Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

DEMS > Unit 4 week 1 > Flashcards

Unit 4 week 1 Flashcards

1
Q

Integrative Health

A

Healing-oriented practice that incorporates the relationship between the provider and whole person (mind, body, spirit)

Emphasizes evidence and makes use of all appropriate therapeutic approaches to achieve optimal health and healing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Dietary Supplement and Health Education Act (DSHEA) 1994

A

evaluates vitamins, herbals, amino acids, and other botanicals

Regulates herbal supplements more like food rather than medication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

DSHEA:

manufacturer vs. FDA responsibilities

A

Manufacturers:

  • Does NOT require manufacturers to register or get FDA approval
  • Require they ensure product is safe and label information is truthful

FDA: only takes action if product is unsafe once on the market
-MedWatch Reporting System is how providers and patients can report adverse events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Higher Quality Supplement Requirements (4)

A

1) Label contains the REQUIRED DISCLAIMER - “not evaluated by FDA, not intended to diagnose, treat, cure, or prevent disease”
2) Label may include a structure-function claim - what to use it for
3) Manufacturer follows Good Manufacture Practices - verify quality of raw materials, FDA inspections, record keeping
4) Label may contain a Supplemental Seal of Approval - Good Manufacturer Practices (GMPs), Consumer Labs (CL), United States Pharmacopoeia (USP), National Sanitation Foundation (NSF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Supplements used for dyslipidemia treatment (4)

A

1) Fish oil / Omega-3 Fatty Acids
2) Fibers
3) Niacin
4) Plant Sterols and Stanols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Fish oil/Omega-3 Fatty Acid

Mechanism of action

A

decrease hepatic secretion of VLDL, increase VLDL clearance, reduces TG transport

O-3 can compete with arachidonic acid in COX and lipoxygenase pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Fish oil/Omega-3 Fatty Acid

Effects

A

20-50% decrease in TGs, can be combined with statins

Not effective for lowering TC or LDL-C

Can be used for primary/secondary prevention of CVD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Fish oil/Omega-3 Fatty Acid

Adverse reactions

A

generally recognized as safe (GRAS)

Fish taste - can decrease by putting in freezer

GI upset, heartburn, belching

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Fish oil/Omega-3 Fatty Acid

Drug interactions

A

anti HTN, anticoag, contraceptives, orlistat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Fish oil/Omega-3 Fatty Acid

Herb interactions

A

Garlic, ginger, ginkgo, ginseng → increase risk for bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Fibers

A

whole wheat, whole oats, barley, corn

“Reduces risk of heart disease” - claim allowed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Niacin

Effects

A

Decreases LDL, and TGs, and increases HDL

Decrease risk of secondary MI, but no significant decrease in all cause mortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Niacin

Side Effects

A

HA, GI, flushing, increase blood glucose, and uric acid - must monitor LFTs for potential hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanism and actions of Sterols

A

inhibit intestinal absorption of 50% of cholesterol

→ decreases TC, LDL, no effect on HDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Adverse reactions of Sterols

A

nausea, indigestion, diarrhea, constipation, gas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanism of action and effects of Stanols

A

inhibits dietary and biliary cholesterol

→ Decrease LDL, combine with statin for decreased TC and LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Adverse reactions with Stanols

A

diarrhea, steatorrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Stanols and Sterols:

clinical pearls

A

Takes 2-3 weeks to be effective

When discontinued, cholesterol levels rise back to baseline

Sterols and stanols appear to be equally effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Supplements/OTC used as weight loss supplements

A

1) Ephedra
2) Bitter orange
3) Calcium
4) Alli (Orlistat)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Ephedra

Mechanism

A

non-selective alpha and beta receptor agonists (stimulants)

Only moderate weight loss benefits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Ephedra

Adverse effects

A

dizziness, anxiety, insomnia, HA, dry mouth, N/V, heartburn, tachycardia, palpitations, increased BP, seizures, cardiomyopathy, MI, arrhythmias, sudden death

Product banned from market

HIGH RISK - low gain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Bitter Orange

A

contains caffeine, generally safe (GRAS)

No evidence this supplement is safer than ephedra**

Due to FDA ban on ephedra, manufacturers switched to bitter orange

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Calcium

A

Used for weight loss

supplement alone does not equal low fat dietary intake of Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Alli (Orlistat)

Mechanism

Effects?

A

FDA approved for long term weight loss

Mechanism: reversible inhibitor of pancreatic and gastric lipase

Patients with BMI > 27 have seen benefits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Alli (Orlistat)

Side effects?

A

HA, oily spotting, abdominal discomfort, gas steatorrhea, and liver related events**

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Supplements used to treat diabetes (2)

A

1) Chromium

2) Vanadium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chromium

A

no reliable data on effectiveness
Caution in hepatic and renal dysfunction

Used to treat type 2 diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Vanadium

Mechanism

A

activates insulin receptor proteins, stimulates glucose oxidation and transport

Liver: stimulates glycogen synthesis

Adipose: inhibits lipolysis

Skeletal muscle: promotes glucose uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Vanadium

Side effects

A

Potential kidney toxicity, GI effects, tongue discoloration, lethargy, fatigue

Risk of bleeding when combined with other RX, OTC, supplements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Vanadium

Effects

A

effective in T2D*, improves insulin sensitivity and possible reduces blood glucose levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Supplements used to treat HTN (2)

A

1) Garlic

2) Coenxyme Q10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Garlic Supplement

A

used to treat HTN

Generally safe (GRAS)

Must be chopped and sit for 10 minutes prior to use for best results

Discontinue 2-3 weeks prior to surgery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Coenzyme Q-10

Indications

A

congestive heart failure, preventing statin-induced myopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Coenzyme Q-10

Mechanism

A

antioxidant properties, cofactor in metabolic pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Coenzyme Q-10

Efficacy

A

no evidence as monotherapy, possible useful with prescription tx for HF, no evidence of benefit for myopathy or statin tolerability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Coenzyme Q10 interactions

A

Increase risk of bleeding, interact with anticoagulants

Increase T4/T8 labs in normalized patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Anterior pituitary

aka __________
derived embryologically from __________

made up of pars _________, _________, and ___________

A

aka adenohypophysis

derived embryologically from Rathke’s pouch (oral ectoderm)

pars distalis
pars tuberalis
pars intermedia (not developed in humans)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Pars distalis

A

-part of anterior pituitary

  • contains cells that synthesize, store, and release:
    1) growth hormone (GH)
    2) prolactin (PRL)
    3) adrenocorticotropin (ACTH)
    4) thyroid stimulating hormone (TSH)
    5) follicle stimulating hormones (FSH)
    6) Luteinizing hormone (LH)
  • Contains extensive vasculature
  • Hormone-secreting cells arranged in rows around capillary endothelial cells (fenestrated for rapid passage of hormones into hypophyseal portal system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

5 types of hormone secreting cells in pars distalis of anterior pituitary

A

1) Somatotrophs (GH) - make up 50 % of secretory cells.
2) Lactotrophs (PRL)- make up 20%
3) Gonadotrophs (FSH, LH) about 5-10%
4) Corticotrophs (ACTH), about 15-20%
5) Thyrotrophs (TSH), about 5-10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Pars tuberalis

A

cells around infundibular stalk, contain blood vessels from capillaries of median hypothalamic eminence to small vessels/capillaries of pars distalis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Blood flow into anterior pituitary

A

enters median eminence from superior hypophyseal arteries → larger vessels in tuberalis → deliver regulatory peptides (TSH-RH, GNRH, CRH, GHRH) secreted by hypothalamic neurons to cells in anterior pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Posterior pituitary

aka ________
derived embryologically from __________

releases _______ and _______
made up of _________ and __________

A

aka pars nervosa

derived from neural ectoderm (extension of hypothalamus)

releases ADH and oxytocin

Infundibular stem/stalk + Median eminance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Posterior pituitary

A

Releases ADH (vasopressin) and oxytocin from axons of neurons with cell bodies in hypothalamus (unmyelinated)

Hormones produced in hypothalamus as prohormones (vasopressin-neurophysin and oxytocin-neurophysin and cleaved during vesicular transport down axons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Herring’s bodies

A

bulbous structures innervated by hypothalamic neurons that contain neurosecretory vesicles, innervated by neurons from hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Thyroid gland structure

A

multi-lobed gland comprised of a series of follicles
-Follicles have single epithelial layer surrounding a central colloid

-Extensive vascularization around follicles

Large storage capability of potential hormone in colloid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What does the extensive vascularization around thyroid follicles allow?

