer 12

Released from distal ileum and colon. Stimulated by glucose and fats

Question 13

Action of enteroglucagon (stimulates/inhibits)

Answer 13

stimulates hepatic bile flow

inhibits acid secretion and overall motility

Question 14

(2) paracrines and their function

Answer 14

Somatostatin: inhibits G-cell release of Gastrin, inhibits all other GI and ALL pancreatic hormones!

Histamine: stimulates gastric acid secretion by the parietal cell

Question 15

List 4 GI neurocrines. Site of release of all 4?

Answer 15

VIP (Vasoactive Intestinal Peptide)
GRP (Gastrin Releasing Peptide)
Enkephalins
Nitric Oxide (neuronal)
*All released from mucosa of GI tract. All but Enkephalins also released from smooth muscle of GI tract

Question 16

Where are paracrine hormones released?

Answer 16

Rather than being released into circulation, like the classic endocrine hormone, Paracrines are released into the interstitial fluid and, there, have an effect on adjacent cells.

Question 17

(2) example of neurocrine hormones coming from the posterior pituitary

Answer 17

Oxytocin and Vasopressin (ADH)

Question 18

Where are neurocrines released into?

Answer 18

the blood stream. Neurocrines are released from nerve terminals, rather than a gland, and go into circulation.

Question 19

What is the derivative of amino acid hormones? Give (4) examples

Answer 19

hormones derived from Tyrosine and include the thyroid hormones, T3 and T4, as well as catecholamines, Epi and NE

Question 20

Hormones that act via cell-surface receptors v. intracellular receptors

Answer 20

Most hormones act via cell-surface receptors. However, the steroid hormones + thyroid hormones (T3 and T4, which are amines!) can penetrate the cell membrane and act via intracellular receptors. They can do this b/c of their fatty acid base and hydrophobicity.

[All other hormones using cell-receptors include polypeptides (charged +/-), glycoproteins, and NE/Epi (amines)]

Question 21

Why can’t peptide hormones be given orally?

Answer 21

B/c they cannot go through the cell membrane, so they are instead broken apart during digestion

Question 22

Define up-regulation and down-regulation of membrane-bound hormones (those that use cell-surface receptors).

Answer 22

Based on fact that the # of receptors at target tissue determines the response of the target cell to that hormone. But many hormones can regulate their own receptor concentrations.
Upregulation = increasing receptor # and increased sensitivity of target cell. May see this w/ a decreased hormone secretion from normal. The cell’s response is to increase the # of receptors. So even though affinity stays same, more receptors means higher likelihood of binding circulating hormones.
Downregulation = decreased receptor # and decreased sensitivity of target cell. Ex. = Type 2 DM. Where cells are bombarded w/ high levels of Insulin, which causes a decrease in those receptors. Thus, cells become less responsive.

Question 23

General signaling pathway of a membrane-bound hormone

Answer 23

hormones that can’t get into a cell (peptides/hydrophillic) MUST stimulate a second messenger to execute the full signal transduction within the cell.

Question 24

What is a plasma binding protein and which hormones use it?

Answer 24

Since protein hormones mix well w/ water, most of them don’t need carrier proteins. But since steroid and thyroid hormones don’t mix in water, the majority of those circulating are carried by a plasma-binding protein (PBP) in solution. There are also “free” circulating steroid and thyroid hormones. As the free levels decrease from binding to receptors, degradation, or excretion, this leads to dissociation of the hormone from the PBP

Question 25

Explain negative feedback control of hormone secretion. What are the 3 types?

Answer 25

Concept that several glands are functionally connected by hormones within a system. Consider loop of hypothalamus --> Anterior Pituitary --> Target cell - Ultra short loop feedback = hormone released and increase in its [ ] is detected by those cells, which turns off further release. Ex. hypothalamic hormone feeding back at the hypothalamus - Short loop = anterior pituitary hormone feeding back at the hypothalamus - Long loop = the target organ hormone feeding back at the hypothalamus and/or anterior pituitary

Question 26

Thyroid hormone: most common v. most potent

Answer 26

T4 (Thyroxin) is by far the hormone produced the most by the thryoid gland. But T3 is the most potent thyroid hormone.

