Physiology Flashcards
(313 cards)
1
Q
Define each of the following: endocrine, paracrine, autocrine, juxtacrine, and neurocrine
A
- endocrine: communication over long distance (through circulation)
- paracrine: cells communicate over relatively short distances (different cell types)
- autocrine: cell signals itself/same cell type by releasing ligand that binds to its own surface
- juxtacrine: cell signal stays attached to secreting cell when it binds to receptor on adjacent cell
- neurocrine: similar to paracrine but w/ neurons
2
Q
How are protein and peptide hormones synthesized?
A
DNA -> mRNA -> preprohormone (ribosome) -> pro hormone (ER) -> hormone (golgi)
3
Q
How are protein and peptide hormones stored and secreted?
A
stored in secretary vesicles until stimulated - increased intracellular Ca -> activation of GPCR -> increased cAMP -> increased PKA
4
Q
What are amine hormones derivatives of? Give 4 examples.
A
- derivatives of tyrosine
- Epi, NE, Dopamine, and thyroid hormones
5
Q
What are steroid hormones derived from? Give 7 examples?
A
- cholesterol
- cortisol, aldosterone, estradiol, estriol, progesterone, testosterone, and calcitriol
6
Q
What is positive feedback?
A
hormone action causes more secretion of hormone; uncommon
7
Q
What is negative feedback?
A
hormone action directly or indirectly inhibits further hormone secretion
8
Q
What are 3 types of negative feedback?
A
- long-loop: hormone down line feeds back to beginning
- short-loop: hormone secreted by gland inhibits further secretion
- ultrashort loop: gland inhibits its own hormone secretion
9
Q
How are receptors up-regulated?
A
increase synthesis, decrease degradation, activation
10
Q
How are receptors down-regulated?
A
decrease synthesis, increase degradation, inhibition
11
Q
What happens when a hormone receptor is down-regulated?
A
response to hormone declines even though levels remain high
12
Q
Explain the adenylyl cyclase system
A
- hormone binds to receptor by Gs or Gi protein
- activation/inhibition of adenylyl cyclase
- increase/decrease cAMP
- second messenger (PKA) amplifies signal for physiological actions
13
Q
Explain the PCL system
A
- hormone binds to receptor
- coupling via Gq to PLC
- intracellular IP3/Ca increased
- second messenger (PKC or calmodulin) amplifies signal
- physiological action
14
Q
Explain steroid hormones secondary messenger system
A
- hormone diffuses across cell membrane
- binds to receptor protein (cytosol or nucleus)
- hormone-receptor complex becomes transcription factor
- new mRNA
- new proteins
15
Q
ANP vs NO in guanylyl cyclase system
A
- ANP: GTP -> cGMP -> activates cGMP dependent kinase -> phosphorylates protein responsible for ANPs physiological affects
- NO: diffuses out of endothelial cells -> binds to and activates cytosolic guanylyl cyclase -> GTP to cGMP -> smooth muscle relaxaion
16
Q
Explain receptor tyrosine kinases. Give 3 examples
A
- insulin, IGF-1, prolactin
- intracellular domain has intrinsic tyrosine kinase (phosphorylates itself when activated)
17
Q
Explain tyrosine kinase associated receptor. Give an example.
A
- growth hormone
- intracellular domain non-covalently associated w/ tyrosine kinase (JAK); associated protein (JAK) phosphorylates tyrosine on itself when activated
18
Q
Where are catecholamines synthesized?
A
in cytosol and secretory granules
19
Q
Where does cholesterol used to make steroid hormones come from?
A
- mostly take up as LDL through receptor mediated endocytosis
- some made de novo from acetyl CoA
20
Q
What 2 actions do steroid hormones have?
A
- genomic: modulate gene transcription by interaction w/ intracellular nuclear receptors
- Nongenomic: specific receptor mediated actions or direct steroid membrane interactions
21
Q
Why do endocrine organs have such a large blood supply?
A
endocrine glands/organs release hormones into the CV system
22
Q
Where is the hypothalamus located?
A
below the thalamus, behind the optic chiasma, surrounding the 3rd ventricle
23
Q
What are the 3 direct targets of the hypothalamus and through what?
A
- anterior pituitary: through releasing hormones (RH) and inhibiting hormones (IH)
- kidneys and uterus: through oxytocin and AHD
- Adrenal medulla: sympathetic innervation
24
Q
Where is the pituitary gland located? How does it connect to the hypothalamus?
A
- below the hypothalamus, within hypophyseal fossa of sphenoid bone
- connected to hypothalamus through infundibulum
25
What is the embryologic origin of the anterior and posterior pituitary?
- derived from ectoderm
- Posterior pituitary and infundibular stalk = infudibulum
- Anterior pituitary = Rathke's pouch
26
What are the 3 parts of the anterior pituitary?
- pars tubercles (wraps around stalk)
- pars intermedia (posterior wall of Rathke's pouch)
- pars distalis (majority of gland where hormone production occurs)
27
What are the 2 parts of the posterior pituitary?
- infundibular stalk (bridge between hypothalamus and posterior pituitary)
- pars nervosa (actual posterior pituitary)
28
How does the hypothalamus communicate w/ both anterior and posterior pituitary?
```
anterior = neurohormones
posterior = axons from hypothalamus
```
29
How would the pars distalis and pars nervosa stain on a histological slide?
pars distalis = darker staining
| pars nervosa = lighter staining (neural tissue)
30
What do each of the 5 cell types of the anterior pituitary secrete: somatotrophic, thyrotropic, corticotropic, gonadotropic, mammotropic
- somatotropic: growth hormone (GH)
- thyrotropic: thyroid stimulating hormone (TSH)
- corticotropic: adrenocorticotropic hormone (ACTH); melanocyte stimulating hormone (MSH)
- gonadotropic: follicle stimulating hormone (FHS) and luteinizing hormone (LH)
- mammotropic: prolactin
31
How do each of the following cells of the anterior pituitary stain on a histologic slide: somatotrophic, thyrotropic, corticotropic, gonadotropic, mammotropic
- Acidphils (red): somatotrophs and mammotrophs
| - Basophils (dark staining): corticotrophs, thyrotrophs, and gonadotrophs; B-FLAT (FSH, LH, ACTH, TSH)
32
What is the function of the posterior pituitary?
stores ADH and oxytocin synthesized by the hypothalamus
33
What is the hypothalamic-hypophyseal portal system?
system of blood vessels that connects anterior pituitary and hypothalamus; indirect method of communication
34
What is the hypothalamic-hypophyseal tract?
neurons that connect the posterior pituitary and hypothalamus; direct method of communication
35
Explain the function of the 2 plexuses of the hypothalamic-hypophyseal portal system
- primary plexus in the median eminence picks up RH/IH from hypothalamus and takes them to anterior pituitary
- secondary plexus in the anterior pituitary is where hormones created in anterior pituitary enter the blood
36
How does the hypothalamic-hypophyseal tract work?