A

→ iodide (I-) pumped from blood → converted to iodine (I2) by epithelial cells

Secrete thyroglobulin into interior of follicle → takes up/digests thyroglobulin → generate thyroid hormones (T3, T4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Calcitonin “C” Cells”

A

contain secretory granules with calcitonin that decreases release of calcium from bones (downregulate osteoclasts) and causes increase in blood calcium levels

present in thyroid gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Blood supply to thyroid gland:

___________ artery branches of ___________

and _____________ artery branches off ___________

Thyroid is drained by ___________ and ________ into ________ and _______ respectively

A

Thyrocervical trunk → inferior thyroid artery

External carotid artery → superior thyroid artery

Drainage from:
inferior thyroid vein → subclavian vein
superior thyroid vein → jugular vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Parathyroid Glands

3 cell types present

A

closely associated with thyroid gland

1) Chief cells
2) Oxyphil cells: contain many mitochondria
3) Adipose cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Chief cells of parathyroid gland

A

produce PTH

→ increase osteoclast release of Ca2+ from bone, increase Ca2+ uptake from GI tract and kidney → increase Ca2+ levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Adrenal gland is made up of the _________ and __________

A

cortex and medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Adrenal cortex

3 regions

A

secretes mineralocorticoids (aldosterone → Na+ balance), glucocorticoids, and sex steroids (e.g. DHEA-S) = salt, sugar, sex

1) Zona glomerulosa (outer)
2) Zona fasciculata
3) Zona reticularis (inner)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Zona glomerulosa

A

outer layer of adrenal cortex

secretes mineralocorticoids (aldosterone)

Lacks 17a-hydroxylase → cannot make GCs or sex steroids

Regulated through angiotensin system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Zona fasciculata

A

secretes glucocorticoids (cortisol)

Controlled by ACTH

High activity of 11B-hydroxylase for cortisol synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Zona reticularis

A

inner layer of adrenal cortex

secretes androgens

Controlled by ACTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Adrenal Medulla

A

derived from neural crest (neuroectodermal cells)

Made up of adrenal chromaffin cells that are stimulated by cholinergic (ACh) preganglionic fibers of SNS

→ Catecholamine release (epinephrine, NE) from secretory granules of chromaffin cells (Ca2+ dependent exocytosis)

Cells arranged in clusters around venous channels/sinusoids that drain toward central medullary vein

Under sympathetic and parasympathetic control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Blood supply to adrenal gland

A

superior, middle, and inferior suprarenal arteries → branch and enter through capsule via short cortical arteries → outer subcapsular arterial plexus → medullary region capillaries

Central medullary vein → suprarenal vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Thyroid gland embryology

Thyroid follicle epithelial cells are derived from ___________ in the __________

A

Thyroid follicle epithelial cells → endoderm

Thyroid diverticulum between first and second pharyngeal pouches

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Thyroid gland embryology

Ectodermal, Calcitonin-Secreting Cells are derived from _________ cells

A

neural crest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Ultimobranchial body

A

cells derived from neural crest (ectodermal) that give rise to calcitonin-secreting or parafollicular cells of the thyroid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Parathyroid gland embryology

A

Glandular cells → endoderm

  • Inferior parathyroids → cells in clefts between 3rd and 4th pouches
  • Superior parathyroids → cleft after 4th pouch

Vasculature → mesoderm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Adrenal Gland Embryology:

Cortex originates from _________

reticularis comes from ________ while the fasciculata and glomerulosa come from _________________

A

Cortex → originates from mesoderm

Originates from coelomic epithelium (mesothelium) in a cleft between gut and urogenital ridge

Reticularis comes from first wave of cells migrating in

Fasciculata and glomerulosa come from second group of cells that layer outside reticularis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Adrenal Gland Embryology:

Medulla originates from ________

Sympathogonia are…

Chromaffin cells are…

A

Medulla → originates from ectoderm

Sympathogonia: neural crest cells that migrate to a region to become sympathetic ganglia

Chromaffin cells: progenitors of epinephrine and NE producing cells of medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Peptides and Proteins:

synthesis and secretion

A

synthesized as pre-prohormone on ribosomes from mRNA → hormone targeted to RER → cleaved → prohormone transported to golgi → processed and packaged into secretory vesicles → secreted in Ca2+ dependent manner

*Transported in blood as free hormone but cleaved by proteases in blood, half-life limited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Peptides and proteins and tyrosine derived hormones:

signaling mechanism:

A

bind specific receptor on plasma membrane of target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

3 types of receptors peptides/proteins/tyrosine derived hormones can bind

A

1) G-protein coupled (cAMP, DAG, IP3)
EX = Hypothalamic hormones

2) Cytokine Family → JAK/STAT receptors coupled to tyrosine kinases → phosphorylation of signal transducer proteins and activators of transcription (STATs)
EX = GH, PRL

3) EGF Receptor Family → Autophosphorylating receptors
EX = Insulin, IGF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Steroids

synthesis and secretion

A

from cholesterol precursor

not stored in cell - synthesized and immediately released into bloodstream

Carried by carrier proteins in bloodstream (some in free form) → freeform is the biologically active, bound form is reservoir

→ Longer half lives (hours to days)

Exists in equilibrium: Hormone + Hormone-Binding Protein ← →[H-HBP]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Steroids:

Signaling Mechanism

A

enter target cell and bind to INTRACELLULAR receptors in cytosol or nucleus → receptor-hormone complex → bind specific hormone responsive elements (HRE) → activate transcription of specific genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Hormones that are tyrosine derivatives (3)

A

Epinephrine, NE, Thyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Measurement of Hormone Levels via which 3 techniques?

A

1) Bioassays
2) Radioimmunoassays (RIA)
3) ELISA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Radioimmunoassays (RIA)

A

measure ab binding to specific region of hormone → not useful if abnormal form of hormone being secreted by pt

Most commonly used method

EX) Radiolabel Insulin + Ab → radiolabel-Insulin-Ab

Then add serum with insulin to this mixture → Insulin-Ab and radiolabel-Insulin-Ab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Regulation of Hormone Secretion

2 general ways…

A

1) Hormone level is regulated variable = Negative Feedback Loop
EX) TRH-TSH-TH

2) Plasma concentration of metabolite or mineral is regulated variable
EX) [glucose] on B-cells and a-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Pituitary testing:

Hormone excess is assessed by _________ test (EX?)

Hormone deficiency is assessed by _______ test (EX?)

A

use known physiologic stimulators and suppressors of pituitary hormone release

Hormone Excess: asses by SUPPRESSION test
-e.g. oral glucose tolerance test for GH suppression to confirm acromegaly

Hormone Deficiency: assessed by STIMULATION test
-e.g. insulin tolerance test to evaluate pituitary ACTH/GH reserves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Normal secretion of GH sequence: _______ –> ______ (cell in pituitary) –> ________ –> __________(organ) –> ________

Somatostatin role in GH?

