Module 7 Flashcards
Adrenal Medulla: Embryology
- Neural crest → neuroblasts → autonomic postganglionic neurons, adrenal medulla, spinal ganglia
- Consists of chromaffin cells (pheochromocytes) = neuroectodermal derivatives and functional analogues of postganglionic fibers (ANS)
- Early fetal life: secretes norepinephrine (NE)
Morphology
- Grossly, reddish-brown
- Enlarged, specialized sympathetic ganglion
- Neuroendocrine transducer (neural signal stimulates hormonal secretion)
- The ONLY autonomic neuroeffector organ w/o a 2-neuron motor innervation
- Innervated by long sympathetic preganglionic, cholinergic neurons forming synaptic connections with chromaffin cells
- Small clumps of chromaffin cells found extra-adrenally and retroperitoneal(aortic and sympathetic ganglia
Adrenal Medulla
Adrenal Medulla: Histology
- 2 adrenomedullary chromaffin cells: 1) NE-secreting 2) Epinephrine (Epi)- secreting
- The hormones are stored in chromaffin granules (osmiophilic, electron-dense, membrane-bound secretory vesicles)
- 80-90% of chromaffin granules synthesize Epi and 10-20% secrete NE
Adrenal Medulla: Histology 2
- Contains dopamine, proteins, lipid, ATP
- Has dopamine β hydroxylase
- Has soluble acidic proteins called chromagranins
- Chromaffin granules are exocytosed in fenestrated capillaries
Adrenal Medulla: Innervation
- Preganglionic sympathetic fibers through the splanchnic nerve
- Myelinated(type B) secretomotor fibers coming from lower thoracic segments (T5 and T9) of the ipsilateral intermediolateral gray column of the spinal cord
- Chromaffin cells are functional analogues of postganglionic fibers; DO NOT HAVE AXONS
Adrenal Medulla: Vascular Supply
- Branches of renal and phrenic arteries reach the outer capsule
- 2 ways the adrenal gland is perfused: 1) portal circulation 2) direct arterial supply via medullary artery traversing the adrenal cortex
- Blood from the capillary plexus on outer adrenal capsule drain into venous sinuses and supply the adrenal medulla
- Single central adrenal vein along the longitudinal axis of the gland
Effector organ: Most vascular smooth muscle, pupils
Relative Affinities: NE>Epi
Signal Transduction Mechanism: activates IP3
Effect on effector organ: Excitatory
Alpha 1
Effector organ: CNS, Platelets, adrenergic nerve terminals (autoreceptors), some vascular smooth muscle, adipose tissue
Relative Affinities: NE>Epi
Signal Transduction Mechanism: inhibits CAMP
Effect on effector organ: Excitatory
Alpha 2
Effector organ: CNS, cardiac muscle, kidney
Relative Affinities: NE = Epi
Signal Transduction Mechanism: activates cAMP
Effect on effector organ: Excitatory
Beta 1
Effector organ: Some blood vessels, respiratory tract, uterus
Relative Affinities: Epi»NE
Signal Transduction Mechanism: activates cAMP
Effect on effector organ: Inhibitory
Beta 2
Effector organ: Adipose tissue
Relative Affinities: NE=Epi
Signal Transduction Mechanism: activates cAMP
Effect on effector organ: Excitatory
Beta 3
Epidemiology: Adults; both sexes; all ages, especially 30-50 years
Biologic behavior: 90% benign, 10% malignant
Secretion: High levels of catecholamines, most secrete norepinephrine
Clinical presentation: Sustained or episodic hypertension, sweating, palpitations, hyperglycemia, glycosuria
- Occasionally asymptomatic (found incidentally on CT scan or MRI)
Macroscopic features: Mass, often hemorrhagic, 10% bilateral, 9-23% extra adrenal
Microscopic features: Nests of large cells, vascular stroma
Pheochromocytoma
Three amines that are synthesized from tyrosine in the chromaffin cells of the adrenal medulla.
dopamine, norepinephrine, and epinephrine
The major product of the adrenal medulla is __.
epinephrine
The conversion of tyrosine to epinephrine requires four
sequential steps:
(1) ring hydroxylation;
(2) decarboxylation;
(3) side-chain hydroxylation to form norepinephrine; and
(4) N-methylation to form epinephrine.
__ is the immediate precursor of catecholamines
Tyrosine
- is the rate-limiting enzyme in catecholamine biosynthesis
- is found in both soluble and particle-bound forms only in tissues that synthesize catecholamines
- it functions as an oxidoreductase, with tetrahydropteridine as a cofactor, to convert l-tyrosine to
l-dihydroxyphenylalanine (l-dopa).
tyrosine hydroxylase
- is a monooxygenase and uses ascorbate as an electron
donor, copper at the active site, and fumarate as modulator. - is in the particulate fraction of the medullary cells, probably in the secretion granule; thus, the conversion of dopamine to norepinephrine occurs in this organelle.
Dopamine a-Hydroxylase (DBH)
- catalyzes the N-methylation of norepinephrine to form epinephrine in the epinephrine-forming cells of the adrenal medulla.
- Since __ is soluble, it is assumed that norepinephrine-
to-epinephrine conversion occurs in the cytoplasm. - synthesis is induced by glucocorticoid hormones that reach the medulla via the intra-adrenal portal system.
Phenylethanolamine-N-Methyltransferase (PNMT)
(Anatomy)
- Firm, reddish brown, smooth
- 2 lateral lobes and connecting central isthmus
- 30-40 g
- Adherent fibrous capsule
- Highly vascular: one of the highest blood flow rates per gram tissue
Thyroid Gland
Thyroid Gland: Histology
- Follicle (acinus) = functional unit surrounded by a rich capillary plexus
- Single, cuboidal epithelium
- TSH has an effect on the cell height of the follicular cells
- Columnar: active; - flat: inactive
- Follicles depleted of colloid when stimulated
- Lumen contains colloid: clear amber, proteinaceous fluid
- Microvilli extending into the colloid from the lumen
- Parafollicular cells ( C cells): secrete calcitonin
Thyroid Gland: Thyroid hormones
- Iodothyronines
- Phenol derivative
- Thyroxine (T4) and T3: biologically active
- Molar activity (T3 /T4) 10: 1
- Secretory ratio (T4 /T3) 10-20:1
- Plasma concentration ratio ( free T4 /T3) 2:1
- Storage ratio to thyroglobulin ( T4 /T3) 10:1
- rT3 : biologically inactive formed by peripheral conversion by 5-deiodinas
Thyrocytes
- 3 functions: 1) synthesize thyroglobulin 2) collect and transport iodine to colloid 3) release thyroid hormones from the thyroglobulin
- Rests on a basal lamina
- Microvilli found adluminal (near apical area)
Thyroid Gland
- Thyroglobulin: 660,000 Da glycoprotein
- Site of T4 and T3 synthesis and storage
- Each contains 134-140 tyrosyl residues
- 25-30 are iodinated
- 6-8 form iodothyronines
Thyroid Gland