Question 27

5 Steps of T3/T4 synthesis. Which is the rate-limiting step?

Answer 27

1) follicular cell produces thyroglobulin (TG) and secretes it into colloid 2) follicular cell TRAPS iodine and secretes it into colloid 3) Iodine attached to TG by enzyme, TPO (thyroid peroxidase) 4) **Rate-limiting step = pinocytotic uptake of a colloid droplet containing T4/T3 5) lysozymes and proteases go into colloid droplet, digest TG, which releases T4/T3 into circulation

Question 28

TRH, TSH, and negative feedback regualtion

Answer 28

Hypothalamus produces TRH (thyrotropic-releasing hormone). An increase in TRH stimulates TSH, which acts on the thyroid gland and causes release of T4. When T4 gets to tissues, converted to T3. BUT T4 also released into circulation and through negative feedback turns off further production of TRH.

Question 29

Free v. bound thyroid hormone and affects on total hormone levels

Answer 29

Most of thyroid hormone is bound to a binding protein. HOWEVER, only the free [ ] of this hormone is regulated, and it is the free amount that stays the SAME: Ex. Pregnant pt will have increase in plasma protein, which causes more thyroid hormone to bind. Result is body making more hormone, thereby regulating amount that is free. So even though total amt of hormone is increased, the amount that is free stays the same!

Question 30

Mechanism of action of thyroid hormones. What are the (4) effects on metabolic rate?

Answer 30

T4 and T3 cross the cell membrane and act INSIDE the cell on nuclear receptors to induce protein synthesis of the Na/K ATPase pumps (and other proteins), thereby increasing metabolism in most tissues. ``` Increased metabolic rate = increased: O2 consumption heat production protein catabolism fat catabolism ```

Question 31

(6) tissues that don't experience increased metabolic rate due to thyroid hormone

Answer 31

``` CNS anterior pituitary testes uterus spleen lymph nodes ```

Question 32

What's the only way to get a goiter? What's the exception? How can iodine deficiency cause a goiter?

Answer 32

Must have excess TSH in order to get a goiter, which means TRH is stimulating it. Exception to this is an excess of something that acts like TSH (Ex. Grave's disease). When there is a lack of iodine, there is not enough T4 made to feedback to and suppress TRH production. So TRH continues production of TSH.

Question 33

Grave's disease. What's the effect on levels of TRH, TSH, and thyroid hormone? Potential sx?

Answer 33

an autoimmune disease that produces TSI (thyroid stimulating immunoglobulin), which acts on the TSH-receptors of the thyroid follicles in the same way that TSH does. So thyroid is stimulated to make more hormone. Thus, TRH and TSH levels would be low. But thyroid hormone secretion is elevated b/c of action of TSI. Sx = potential goiter and exopthalmos (bulging eyes)

Question 34

primary, secondary, and tertiary hypothyroidism

Answer 34

Primary = defect in thyroid gland. Low T4 removes feedback suppression of TRH and TSH, which can lead to goiter. Secondary = defect in Ant. pituitary where there is decreased amounts of TSH produced. Thyroid is atrophied and not stimulated to produce adequate T4. TRH is elevated by lack of T4 feedback. However, TSH is still low b/c of defect in pituitary. Thus, no goiter. Tertiary = hypothalamic defect and low TRH production. Thus, TRH, TSH, and T4 are ALL low and thyroid gland is atrophied.

Question 35

Why is there no goiter formation in tertiary hypothyroidism?

Answer 35

a fall in thyroid hormone would normally stimulate TRH production. However, in teritary hypothyroidism, the defect is at the hypothalamus. Therefore, no stimulation for TSH production, which means no goiter formation

Question 36

(3) causes of hyperthyroidism and affect on levels of T4 and TSH

Answer 36

1) Grave's disease (TSI) = high T4 w/ low TSH 2) T4 secreting tumor = high T4 w/ low TSH 3) TSH secreting tumor = high TR w/ HIGH TSH!

Question 37

function of the posterior pituitary

Answer 37

Posterior pituitary is the site of release of Oxytocin and Arginine Vasopressin (ADH). The hypothalamic neurons that make these hormones have axons that extend from the hypothalamus into the post pit.

Question 38

target organs and effects of oxytocin

Answer 38

- Induces contraction of the uterus ("pit drip") - induces contraction of myoepithelial cells of breast for milk let-down or ejection Remember that oxytocin does NOT cause milk production, just the expression of it.

Question 39

stimuli for oxytocin release

Answer 39

release due to a neuroendocrine reflex of suckling. Sound or visual stimuli of suckling can also stimualte

Question 40

target cells for vasopressin. Why is vasopressin also known as an antidiuretic?

Answer 40

Target cells = vascular SM and distal tubules and collecting ducts. Vasopressin has 2 major effects: 1) vasoconstriction (binding to V1 receptor causes release of intracell Ca, which binds to calmodulin and causes contraction to occur) 2) and acts on distal tubules and collecting ducts as an anti-diuretic.

Question 41

Stimuli and mechanisms that control vasopressin secretion

Answer 41

vasopressin release is stimulated by osmoreceptors and vascular stretch receptors. (2) major mechanisms regulate ADH: 1) change in plasma osmolality. Dehydration = increased serum osmolality. Osmoreceptors in hypothalamus detec and release ADH to dilute those particles. 2) change in BP. Decrease in blood volume detected by atrial stretch receptors; leads to increased release of ADH, which absorbs more water in the kidney.

Question 42

Cause and principal sx of diabetes insipidus (neurogenic and nephrogenic)

Answer 42

- In neurogenic diabetes insipidus, don't have any any ADH being produced. So blood is hyperosmotic and these pts are excreting a lot of water that they are unable to reabsorb. Can tx w/ vasopressin analogs. - In nephrogenic diabetes insipidus, the problem is a lack of vasopressin receptors in the kidneys. Either the receptors are missing or don't work. Both blood osmolality AND vasopressin levels are high. Can't tx these pts with vasopressin, b/c they simply don't have the ability to retain water.

Question 43

function and (6) secretions of the anterior pituitary

Answer 43