A

GHRH → Somatotroph cell in anterior pituitary → GH → Liver→ IGF-1

Somatostatin inhibits GH release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Regulation of GH release (2 factors)

A

GH inhibits pituitary and hypothalamus

IGF-1 inhibits pituitary and hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Actions of growth hormone (4)

A

Increase bone and cartilage mass/growth
Increase protein synthesis / muscle mass
Increase fat breakdown and TGA levels
Increase salt and H2O retention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Gigantism

A

GH excess before puberty (before closure of growth plates)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Acromegaly

A

GH excess after puberty (linear growth complete)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Diagnosis of growth hormone excess (4)

A

1) Clinical features
2) Elevated IGF-1 level = BEST screening test
3) GH levels less reliable (fluctuate widely over 24hrs)
4) Pituitary MRI-macroadenomas detected in > 80% of acromegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Treatment of growth hormone excess?

A

surgery (first line)
medical therapies (somatostatin analogs, GH receptor antagonist)
radiation therapies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Manifestations of growth hormone deficiency (4)

A

1) Body composition: increased fat deposition, decreased muscle mass, strength, exercise capacity
2) Bone strength: increase bone loss and fracture risk
3) Metabolic and CV Effects: increased cholesterol, increased inflammatory/prothrombotic markers (CRP)
4) Psychological well-being: impaired energy and mood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Treatment of GH deficiency

A

GH supplement is frequently abused

GH therapy is still controversial in adults (only modest benefits)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Diagnosis of growth hormone deficiency (2)

A

1) Insulin induced hypoglycemia (gold standard)

2) Low IGF-1 Level (gender/age matched)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Normal secretion of prolactin:

______ (releasing hormone) –> __________ (cell in pituitary) –> ________ –> ________ (tissue in body) –> _____________

________ inhibits prolactin secretion

A

TRH → Lactotrope → Prolactin → breast → lactation

DA inhibits Prolactin secretion from lactotrophs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Hyperprolactinemia

causes:

physiological
pharmacological
pathological

A

1) Physiological: pregnancy, suckling, sleep, stress
2) Pharmacological: Estrogens (OCPs), antipsychotics, antidepressants (TCAs), antiemetics (reglan), opiates

3) Pathological:
- Pituitary stalk interruption
- Hypothyroidism
- Chronic Renal/Liver Failure
- Prolactinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Prolactinoma

clinical features (males vs. females)

A

Female:Male = 10:1
Most common functional pituitary adenoma

Female = galactorrhea, menstrual irregularity, infertility, impairs GnRH pulse generator, microadenomas

Male = galactorrhea (less common), visual field abnormalities, headache, impotence, EOM paralysis, ant. pit. malfunction, macroadenomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Diagnosis of prolactinoma (2)

A

Random PRL level - correlates with tumor size

Pituitary MRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Treatment of prolactinoma

A

pharmacological (surgery not usually done)

  • Bromocriptine (DA agonist)
  • Cabergoline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Prolactin deficiency can arise how?

A

Severe pituitary (lactotrope) destruction from any cause…

Pituitary tumor, infiltrative disease, infectious diseases, infarction, neurosurgery, radiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Clinical presentation of prolactin deficiency

A

failed lactation in postpartum females
No known effect in males

DX with low basal PRL level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Normal secretion of FSH/LH:

_______ (releasing hormone)–>_________ (cell in pituitary) –> ________ –> _______ (organ) –> __________

A

GnRH → Gonadotroph (anterior pituitary cell) → FSH, LH → Gonads → sex steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

High FSH/LH = hypergonadotropic

Causes?

A 
Congenital Anorchia
Klinefelter’s Syndrome
Testicular injury
Autoimmune testicular disease
Glycoprotein tumor (rare)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Hypergonadotropic (gonadotrope adenoma)

clinical presentation?

A

**Majority are clinically silent

Typically middle-aged patients (males > females) with macroadenomas and related mass effects

→ headaches, vision loss, cranial nerve palsies, and/or pituitary hormone deficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

Diagnosis of gonadotrope adenoma (hypergonadotropic)

A
  • Blood tests: usually low FSH/LH, T/E2
  • Pituitary MRI
  • Immunohistochemical analysis (+FSH, LH, or ASU stain) of resected tumor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Causes of low FSH/LH (hypogonadotropic hypogonadism)

A

Hypothalamic/Pituitary diseases:

  • Macroadenomas
  • Prolactinomas
  • Isolated GnRH deficiency
  • Hemochromatosis

“Functional” Deficiency:
-Critical illness, OSA, starvation, Meds (opiates, glucocorticoids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

Clinical features of hypogonadotropic hypogonadism

Females?

A

anovolatory cycles (oligo/amenorrhea, infertility), vaginal dryness, dyspareunia, hot flashes, decreased libido, breast atrophy, reduced bone mineral density

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Clinical features of hypogonadotropic hypogonadism

Males?

A

reduced libido, ED, oligospermia or azoospermia, infertility, decreased muscle mass, testicular atrophy and decreased bone mineral density, hot flashes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Normal secretion of ACTH

_______ (releasing hormone) –> _______ (cell in pituitary) –> _________ –> _________ (organ) –> _________

when is cortisol secretion at its highest?

A

CRF → Corticotrope → ACTH → Adrenals → cortisol and DHEA-S

Cortisol Rhythms: Major ACTH/cortisol burst in early morning (before awakening)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Cortisol

primary function? (3)

A

catabolic “stress” hormone essential for life

Primary functions:

1) Gluconeogenesis
2) Breakdown of fat and protein for glucose
3) Control inflammatory reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

ACTH actions on adrenal cortex (3)

A

Zona fasciculata → stimulate glucocorticoid production

Zona glomerulosa → mineralocorticoids increased with very high ACTH

Zona reticulata → stimulate steroid hormone synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Complications of hypercortisolism? (15)

A

1) Changes in carb, protein, and fat metabolism
2) Peripheral wasting of fat/muscle
3) Central obesity, fat pads
4) Moon facies
5) Wide (> 1 cm violaceous striae)
6) Osteoporosis
7) Diabetes
8) Hypertriglyceridemia

9) Changes in sex hormones
10) Amenorrhea/Infertility
11) Excess hair growth
12) Impotence

13) Salt and water retention → HTN and edema
14) Impaired immunity
15) Neurocognitive changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

ACTH dependent vs. ACTH independent

A

1) ACTH Dependent → 70-75% of cases
- Corticotrope Adenoma (Cushing’s Disease)
- Ectopic Cushing’s (ACTH/CRH tumors)

2) ACTH independent → 25-30% of cases (high cortisol, nml ACTH)
- Adrenal adenoma
- Adrenal carcinoma
- Nodular hyperplasia (micro or macro)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Pseudo-Cushing’s Disease

A

overactivation of HPA axis without tumorous cortisol hypersecretion

Occurs with: severe depression, anxiety, OCD, severe obesity, obstructive sleep apnea, alcoholism, poorly controlled DM, physical stress (acute illness, surgery, pain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Causes of central adrenal insufficiency

A

Suppression of HPA axis due to…

S/p tumor resection for Cushing’s

Supraphysiologic exogenous glucocorticoid use

Drugs (opioids, megace)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Clinical presentation of adrenal insufficiency (6)

A

1) Fatigue
2) Anorexia, nausea, vomiting, weight loss
3) Generalized malaise/aches
4) Scant axillary/pubic hair
5) Hyponatremia
6) hypoglycemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Diagnosis of adrenal insufficiency (2)

A

Basal testing: random a.m. cortisol level

Stimulation tests:
-Insulin-induced hypoglycemia (gold standard)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

