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Endocrine Rachel Boggus Boggusrl@email.uc.edu
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10/19/2015Template copyright 2005 www.brainybetty.com2 Endocrine Secretion What is it? What is a feature common to endocrine tissues? Where are endocrine cells found?
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10/19/2015Template copyright 2005 www.brainybetty.com3 Endocrine Secretion What is it? Secretion of chemical messengers (hormones) directly into the blood stream to act on distant tissues What is a feature common to endocrine tissues? Usually highly vascular to facilitate rapid dissemination of secretory products Where are endocrine cells found? Dispersed as single cells in epithelial tissues (gut and respiratory tract) As discrete clusters in another organ (pancreas, ovary, testis) Gathered in one specialized organ (pituitary, thyroid, parathyroid, adrenal, pineal glands)
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10/19/2015Template copyright 2005 www.brainybetty.com4 The Pituitary gland What is the other name for it? What are the two parts of it? Where are each of the parts derived? What does each part consist of?
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10/19/2015Template copyright 2005 www.brainybetty.com5 The Pituitary gland What is the other name for it? hypophysis What are the two parts of it? Adenohypophysis and neurohypophysis Where are each of the parts derived? Adeno—from oral ectoderm, neuro—from neural ectoderm What does each part consist of? Adeno—pars distalis, pars tuberalis, and pars intermedia Neuro—pars nervosa and infundibulum
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10/19/2015Template copyright 2005 www.brainybetty.com6 Adenohypophysis What are the cell types in the adenohypophysis? How are the major cell types classified?
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10/19/2015Template copyright 2005 www.brainybetty.com7 Adenohypophysis What are the cell types in the adenohypophysis? Acidophils and Basophils, Chromophobes, Folliculostellate cells How are the major cell types classified? Based on affinity of dyes for granules
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10/19/2015Template copyright 2005 www.brainybetty.com8 Acidophils Stain pink in H&E, PAS What are the two types of acidophils and their products?
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10/19/2015Template copyright 2005 www.brainybetty.com9 Acidophils Stain pink in H&E, PAS What are the two types of acidophils and their products? (remember the Ms) Somatotrophs—growth hormone— stimulate growth, RNA and protein synthesis, synthesis of somatomedins stimulate growth of long bones Mammotrophs—Prolactin—stimulates milk synthesis from the nips
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10/19/2015Template copyright 2005 www.brainybetty.com10 Basophils Stain poorly with H&E, PAS What are the cell types and their products
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10/19/2015Template copyright 2005 www.brainybetty.com11 Basophils Stain poorly with H&E, PAS What are the cell types and their products Thyrotrophs—thyroid stimulating hormone—stims thyroid hormone syn & secretion Gonadotrophs—Follicle stimulating hormone— promotes ovarian follicle development and estrogen secretion in females and spermatogenesis in males, Lutenizing Hormone—stims ovarian follicle maturation and progesterone secretion in females, stimulates leydig cells to secrete androgens in males Corticotrophs (POMC)—Post trans processing of POMC Adrenocorticotropic hormone (ACTH) Lipotropic Hormone, Melanocyte stimulating hormone, B-endorphin
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10/19/2015Template copyright 2005 www.brainybetty.com12 Chromophobes & Folliculostellate Cells Chromophobes—few or no granules, no affinity for stain –What are they? Folliculostellate cells—supportive cells –What do they look like?
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10/19/2015Template copyright 2005 www.brainybetty.com13 Chromophobes & Folliculostellate Cells Chromophobes—few or now granules, no affinity for stain –What are they? –Degranulated secretory cells, undifferentiated secretory cells Folliculostellate cells—supportive cells –What do they look like? –Appear stellate and extend branching processes among secretory cells, and are GFAP +
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10/19/2015Template copyright 2005 www.brainybetty.com14 Pituitary – note vascularity of distalis
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10/19/2015Template copyright 2005 www.brainybetty.com16 Pars intermedia What does it develop from? What does it contain? Note that fluid can accumulate giving rise to a cyst
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10/19/2015Template copyright 2005 www.brainybetty.com17 Pars intermedia What does it develop from? The dorsal portion of Rathke’s pouch What does it contain? Mostly basophils and a few chromophobes Note that fluid can accumulate giving rise to a cyst
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10/19/2015Template copyright 2005 www.brainybetty.com18 Pituitary Vascular Supply YOU MUST KNOW THIS! It shows you just how much control the hypothalamus has on adenohypophyseal (i.e. pituitary) secretion
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10/19/2015Template copyright 2005 www.brainybetty.com20 Pituitary vascular supply (cont) Superior hypophyseal arteries primary capillary plexus irrigating median eminance and the stalk Small veins (portal) from primary plexus form secondary capillary plexus in adenohypophysis Why is the portal system important?