``` Unlike the post pit, the anterior pituitary gland DOES produce hormones. (6) = ACTH: acts on adrenal cortex Growth hormone: acts on liver TSH: acts on thyroid Prolactin: acts on breast = not tropic! and FSH and LH ```

Question 44

What is the route of transport of the hypothalamic hormones controlling anterior pituitary secretions?

Answer 44

route of transport = hypothalamic-hypophyseal portal system. First, the neurocrines (hypothalamic hormones) are released onto the capillary bed of the median eminence. This capillary bed in the hypothalamus picks up the releasing hormones and travels a short distance to release them in the pituitary capillary bed. These go through the capillaries into interstial space and activate receptors on the anterior pituitary.

Question 45

What's the relationship between growth hormone and insulin-like growth factors (IGF-1) and their binding proteins in the regulation of growth?

Answer 45

In general, GH is antagonistic to insulin. GH raises blood glucose, while insulin lowers it. One of growth hormone's 3 main endocrine actions are on the liver. It decreases insulin actions in liver (to help cause increased blood glucose) and stimulates production and release of IGF-1. IGF-1 is the major growth hormone that causes skeletal growth, protein synthesis, and cartilage cell proliferation. IGF-1 circulates bound to a carrier protein that has a long half-life, which helps protect it from degradation.

Question 46

Role of hypothalamic factors, gluocse, and IGF-1 in regulating growth hormone secretion

Answer 46

- hypothalamic factors = GRH and somatostatin. GRH stimulates GH and somatostatin inhibits it. - blood glucose: low blood glucose increases GH release - IGF-1 = the other inhibitor besides somatostatin

Question 47

What are the primary and secondary actions of growth hormone?

Answer 47

GH is one of 4 major hormones that acts to maintain glucose levels during fasting. Thus, its primary action is on metabolism--causing breakdown of lipids in adipose tissue; increased protein synthesis in muscle ; and decreased sensitivity to insulin in the liver, which causes increased synthesis and release of glucose in form of glycogen. The actual growth is the secondary action.

Question 48

Name the hypothalamic factors that control secretion of each anterior pituitary hormone

Answer 48

- GRH (growth hormone-releasing hormone) stimulates GH - GIH (growth hormone-inhibiting hormone) aka Somatostatin inhibits GH - CRH (corticotropic releasing hormone) stimulates ACTH - TRH stimulates TSH - GnRH stimulates LH and FSH - PRF (prolactin-releasing factor) stimulates prolactin release - PIH (prolactin-inhibiting hormone) inhibits prolactin release

Question 49

If you were to remove the connection between the hypothalamus and anterior pituitary gland, what would happen to secretions from the anterior pituitary?

Answer 49

they would all go down EXCEPT prolactin.