Normal secretion of TSH:

________ (releasing hormone) –> _________ (pituitary cell) –> _______ –> _________ (organ/tissue) –> ________

______ inhibits TSH secretion

A

TRH → Thyrotrope → TSH → Thyroid → T4, T3

SRIF (somatostatin) inhibits thyrotrope secretion of TSH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Clinical presentation of Thyrotropin (TSH) elevation

A

goitre, tremor, weight loss, heat intolerance, hair loss, diarrhea, irregular menses, mass effect symptoms from macroadenoma (headaches, vision loss, loss of pituitary gland function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Diagnosis of Thyrotropin (TSH) elevation (2)

A

elevated free T4 and non-suppressed TSH**

Pituitary MRI (> 80% macroadenomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Central TSH deficiency:

clinical presentation

A

fatigue, weight gain, cold intolerance, constipation, hair loss, irregular menses, possible mass effect

111
Q

Central TSH deficiency:

Diagnosis (1)

A

low free T4 levels in setting of low/normal TSH**

112
Q

Hypopituitarism

A

deficiency of 1 or more pituitary hormone

Panhypopituitarism = loss of all pituitary hormones

Typically progresses from GH (LH/FSH) → TSH (ACTH) → PRL loss = Predictable pattern of loss of ant. Pit hormones

113
Q

Causes of hypopituitarism

A

1) Congenital-Genetic Diseases

2) Acquired pituitary lesions and/or their treatments = 75%
- Macroadenomas/Pituitary surgery/Radiation
- Infiltrative, infectious, granulomatous disease
- TBI, subarachnoid hemorrhage
- Apoplexy

114
Q

Apoplexy

A

clinical syndrome of headache, vision changes, ophthalmoplegia, AMS caused by sudden hemorrhage or infarction of pituitary gland

Occurs in 10-15% of pituitary adenomas

Dx: pituitary MRI or CT

Tx: emergent surgery

115
Q

Management of hypopituitarism

A

Treat hormone deficiency with end hormone replacement

Thyroid → multiple L-thyroxine formulations available

Adrenal → hydrocortisone, prednisone

Gonadal → oral/transdermal E2, transdermal/IM testosterone, or GnRH therapy

Growth Hormone: SQ shots (not orally active)

116
Q

ADH

Mechanism of action at its 2 receptors (V1 vs. V2)

A

V1: vascular vasoconstriction, platelet aggregation

V2: antidiuretic effects in kidney
AC activation → movement of aquaporin water channels to cell membrane → water reabsorption

117
Q

SIADH

A

syndrome of inappropriate ADH release/action in absence of physiologic osmotic or hypovolemic stimulus

Hallmark = excretion of inappropriately concentrated urine in setting of hypoosmolality and hyponatremia

MOST frequent cause of hyponatremia

118
Q

Causes of SIADH

A

Malignant disease - carcinoma, lymphoma, sarcoma
Pulmonary disorders - infections, asthma, CF, positive pressure ventilation
CNS disorders - infection tumors, trauma, bleeds
Drugs - stimulate/potentiate ADH release/actions
Narcotics, nicotine, antipsychotics, carbamazepine, vincristine
Other - nausea, stress, and pain

119
Q

Presentation of SIADH:

Na+ = 130-135 → ?
Na+ = 125-130 → ?
Na+ = 115-125 → ?
Na+ < 115 → ?

A

depends on severity of hyponatremia and rapidity of development (acute is < 48hrs)

-Manifests with neuro symptoms from osmotic fluid shifts and brain edema

Na+ = 130-135 → asymptomatic
Na+ = 125-130 → anorexia, N/V, headaches, irritable
Na+ = 115-125 → altered sensorium, gait disturbance
Na+ < 115 → Seizure, coma, death

120
Q

Diagnosis of SIADH

4 main criteria

A

1) Hyponatremia (Na < 135 mmol/L) + hypotonic plasma (osmolality < 275 mOsm/kg)
2) Inappropriate urine concentration (urine Osm > 100 mOsm/kg) with NORMAL renal function
3) Euvolemic status (no orthostatic hypotension)
4) Exclusion of other potential causes of euvolemic hypo osmolality = hypothyroidism, hypocortisolism

121
Q

Treatment of hyponatremia

A

depends on severity of hyponatremia

Identify and reverse underlying disorder

Mild-Moderate = Na+ 120-134
Water restriction
–> V2 receptor antagonists
–> Salt tablets, lasix, urea

Severe = Na+ <120
–> Hypertonic saline (if pt symptomatic)

*Correct slowly to prevent complications

122
Q

Diabetes Insipidus

A

syndrome of hypotonic polyuria as a result of either inadequate ADH secretion or inadequate renal response to ADH

Hallmark = Voluminous dilute urine

123
Q

Main causes of Diabetes insipidus (4)

A

Central DI: neoplasms, idiopathic, congenital defects, inflammatory/infectious/granuloma/pit. Disease, trauma/vascular event

Nephrogenic DI:
Congenital, drugs, electrolyte abnormalities, infiltrative kidney diseases, vascular disease

Pregnancy

Psychogenic Polydipsia

124
Q

Diagnosis of diabetes insipidus (4)

A

1) Confirm polyuria with 24 hr urine volume collection
2) Exclude hyperglycemia, renal insufficiency, and electrolyte disturbances
3) Assess urine and plasma osmolality
4) Water deprivation test: fluid restricted to limit ADH release → measure Uosm, Posm, serum Na+, and urine output

125
Q

Pituitary Adenoma

A

85% of sellar region masses, typically grade I (DO NOT invade blood vessels)

Can invade bone and dura

Treated with surgical resection

Can be an incidental finding on autopsy

Typically SPORADIC, syndromic is rare but possible (EX - MEN1)

Pediatric/young adults may have syndromic constellation of sx

Functional or nonfunctional

Micro (<1cm) / Macro (>1cm) adenoma

126
Q

Functional vs. Non-functional pituitary adenomas

A
  • Can be hyperfunctioning → produce physiologically unregulated excess of endocrine hormones
  • Can be non-functioning and produce mass effect due to compression of nearby structures

–> Visual disturbances, headache, CN palsies (ptosis, diplopia), pituitary hormone deficits (panhypopituitarism), seizures, stroke, CSF leak

127
Q

List pituitary masses in order of frequency

A

1) Pituitary adenoma (85% of cases)
2) Craniopharyngioma
3) Hypophysitis
4) Pituicytoma
5) Spindle cell oncocytoma

128
Q

Pituitary blastoma

A

rare infantile pituitary masses
DICER1 mutation
ACTH IHC (+)

129
Q

Craniopharyngioma

A

Predominantly kids (5-15 yrs) and middle-aged adults (45-60 yrs)

2nd most common sellar region mass

130
Q

ACTH (corticotroph) secreting adenomas

positive for what transcription factor?
main features?

A

Tpit + (Transcription factor)

85% are microadenomas

Can present with Cushing’s disease

131
Q

Gonadotroph adenoma

positive for what transcription factor?
main features?

A

most common type of clinically nonfunctioning adenoma

most common adenoma type to come to surgery

SF-1 + (steroidogenic factor)

132
Q

prolactinomas

positive for what transcription factor?
main features?

A

Most prolactinomas in premenopausal women are microadenomas

Symptoms: amenorrhea, galactorrhea, impotence (men)

NOT related to birth control pill use

Pit-1 + (pituitary TF)

133
Q

Growth hormone adenoma

positive for what transcription factor?
main features?