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10/19/2015Template copyright 2005 www.brainybetty.com21 Pituitary vascular supply (cont) Why is the portal system important? For the delivery of concentrated releasing and inhibiting hormones from median eminance (where 1 st cap. Plexus is) to adenohypophysis (where 2 nd cap plexus is)
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10/19/2015Template copyright 2005 www.brainybetty.com22 Inferior hypophyseal arteries provide blood to neurohypophysis and the stalk THERE IS NO DIRECT ARTERIAL SUPPLY TO THE ADENOHYPOPHYSIS – this will be on your test!!!
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10/19/2015Template copyright 2005 www.brainybetty.com23 Neurohypophysis What does it consist of?
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10/19/2015Template copyright 2005 www.brainybetty.com24 Neurohypophysis What does it consist of? Unmyelinated axons of supraoptic and paraventricular neurons from hypothalamus Neurosecretory material (herring bodies) Pituicytes (highly branched glial [i.e. supportive] cells) Rich capillary plexus
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10/19/2015Template copyright 2005 www.brainybetty.com25 Products of Neurohypophysis ***** NOTHING!!!!****** –This will be on your test too! How is that possible?
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10/19/2015Template copyright 2005 www.brainybetty.com26 Products of Neurohypophysis ***** NOTHING!!!!******* How is that possible? Vasopressin (ADH) and oxytocin are only STORED in the neurohypophysis but are MADE in the hypothalamus! What do these two hormones do? ADH—stims reabsorption of water Oxytocin stimulates milk let down
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10/19/2015Template copyright 2005 www.brainybetty.com27 Neurohypophysis
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10/19/2015Template copyright 2005 www.brainybetty.com28 The Thyroid gland What does it produce? What do these hormones do?
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10/19/2015Template copyright 2005 www.brainybetty.com29 The Thyroid gland What does it produce? Thyroid hormones T3 and T4 What do these hormones do? Regulate mitochondrial respiration, I.e regulate basal metabolic rate
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10/19/2015Template copyright 2005 www.brainybetty.com30 Structure Slips from thin fibroelastic capsule divide it into lobules Lobules consist of follicles –What do follicles consist of?
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10/19/2015Template copyright 2005 www.brainybetty.com31 Structure Slips from thin fibroelastic capsule divide it into lobules Lobules consist of follicles –What do follicles consist of? –Simple cuboidal epithelial cells called principal cells that secrete thyroglobulin into center –Thyroglobulin is stored as colloid EXTRACELLULARY –This will be on your test too!!!!!!
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10/19/2015Template copyright 2005 www.brainybetty.com32 THYROID
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10/19/2015Template copyright 2005 www.brainybetty.com34 Principle cells What are their features?
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10/19/2015Template copyright 2005 www.brainybetty.com35 Principle cells What are their features? Rest on basal lamina, apices point to center of follicle Typical apical junctional complexes (what are the three components?), short microvilli, well-developed supranuclear golgi, numerous RER, abundant lysosomes, mitochondria, and multivesicular bodies
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10/19/2015Template copyright 2005 www.brainybetty.com36 Thyroid Hormone Synthesis Where is thyroglobulin synthesized? Modified? Released? How is iodide taken up? What happens to it once it is in the cell? What happens once it leaves the cell? What happens upon TSH stimulation?
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10/19/2015Template copyright 2005 www.brainybetty.com37 Thyroid Hormone Synthesis Where is thyroglobulin synthesized? Modified? Released? RER. RER and Golgi (carbs added). apical surface via vesicles How is iodide taken up? Iodide pump at basal membrane What happens once it leaves the cell? Covalently bound to tyrosyl residues of thyroglobulin at apical memb by thyroid peroxidase What happens upon TSH stimulation? Principal cell takes up colloid via pinocytosis and releases iodinated tyrosines via lysosomal- derived protease activity
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10/19/2015Template copyright 2005 www.brainybetty.com38 Parafollicular cells Where are they? What are they?