Hypothalamic neurons synthesize oxytocin and ADH -> travel to posterior pituitary -> stored in neurosecretory bodies -> released when associated hypothalamic neurons fire to neurosecretory bodies
37
What is the function of ADH?
targets the kidneys to retain Na and water; increase BP
38
What is the function of oxytocin?
targets uterine smooth muscle (contractions) and stimulates lactation; also involved in sexual arousal as well as muscle mass
39
What causes gigantism? When in life does it occur
- excess production of GH due to a tumor
| - occurs in childhood (before growth plates close)
40
What causes pituitary dwarfism? What do these people look like?
hyposecretion of growth hormone; normal body proportion but rarely taller than 4ft
41
What is the function of the pineal gland and what does it secrete?
- role in growth, development and circadian rhythms
| - secretes melatonin and serotonin
42
Where is the thyroid gland located?
below the larynx and anterior to the trachea
43
What makes up a thyroid follicle?
follicular cells surrounding colloid (fluid that contains thyroglobulin -> storage for of T3/T4)
44
What are parafollicular C cells and what do they secrete?
thyroid cells located outside the follicles; secrete calcitonin
45
What is the function of calcitonin what are its action (3)?
lower circulating Ca levels
- stimulate secretion by kidneys
- decrease Ca-releasing activity of osteoclasts
- increase osteogenesis by osteoblasts
46
What is Grave's disease? Sx and tx?
- over secretion of T3/T4 due to abnormal antibodies that stimulate TSH receptors
- Sx: elevated metabolism, rapid HR, weight loss, protruding eyes
Tx: thyroidectomy or anti-thyroid drugs
47
What is hypothyroidism? Sx and tx?
- insufficient T3/T4 production
- Sx: low metabolic rate, weight gain, lethargy
- Tx: synthetic T3/T4
48
What causes goiters?
thyroid enlargement due to iodine deficiency - follicles make thyroglobulin but cannot make TH
49
What do parathyroid glands produce and what is its function? What cells produce this hormone?
produce parathyroid hormone (PTH) - increases blood Ca levels when low; produced by chief (principle) cells
50
What actions does PTH have (3)?
- stimulates osteoclasts to resorb bone and release Ca stores
- increase Ca retention in kidneys
- kidney create calcitriol (active form of vitamin D) -> increases Ca absorption by intestines
51
What are the 3 zones of the adrenal cortex and how does each look histologically?
- zona glomerulosa: thin layer on top next to capsule; stains dark pink
- zona fasciculata: larger middle zone; lighter pink/purple columns
- zona reticularis: right next to medulla; medium pink
52
What is produced in the zona glomerulosa? Class of hormone and function?
- aldosterone: influence Na/K levels and secreted in response to low BP
- mineralocorticoid
53
What is produced in the zona fasciculata? Class of hormone and function?
- cortisol: mediates glucose metabolism and acts as anti-inflammatory in immune system
- glucocorticoid
54
What class of hormones are produced in the zona reticuluaris? Function?
androgens - influence secondary sex characteristics
55
What is the primary cell type of the adrenal medulla? What does it produce?
chromaffin cells - secrete Epi and NE
56
Describe Epi cells and NE cells histologically
- Epi cells: smaller w/ less granules; less electron density (stain gray)
- NE cells: larger w/ granules; more electron dense (stain black)
57
What is Addison's disease? Sx?
hyposecretion of both glucocorticoids and mineralocorticoids -> blood glucose and Na levels drop -> severe dehydration and low BP along w/ fatigue and loss of appetite
58
What is Cushing's syndrome? Sx?
hyper secretion of glucocorticoids due to ACTH-secreting pituitary tumor or adrenal cortex tumor
- Sx: high serum glucose, muscle weakness, lethargy, fat redistribution (buffalo hump and moon face)
59
What is secreted by each of the following endocrine pancreas cells: alpha, beta, delta, and F-cells?
- alpha: glucagon
- beta: insulin
- delta: somatostatin
- F-cells: pancreatic polypeptide
60
Describe the insuloacinar portal system
- arterials break into capillary beds and surround pancreatic islets (supplies O2 and nutrients and picks up anything islets want to release into blood stream)
- go past acinar cells -> helps islets regular acinar cells (local action)
61
What is the acinar vascular system?
vessels that supply only the pancreatic acini and not the islets
62
What type of sx usually show up w/ pituitary cancers?
dizziness and vision problems -> expand up into brain against optic nerves
63
What neurons in the hypothalamus produce ADH and oxytocin?
```
ADH = supraoptic nucleus (SON)
Oxytocin = paraventricular nucleus (PVN)
```
64
Explain primary, secondary, and tertiary endocrine disorders
- primary: defect in peripheral endocrine gland
- secondary: defect in pituitary gland
- tertiary: defect in hypothalamus
65
What does GH bind directly to?
bones and muscle
66
What are the 3 direct actions of GH?
growth, cell reproduction, and metabolism
67
Name 3 indirect actions of GH
signals liver to produce IGF, stimulates hypertrophy and hyperplasia
68
What 2 hormones does the hypothalamus make that relate to GH? What does each do?
- growth hormone releasing hormone (GHRH) -> stimulates anterior pituitary to secrete GH
- growth hormone inhibiting hormone (GHIH) = somatostatin (SS) -> inhibits anterior pituitary from secreting GH
69
What is another name for GH? What cells in the anterior pituitary secrete it?
somatotropin -> secreted by somatotrophs
70
What is produced by the liver in response to GH? What is its 2 functions?