A

stained so you can treat GH effects

Pit-1 + (pituitary TF)

134
Q

Blood enters median eminence via __________ arteries and forms capillary plexus

A

Superior hypophyseal

135
Q

Nerve terminals of hypothalamic neurons located in capillary plexus in median eminence →

A

release neurohormones into capillary plexus

136
Q

Neurohormones in capillary plexus —>

A

transported via hypothalamo-hypophyseal portal system to second capillary plexus in anterior lobe of pituitary

137
Q

Adenohypohysis

A

Anterior pituitary

138
Q

Anterior pituitary is derived from?

A

Rathke’s pouch

139
Q

Structure of anterior pituitary

A

pars tuberalis, pars intermedia, pars distalis (anterior lobe)
Anterior lobe secretes hormones

140
Q

Anterior lobe (pars distalis)

A

secretes hormones under control of hypothalamic hormones secreted into hypothalamo-hypophyseal portal system

141
Q

All hypothalamic hormones are _______ and act via _________ receptors

A

peptides

G-protein coupled

142
Q

Gs →

A

AC, cAMP = CRH, GHRH

143
Q

Gi →

A

decrease AC, cAMP = Somatostatin, DA

144
Q

Gq →

A

PIP2 → IP3/Ca2+ and DAG/PKC

145
Q

Thyrotropin releasing hormone (TRH)

A

Thyrotrophs → TSH, PRL

PRL = polypeptide

146
Q

Gonadotropin releasing hormone (GNRH)→

A

Gonadotrophs →LH/FSH

LH, FSH, TSH = glycoproteins

147
Q

Corticotropin releasing hormone (CRH) →

A

Corticotrophs → POMC, ACTH (ACTH is a derivative of POMC)

148
Q

Growth hormone releasing factor (GHRH) →

A

Somatotrophs → GH

GH = polypeptide

149
Q

Somatostatin (GH inhibiting hormone, GIH) →

A

Somatotrophs → decrease GH and TSH

150
Q

Prolactin inhibiting factor (PIH) (aka Dopamine)→

A

Lactotrophs → decrease PRL

151
Q

Pulsatile Secretion and Circadian Secretion

A

Release of hormones from ant. pituitary not constant over time (pulses)

Circadian = ACTH highest during early morning hours, GH secretion elevated sPosterior pituitary dervidehortly after sleep onset

Circadian and pulsatile secretion patterns are superimposed

152
Q

Neurohypophysis

A

Posterior pituitary

153
Q

Posterior pituitary derived from?

A

Derived from neural tissue arising from embryological evagination of diencephalon

154
Q

Posterior pituitary directly connected to

A

hypothalamus and brain

155
Q

_____ and _____ synthesized in cell bodies of large hypothalamic neurons (_______ neurons) → prohormone packaged into secretory vesicles → cleaved into _____ + ______→ vesicles travel down axon of neuron into posterior pituitary → released when AP reaches terminal and ______ channels open

A

ADH and oxytocin synthesized in cell bodies of large hypothalamic neurons (magnocellular neurons) → prohormone packaged into secretory vesicles → cleaved into hormone + neurophysin → vesicles travel down axon of neuron into posterior pituitary → released when AP reaches terminal and Ca2+ channels open

156
Q

ADH secreted in response to? (2)

A

secreted in response to an increase in plasma osmolarity or a decrease in blood pressure

157
Q

ADH actions

A

Acts on cells of renal tubule and collecting ducts to alter water permeability and conserve water

158
Q

Two types of ADH receptors

A

V1 → Gq → PLC pathway → mediate vasopressive action of ADH

V2 → Gs → cAMP → regulate effect of ADH on glomerular filtration rate in kidney

159
Q

Oxytocin secreted during (3)

A

1) Passage of infant through cervix at childbirth
2) During sexual intercourse
3) Response to suckling by infant during breastfeeding

160
Q

Actions of oxytocin

A

Acts to cause contraction of myometrium (during childbirth), contraction of myoepithelial cells (milk ejection)

161
Q

Structure of posterior pituitary

A

median eminence, infundibular stem, infundibular process (pars nervosa)

162
Q

Paraventricular nucleus and supraoptic nucleus:

A

part of hypothalamus that synthesize and secrete hormones into posterior pituitary

163
Q

Two cell types of paraventriclar and supraoptic nucleus

A
  1. Magnocellular neurons

2. Parvocellular neurons

164
Q

Magnocellular neurons

A

processes extend into post. Pituitary and end in pars nervosa

165
Q

Parvocellular neurons

A

end at median eminence close to endings of hypothalamic neurons that produces ant. Pit regulating hormones

→ ADH can increase ACTH production, and cortisol (regulated by ADH) can inhibit ADH in kidneys and hypothalamus

166
Q

General Principles of Hormone Release from Hypothalamic Neurons:

A

Hormones released from hypothalamic neurons when appropriate stimulus generates an AP → Ca2+ entry at nerve terminal via Ca2+ voltage dependent channels → hormone release from secretory vesicles

167
Q

Receptors and Signal Transduction Mechanisms for Hypothalamic Hormones:

  1. CRH and GHRH
  2. Somatostatin
  3. DA
A

Hypothalamic hormones interact with specific receptors on their appropriate target cells in the anterior pituitary

  1. CRH and GHRH → Gs → increase cAMP in corticotrophs and somatotrophs
  2. Somatostatin → Gi → decrease cAMP
  3. DA → Gi → decrease cAMP in lactotrophs
168
Q

Growth hormone secreted by?

A

secreted by somatotrophs from anterior pituitary

169
Q

Secretion and synthesis of growth hormone

A

GH synthesized as part of prohormone → signal peptide cleaved → GH stored in secretory granules of somatotrophs of adenohypophysis

170
Q

GH secretion is under control of?

A

GHRH and Somatostatin

GHRH → increase cAMP in pituitary somatotrophs

Somatostatin → decrease cAMP in pituitary somatotrophs

171
Q

Negative feedback control of GH

A

GH inhibits GHRH secretion and activates somatostatin secretion

172
Q

Effect of GH on organs and systems (4)

A

stimulate somatic growth, regulate metabolism

1) Adipose tissue: increased lipolysis (hormone sensitive lipase), increased plasma free fatty acids (FFAs) → loss of subcutaneous fat
2) Muscle: increase AA transport into muscle and protein synthesis

3) Liver: increase RNA, protein, and gluconeogenesis
Counter-regulatory hormone to insulin = “Anti-Insulin” actions
Excess GH = Diabetogenic
Protein is spared

4) IGF-1 secreted → mediate indirect growth effects

173
Q

Extrinsic factors that stimulate GH (6)

A

1) Hypoglycemia
2) Increased AAs (arginine)
3) Low FFAs
4) a-adrenergic agonists (clonidine)
5) B-adrenergic antagonists (propranolol)
6) Estrogens

174
Q

Extrinsic factors that inhibit GH (6)

A

hyperglycemia, FFAs, obesity, a-adrenergic antagonists, B-adrenergic agonists, corticosteroids

175
Q

GH mechanism of action

A

Binds cytokine receptor family → JAK/STAT pathway activated

176
Q

Hyper-GH (4)

A
  1. High levels of serum glucose → diabetogenic
  2. High levels of insulin (because of high glucose)→ excess IGF production → gigantism
  3. Cardiac hypertrophy
  4. Acromegaly (high GH post puberty)
177
Q

Hypo-Growth Hormone (2)

A

Dwarfism

  1. Laron Dwarfism - due to GH receptor problem
  2. African Pygmies - due to low IGF response
178
Q

Production of IGF-1 reqires

A

Production of IGF requires BOTH insulin and GH

179
Q

Regulation of IGF-1 secretion (2)

A
  1. High glucose, high AA → insulin and GH present → IGF secreted
  2. Low glucose, low AA → low insulin, low GH → IGF NOT secreted
180
Q

Function of IGF-1

A

powerful mitogen and growth-promoting agent

  1. IGF-1 levels increase slowly from birth until puberty
  2. Bone/Cartilage: promote long bone growth via proliferation of epiphyseal cartilage
    After puberty, epiphyses seal, and IGF-1 no longer works here
  3. Muscle: stimulate proliferation, differentiation, and protein synthesis
  4. Adipose tissue: stimulate uptake of glucose and inhibit lipolysis (antagonizes GH)
181
Q

IGF-1 mechanism of action

A

IGF-1 receptors (EGF family receptors) have inherent tyrosine kinase activity upon ligand binding

Insulin receptor associated proteins bind IGF receptors → autophosphorylation of receptor and IRS protein → MAP kinase pathway or PI-3 kinase transduction

182
Q

Prolactin secreted by?

