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SM_180b: Adrenal Medulla Flashcards

1
Q

Adrenal gland is composed of ____ and ____

A

Adrenal gland is composed of medulla and cortex

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2
Q

Adrenal cortex is derived from the ____ and secretes ____ hormones

A

Adrenal cortex is derived from the mesoderm and secretes steroid hormones

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3
Q

Adrenal medulla is derived from ____ and secretes ____

A

Adrenal medulla is derived from ectodermal chromaffin tissue and secretes catecholamines

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4
Q

Describe the development of the adrenal medulla

A

Adrenal gland medulla

  • 7 week gestation: chromaffin cells from the celiac plexus collect on the medial side of the primordial cortex and migrate inward
  • 4 months gestation: chromaffin tissue occupies a central position in a gland
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5
Q

Describe histology of the adrenal gland

A

Adrenal gland

  • Capsule
  • Zone glomerulosa
  • Zona fasciculata
  • Zona reticularis
  • Adrenal medulla
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6
Q

Adrenal medulla functions like a ____ but releases ____ into the ____

A

Adrenal medulla functions like a postganglionic sympathetic neuron but releases epinephrine into the blood stream

(receptors and effector cells located throughout body)

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7
Q

Adrenal medulla is part of the ____ system and derived from the ____

A

Adrenal medulla is part of the sympathetic nervous system and derived from the neuroectoderm (neural crest) cells that migrate from the vertebral column to the periaortic region

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8
Q

Paraganglia are ____

A

Paraganglia are sympathetic preganglionic nerve fibers that terminate in paravertebral and prevertebral nerve ganglia

  • Chromaffin cells aggregated in close approximation to autonomic ganglia and plexuses
  • (Postganglionic nerve fibers secrete norepinephrine)
  • Develop at 2 months of gestation
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9
Q

Paraganglia contain ____ cells similar to ____ cells

A

Paraganglia contain neuroendocrine cells similar to adrenal medullary cells

(catecholamines present)

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10
Q

Describe locations of the paraganglia

A

Paraganglia locations

  • Mediastinum
  • Abdomen: along sympathetic nerve chains in paravertebral and prevertebral positions
  • Around the celiac axis
  • Renal medullae
  • Aortic bifurcation (organ of Zuckerandl)
  • Adjacent to bladder
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11
Q

Pheochromocytes are ____

A

Pheochromocytes are axonless neurons producting catecholamines

  • Respond to synaptic activation by releasing preformed catecholamines: epinephrine (80%), norepinephrine (20%)
  • Regulated by sympathetic cholinergic fibers acting on nicotinic receptors
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12
Q

____ and ____ are common chromaffin cell tumors

A

Pheochromocytomas and paragangliomas are common chromaffin cell tumors

(pheochromocytomas are most common)

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13
Q

Chromogranins are ____ that can serve as ____

A

Chromogranins are chromaffin cell proteins that can serve as clinical markers (Chromogranin A)

  • Found in adrenal medulla or ganglia tumors (pheochromocytomas, paragangliomas)
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14
Q

Circulating catecholamines are metabolized in ____ and ____

A

Circulating catecholamines are metabolized in neuronal tissues and liver

  • Metabolites are excreted in the urine: 24 h urine metanephrines (catecholamine metabolites) are very valuable diagnostic tool
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15
Q

Describe catecholamine metabolite synthesis

A

Catecholamine metabolite synthesis

  • MAO degrades epinephrine and norepinephrine
  • COMT converts dihydroxymandelic acid to vanillylmandelic acid
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16
Q

Adrenal medulla secretes ____ and ____

A

Adrenal medulla secretes epinephrine and norepinephrine

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17
Q

Alpha receptors mediate ____ in vasculature and ____ in endocrine pancreas

A

Alpha receptors mediate constriction (arteries and veins) in vasculature and inhibition of secretion in endocrine pancreas

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18
Q

Beta receptors mediate ____ in vasculature and ____ in endocrine pancreas

A

Beta receptors mediate dilatation (arteries) in vasculature and stimulation of secretion in endocrine pancreas

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19
Q

Catecholamines (epinephrine and norepinephrine) are responsible for ____, ____, and ____

A

Catecholamines (epinephrine and norepinephrine) are responsible for fright, flight, and flight

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20
Q

Tumors in the adrenal medulla are ____

A

Tumors in the adrenal medulla are pheochromocytomas

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21
Q

Tumors from extra-adrenal sympathetic and parasympathetic ganglia are ____

A

Tumors from extra-adrenal sympathetic and parasympathetic ganglia are paragangliomas

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22
Q

Patients with disease-causing germline mutations are likely to have ____

A

Patients with disease-causing germline mutations are likely to have pheochromocytomas or paragangliomas

23
Q

Pheochromocytomas are tumors arising from ____ cells producing one or more ____

A

Pheochromocytomas are tumors arising from adrenomedullary chromaffin cells producing one or more catecholamines

(epinephrine, norepinephrine, and dopamine)