- insulin-like growth factor (IGF-1) = somatomedin C -> inhibits GH from anterior pituitary and stimulates GHIH from hypothalamus
71
Name 6 things that stimulate GH secretion
fasting, hunger, starvation, hypoglycemia, sleep, and Ghrelin
72
Name 3 things that inhibit GH secretion
somatostatin, IGF-1, and inadequate AAs
73
Describe primary GH insensitivity
ghrelin and GHRH activate GH -> GH targets liver but liver is insensitive to it
74
Describe secondary GH insensitivity
GH does not respond to signals from hypothalamus
75
Describe tertiary GH insensitivity
issue w/ GHRH or ghrelin or hypothalamus is insensitive to them
76
What actions does GH promote in the liver in a fed state?
liver produces IGF-1 -> mitogenesis, lipolysis, and differentiation
77
Explain what happens to GH with normal carb intake but inadequate AA availability
GH inhibited -> liver doesn't produce IGF-1 -> lipogenesis and carb storage
78
Explain what happens to GH with decreased carbs and normal AA availability
GH levels increase -> liver produces IGF-1 -> lipolysis, ketogenic metabolism
79
How does decreased carbs/normal AAs promote insulin insensitivity?
less glucose uptake and increased insulin levels in the blood
80
What causes acromegaly? Sxs?
- caused by prolonged and excessive secretion of GH in adult life (after closer of growth plates)
- excessive growth of soft tissue, cartilage, and bones in hands, feet, and face
81
How would you dx acromegaly?
increase serum in GH and IGF-1, failure of oral glucose to suppress serum GH, pituitary enlargement on MRI
82
What is the HPA axis?
hypothalamus-pituitary -adrenal axis
83
HPA Axis: What is produced by the hypothalamus (PVN)?
corticotropin-releasing hormone (CRH)
84
HPA Axis: What stimulates the release of CRH from the hypothalamus?
stress: physical (surgery, infection), emotional (fear), chemical (hypoglycemia)
85
HPA Axis: What is produced by the anterior pituitary in response to CRH? What cells secrete it?
Adrenocorticotropic hormone (ACTH) secreted by the corticotrophs
86
HPA Axis: What does ACTH stimulate the adrenal glands to secrete?
Cortisol
87
HPA Axis: What inhibiting loops exist in this axis?
- Long loop - cortisol inhibits ACTH and CRH
| - Short loop - ACTH inhibits CRH
88
What is the HPT Axis?
hypothalamus-pituitary-thyroid
89
HPT Axis: What is produced by the hypothalamus (PVN)?
Thyroid Releasing Hormone (TRH)
90
HPT Axis: What is produced by the anterior pituitary in response to TRH? What cells secrete it?
Thyroid Stimulating Hormone (TSH) -> thyrotrophs
91
HPT Axis: What is produced by the thyroid gland in response to TSH?
T3 and T4
92
How is the regulation of prolactin secretion different compared to most other anterior pituitary hormones?
- most hormones stimulated through positive regulation (must be signaled to be made)
- prolactin controlled through negative regulation (inhibited by hypothalamic dopamine)
93
What cells synthesize prolactin? What is its main action?
synthesized by lactotrophs -> stimulates and maintains lactation
94
HPT Axis: What factors inhibit TRH secretion?
stress (physical, starvation, and infection)
95
What action does prolactin have on other hormones not in its axis? What is the purpose of this?
- suppresses GnRH (inhibits LH and FSH)
| - decreases reproductive function and suppresses sexual drive
96
What factors stimulate the release of prolactin (4)? What hormone is used?
- pregnancy, breast feeding, sleep, stress
| - stimulated by TRH from the hypothalamus
97
What factors inhibit the release of prolactin (3)?
Dopamine + agonists and somatostatin
98
How does prolactin inhibit itself?
stimulates hypothalamic dopamine release -> dopamine inhibits prolactin
99
What 2 hormones are secreted by gonadotrophs? What is their function?
- Luteinizing hormone (LH) and Follicle Stimulating Hormone (FSH)
- promotes estrogen and progesterone in females and promotes testosterone in males
100
What stimulates the secretion of FSH and LH from the anterior pituitary? What hormone can inhibit this process?
- gonadotropin releasing hormone (GnRH) stimulates FSH and LH
- prolactin inhibits GnRH -> inhibits FSH and LH
101
What factors can inhibit GnRH besides prolactin?
extreme energy deficits and extreme exercise
102
What is a pituitary adenoma? Name the 3 most common?
- hormone producing tumor in anterior pituitary
- Prolactinoma (60%)
- Acromegaly/giantism (20%)
- Cushing's disease (10%)
103
Name 4 common causes of hyperpituitarism?
brain damage, pituitary tumors, infections, infarctions
104
What would hyperpitiuitarism of each of the following hormones be called: ACTH, TSH, GH, PRL, LH and FSH?
- ACHT = Cushing's disease
- TSH = TSH secreting adenoma
- GH = acromegaly/gigantism
- PRL = prolactinoma
- LH and FSH = non-functioning adenoma
105
What would sx be of decreased GH release?
short stature in children, no effect in adults
106
What would sx be of decreased FSH/LH release?
infertility/reduced sperm count (males); menstrual irregularity (females)
107
What sx would be seen with a decrease in each of the following hormones: TSH, ACTH, ADH (posterior pituitary)?
- TSH: hypothyroidism
- ACTH: loss of pigmentation
- ADH: diabetes insipidus
108
What is Sheehan syndrome? What are some of the sx?
- postpartum hypopituitarism due to excessive blood loss during childbirth and damage to the pituitary gland
- Sx: agalactorrhea, amenorrhea, hypothyroidism
109
What are the main target tissues of oxytocin? What is its main action in each?
breast (milk ejection) and uterus (uterine contraction)
110
What is pitocin?
oxytocin analog given to induce labor
111
What are the 3 main factors that trigger the release of ADH from the posterior pituitary? How is each measured? Which is most sensitive?
- decreased BP (cardiac and aortic baroreceptors)
- low blood volume (arterial stretch receptors)
- increased osmolarity (>280)( hypothalamic osmoreceptors) -> most sensitive
112
What receptors does ADH affect in the vasculature and kidney?
V1 in vasculature
| V2 in kidney
113
What is the overall function of ADH?
increases BP and blood volume, decreases osmolarity
114
What is central neurogenic diabetes insipidus? How does it affect plasma ADH levels?
- failure of hypothalamus to produce ADH or release it from posterior pituitary -> decrease in plasma ADH
115
What are the causes and sxs of central DI? What is the tx?