A

secreted by lactotrophs in anterior pituitary

183
Q

Charles Ventriglia

A

An alright guy

184
Q

Secretion of prolactin (3)

A
  1. Hypothalamus tonically inhibits secretion of PRL via DA
    DA → Gi → reduce synthesis of PRL, inhibit lactotroph cell division / DNA synthesis, increase destruction of PRL secretory granules
    - Dopamine is primary controller of PRL release
  2. TRH increases prolactin secretion
  3. Estrogen and progesterone activate mammogenesis and inhibit lactogenesis and galactopoiesis
185
Q

Chilliam Tran

A

A great guy

186
Q

Actions of prolactin

A

1) Breast (mammary gland) = principal target → stimulates…
- Mammogenesis
- Lactogenesis
- Galactopoiesis

2) Inhibits reproduction due to inhibition of GnRH production

PRL has a short half life

187
Q

Prolactin mechanism of action

A

prolactin binds to GH/cytokine receptor on target cell → JAK/STAT (signal transducers and activators of transcription) pathway activation

188
Q

Hyperprolactinemia (4)

A

Galactorrhea, amenorrhea, loss of libido, overgrowth of mammary gland

189
Q

Hypoprolactinemia

A

rare, usually due to panhypopituitarism

190
Q

Sheehan’s syndrome

A

during childbirth, hemorrhagic destruction of pituitary gland

191
Q

Treatment Goals for Pituitary Tumors: (6)

A 
Control tumor growth/mass effects
Preserve pituitary function
Prevent recurrence
Relieve symptoms
Control hormone hypersecretion
Improve mortality rates
192
Q

Types of pituitary tumors that most often require surgical treatment

A

Surgery is first line treatment for all pituitary tumors EXCEPT for tumors that secrete prolactin

IF they secrete prolactin AND growth hormone → surgery

193
Q

Complications from surgery on the pituitary gland (7)

A

1) Postoperative spinal fluid leakage
- -> Requires placement of spinal drain and increased hospital stay

2) Diabetes insipidus: inability to concentrate urine
- -> Due to injury to posterior pituitary gland
- -> Requires tx with DDAVP
- -> Usually transient

3) Injury to optic nerves
4) Injury to carotid artery (stroke)
5) Injury to normal pituitary gland
6) Chronic sinusitis
7) Meningitis

194
Q

Cholesterol molecule

-molecules synthesized from cholesterol? (3, how many carbons do they have)

A

27-carbon steroid molecule
All 27 carbons derived from acetyl CoA

Molecules synthesized from cholesterol:

1) Glucocorticoids: cortisol (C-21)
2) Mineralocorticoids: aldosterone (C-21)
3) Sex steroids

195
Q

Sex steroids (3), how many carbons do they have?

all sex steroids are derived from _________ (__-C) via __________ (enzyme) located in the mitochondrial membrane

A

progestins (C-21), androgens (C-19), estrogens (C-18)

All sex steroids derived from pregnenolone (21-C)

Cholesterol → pregnenolone via 20, 22 desmolase (rate limiting step) located in mitochondrial membrane

196
Q

Biosynthesis of sex steroids

occurs where? (6)

A

Involves a progressive reduction in number of carbon atoms

Location: primarily in gonads

Extra-gonadal tissue:

  • Placenta, adrenal cortex → source of sex steroids
  • Liver, skin, adipose tissue → convert metabolites to sex steroids
197
Q

Transport of sex steroids (3)

A

Hydrophobic, so predominantly in bloodstream bound to plasma proteins

1) Albumin
2) Sex hormone binding globulin (SHBG):
- Produced in liver
- Oral exogenous estrogens stimulate hepatic synthesis of SHBG

3) Corticosteroid binding globulin (CBG)

198
Q

Progestins have _____ carbons

3 types of progestins

A

21-C

1) Pregnenolone, 17-alpha-hydroxypregnenolone
2) Progesterone
3) 17-alpha-hydroxyprogesterone (17-OH-P)

199
Q

Progesterone

A

type of progestin (21-C)

  • Major circulating progestin
  • Present in higher concentrations in females
  • Levels fluctuate during normal menstrual cycle

Function: growth/development of tissues and organs related to ovulation, menses, pregnancy, and lactation

Key feedback inhibitor of hypothalamus and pituitary

200
Q

17-alpha-hydroxyprogesterone (17-OH-P)

used as a marker for what?

A

type of progestin (21-C)

Major circulating progestin

Used as marker for late onset congenital adrenal hyperplasia

201
Q

General function of progestins:

progestins are precursors for production of ________ and _______ by _________

Progestins act on _______, _______, and __________

A

Precursors for production of aldosterone and cortisol by adrenal gland

Affect uterus, ovaries, and breasts

202
Q

Androgens have _____ carbons

Types of androgens (4)

A

19 carbons

1) Testosterone
2) Dehydroepiandrosterone (DHEA)
3) Dihydrotestosterone (DHT)
4) Androstenedione

203
Q

Testosterone

A

Type of androgen (19C)
95% produced in testes
Major feedback inhibitor of hypothalamus and pituitary

204
Q

Function of testosterone - 2 major categories of effects

A

Androgenic effects: growth/development of internal and external genitalia, development/ maintenance of secondary sex characteristics, spermatogenesis, libido, sebum production

Anabolic effects: growth-promoting effects on somatic tissues (bone, muscle)

205
Q

Dehydroepiandrosterone (DHEA)

  • produced where?
  • marker of what?
A

Type of androgen (19C)

Majority produced in adrenal cortex

Excellent marker of adrenal androgen activity

206
Q

Dihydrotestosterone (DHT)

_______ converts ______ to DHT in target cells, however DHT CANNOT be converted to _________

DHT vs. testosterone

A

Type of androgen (19C)

5-alpha-reductase converts testosterone → DHT in target cells
DHT CANNOT be converted to estrogens

DHT is 30-50x more active than testosterone

207
Q

Androstenedione

Produced by _______ cells in _______

Precursor for ovarian _________ production by _______ cells and precursor for extraglandular _______ formation in ______ and ______ tissues

A

Type of androgen (19C)

Produced by THECA cells in ovary

Precursor for ovarian ESTRADIOL production by GRANULOSA cells and precursor for extraglandular ESTROGEN formation in LIVER and ADIPOSE tissues

208
Q

Estrogens (18-C)

what is the sequence of estrogen production starting from cholesterol?

what main enzyme is involved and at what step?
what tissues (4) is this enzyme present in?
A

Cholesterol → Pregnenolone → Progestins → Androgens → Estrogens

Androgen → Estrogens via AROMATASE

Aromatase present in gonads, adipose, liver, CNS

209
Q

Types of estrogens (3)

A

Estrone (E1) - one hydroxyl group
Estradiol (E2) - two hydroxyl groups
Estriol (E3) - three hydroxyl groups

210
Q

Estrone (E1)

derived from __________ in ________

A

Derived from androstenedione in adipose tissue

211
Q

Estradiol (E2

A

Most potent estrogen

Major circulating estrogen

Produced by granulosa cells of ovary and sertoli cells of testes

Function: growth/development of tissues and organs related to ovulation, menses, pregnancy, and lactation

Levels fluctuate during normal menstrual cycle

Key feedback inhibitor of hypothalamus and pituitary

212
Q

Estriol (E3)

A

Least potent estrogen

Important placental product

213
Q

Hypothalamic-Pituitary-Gonadal Axis:

1) Hypothalamus secretes _________ from ________ and _________ in a _______ pattern
2) Anterior pituitary secretes _____ and _____ from ________ in response to GnRH from
3) FSH and LH stimulate production of ________ and ______ which each act to negatively feedback on what?