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10/19/2015Template copyright 2005 www.brainybetty.com39 Parafollicular cells Where are they? Within follicular epithelium scattered in CT among follicles What are they? Produce calcitonin—lowers blood calcium levels; calcitonin keeps the Ca in (the bones, that is) Lots of RER and large Golgi
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10/19/2015Template copyright 2005 www.brainybetty.com40 Parathyroid Gland What do they look like microscopically? What are the two cell types?
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10/19/2015Template copyright 2005 www.brainybetty.com41 Parathyroid Gland What do they look like microscopically? Septa from capsule separate gland into lobules of dense anastomosing cords of cells What are the two cell types? Chief and oxyphil
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10/19/2015Template copyright 2005 www.brainybetty.com42 Chief Cells What do they secrete? What does it do? What do they look like in LM and EM?
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10/19/2015Template copyright 2005 www.brainybetty.com43 Chief Cells What do they secrete? What does it do? Parathyroid Hormone, increases blood calcium concentration What do they look like in LM and EM? LM—sm, centrally located nuclei in pale cytoplasm EM—mod. RER and Golgi, lots of glycogen, sm. Dense granules
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10/19/2015Template copyright 2005 www.brainybetty.com44 Oxyphil What do they do? What do they look like?
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10/19/2015Template copyright 2005 www.brainybetty.com45 Oxyphil What do they do? Not sure but they contain PTH What do they look like? Larger than chief cells but nuclei smaller and more heterochromatin (what does that mean) Very eosinophilic cytoplasm (MITOCHODRIA), small RER, golgi and few granules
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10/19/2015Template copyright 2005 www.brainybetty.com47 The Adrenal Gland What is the cortex derived from? What is the medulla derived from?
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10/19/2015Template copyright 2005 www.brainybetty.com48 The Adrenal Gland What is the cortex derived from? Intermediate mesoderm What is the medulla derived from? Neural crest
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10/19/2015Template copyright 2005 www.brainybetty.com49 Cortex What are the three zones of the cortex? What do the cells do? What are the features of the cells?
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10/19/2015Template copyright 2005 www.brainybetty.com50 Cortex What are the three zones of the cortex? Zona glomerulosa, zona fasciculata, zona reticularis What do the cells do? Synthesize and secrete (but DON’T store) steroid hormones What are the features of the cells? Numerous lipid droplets, abundant smooth ER and mitochondria with TUBULAR CRISTAE
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10/19/2015Template copyright 2005 www.brainybetty.com51 Zona Fasciculata & Reticularis (75% of cortex) What do they secrete? What do they do? What is secretion regulated by?
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10/19/2015Template copyright 2005 www.brainybetty.com52 Zona Fasciculata & Reticularis (75% of cortex) What do they secrete? Glucocorticoids cortisol and corticosterone What do they do? Promote natural metabolism, esp. carb metabolism. Also provide resistance to stress and supress inflammatory response What is secretion regulated by? ACTH – from POMC REMEMBER????
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10/19/2015Template copyright 2005 www.brainybetty.com53 Zona Glomerulosa What does it secrete? What is the function? What is secretion regulated by?
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10/19/2015Template copyright 2005 www.brainybetty.com54 Zona Glomerulosa What does it secrete? Mineralocorticoids (aldosterone) What is the function? Maintaining normal mineral balance and body fluid volume What is secretion regulated by? Renin-angiotensin system and plasma levels of sodium and potassium
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10/19/2015Template copyright 2005 www.brainybetty.com55 Adrenal
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10/19/2015Template copyright 2005 www.brainybetty.com56 Blood Supply to the Adrenal Gland What gives rise to the subcapsular plexus? What does the subcapsular plexus give rise to?
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10/19/2015Template copyright 2005 www.brainybetty.com57 Blood Supply to the Adrenal Gland What gives rise to the subcapsular plexus? Superior, middle and inferior suprarenal arteries What does the subcapsular plexus give rise to? 1. Arterioles supplying capsule 2. Arterioles of the cortex sinusoidal vessels running between columns of fasciculata before forming deep plexus in reticularis that communicates with plexus in medulla 3. Arterioles that directly supply the medulla and forms medullary sinusoidal plexus
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10/19/2015Template copyright 2005 www.brainybetty.com58 Venous Drainage Venous channels drain medullary plexus and empty into medullary vein –Has longitudinally oriented smooth muscles –Thought to act as a gate regulating entry of blood from the reticularis and medullary sinusoidal plexus
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10/19/2015Template copyright 2005 www.brainybetty.com59 Fetal Adrenal Cortex What are the zones? What do they do?