- results from damage to pituitary or destruction of hypothalamus
- Sx include producing a large amount of dilute urine
- Tx is desmopressin (synthetic analog of ADH)
116
What is nephrogenic DI? How does it affect plasma ADH levels?
kidneys unable to respond to ADH -> increase plasma ADH
117
What are the causes and sxs of nephrogenic DI?
- drugs such as lithium and tetracyclines, chronic disorders (PKD and sickle cell anemia)
- sx include producing a large amount of dilute urine
118
What is SIADH?
syndrome of inappropriate ADH secretion -> excessive ADH secretion
119
What does SIADH cause and what is the tx?
- causes excessive water retention and hypoosomolarity
| - Tx include fluid restriction, hypertonic saline, V2 receptor antagonist
120
How many iodines are connected to T3 and T4? Which is secreted more? Which is more potent?
```
T4 = 4 iodine, 90% secreted
T3 = 3 iodine, more potent
```
121
How is T4 converted to T3 in the periphery and anterior pituitary?
- Type 1 deiodinase in periphery
| - Type 2 deiodinase in anterior pituitary
122
What is the backbone of T3 and T4?
tyrosine
123
What are the 2 intermediates of T3 and T4? How is each made?
- MIT (1 iodine); DIT (2 iodine)
- DIT + MIT = T3
- DIT + DIT = T4
124
What are factors that reduce the conversion of T4 to T3?
fasting, medical/surgical stress, catabolic disease
125
What is organification?
process of binding iodine w/ thyroglobulin
126
What 2 hormones are synthesized in the posterior pituitary?
NONE!!! It only stores, does not produce or synthesize!
127
What 2 transporters are on the basolateral membrane of thyroid follicular cells? Functions?
- Na/I symporter: brings Iodine into the cell along w/ Na
| - Na/K ATPase: removes Na from cells and brings K in (Na gradient)
128
What 2 transporters are on the follicular lumen side of thyroid follicular cells? Functions?
- Pendrin: Cl/I counter-transporter -> Cl into cell; I into colloid
- Peroxidase (TPO) - oxidizes iodine in lumen for combo w/ thyroglobulin
129
What does thyroglobulin bind to while in the colloid?
T4, T3, and intermediates (MIT and DIT)
130
How does T3 and T4 go from being in the colloid to being released into the blood?
- Tg granules pinocytosed back into cell
| - Protease cleaves off T3 and T4 form thyroglobulin and releases them
131
What occurs to MIT and DIT after T3/T4 is released?
undergo deiodination into tyrosine and iodine -> recycled in the cell
132
How would perchlorate and thiocyanate inhibit thyroid hormone production?
inhibits the Na/I symporter
133
What is PTU and what does it do? What is it used to treat?
- propylthiouracil (PTU) - inhibits peroxidases in thyroid follicles
- used to treat hyperthyroid/Grave's disease
134
What is the Wolff-Chaikoff effect?
inhibits organifaction
135
How much ingested iodine is usually taken up into the thyroid? What happens to the rest of it?
about 25% taken into the thyroid; the rest is excreted by the kidneys
136
In what 2 forms can thyroid hormones circulate in blood?
plasma proteins (99%) or free (1%)
137
What are the 3 binding proteins thyroid hormones will bind to?
- Thyroxin-binding protein (TBG)
Transthyretin (TTR)
Albumin
138
What synthesizes TBG? Which thyroid hormone does it have a greater affinity for?
synthesized by the liver; greater affinity for T4
139
Which thyroid hormone has a longer half life? How long does it take each of them to reach maximum activity?
- T4 - longer half life, reaches max in 10-12 days
| - T3 - shorter half life, reaches max in 2-3 days
140
What does a higher level of T3 resin uptake mean?
resin picks up whatever T3 is not bound to TBG (higher affinity for T4); higher resin uptake = higher levels of free T3
141
What would you expect resin uptake to look like in hyperthyroidism?
increased T4 -> fewer spaces on TBG for T3 -> increased T3 resin uptake
142
What would you expect resin uptake to look like in hypothyroidism?
decreased T4 -> more space on TBG for T3 -> decreased T3 resin uptake
143
Explain what changes occur for thyroid hormones in the blood w/ hepatic failure?
decreased TBG (synthesized in liver) -> increased T3 resin uptake -> transient increase in free T3/T4 -> inhibition of synthesis (negative feedback)
144
Explain what changes occur for thyroid hormones in the blood w/ pregnancy? What is the overall affect?
- increased TBG -> decreased T3 resin uptake -> transient decreased in free T3/T4 (before 20 weeks) -> increase in synthesis and secretion of T3/T4
- increase in the total levels of T3 and T4 but levels of free hormones are normal
145
Name 7 functions of thyroid hormone?
- activates nuclear receptors and cAMP second messenger
- increased metabolic activity
- conversion of carotene to Vitamin A (hypothyroid = possible blindness)
- growth
- maintain cardiac output
- stimulates GI motility
- CNS development and excitation
146
How is cholesterol synthesis related to thyroid hormone? What does this mean for hypo- and hyperthyroidism?
- cholesterol and triglycerides in blood inversely related to thyroid hormone
- hypothyroid = increased cholesterol
- hyperthyroid = decreased cholesterol
147
Describe the pathophysiology of thyroid hormone on metabolism
- excess: heat intolerance, weight loss, increased BMR
| - deficiency: cold tolerance, weight gain, decreased BMR
148
Describe the pathophysiology of thyroid hormone on bone
- excess (adults): osteoporosis
- excess (children/adolescents): stunted growth
- deficiency: stunted growth
149
Describe the pathophysiology of thyroid hormone on the CNS
- excess: agitation, anxiety, hyperreflexia
| - deficiency: cretinism, slowed movement, impaired memory
150
Describe the pathophysiology of thyroid hormone on the CV system
- excess: tachycardia, increased CO, increased B1 adrenergic receptors (sympathetic)
- deficiency: bradycardia, decreased CO, heart failure
151
Describe the pathophysiology of thyroid hormone on the GI tract
- excess: diarrhea
| - deficiency: constipation
152
What are some of the sx of hyperthyroidism? What is primary and secondary hyperthyroidism called?
- Sx: weight loss, sweating, rapid HR, high BP, heat intolerance
- Primary: Grave's disease
- Secondary: TSH secreting pituitary adenoma
153
What are 4 primary causes of hypothyroidism?