A

1) Hypothalamus secretes GNRH from ARCUATE NUCLEUS and PREOPTIC AREA in a PULSATILE pattern
- constant GnRH administration actually SUPPRESSES pituitary response

2) Anterior pituitary secretes FSH and LH in response to GnRH from GONADOTROPHS
3) FSH and LH stimulate production of SEX STEROIDS and INHIBIN

→ negative feedback control on reproductive axis
Inhibin = negative feedback on pituitary only

214
Q

Hypothalamic-Pituitary-Gonadal Axis:

Men

A

GnRH pulses 8-14x every 24 hrs

FSH/LH also important for male gonadal function

215
Q

Hypothalamic-Pituitary-Gonadal Axis:

Women

A

GnRH pulses and FSH and LH secretion vary throughout menstrual cycle

FSH/LH in ovulatory women vary throughout menstrual cycle
-Peak shortly before ovulation

Estradiol and progesterone produced in response to FSH/LH
-Estradiol mid cycle in ovulatory women exert POSITIVE feedback on pituitary gland → surge in FSH/LH

216
Q

Men have ______ and ______ cells in their testes

Women have _______ and ______ cells in their ovaries

A

Men: in testes, Leydig and Sertoli Cells

Women: in ovary, Theca and Granulosa Cells

217
Q

Leydig Cells

A

Located in interstitial layer surrounding seminiferous tubules

In response to LH → produce 95% of testosterone in males

Testosterone then acts on Sertoli cells to support spermatogenesis

Negative feedback onto hypothalamus/pit

218
Q

In Leydig cells, LH stimulates rate limiting conversion of cholesterol into pregnenolone by: (2)

A

1) Increasing amount of desmolase

2) Enhancing affinity of desmolase for cholesterol

219
Q

Sertoli Cells

A

Located in direct contact with developing spermatozoa

Support/nurse cells of developing spermatozoa

Organized into tubular epithelium = seminiferous tubule

Tight gap junctions between cells

220
Q

Spermatogenesis requires…

A

Spermatogenesis requires LH, FSH, Leydig cells, Sertoli cells, and testosterone

221
Q

FSH acts on sertoli cells to… (3)

A

1) Produce androgen binding protein
2) Enhance conversion of testosterone from Leydig cells → estradiol
3) Production of inhibin

222
Q

Theca Cells

A

Located in ovarian stroma surrounding follicles

LH acts on theca cells to produce progesterone and androgens

223
Q

Granulosa cells

A

In direct contact with oogonia

Gametes + surrounding granulosa cells = primordial follicles

One follicle matures each month in women of reproductive age

224
Q

Oogensis and ovulation requires…

A

Oogenesis and ovulation requires LH, FSH, granulosa cells, theca cells, estradiol, and testosterone

225
Q

Granulosa cells lack enzyme to convert _______ –> ________

Thus ______ from granulosa cells must diffuse to Theca cells to be converted into _________ and diffuse back into granulosa cells for conversion to ________

A

Lack enzyme to convert progesterone → androgens

Progesterone

Andrsostenedione

Estradiol

226
Q

Leydig (male) and Theca (female) Cells

4 shared characteristics

A

Interstitial cells
Contain LH receptors
Make androgens
Cannot make estrogens due to absence of aromatase

227
Q

Sertoli (male) and Granulosa (female) Cells

4 shared characteristics

A

Adjacent to developing gametes
Contain FSH receptors
Make inhibin
Convert androgens → estrogen in presence of aromatase

228
Q

Treatment of GH Hyposecretion (2)

A

1) Sermolin (GHRH analog)

2) Somatropin (GH analog)

229
Q

Sermorelin

mechanism of action

A

activates anterior pituitary release of growth hormone

GHRH analog: stimulate GH synthesis and secretion via binding to GPCR (Gs) on somatotrophs

230
Q

Sermorelin

Uses (2)

A

potential use in GH-deficiency children

diagnostic eval of patients with GH deficiency

231
Q

Somatropin (GH analog)

uses (4)

A

1) Replacement therapy in children with GH deficiency (can be very expensive)
- Daily bedtime SC injection
- If GH insensitive, can treat with recombinant IGF-1

2) Poor growth due to Turner Syndrome, Prader-Willi, or chronic renal insufficiency
3) Adults with GH deficiency
4) Illicit use (athletes, “anti-aging”)

232
Q

Somatropin (GH analog)

Side effects (5)

A

1) Generally safe in children
2) Insulin resistance, glucose intolerance
3) Increased risk for idiopathic intracranial hypertension
4) Rarely pancreatitis, Gynecomastia, Nevus growth
5) Misuse in athletes → acromegaly, arthropathy, visceromegaly, extremity enlargement

233
Q

Treatment of GH and Prolactin Hypersecretion (3)

A

1) Octreotide (Somatostatin)
2) Bromocriptine (DA agonist, D2/D1)
3) Cabergoline (DA agonist, D2)

234
Q

Octreotide (Somatostatin)

mechanism (3 main actions)

A

1) Inhibit GH release via Gi → decrease cAMP, activate K+ channels
2) Decrease GI motility, decrease gastric enzyme secretion
3) Decrease insulin/glucagon release

235
Q

Octreotide (Somatostatin)

uses (2)

A

1) Pituitary excess of growth hormone (Acromegaly, gigantism)
2) Control bleeding from esophageal varices and GI hemorrhage

**More effective than DA to treat GH excess

236
Q

Octreotide (Somatostatin)

Side effects (3)

A

1) Hyperglycemia
2) Abdominal cramps, loose stools
3) Cardiac effects (sinus bradycardia, conduction disturbances)

237
Q

Bromocriptine

Mechanism

A

inhibits anterior pituitary secretion of growth hormone

Mechanism: dopamine agonist

  • Not as effective as SST analog for GH suppression
  • DA inhibits prolactin secretion via D2 receptors, but works on D1 receptors also
238
Q

Bromocriptine

Uses

A

Hyperprolactinemia (pituitary adenoma) → DA decreases secretion of PRL and reduces tumor size

239
Q

Bromocriptine

Side effects

A

nausea, vomiting, headache, postural hypotension, psychosis, insomnia

Mostly due to D1 actions also

240
Q

Cabergoline

mechanism and use

A

preferred agent for hyperprolactinemia

Dopamine agonist, more selective for D2 receptors

241
Q

Cabergoline

side effects

A

better tolerated than Bromocriptine, may cause hypotension and dizziness

242
Q

Desmopressin

use and mechanism?