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10/19/2015Template copyright 2005 www.brainybetty.com60 Fetal Adrenal Cortex What are the zones? Fetal/provisional zone and definitive zone What do they do? Fetal zone degenerates rapidly after birth Produces inactive androgens that are converted to active in the placenta and enter maternal circulation Definitive zone differentiates into adult cortex
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10/19/2015Template copyright 2005 www.brainybetty.com61 Medulla What are cell types present? What is the vascular supply like?
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10/19/2015Template copyright 2005 www.brainybetty.com62 Medulla What are cell types present? Chromaffin cells in clumps or cords Few ganglion What is the vascular supply like? Dilated capillary network surrounding medullary secretory cells and drain into medullary vein
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10/19/2015Template copyright 2005 www.brainybetty.com63 Chromaffin Cell What does it contain, what do they do? What causes release?
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10/19/2015Template copyright 2005 www.brainybetty.com64 Chromaffin Cell What does it contain, what do they do? Membrane-limited secretory granules Contain catecholemines (epinephrine, norepinephrine) What causes release? Released upon stimulation of preganglionic sympathetic neurons in response to intense emotional reactions
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10/19/2015Template copyright 2005 www.brainybetty.com67 Pineal Gland CT septa originate in pia mater and separate gland into irregular lobes What are the two cell types? What are concretions?
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10/19/2015Template copyright 2005 www.brainybetty.com68 Pineal Gland CT septa originate in pia mater and separate gland into irregular lobes What are the two cell types? Pinealocytes—slight basophilic cyto, irregular nuclei, long tortuous processes Astroglial—more basophilic lots of intermediate filaments What are concretions? Corpora aremacea (brain sand) made of calcium phosphate or calcium carbonate and indicate the secretory activity of the gland
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10/19/2015Template copyright 2005 www.brainybetty.com70 Pineal Gland What do pinealocytes secrete? How is it regulated?
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10/19/2015Template copyright 2005 www.brainybetty.com71 Pineal Gland What do pinealocytes secrete? How is it regulated? Melatonin Diurnal cycle under control of sympathetic division of ANS. Specifically entrained by light. More light less melatonin release.
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10/19/2015Template copyright 2005 www.brainybetty.com72 Melatonin Secretion Why is it important in humans?
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10/19/2015Template copyright 2005 www.brainybetty.com73 Melatonin Secretion Why is it important in humans? Possible antigonadal effect Size of pineal decreases after puberty Exogenous melatonin appears to help some people as a sleep inducer.
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Image Review
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10/19/2015Template copyright 2005 www.brainybetty.com75 Pituitary from far away
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10/19/2015Template copyright 2005 www.brainybetty.com77 The cellular region to the left is the pars distalis. The fibrous region to the right is the pars nervosa. You can also see a teeny bit of the intermedia in between the two.
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10/19/2015Template copyright 2005 www.brainybetty.com78 The intermediate lobe is ill-defined in humans. It consists of a thin zone of cells. Observe the cysts which represent the residual lumen of Rathke’s pouch.
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10/19/2015Template copyright 2005 www.brainybetty.com80 pituitary gland: (1) chromophobe; (2) acidophil; (3) basophil
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10/19/2015Template copyright 2005 www.brainybetty.com81 How to distinguish acidophils and basophils: –look at the color of the red blood cells in the vessels (V). –Then, match the color to cells in the pituitary. Those are the acidophils (A). –Cells that are more "purple", or blue are the basophils (B). –Cells that have hardly any color are the chromophobes
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10/19/2015Template copyright 2005 www.brainybetty.com82 Anterior pit – sick of this yet?
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10/19/2015Template copyright 2005 www.brainybetty.com83 Somatotroph from the anterior pituitary. Notice the numerous, spherical secretory granules. The granules are full of GH
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10/19/2015Template copyright 2005 www.brainybetty.com84 Mammotroph from the anterior pituitary. The secretory granules are sparse and elliptical. Granules = prolactin
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10/19/2015Template copyright 2005 www.brainybetty.com85 The posterior lobe is smaller and lighter staining than the anterior lobe. It does not have the appearance of a glandular organ (i.e. FEWER nuclei). Note the masses of unmyelinated nerve fibers and pituicytes (round, dark nuclei).
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10/19/2015Template copyright 2005 www.brainybetty.com86 Pars nervosa: This region consists of a mass of nerve fibers and endings from a fiber tract that extends down from the hypothalamus. The hormones are stored in the nerve endings which can be quite large (called Herring bodies).
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10/19/2015Template copyright 2005 www.brainybetty.com88 pituicytes (purple nuclei throughout image) are neuroglia, which are supportive cells for the axons. ALL the nuclei are from pituicytes
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PINEAL
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10/19/2015Template copyright 2005 www.brainybetty.com90 The most distinctive feature of this gland is the presence of "corpora arenacea" or "brain sand" in the aging pineal - it will help you identify the pineal. It is shown in the above photo as a large blue-purple mass in the tissue.
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10/19/2015Template copyright 2005 www.brainybetty.com93 Pinealocytes, with their pale, round nuclei can be seen along with a few glial cells. The smaller, dense nuclei belong to glial cells. Capillaries are also evident.
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PARATHYROID
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10/19/2015Template copyright 2005 www.brainybetty.com95 The parathyroid gland is distinguished by scattered clumps of adipose cells lying among the parenchymal cells. There are two types of parenchymal cells: chief cells and oxyphil cells.
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10/19/2015Template copyright 2005 www.brainybetty.com96 parathyroid glands synthesize parathyroid hormone. Each gland is surrounded by a capsule from which connective tissue septa extend inward and divide it into lobules. Two parenchymal cell types can be distinguished by H and E: the abundant chief cells (pale staining cytoplasm) and rarer LARGER oxyphil cells (acidophilic granules).
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10/19/2015Template copyright 2005 www.brainybetty.com97 THERE ARE NO DUCTS IN THE PARATHYROID GLAND. THIS IS HOW YOU TELL IT APART FROM THE PAROTID AND PANCREAS!!!! YOU’VE BEEN WARNED
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10/19/2015Template copyright 2005 www.brainybetty.com98 The chief cells have a low cytoplasm:nucleus ratio. Oxyphil cells are larger than chief cells and have slightly smaller and more intensely staining nuclei. These cells can be easily identified because a unit area contains few nuclei than a comparable unit area of chief cells.
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THYROID
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10/19/2015Template copyright 2005 www.brainybetty.com102 The thyroid gland produces the thyroid hormones T3 and T4 or (thyroxin). The functional unit of the gland which synthesizes these hormones is the follicle. It consists of a layer of cuboidal epithelium (principal cells) enclosing the follicular cavity, which is usually filled with colloid
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10/19/2015Template copyright 2005 www.brainybetty.com103 A rich capillary network is present in the connective tissue separating the follicles. The principal thyroid cells (follicle cells) appear to form a “ring around the colloid.”
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10/19/2015Template copyright 2005 www.brainybetty.com104 EM of thyroid principal cell showing sparse microvilli on the apical surface that lies next to the stored colloid in the follicle.
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10/19/2015Template copyright 2005 www.brainybetty.com105 Parafollicular cells/C cells are found outside the colloid
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ADRENAL GLANDS
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10/19/2015Template copyright 2005 www.brainybetty.com108 3 regions of the cortex: –The outer region near the capsule has cells arranged in clusters, like grapes. This is called the Zona Glomerulosa. –The middle region has cells arranged in straight cords. It is called Zona Fasciculata The innermost region has cells arranged in a branching network. This is called the Zona reticularis.
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10/19/2015Template copyright 2005 www.brainybetty.com109 To remember the order: remember GFR, which you loved to learn about in phys
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10/19/2015Template copyright 2005 www.brainybetty.com114 A higher magnification of the zona glomerulosa and the Zona fasciculata is shown in this photo. Note the many lipid droplets seen in the zona fasciculata cells.
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10/19/2015Template copyright 2005 www.brainybetty.com116 In the medulla
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And something that was on our final….. In the liver, central veins drain into sublobular veins…..
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10/19/2015Template copyright 2005 www.brainybetty.com119 Central draining into sublobular
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QUIZ TIME
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10/19/2015Template copyright 2005 www.brainybetty.com121 WHAT CELL IS THE BLUE ARROW POINTING TO
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10/19/2015Template copyright 2005 www.brainybetty.com122 pituicyte
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10/19/2015Template copyright 2005 www.brainybetty.com123 WHAT TISSUE IS THIS
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10/19/2015Template copyright 2005 www.brainybetty.com124 PARATHYROID – 2 types of cells, NO DUCTS
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10/19/2015Template copyright 2005 www.brainybetty.com125 A? B? C?.
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10/19/2015Template copyright 2005 www.brainybetty.com126 a = pale chromophobes b = blue basophil c = red acidophil The cells are separated by a fine reticular fibers (thin blue lines), where the blood capillaries lie.
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10/19/2015Template copyright 2005 www.brainybetty.com127 TISSUE?
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10/19/2015Template copyright 2005 www.brainybetty.com128 PINEAL (note brain sand)
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10/19/2015Template copyright 2005 www.brainybetty.com129 What cell is this?
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10/19/2015Template copyright 2005 www.brainybetty.com130 purple basophil Can be a thyrotroph, corticotroph, gonadotroph
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10/19/2015Template copyright 2005 www.brainybetty.com131
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10/19/2015Template copyright 2005 www.brainybetty.com132 COLLECTING DUCT You know bc you see thin limbs, so nothing else it can be
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10/19/2015Template copyright 2005 www.brainybetty.com133 arrow
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10/19/2015Template copyright 2005 www.brainybetty.com134 PARAFOLLICULAR or C-cell in thyroid If its not a follicular cell, it’s a parafollicular/c-cell In BETWEEN follicles
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10/19/2015Template copyright 2005 www.brainybetty.com135 Name that tissue
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10/19/2015Template copyright 2005 www.brainybetty.com136 Pars nervosa of pituitary Note Herring bodies, collections of secretion in the pars nervosa of the pituitary. They represent accumulations of neurosecretion within the axons of neurons whose cell bodies lie in the hypothalamus of the brain.
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10/19/2015Template copyright 2005 www.brainybetty.com137 What is this?
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10/19/2015Template copyright 2005 www.brainybetty.com138 THICK SKIN Lots of corneum
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10/19/2015Template copyright 2005 www.brainybetty.com139 Tissue??
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10/19/2015Template copyright 2005 www.brainybetty.com140 PARATHYROID The larger cells to the left are oxyphil cells whose function is unknown. They are found only in humans and increase with age. The intense eosinophilia in their cytoplasm reflects an abnormally high number of mitochondria in these cells.
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10/19/2015Template copyright 2005 www.brainybetty.com141 Tissue?
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10/19/2015Template copyright 2005 www.brainybetty.com142 THYROID This is the only endocrine gland that typically stores its hormonal secretion extracellularly before releasing it into the bloodstream.
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10/19/2015Template copyright 2005 www.brainybetty.com143 What is this be specific
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10/19/2015Template copyright 2005 www.brainybetty.com144 DUCT OF AN ECCRINE SWEAT GLAND Cuboidal Darker than the secretory end pieces
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10/19/2015Template copyright 2005 www.brainybetty.com145 Ignore the arrow. What is this
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10/19/2015Template copyright 2005 www.brainybetty.com146 GANGLION Fried eggs
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10/19/2015Template copyright 2005 www.brainybetty.com147 In general, where would be find this cell??
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10/19/2015Template copyright 2005 www.brainybetty.com148 adrenal cortex cytoplasm filled with smooth endoplasmic reticulum, typical of steroid - secreting cells. Parts of two mitochondria are also visible here.
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10/19/2015Template copyright 2005 www.brainybetty.com149 Tissue?
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10/19/2015Template copyright 2005 www.brainybetty.com150 DENSE REG CONNETIVE TISSUE Aka tendon Flat nuclei Wavy appearance
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10/19/2015Template copyright 2005 www.brainybetty.com152 PARS RADIATA Found here are TAL and TDL and cortical collecting duct In pars convoluta are PCT, DCT, glomeruli, and connecting tubule
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10/19/2015Template copyright 2005 www.brainybetty.com153 Tissue?
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10/19/2015Template copyright 2005 www.brainybetty.com154 PANCREAS Look for the islets
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10/19/2015Template copyright 2005 www.brainybetty.com155 Where are we?
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10/19/2015Template copyright 2005 www.brainybetty.com156 In the gallbladder Do we see any goblets??????? Do we see a muscularis mucosa???
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10/19/2015Template copyright 2005 www.brainybetty.com157 QUESTIONS?
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