- agenesis
- gland destruction: Hashimoto's
- inhibit of hormone synthesis and release
- Transient: post surgical, postpartum
154
What hormone levels would you expect to see in someone with an iodine deficiency?
- decrease in thyroid hormone synthesis
- increase in TSH levels
- possible goiter
155
What is the tx for hypothyroidism?
replacement doses of T4
156
What is cretinism? What causes it?
congenital iodine deficiency/hypothyroidism
| Causes: iodine deficiency, maternal intake of anti-thyroid medications, impaired thyroid gland development, genetics
157
Sx of cretinism?
feeding problems, respiratory difficulty, protruding tongue, curse facial features, growth/mental retardation, jaundice, dry skin, hypotonia (due to demyelination)
158
What is Hashimoto's Thyroiditis? What hormone levels would you expect to see?
- thyroid hormone synthesis impaired by thyroglobulin or antibody disruption of TPO (peroxidase)
- decreased T3/T4 secretion
- increased TSH levels
- possible goiter
159
What causes Grave's disease? Type of endocrine disorder?
thyroid stimulating immunoglobulins (TSI) stimulate TSH receptor w/o TSH (primary endocrine disorder)
160
Sx of Grave's disease?
exophthalmos (protrusion of eyeballs) and periorbital edema
161
What hormone levels would you expect to see in someone w/ Grave's disease? What is the tx?
- decreased TSH levels (loss of feedback)
- elevated serum free T3/T4
- circulating TSI (distinguishes Grave's disease)
- Tx: PTU (inhibits peroxidase)
162
What can cause goiter?
- Hyperthyroidism: Grave's disease, TSH producing tumor (secondary)
- Primary hypothyroidism: iodine deficiency, sporadic hypothyroidism, chronic thyroiditis (Hashimotos)
163
Where would you find GLUT2 and GLUT4 transporters? What does GLUT4 require?
- GLUT2: pancreas (B cells) and liver
| - GLUT4: skeletal muscle and adipose tissue (requires insulin)
164
What do pancreatic B cells secrete? Where are they located in islets?
- secrete insulin and peptide C
| - located in the center
165
What do pancreatic A cells secrete? Where are they located in islets?
- secrete glucagon
| - located peripherally
166
What do pancreatic D cells secrete? What do they use to communicate w/ pancreatic B cells?
- secrete somatostatin
| - send dendrite-like processes to B cells
167
What do pancreatic F cells secrete and what does this do?
- secrete pancreatic peptide
| - acts like a satiety signal (NPY, PYY)
168
How do cells of islets rapidly communicate w/ each other?
through gap junction
169
Describe the blood flow through pancreatic islets and how it aids in communication
- islets receive 10% of pancreatic blood flow
- blood hits B cells first -> if glucose present, releases insulin -> bathes over other cells -> informs them that insulin has been released
170
Explain the synthesis of insulin?
preproinsulin -> proinsulin -> insulin + peptide C
171
What is preproinsulin?
signal peptide A and B chains w/ connecting C peptide; no disulfide bonds
172
Describe preproinsulin -> proinsulin?
proinsulin still has C peptide attached but no signal peptide
173
How is insulin packaged? What is the final structure of insulin?
- packaged into secretory granules as proinsulin and cleaved into insulin and peptide C
- insulin = A and B chains connected by disulfide bonds
174
What is C peptide used as a marker of? When does this not work?
used as a marker of endogenous insulin secretion, does not work w/ insulin injections (lack peptide C)
175
How does glucose enter pancreatic B cells?
GLUT2 through facilitated diffusion
176
What does glucose do once it enters pancreatic B cells?
phosphorylated by glucokinase -> G6P -> ATP via glycolysis
177
Explain what ATP synthesized in pancreatic B cells does and what this leads to?
closes ATP dependent K channels -> depolarization -> opening of voltage-gated Ca channels -> Ca enters cell
178
What does Ca cause when it enters pancreatic B cells?
initiates mobilization of insulin and peptide C vesicles to plasma membrane for exocytosis
179
What are the 2 phases of insulin release? Which one is lost in NIDDM pts?
initial burst of insulin and then backs off to become a more gradual release; NIDDM lose that first initial burst
180
To what type of receptor does insulin bind?
RTKs
181
What receptor pathway leads to the metabolic effects of insulin?
IRS 1-4 -> PKB/AKT -> metabolic effects
182
What receptor pathway leads to the growth effects of insulin?
IRS 1-4 -> RAS/GPT -> MAPK -> growth effects
183
What happens to the insulin receptor after insulin binds to it?
insulin-receptor complex is internalized by the target cells -> down regulation of receptor by insulin
184
How does insulin affect glucose uptake
insulin binds to receptor -> activates downstream pathways -> translocation of GLUT4 to membrane -> glucose enters via facilitated diffusion
185
What can stimulate GLUT4 translocation to plasma membrane independent of insulin?
muscle contractions (activates AMPK) -> Exercise good for NIDDM
186
How can exercise cause problems in IDDM?
muscle contractions stimulate GLUT4 -> need to time insulin injections around exercise; exercising and the eating and taking insulin will cause BS to drop
187
How does glucagon affect insulin secretion?
Though to facilitate insulin secretion - increases slowly between meals and decreases after insulin has been released
188
Name 9 stimulatory factors of insulin secretion
- glucose, FAs, and AAs
- Cortisol
- Glucagon
- GIP/GLP-1 (incretin hormones)
- K
- vagal stimulation -> ACh
- Sulfonylurea drugs
189
Name 6 inhibitory factors of insulin secretion
- decreased blood glucose
- fasting
- exercise
- Somatostatin
- alpha-adrenergic agonists -> NE
- Diazoxide (K channel activator)
190
Name the pathway and action of each of the following modulators of insulin secretion: CCK/ACh, GLP-1, Somatostatin
- CCK/ACh - Gq - activate insulin
- GLP-1 - Gs - activate insulin
- Somatostatin - Gi - inhibit insulin release
191
Name 4 actions of insulin on skeletal muscle
- increase glucose uptake (GLUT4)
- increased glycogen synthesis
- increased protein synthesis
- increased FA uptake in muscle cells
192
Name 4 actions of insulin on the liver
- promotes glycogen synthesis
- decreased glujconeogeneis
- increased lipid storage
- increased protein synthesis
193
Name 4 actions on insulin on adipose tissue
- increased glucose uptake (GLUT4)
- increased glycolysis
- decreased lipolysis
- promotes FA uptake and storage
194
What affect does insulin have on blood levels of glucose, AAs, FAs, and keto acids?
decreases blood levels of all of them
195
What causes IDDM?
destruction of B cells -> can't produce insulin
196
How does IDDM lead to DKA?
increased blood levels of ketoacids and decreased utilization of them -> acidosis
197
What is the normal effect of insulin on K?
helps Na/K ATPase maintain activity -> brings K into cells and decreases blood levels
198
What affect can IDDM have on K levels?
intracellular hypokalemia and extracellular hyperkalemia (K shifts out of cells)
199
How does diabetes causes osmotic diuresis/glucosuria?
increased blood sugar exceeds reabsorption capacity of kidneys -> water/electrolyte reabsorption decreases - increased urination and increased glucose in urine
200
What is the current tx for IDDM?
insulin replacement
201
Explain the process of insulin resistance in a NIDDM pt
takes more insulin to maintain normal blood sugar levels -> eat a meal and exaggerated sugar response -> pancreas creates exaggerated amount of insulin -> liver, skeletal muscle and adipose tissue don't respond to insulin -> liver continues to release glucose b/c its not receiving any
202
What will appear on blood work of a pt w/ NIDDM?
increased blood glucose levels and increased insulin levels
203
What can be an early sign of NIDDM?
Non-Alcoholic fatty liver disease
204
What are treatments for NIDDM?
- calorie restriction
- weight reduction
- exercise
- sulfonylurea drugs
- incretin analog of GLP-1
- insulin sensitizers (Metformin)
- Bariatric surgery
205
What is the incretin effect?
GI tract hormones that are needed to facilitate release of insulin -> lost in NIDDM
206
What is the main stimulator of glucagon? What else can stimulate it?
- decreased blood glucose (main)
- CCK
- Fasting
- B-adrenergic agonists
- ACh
207
What 2 main things inhibit glucagon secretion?
Insulin and somatostatin
208
What are 3 main actions of glucagon?
- increase blood glucose (through liver)
- stimulate lipolysis (adipose and skeletal)
- ketoacids produced from FAs
209
What effect does extracellular Ca have?
effects cell excitability (especially nerve fibers)
210
Where is 99% of Ca stored? What is the biologically active form of Ca?
99% stored in bones and teeth; free, ionized form is active
211
What effect does hypocalcemia have on APs? What are some sx of hypocalcemia?
- reduces activation threshold for Na channels -> spontaneous APs
- Sx: hyperreflexia, spontaneous twitching, muscle cramps, numbness/tingling
212
What effect does hypercalcemia have on APs? What are some sx of hypercalcemia?
- decreases membrane excitability
| - Sx: constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy
213
How do acidemia and alkalemia affect free ionized Ca levels?
- academia: increased free ionized Ca (less space on albumin due to high H)
- alkalemia: decreased free ionized Ca (more space on albumin due to lack of H)
214
What is PTH's overall effect on Ca levels? How does it do this?
- overall: increases plasma Ca
- bone: increases bone resorption (indirectly through osteoclasts)
- kidneys: increases Ca reabsorption and urinary cAMP
- intestines: increases Ca absorption (indirectly by activating vitamin D)
215
What is PTH's overall effect on Pi levels? How does it do this?
- overall: decreases serum Pi
- intestine: increases Pi absorption (indirectly by activating vitamin D)
- kidney: decreases Pi reabsorption (inhibits Na/P symporter in
216
What is Vitamin D (Calcitriol) overall effect on Ca levels? How does it do this?
- overall: increases serum Ca
- bone: promotes osteoclast formation and bone resorption
- kidney: increases Ca reabsorption
- intestines: increases Ca absorption
217
What is Vitamin D (Calcitriol) overall effect on Pi levels? How does it do this?
- overall: increases serum Pi
- intestine: increases Pi absorption
- kidney: increases Pi reabsorption
218
What is Calcitonin's overall effect on Ca and Pi levels? How does it do this?
- overall: decreases serum Ca and Pi
- bone: inhibits osteoclastic-mediated bone resorption
- kidney: promotes Pi and Ca excretion
219
Where is the majority of Pi stored?
bone (85%)
220
What cells synthesize and secrete PTH? What is the stimulus for secretion?
- synthesized by chief (principle) cells in parathyroid gland
- stimulated by decrease in plasma Ca levels
221
Via what receptor does PTH work?
GPCR (Gs) - stimulates cAMP
222
What is the CaSR and where is it located?
calcium sensor receptor located in the kidney and parathyroid gland to sense Ca levels
223
What inhibits PTH secretion?
high Ca levels
224
What inhibits the PTH gene specifically?
Vitamin D - PTH needed to activate vitamin D in the kidney (negative feedback)
225
What does vitamin D promote in the kidney and parathyroid gland?
CaSR
226
What does chronic hypercalcemia do to PTH levels?
decreases synthesis and storage of PTH and increased breakdown
227
What does chronic hypocalcemia do to PTH levels? What effect does this have on the parathyroid gland?
increases synthesis and storage of PTH -> hyperplasia of parathyroid gland (secondary hyperparathyroidism) due to low Ca
228
What does severe hypomagnesemia do to PTH?
inhibits PTH synthesis
229
What type of hormones are PTH and Vitamin D?
PTH: peptide
| Vitamin D: steroid
230
What form of vitamin D comes from UV light and diet? Is it active?
- cholecalciferol (Vitamin D3)
| - no, inactive prohormone
231
What is the main circulating form of Vitamin D? Where does it come from?
25-OH-cholecalciferol made in the liver via 25-hydroxlase
232
What is the active form of Vitamin D and what makes it? Where is it made?
1,25-(OH)2-cholecalciferol made in the kidney via 1a-hydroxylase
233
What stimulates and inhibits 1a-hydroxylase expression
- Stimulated by PTH
| - Inhibited by high levels of Ca and Vitamin D (negative feedback)
234
What is PTH's short term and long term effects on bone?