A

ADH analog, more stable to degradation

Use: central DI

243
Q

Desmopressin

Side effects

A

nasal irritation (intranasal application), GI sx, asthenia, mild liver enzyme elevations, headache, nausea, abdominal cramps, allergic reaction, water intoxication

244
Q

Vasopressin (ADH) is released from _________ of the hypothalamus

Its main stimulus for release is ___________, but can also be released in response to __________

ADH release is inhibited by _________

A

Released from supraoptic nuclei of hypothalamus

Main stimulus is rising blood OSMOLALITY

Also released in response to decrease in circulating blood volume

Release inhibited by alcohol

245
Q

Vasopressin actions at V2 receptor

A 
Renal actions (Gs)
-Increase rate of insertion of aquaporins into luminal membrane of collecting duct → increase water permeability → antidiuretic effect

NON-RENAL actions = release of coagulation factor 8 and vWF

246
Q

Vasopressin actions at V1 receptor

A

V1 Receptors: (Gq) → vasoconstriction of vascular smooth muscle

247
Q

Central DI

what is it?
what causes it?

A

inadequate ADH secretion from posterior pituitary

Due to head injury, pituitary tumors, cerebral aneurysm, ischemia

248
Q

Best 2 drugs used to treat central DI

A

Desmopressin, Chlorpropamide

249
Q

Nephrogenic DI

what is it?
what causes it (2 drugs + 1 other)

A

inadequate ADH actions

Causes:

1) Congenital - receptor/aquaporin mutations
2) Drug induced - Lithium (V2 stimulation of AC), Demeclocycline (tetracycline abx)

250
Q

Treatment of Nephrogenic DI (3)

A

Low salt, low protein diet
Thiazide diuretics
NSAIDs

251
Q

SIADH

what is it?
what drugs can cause it? (4)

A

incomplete suppression of ADH secretion under hypoosmolar conditions

Drug causes:

1) Psychotropic agents (SSRIs, haloperidol, TCAs)
2) Sulfonylureas (Chlorpropamide)
3) Vinca alkaloids (chemo)
4) MDMA

252
Q

SIADH treatment (3)

A

1) Water restriction
2) Demeclocycline: inhibit ADH effect on distal tubule
3) V2 receptor antagonist: Tolvaptan, Conivaptan

253
Q

Tolvaptan

A

V2 receptor antagonist

oral, can cause hepatotoxicity

254
Q

Conivaptan

A

V2 receptor antagonist

IV, given in hospital

255
Q

Steroid hormone biosynthesis:

How is cholesterol made available for steroid synthesis?

Cholesterol –> __________

via what enzyme?
occurs where in the adrenal gland? where in the cell?

A

1) Cholesterol released from lipid droplets by removal of esters
LDL endocytosed into cell → esterified and stored in lipid droplets
-Cholesterol can also be synthesized from acetyl CoA

2) In MITOCHONDRIA or ER → rate limiting step
Cytochrome P450 enzymes or 20, 22 desmolase → Pregnenolone

Occurs throughout the cortex

256
Q

21-hydroxylase:

converts ________ and __________ to ________ and __________

A

converts 17-hydroxyprogesterone and progesterone → precursors of cortisol/aldosterone (11-deoxycortisol, 11-deoxycorticosterone)

257
Q

21-hydroxylase deficiency

aldo, cortisol, sex steroid levels?

A

decreased aldosterone
decreased cortisol
increased sex steroids

258
Q

11-hydroxylase

converts ________ and _______ to ________ and ___________

A

11-Deoxycortison and 11-deoxycortisol to corticosterone and cortisol respectively

259
Q

11-hydroxylase deficiency

aldo, cortisol, sex steroid levels?

A

some aldosterone still made –> decrease Na+ wasting –> HTN

Decreased cortisol
Increased sex steroids

260
Q

17-hydroxylase

converts ________ and _______ to ________ and ___________

A

converts prenenolone and progesterone to 17-OH pregnenolone and 17-OH progesterone respectively

261
Q

Transport of Glucocorticoids (cortisol) in Plasma

A

10% circulates in free form (regulated form)

90% bound to proteins → 75% bound to cortisol binding globulin (CBG), 15% bound to albumin

262
Q

Benefits of cortisol being bound to proteins in blood (CBG and albumin)

A 
Increases plasma concentration of hormone
Prevents excretion by kidney
Prolongs half-life
Reservoir of extra hormone
NOT biologically active
263
Q

Free cortisol actions

A

regulated form

Binds cortisol receptor in cytosol

HSP-90 (heat shock protein) holds cortisol receptor in cytosol, and dissociates from receptor after cortisol binds receptor

Allows cortisol-receptor complex to travel into nucleus

264
Q

Actions of cortisol (11)

A

1) Stimulate gluconeogenesis in liver 2) Increase proteolysis in muscle
3) Muscle weakness
4) Thinning of skin, increased capillary fragility (easy bruising)
5) Interfere with Ca2+absorption/bone formation → osteoporosis, bone fx
6) Adipose tissue deposition on trunk, abdomen, and face, and fat mobilization from extremities
7) Increase water excretion (inhibit ADH function)
8) Increase gastric acid secretion
9) Paracrine effect on adrenal medulla → stimulate synthesis and activity of phenyl-N-methyl transferase (PNMT) → increase epi/NE production
10) Anti-inflammatory and immunosuppressant effects
11) Cushing’s disease

265
Q

Regulation of ACTH production and release

3 levels of control

A

1) Hypothalamus, CRH → anterior pituitary, ACTH
- Ca2+-dependent ACTH release via AC activation
- POMC (proopiomelanocortin) gene transcription activated

2) ACTH → zona fasciculata and reticularis, cortisol
3) Cortisol → feedback onto hypothalamus and pituitary to inhibit CRH and ACTH

266
Q

Actions of ACTH

A

ACTH increases cAMP levels in adrenal cortex

→ increase rate of synthesis of pregnenolone, LDL uptake, and transport of cholesterol into mitochondria

267
Q

Mineralocorticoids (aldosterone)

A

Secretion regulated by RAAS - angiotensin II = major stimulus for aldo secretion

Aldo secretion increased in response to high plasma K+

Actions: stimulate Na+ absorption, K+/H+ excretion to maintain or increase blood volume

268
Q

Catecholamine synthesis:

occurs in ________ cells of adrenal __________

A

chromaffin cells

adrenal medulla

269
Q

Catecholamine synthesis

1) ________ converts tyrosine –> __________
2) DA –> taken up into secretory granules via _______ –> DA converted into ________ in vesicle by __________
3) NE transported out of vesicle and converted into _________ by ____________
4) Epinephrine pumped back into vesicle

A

1) Tyrosine hydroxylase converts tyrosine → L-DOPA
2) Dopamine → taken up into secretory granules via VMAT1 (vesicular monoamine transporter) → DA converted to NE in vesicle by dopamine B-hydroxylase
3) NE transported out of vesicle and converted into epinephrine by PNMT (phenylethanolamine N-methyltransferase)
4) epinephrine pumped back into vesicle

270
Q

Mechanism of epinephrine release

A

Final common pathway of activation is greater splanchnic nerve ACh release onto chromaffin cells

1) ACh binds nicotinic ACh receptors (nAChRs) on chromaffin cells → depolarization → Ca2+ increase in cell

2) ACh binds muscarinic ACh-R → Gq → IP3 → Ca2+ release
- Takes longer, lasts longer

271
Q

Body’s Integrated Response to Stress

2 regions of activated - each have what effects?

A

1) Stressor activate CRH, ADH, NE neurons in HYPOTHALAMUS
- CRH → activate ACTH-cortisol axis
- Stimulation of splanchnic nerve → release epinephrine from adrenal medulla

2) LOCUS COERULEUS → releases NE
→ arousal

272
Q

Adrenergic recptors: a1 and a2

mechanism

preferentially activated by what?

A

activated preferentially by NE**

A2 → G1 → inhibit cAMP production

A1 → Gq → PLC → increase Ca2+ and PKC

273
Q

B-adrenergic receptors: B1 and B2, B3

mechanism

preferentially activated by what?

A

B1, B2, B3 → Gs → AC → cAMP

Activated preferentially by epinephrine

DEMS (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions