endocrine - Feb 27th to 29th Flashcards

1
Q

Where is calcium found?

A
  • bones
  • soft tissues (intracellular and extracellular)
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2
Q

What is calcium stored as in bones? What is it made up of?

A

hydroxyapatite (calcium salts + phosphate)

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3
Q

How do you calculate total body calcium?

A

intake (diet) - output (kidneys)

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4
Q

What 3 hormones regulate movement of calcium between bone, kidneys, & intestine?

A
  1. Parathyroid hormone (PTH)
  2. Calcitriol (vitamin D3)
  3. Calcitonin

(1 & 2 most important in adults)

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5
Q

What is PTH? (3)

A
  • secreted continuously by the parathyroid gland
  • helps to regulate calcium
  • essential for life (cannot be removed)
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6
Q

What are the 2 types of parathyroid gland cells?

A
  1. Chief cells (produce PTH)
  2. Oxyphils (function unknown)
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7
Q

What plasma Ca2+ falls, how does PTH get it back to normal?

A
  1. Stimulates osteoclasts to resorb bone (primary mechanism)
  2. Stimulates kidneys to resorb Ca2+
  3. Stimulates kidneys to produce enzyme needed to activate vitamin D,
    which promotes better absorption of Ca2+ from food/drink across
    intestinal epithelium
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8
Q

What is Hypocalcaemia? How is it corrected?

A
  • Plasma calcium too low
  • ↑ PTH secretion (stimulates resorption to get more Ca2+ back into blood)
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9
Q

What is Hypercalcaemia? How is it corrected?

A
  • Plasma calcium too high
  • ↓ PTH secretion
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10
Q

Describe the process of bone deposition and reposition

A

Bone deposition:

  • Osteoblasts secrete a matrix of
    collagen protein, which becomes
    hardened into deposits of
    hydroxyapatite

Bone resorption:

  • Osteoclasts dissolve
    hydroxyapatite & return the bone
    Ca2+ (& phosphate) to the blood
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11
Q

Describe the process of vitamin D synthesis

A
  1. Vitamin D3 produced
    from it’s precursor
    molecule, 7-
    dehydrocholesterol
    under the influence of
    UVB sunlight
  2. Vitamin D3 secreted
    into blood from
    skin/intestine (functions
    as a pre-hormone i.e.
    inactive)
  3. Vitamin D3 pre-hormone goes to liver & is chemically changed (hydroxyl group added
    to C25)
  4. Requires hydroxyl
    group addition to C1
    to become active
    (done by enzyme in
    kidneys that is
    stimulated by PTH)
  5. Active vitamin D can then stimulates intestinal absorption of Ca2+, and directly stimulates bone resorption by promoting formation of
    osteoclasts
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12
Q

How is vitamin D synthesized in human?

A
  • Synthesized from 7-dehydrocholesterol with UV light in skin + obtained from dietary sources
  • Those far from the equator don’t have enough sunlight, so they need to ingest it via diet or suppliments
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13
Q

How is vitamin D synthesized in dogs and cats?

A

haha tricked you, it can’t be synthesized – only from diet

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14
Q

What is Calcitonin?

A
  • Made in C cells of thyroid in response to high Ca2+
  • Thought to only play minor role in adult humans (thyroidectomy patients are not hypercalcaemic)
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15
Q

How is phosphate metabolism regulated?

A

by the same mechanisms that
regulate Ca2+ metabolism (but not as tightly) – return/receive
phosphate to/from bone, kidney filtrate, & GI tract

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16
Q

Describe Hyperparathyroidism (5)

A
  • Parathyroid too active
  • Hypercalcaemia (too much
    Ca2+ in blood)
  • Increased bone resorption
    (fractures)
  • Mineralization of soft tissues
  • Increased thirst & urination
    (Ca2+ blocks ADH effects)
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17
Q

Describe Hypoparathyroidism (4)

A
  • Parathyroid not active enough
  • Hypocalcaemia (not enough
    Ca2+ in blood)
  • Muscular weakness, ataxia
  • Cardiac arrhythmias
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18
Q

Describe vitamin D deficiency (differences between adults and children, etc.)

A

Results in poor bone mineralization

In children = Rickets
* Bone pain, stunted growth, deformities

In adults = Osteomalacia
* Bone pain, fractures

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19
Q

Describe Osteoporosis (and its risk factors/treatments)

A
  • Most common disorder of bone
  • Reduction of bone quality due to excess absorption
  • Risk of bone fractures

Known risk factors:
- Sex (females,
especially after menopause)
- Lack of exercise
- Calcium deficient diet

Treatment:
- Adequate calcium & vitamin D intake
- Hormone therapy, PTH, calcitonin (may be associated with cardiovascular disease, stroke, cancer)
- Exercise
- Best treatment is prevention!