- Short term: bone formation (direct effect on osteoblasts)
| - Long term: increases bone resorption (indirect effect on osteoclasts)
235
Explain what each of the following factors are in bone: M-CSF, RANK, RANKL, OPG
- M-CSF (macrophage colony stimulating factor): induce stem cells to osteoclasts
- RANK: cell surface receptor on osteoclasts/precursors
- RANKL: cell surface protein produced by osteoblasts (mediator of osteoclast formation) -> binds to RANK
- OPG (osteoprotegerin): protein produced by osteoblasts; decoy for RANKL -> inhibits RANKL/RANK interaction
236
What is the action of PTH and Vitamin D on RANKL and OPG?
- PTH: increases RANKL, decreases OPG
| - Vitamin D: increases RANKL
237
What is the action of PTH in the PCT of kidneys?
inhibits Na/P symporter -> Pi excreted in urine
238
In which part of the nephron does PTH increase Ca reabsorption?
DCT
239
What specific action does active vitamin D have on intestinal cells? How does this increase Ca absorption?
- increases protein synthesis of calbindin -> Ca binding protein that shuttles Ca from intestinal lumen through cell
- some Ca can diffuse paracellularly but to increase absorption, calbindin is required b/c high intracellular Ca concentrations can cause apoptosis
240
What transporters are used to move Ca in and out of intestinal cells?
- into cell: TRPV6 Ca channel (diffuses down its gradient)
| - out of cell: Ca ATPase
241
What causes primary hyperparathyroidism? What effect does it have on PTH, Ca, Pi, and active vitamin D levels?
- due to parathyroid adenoma
- increased PTH secretion
- increased plasma Ca (hypercalcemia)
- decreased Pi (hypophosphatemia)
- increased activation of vitamin D
242
What are 2 causes of secondary hyperparathyroidism?
- increased PTH levels secondary to low Ca
- Renal failure
- Vitamin D deficiency
243
How will renal failure effect PTH, Ca, Pi, and vitamin D levels?
- decreased vitamin D (due to kidney damage)
- increase PTH (due to low vitamin D and Ca)
- decrease Ca (due to decreased vitamin D)
- increase Pi (due to decreased GFR)
244
How will Vitamin D deficiency effect PTH, Ca, Pi, and vitamin D levels?
- decreased vitamin D (obviously)
- increased PTH (due to low vitamin D and Ca)
- decrease Ca (due to decreased vitamin D)
- decreased Pi (due to increased PTH)
245
How will hypoparathyroidism effect PTH, Ca, Pi, and vitamin D levels?
- decreased secretion of PTH
- decreased vitamin D
- decreased Ca
- increased Pi
246
What are the sxs and tx of hypoparathyroidism?
Sx mostly associated w/ hypocalcemia: muscle cramps, numbness/tingling, seizures
Tx: oral Ca supplement and active form of vitamin D
247
What is albright heredity osteodystrophy?
- pseudohypoparathyroidism type 1A
| - Gs for PTH in bone and kidney defective (does not form cAMP)
248
How will albright hereditary osteodystrophy effect PTH, Ca, Pi, and vitamin D levels?
- increased PTH (can't perform actions)
- decrease Ca
- increase Pi
- decrease vitamin D
249
What is the phenotype of albright heredity osteodystrophy?
short stature, short neck, obesity, subcutaneous calcifications
250
What is PTH-related peptide (PTHrP)?
peptide produced by malignant tumors - binds and activates PTH receptors w/o requiring PTH
251
How will humoral hypercalcemia of malignancy effect PTH, Ca, Pi, and vitamin D levels? What else will be increased?
- PTHrP increased
- decreased PTH
- increased Ca
- decreased Pi
- decreased vitamin D (normal for cancer)
252
What is familial hypocalciuric hypercalcemia?
mutation that inactivates CaSR in parathyroid glands and Ca receptors in ascending limb of kidney - decreased sensitivity to Ca levels (requires higher levels of Ca to stimulate receptor)
253
How will familial hypocalciuric hypercalcemia effect PTH, Ca, Pi, and vitamin D levels?
- normal/high levels of PTH
- increased Ca
- normal Pi and vitamin D
254
What causes rickets?
insufficient amount of Ca and Pi available to mineralize growing bone in children
255
Pseudovitamin D-deficient rickets type I vs type II
- Type I: decreased 1a-hydroxylase
| - Type II: decreased vitamin D receptor - vitamin D resistance
256
How does estradiol affect Ca levels through the bone, kidney, and intestines?
- kidney: increases Ca reabsorption
- intestines: increases Ca absorption
- bone: promotes survival of osteoblasts and apoptosis of osteoclasts (bone formation)
257
Which population is most at risk for osteoporosis and why?
postmenopausal women due to decreased strong (decreased bone formation)
258
Which catecholamine does the adrenal medulla produce more of?
Epi - 80%
259
What hormones are decreased and increased w/ 21-hydroxylase deficiency?
- sex hormones increased
| - decreased cortisol and mineralcorticoids
260
What are some sx of 21-hydroxylase deficiency?
hypotension (decreased aldosterone), Na and volume loss, hyperkalemia, elevated renin
261
How would males and females present w/ 21-hydroxylase deficiency?
Females: sexual ambiguity
Males: normal phenotype w/ precocious pseudo-puberty
262
What group of hormones increases w/ 11B-hydroxylase deficiency? What does this cause in females?
increased androgens; causes virilization of female fetuses
263
What specific hormone is increased in 11B-hydroxylase deficiency and what does it do?
11-deoxycorticosterone (can stimulate MR -> HTN)
264
What are some sx of 11B-hydroxylase deficiency?
HTN, hypokalemia, suppressed renin secretion
265
What hormone groups are decreased and increased in 17a-hydroxylase deficiency? What are some sx?
- decreased androgens and cortisol
- increased mineralocorticoids
- Sx: HTN, hypokalemia, hypogonadism
266
What effect does cortisol have on each of the following: liver, muscle, fat, skin, immune system, endocrine, and GI?
- liver: increased gluconeogenesis
- muscle: protein breakdown
- fat: lipolysis in extremities, central fat deposition
- Skin: collagen breakdown and fragile blood vessels
- Immune: decreased inflammation -> increased infections
- Endocrine: insulin resistance
- GI: decreased Ca absorption (risk of osteoporosis)
267
What do glucocorticoids inhibit as part of negative feedback?
CRH and ACTH
268
What is ACTH derived from?
POMC
269
How is ACTH connected w/ MSH? What can occur if you have excess ACTH?