24
Q

Adrenal masses are most commonly ____

A

Adrenal masses are most commonly non-functioning adenomas

25
Multiple endocrine neoplasia is ____ with ____ inheritance
Multiple endocrine neoplasia (MEN) is familial endocrine neoplasms with autosomal dominant inheritance * Due to gene mutations affecting the germline * Tumors are often bilateral or multifocal * Hyperplasia may occur in conjunction with neoplasia
26
MEN 2A involves \_\_\_\_, \_\_\_\_, and \_\_\_\_
MEN 2A involves medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism
27
MEN 2B involves \_\_\_\_, \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_
MEN 2B involves medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, GI tract ganglioneuromatosis, and marfanoid habitus
28
Thin face, big lips, and nodules on the tongue are indicative of \_\_\_\_
Thin face, big lips, and nodules on the tongue are indicative of MEN 2B
29
MEN 2 involves activation of \_\_\_\_
MEN 2 involves activation of RET proto-oncogene * RET: cell surface tyrosine kinase receptor * RET germline poitn mutations are found in the majority of MEN 2A and 2B patients * Mutations are few and clustered * Genotype-phenotype correlation
30
RET is a \_\_\_\_
RET is a cell surface tyrosine kinase receptor
31
Von Hippel Lindau Disease involves \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_
Von Hippel Lindau Disease involves retinal angiomas, CNS hemangioblastomas, renal cysts / carcinomas, pancreatic cysts, pheochromocytomas * VZHL gene on chromosome 3 (3 exons, 284 codons)
32
Pheochromocytoma in Von Hippel Lindau disease involves ___ mutations in the ___ gene
Pheochromocytoma in Von Hippel Lindau disease involves missense mutations in the VHL tumor suppressor gene * Chromosome 3p25-26 * Encodes a protein regulating hypoxia-induced protein * Specific mutations associated with particular patterns of tumor formation
33
Neurofibromatosis-1 is an ____ disorder characterized by \_\_\_\_, \_\_\_\_, \_\_\_\_, and \_\_\_\_
Neurofibromatosis-1 is an autosomal dominant disorder characterized by neurofibromas, cafe au lait spots, axillary and inguinal freckling, and iris hamartomas (Lish nodules)
34
Some people with NF-1 develop \_\_\_\_
Some people with NF-1 develop catecholamine-secreting tumors * Solitary benign adrenal pheochromocytoma * Bilateral adrenal pheochromocytoma * Peri-adrenal abdominal paraganglioma
35
Paragangliomas are characterized as ____ or ____ depending on the type of paraganglia of origin
Paragangliomas are characterized as sympathetic or parasympathetic depending on the type of paraganglia of origin * Sympathetic: arise from chromaffin cells of paraganglia along sympathetic chains in the chest, abdomen, or pelvis * Parasympathetic: arise from glomera along parasympathetic nerves in the head / neck / upper mediastinum
36
Parasympathetic paragangliomas are usually ____ and produce \_\_\_\_
Parasympathetic paragangliomas are usually non-functional and produce no or low levels of catecholamines
37
Paragangliomas usually present as \_\_\_\_
Paragangliomas usually present as slow-growing painless cellular masses * Many patients are asymptomatic * Tumor space occupation may cause pain, hearing disturbances, hoarseness, and dysphagia
38
Familial paragangliomas are ____ disorders with location most commonly in the \_\_\_\_
Familial paragangliomas are autosomal dominant disorders with location most commonly in the abdomen (second most common location in head / neck)
39
Familial paragangliomas result from genetic mutations in the ____ genes
Familial paragangliomas result from genetic mutations in the SDH succinate dehydrogenase subunit genes (SDHB, SDHC, SDHD)
40
Succinate dehydrogenase is a component of the ____ that \_\_\_\_
Succinate dehydrogenase is a component of the mitochondrial ETC complex II that catalyzes oxidation of succinate to fumarate in the Krebs cycle
41
Subunits SDHA and SDHB constitute the ____ of succinate dehydrogenase, while subunits SDHC and SDHD \_\_\_\_
Subunits SDHA and SDHB constitute the catalytic core of succinate dehydrogenase, while subunits SDHC and SDHD anchor the complex to the matrix face of the mitochondrial inner membrane
42
Defects in SDHA cause \_\_\_
Defects in SDHA cause neurodegenerative disorders
43
Mutations in SDHB, SDHC, and SDHD predispose to \_\_\_\_
Mutations in SDHB, SDHC, and SDHD predispose to familial paraganglioma syndromes (PGLI 1, 2, 3, 4)
44
SDHB mutation carriers develop paraganglioma \_\_\_
SDHB mutation carriers develop paraganglioma early * More likely to develop malignant paragangliomas and additional neoplasms (e.g. renal cell carcinoma)
45
Patients with sporadic pheochromocytomas / paragangliomas present at a ___ age
Patients with sporadic pheochromocytomas / paragangliomas present at a later age
46
Headache, palpitations, diaphoresis, HTN, and abdominal pain indicate \_\_\_\_
Headache, palpitations, diaphoresis, HTN, and abdominal pain indicate pheochromocytomas / paragangliomas
47
\_\_\_\_, \_\_\_\_, \_\_\_\_, and ____ increase catecholamine levels
Pheochromocytomas, caffeine, marijuana, and nicotine increase catecholamine levels
48
Paragangliomas are commonly associated with \_\_\_\_
Paragangliomas are commonly associated with syndromes (such as due to SDHB mutations)
49
These are \_\_\_\_
These are pheochromocytomas
50
Pheochromocytomas is treated with ___ after \_\_\_
Pheochromocytomas is treated with surgical resection after preparation with alpha and beta blockade to control HTN and expand volume
51
\_\_\_\_ and ____ blockade is utilized to control BP and prevent intraoperative hypertensive crisis in patients with pheochromocytoma
Combined alpha and blockade is utilized to control BP and prevent intraoperative hypertensive crisis in patients with pheochromocytoma
52
\_\_\_\_ is given first in pharmacological preparation of pheochromocytoma
Phenoxybenzamine (alpha adrenergic blockade) is given first in pharmacological preparation of pheochromocytoma * NEVER start beta adrenergic blockers before alpha blockers b/c can further elevate BP
53
High Na+ diet is used in preparation of pheochromocytoma for surgery by ____ and \_\_\_\_
High Na+ diet is used in preparation of pheochromocytoma for surgery by counteracting catecholamine induced volume contraction and orthostasis associated with alpha blockade (\> 5 g Na/day)

Endo (25 decks)

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