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20
Q

What is the Somatotropic Axis?

A
  • GH secretion inhibited by
    somatostatin from hypothalamus
  • GHRH stimulates GH secretion from anterior pituitary
  • GH has many targets (direct
    or through stimulation of liver’s production of somatomedins e.g. IGF-1)
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21
Q

What is Growth Hormone / GH (Somatotropin)?

A
  • Synthesized, stored, & secreted by somatotropic cells in the lateral wings of the anterior pituitary gland
  • Most bound to binding protein (GHBP) but may be transported
    as free hormone
  • Most abundant anterior pituitary hormone
  • Plays an important role in growth
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22
Q

Describe GH secretion patterns (very brief)

A
  • Occurs in peaks/pulse
  • Largest GH peak occurs ~1 hr after
    onset of sleep (circadian rhythm)
  • Basal levels highest early in life
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23
Q

What factors decrease GH secretion?

A
  • Hyperglycemia
  • Glucocorticoids
  • Endocrine disruptors
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24
Q

What are Somatomedins?

A

Insulin-like growth factors

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25
Q

Describe Somatomedins (mostly just IGF-1)

A
  • GH acts on the liver to produce IGFs (IGF-1, IGF-2)
  • IGF-1 almost entirely bound to transport proteins (IGF-BPs)
  • Some IGF-1 transport/binding proteins have an endocrine
    function (i.e. there are receptors for these proteins)
  • GH stimulates the synthesis/release of IGF-1 in other tissues
    besides the liver i.e. it is difficult to differentiate between direct
    actions of GH & IGF-1
  • GH & IGF-1 appear to exert opposite actions in some tissues,
    suggesting independent roles
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26
Q

Describe the metabolic effects of GH (what does it act on and what do it do to it)

A

Liver:
- stimulates IGF-1to trigger bone/cartilage growth and protein synthesis in organs

Adipose Tissue:
- lipolysis
- release of fatty acids

Most other tissues:
- decreased glucose use

Basically, GH plays an especially important role in endocrine regulation of growth (muscle & bone)

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27
Q

What does Hypertrophy refer to (concerning GH)

A

increased cell size

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28
Q

What does Hyperplasia refer to (concerning GH)

A

increased cell number

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29
Q

What are the two types of bone growth, and what do they do?

A

Bone diameter increase:
* Growth occurring around the bone
* Matrix deposits on the outer surface of bone

Bone length increase:
- Growth occurring at epiphyseal plates (near end of bone)
- Epiphyseal plate contains chondrocytes (columns of collagen-producing cells)
- As collagen layer thickens, old cartilage calcifies & chondrocytes
degenerate
- Osteoblasts invade & lay bone matrix on top of cartilage base

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30
Q

What disease(s) appear in growing animals with GH under-
production/decreased
sensitivity?

A

Pituitary Dwarfism: small size,
juvenile proportions, normal shape at maturity but stunted

Pygmies (Laron-Type Dwarfism): decreased responsiveness to GH
(receptor deficiency)

31
Q

What disease(s) appear in adult animals with GH under-
production/decreased
sensitivity?

A

Acromegaly: thickening of bones/joints & skin, enlargement of internal organs (tongue, liver, spleen)

32
Q

What disease(s) appear in growing animals with GH over-production?

A

Pituitary Gigantism

33
Q

What disease(s) appear in adult animals with GH over-production?

A

Alopecia (dogs): thin skin, hair loss (poodles)

Cushing’s Syndrome: increased cortisol inhibits GH synthesis

34
Q

What’s a GH-related disorder in humans caused by severe GH or (GHR) deficiency in children?

A

Dwarfism

35
Q

What’s a GH-related disorder in humans caused by over secretion of GH in children

A

Gigantism

36
Q

What’s a GH-related disorder in humans caused by Severe GH or (GHR) deficiency in adults?

A

Acromegaly (lengthened jaw, coarse facial features, growth of hands & feet)

37
Q

What is rHGH Treatment?

A
  • Used to treat children with short
    stature (bottom 1% on growth charts)
  • Daily injections for ~2 years increased their height by 1.3”
  • $22,000/year cost
  • Side effects: glucose intolerance, pancreatitis, & psychological problems surrounding height
38
Q

What are the causes of disproportioned miniature, dwarf, and teacup cats?

A

Miniature:
* Selective breeding

Dwarf:
* “Munchkin” genetic mutation
* Chondrodysplasia, short-legged

Teacup
* Dwarf breed, normally proportioned
* Severe delay in growth may cause bone, muscle, & other endocrine problems

39
Q

What is Ateliotic (caused by pituitary dwarfism in dogs)?