- ACTH cleaved into MSH in non-pituitary tissues
| - excess = hyperpigmentation
270
At what time of the day is there a major increase in cortisol? How is this used clinically?
early in the morning; dexamethosome suppression test is given overnight to get results in the morning
271
What is a normal response for low dose dexamethosome suppression test? What is abnormal and what does it indicate?
- normal: suppression of ACTH and cortisol secretion
| - no suppression = cushing
272
What is a normal response to the cosyntropin stimulation tests (CST)? How would adrenal insufficiency (primary and secondary) respond?
- normal: cortisol increases
- primary adrenal insufficiency: cortisol remains the same or rises small amount
- secondary adrenal insufficiency: cortisol greatly increases
273
What is Cushing syndrome? What happens to cortisol and ACTH levels?
- hypersecretion of cortisol (elevated cortisol levels)
| - ACTH depends on etiology: adrenal tumor = low ACTH; non-pituitary neoplasms can secrete high ACTH
274
How will Cushing syndrome respond to a high dose dexamethosome test?
- Adrenal tumor: ACTH decreases but cortisol remains high
| - Ectopic ACTH secreting tumor: ACTH and cortisol remain high
275
What is Cushing disease and what causes it? What happens to cortisol and ACHT levels?
- hypersecretion of ACTH due to a pituitary tumor
| - high ACTH and cortisol
276
How will Cushing disease respond to high dose dexamethosome test?
suppresses ACTH and decreases cortisol down to normal-high levels
277
Name 6 signs/sxs of Cushing's
- moon face
- hirsutism
- bruising (breakdown of collagen)
- ABD adiposity
- stretch marks
- Buffall hump (excess fat deposit on back of neck)
278
What is Addison disease and what causes it?
primary adrenal insufficiency (hyposecretion of all adrenal steroids) usually due to autoimmune restriction of adrenal gland
279
What will ACTH and cortisol levels be in Addison's disease?
high ACTH and low cortisol
280
How will Addison's disease respond to the Cosyntropin test?
no change in cortisol levels (adrenals can't respond to ACTH)
281
What are the signs and sxs of Addison's disease?
- hyperpigmentation (MSH from high ACTH)
- weight loss and muscle weakness
- hypoglycemia
- hypotension
- hyponatremia and hyperkalemia (due to loss of aldosterone)
282
What causes secondary adrenal insufficiency? What will ACTH and cortisol levels be?
- caused by exogenous glucocorticoid administration (pituitary problem)
- low ACTH and cortisol
283
How will secondary adrenal insufficiency respond to the cosyntropin test?
increase in cortisol (adrenals are functional)
284
What is the overall function of aldosterone?
increases Na reabsorption, increases K excretion, and increases H excretion
285
What is the function of 11B-HSD2? Why is it important?
- metabolizes cortisol to cortisone in kidney
| - protects MR from cortisol binding and keeps it available for aldosterone
286
What is Conn syndrome?
primary hyperaldosteronism - hyper secretion of aldosterone due to adrenal neoplasm
287
What effect does excess aldosterone (Conn syndrome) have?
Increased aldosterone -> increased Na and H20 reabsorption -> increased blood volume/BP -> hypokalemia
288
What is primary hypoaldosteronism?
hyposecretion of aldosterone due to destruction of the renal cortex or defects in aldosterone synthesis
289
What is secondary hypoaldosteronism?
hyposecretion of renin from juxtaglomerular cells of kidney - inadequate stimulation of aldosterone
290
What effect does ACTH deficiency have on aldosterone?
very little/no effect due to RAAS still being functional
291
What is the rate limiting step in catecholamine production?
tyrosine -> DOPA via tyrosine hydroxylase
292
Where is dopamine stored after production and what happens to it?
stored in chromaffin granules and converted to NE
293
What stimulates tyrosine to DOPA and dopamine to NE?
sympathetic stimulation
294
What stimulates NE to Epi and where does it occur?
cortisol stimulation - occurs in the cytoplasm of chromaffin cells
295
What are 2 enzymes that metabolize catecholamines?
- monoamine oxidase (MAO)
| - COMT
296
What is used to determine the amount of catecholamine production?
Vanillylmandelic acid (VMA)
297
What is a pheochromocytoma?
tumor of chromaffin tissue -> produces excess catecholamines
298
What are the sxs of a pheochromocytoma?
HTN, orthostatic hypotension, headaches, sweating, palpitations, CP, flushing, anxiety
299
Describe the RAAS system?
decreased renal perfusion -> renin secreted -> Ang II -> ADH (water reabsorption) and Aldosterone (salt reabsorption) -> increased blood volume
300
What is MEN?
AD group of diseases w/ tumors in at least 2 endocrine glands
301
What group of cells are affected in MEN?
amine precursor uptake and decarboxylation cells (APUD) - neuroendocrine cells that secrete amines
302
What is mutated in MEN Type 1?
MEN1 gene -> menin (tumor suppressor)
303
What are the 3 locations of tumors in MEN1?
parathyroid, endocrine pancreas, pituitary
304
Which organ is most frequently involved in MEN1? What is the first clinical manifestation from this organ?
parathyroid glands -> hyperparathyroidism
305
What is the 2nd most common manifestation of MEN1 and what disease is it associated with?
pancreas (pancreatic islets) -> involves gastronomas (ZE syndrome)
306
What do most pituitary tumors in MEN1 secrete? How does this manifest in men and women?
- secrete prolactin -> prolactinemia
- women: galactorrhea and amenorrhea
- men: impotence
307
What is mutated in MEN Type 2?
RET protooncogene (codes for RTK important for cell growth and development)
308
What is the most common manifestation in MEN2?
medullary thyroid carcinoma (MTC) - malignant transformation of parafollicular C cells
309
What 3 manifestations appear in MEN2A?
medullary thyroid carcinoma, pheochromocytoma (adrenal), and parathyroid
310
What is different about pheochormocytomas in MEN2A than sporadic pheohromocytomas?
secrete greater amounts of Epi
311
What are the 3 most common manifestations in MEN2B?
mucosal neuromas, medullary thyroid carcinoma (MTC), and pheochromocytoma
312
What manifestation is not usually seen in MEN2B?
hyperparathyroidism
313
What is cutaneous lichen amyloidosis?
itchy skin condition present in MEN2A