A
  • GH deficiency, uniformly small body
  • Most “toy” breeds (Chihuahuas, Boston Terriers, Italian Greyhounds, Maltese, Miniature Pinschers, Miniature Spaniels, Pomeranians, Toy Poodles, Yorkies, etc.)
40
Q

What is Micromelic (caused by pituitary dwarfism in dogs)?

A
  • Short legs
  • Basset Hounds, Bulldogs, Corgis, Dachshunds, Lhasa Apsos, Scottish Terriers, Shetland Sheepdogs, etc.
41
Q

What is Brachycephalic (caused by pituitary dwarfism in dogs)?

A
  • Shortened skull bones & short muzzle (e.g. Boxers)
42
Q

What cells are the testes made up of?

A
  • Sertoli cells
  • Leydig cells
43
Q

What do Leydig cells do?

A

secrete testosterone

44
Q

What do Sertoli cell do?

A

support sperm

45
Q

What hormones play a role in the male Hypothalamic-pituitary-
gonadal axis?

A
  • GnRH = gonadotropin releasing
    hormone secreted into portal vessels
  • FSH = follicle stimulating hormone
    (gonadotropin)
  • LH = luteinizing hormone
    (gonadotropin)
  • Testosterone will travel to other
    target cells, resulting in development
    of secondary sex characteristics
46
Q

Describe the negative feedback that occurs in the male Hypothalamic-pituitary- gonadal axis? (there are 3 main ways, hint: they involve testosterone and inhibitin)

A
  • Testosterone inhibits GnRH secretion from hypothalamus
  • Testosterone inhibits the anterior pituitary’s response to GnRH
  • Sertoli cells secrete Inhibin which inhibits the anterior pituitary’s secretion of FSH without affecting LH
47
Q

Describe testosterone, and its roles

A
  • Secreted by the Leydig cells, located between seminiferous tubules

Testosterone in the fetus:
- Masculinizes tract & external genitalia

Testosterone during puberty & adulthood:
- Growth, maturation, & maintenance of male reproductive system
- Libido
- Secondary sex characteristics (hair growth, voice, skin, body shape)
- Bone, muscle
- Brain (behaviour, cognition)

48
Q

How do anabolic steroids cause infertility?

A
  1. Mimic the effects of testosterone
  2. Excess testosterone shuts down pathway
  3. Testes stop producing sperm
  4. Testes stop producing testosterone
  5. Decreased libido & fertility
49
Q

What are the 3 layers of the uterus (from outside to inside)?

A
  1. Perimetrium (outer, connective tissue)
  2. Myometrium (middle, smooth
    muscle)
  3. Endometrium (inner, epithelial)
50
Q

Describe the hypothalamic-pituitary-gonadal axis in females

A
  1. hypothalamus produces gonadotrophin-releasing hormone (GnRH)
  2. GnRH stimulates anterior pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
  3. FSH and LH act on the ovaries to produce oocytes and sex hormones (estrogen and progesterone)
51
Q

What are Overt mensus?

A

endometrial spiral
arteries responsible for menstrual
bleeding (humans, apes)

52
Q

What are Covert mensus?

A

endometrium is shed
without bleeding due to lack of
endometrial spiral arteries (dogs, cats)

53
Q

What is the ovarian cycle?

A

Series of changes in the ovary where
the follicle matures, the ovum is shed, & the corpus luteum develops

54
Q

What is the uterine (menstrual) cycle?

A

Series of changes in hormone
production & the structures of the
uterus & ovaries that make pregnancy possible

55
Q

Which occurs first, uterine (menstrual) cycle or the ovarian cycle?

A

sike, they both happen at the same time :D

56
Q

What happens in Stage 0 (just before day 1) of the ovarian/menstrual cycle?

A

HPG axis:
- gonadotropin secretion from anterior pituitary increases

Ovaries:
- FSH influences several ovarian follicles to begin maturation

Uterus:
- day 1 of menstrual bleeding begins

57
Q

What happens in Stage 1 (Follicular Phase) of the ovarian/menstrual cycle?

A

HPG axis:
- Early: estradiol increases frequency of GnRH pulses
- Late: increase in FSH & LH (cumulates in LH surge)

Ovaries:
- Slight decline in FSH secretion but increased sensitivity (due to estradiol), LH & estradiol increasing
- Early: Some primary follicles grow, develop vesicles, & become secondary follicles
- Late: 1 follicle in 1 ovary reaches maturity (Graafian follicle)

Uterus:
- Estrogen stimulates endometrial growth

58
Q

What happens is Stage 2 (Ovulation) of the ovarian/menstrual cycle?

A
  • Requires an LH surge, stimulated
    by increase in estradiol
  • Mature (Graafian) follicle grows
    under FSH stimulation & ruptures
  • Secondary oocyte & surrounding
    cells released & swept into uterine tube
  • Tissue left behind forms corpus luteum
59
Q

What happens is Stage 3 (Luteal Phase & Menstruation) of the ovarian/menstrual cycle?

A

HPG axis:
- Early: Corpus luteum produces progesterone & estradiol resulting in negative feedback on HPG axis (decrease in FSH & LH, halting development of new follicles)
- Late: negative feedback removed, FSH & LH increase

Ovaries:
- Early: LH stimulates development of corpus luteum which secretes estradiol & progesterone, FSH & LH secretion then declines
- Late: corpus luteum regresses, decrease in estrogen & progesterone

Uterus:
- Early: endometrium anticipating pregnancy, progesterone causes cervical mucosal barrier to thicken
- Late: endometrium requires progesterone, otherwise vascular contracts & dies, sloughs off, & menstruation begins

60
Q

What are the 3 phases of cyclic changes the endometrium goes through? When do they happen? What are their characteristics?

A

Proliferative phase:
- Occurs during follicular phase
- Increased estradiol stimulates growth of endometrium

Secretory phase:
- Occurs during luteal phase
- Increased progesterone from corpus luteum stimulates development of uterine glands
- Endometrium grows in thickness due to estradiol & progesterone

Menstrual phase:
- Result of decrease in ovarian hormone secretion during late luteal phase
- Necrosis & sloughing of endometrium

61
Q

Starting at 1 day after
the LH peak (follicular phase), basal
body temp sharply rises…which hormone causes this?

A

progesterone

62
Q

How do birth control pills work?

A
  • Synthetic estrogen & progesterone
  • Elevation of these ovarian hormones (due to the pill), leads
    to negative feedback inhibition of gonadotropin secretion, so
    ovulation never occurs
  • Simulates a false luteal phase
63
Q

What is menopause?

A
  • At menopause, ovaries depleted of follicles & stop secreting
    estrogen (i.e. change at ovarian not pituitary level)
  • Weak form of estrogen made in adipose tissue (women with
    more adipose tissue have higher levels of estrogen & are at
    less risk of osteoporosis)
  • Menopause associated with increased risk of osteoporosis,
    hot flashes, & aging
64
Q

What is current thinking on menopause studies (estrogen and progesterone supplementation)?

A

Bad! The risks outweigh the benefits (great risk of cancer, cardiovascular issues and strokes)

65
Q

What are the components of The Melanocortin System (13 components from POMC)?

A

4 posttranslational peptides:
- α-MSH, β-MSH, γ-MSH, ACTH

5 melanocortin receptors (7-membrane, G-coupled protein receptors):
- MC1R, MC2R, MC3R, MC4R, MC5R

2 melanocortin antagonists:
- Agouti, AGRP

2 proteins that modulate melanocortin activity:
- Mahogany, syndecan-3

1 opioid peptide (product of POMC but not part of melanocortin system)
- β-endorphin

66
Q

What’s the role of the Melanocortin System?

A
  • Posttranslational processing of POMC is tissue-specific
  • Different POMC peptides produced by different cell types
  • Control of range of many physiological functions by same
    prohormone
  • Mutations in POMC gene/processing rare but possible
67
Q

What does α-MSH do?

A
  • α-MSH produced in brain inhibits food intake (mutation here results in early onset diabetes)
  • α-MSH produced in skin acts on melanocytes, and contain melanin/pigment which influence human skin colour & rodent
    coat colour (mutation here results in altered pigmentation)
68
Q

How does α-MSH increases dark pigment in skin?

A
  • α-MSH binds MC1R
  • Activates signal pathways
    (G-protein-coupled
    receptors, cAMP, PKA,
    CREB)
  • Synthesis of MITF
    (microphthalmia-associated
    transcription factor)
  • Transcription of Tyr & DCT
    which influence
    pigmentation
69
Q

What is the role of MCR?

A

MCR is produced in adrenals, skin, brain, penis, etc. (penile MCR mutation associated with sexual function/dysfunction)

70
Q

What is the role of the Agouti protein?

A
  • Agouti protein is an antagonist to MCR1 in the skin (results in yellow pigmentation)
  • Agouti protein is an antagonist to MCR4 in the brain (results in overeating & obesity; model for adult-onset obesity, hyperglycemia, & insulin resistance)
71
Q

Why are Black Jaguars black?

A

They have a condition
known as melanism
(dominant gene mutation
in MC1R)

72
Q

What causes red hair?

A

Results from 2 copies of
a recessive mutation in
the MC1R protein

73
Q

What causes Erectile Dysfunction? How is it treated?

A
  • Linked to MC4R
    mutations (α-MSH analogs used to
    treat erectile dysfunction; e.g. Melanotan II)