Endocrine Flashcards
What is emiocytosis vs exocytosis
Secretion of entire secretory granules into extracellular space vs fusion of granules with cell membrane
What hormone types utilize secretory granules?
Polypeptide and catecholamine-secreting endocrine cells only
Features of polypeptide producing endocrine cells
ER with ribosomes, prominent golgi, secretory granules
Features of steroid producing endocrine cells
Large lipid vacuoles that contain cholesterol esters and other precursors, smooth ER, large mitochondria with cytochrome p450 systems
*Lack secretory granules, don’t store product
How do peptide hormones signal? steroids?
Peptides- GPCR (cell membrane)
Steroids- lipid soluble, travel through membrane and bind receptors in cytoplasm, travel to nucleus
Half life of peptide vs steroid hormones
Short vs long
Features of catecholamines and iodothyronine hormones
Tyrosine derivatives
Catecholamines from adrenal medulla, iodothyronines from follicular cells of thyroid
Catecholamines act like polypeptide hormones
Iodothyronines act like steroid hormones
Mechanism of humoral hypercalcemia of malignancy
Cancer cells produce PTHrp, which activates PTH receptors in bone and kidney, producing hypercalcemia
Common tumors that cause humoral hypercalcemia of malignancy
T cell lymphoma
AGASACA
Clin path findings with HHM
Hypercalcemia
Hypophosphatemia
Hypercalciuria
Osteoclastic bone resorption
How do NWPs differ in their vitamin D requirements
Require higher levels of vitamin D3, so prone to Vit D Resistant Rickets (type II) and osteomalacia
Causes of prolonged gestation in ruminants
Guernsey and Jersey cattle- adenohypophyseal aplasia causes hypoplasia of target organs (Adrenal cortex, thyroid follicular cells, gonads)
Ewes ingesting veratrum californicum- CNS malformations, so no hypothalamic stimulus for pituitary
Types of cells in the pituitary following Pit1 action and GATA2 expression
Somatrophs- GH
Lactotrophs- Prolactin
Thyrotrophs- TSH
Type of cells in the pituitary that are Pit1 independent, via Tbx19 and Sf1
Corticotrophs- POMC –> ACTH
Melanotrophs- POMC –> MSH
Gonadotrophs- LH/FSH
What cells in the pituitary are acidophilic?
Somatotrophs
Lactotrophs
What cells in the pituitary are basophilic? Additional positive stain?
Gonadotrophs
Thyrotrophs
PAS
What cells do not have obvious secretory granules (are not acidophilic or basophilic)
Chromophobes- corticotrophs and melanotrophs
What does the neurohypophysis do?
Contains terminal, unmyelinated axons from neurosecretory neurons from the hypothalamus that secrete oxytocin and ADH
Who is most likely to get juvenile pan hypopituitarism; associated genetic defect in dogs
Dogs- GSD, Spitz, Toy Pinscher, Wolfdogs
Eurasian badger; LHX3 gene, autosomal recessive
Which hormones are deficient in panhypopituitarism? Which are not?
GH, TSH, prolactin, gonadotropins; ACTH normal maybe
Remnant of distal craniopharyngeal duct- location and who gets it
Brachycephalic dogs, periphery of pars tuberalis and distalis
Remnant of proximal craniopharyngeal duct- location and who gets it
Brachycephalic dogs, dorsal oral cavity/nasopharynx
Rathke’s pouch ectoderm differentiation failure- location and who gets it
Entire pars distalis replaced, causes pituitary dwarfism in GSDs
Most common cause of Cushing’s
Corticotroph pituitary adenoma in pars distalis or pars intermedia
Cause of clinical signs in Cushing’s
Hyperplasia of adrenal cortices and chronically high cortisol
Which zones are hyperplastic in Cushing’s?
Zona fasciculata and reticularis
Who gets adenomas of the pars distalis? Pars intermedia?
Brachycephalic; nonbrachycephalic
Difference between adenomas of pars intermedia and pars distalis?
Intermedia has numerous colloid-filled follicles between neoplastic cells
Most common pituitary tumor in the horse? Clinical syndrome?
Pars intermedia adenoma; Pituitary pars intermedia dysfunction
Who gets PPID more?
Females, older
Key histo with equine pars intermedia adenoma
Spindle to polygonal eosinophilic cells; Follicles lined by cuboidal cells with colloid
Clinical signs with PPID; pathogenesis?
PU/PD, hirsutism, hyperhidrosis, laminitis; Most signs due to compression of hypothalamus, also elevated POMC and MSH, CLIP, beta endorphin
Most common pituitary tumor in cats; predisposes to
Somatotroph; acromegaly, diabetes mellitus
Most common pituitary tumor in rats
Lactotroph
What pituitary tumor do budgies get?
Somatotroph
Where is the adrenal cortex derived from? Medulla?
Mesoderm; neural crest ectoderm
Role of zona glomerulosa, fasciculata, and reticularis
G- Mineralocorticoids, columns
F- Glucocorticoids, abundant lipid, most of cortex (70%)
R- Sex steroids
Effects of glucocorticoids
Sparing of glucose, hyperglycemia, increased gluconeogenesis
Suppress inflammation and immune system
Phagocyte inhibition
Stability of lysosomal membranes
Decreased wound healing
Renin-angiotensin system summary
Renin produced by juxtaglomerular apparatus, cleaves angiotensinogen to angiotensin I, which is then converted to angiotensin II
Angiotensin II is a vasoconstrictor and trophic for glomerulosa, increasing aldosterone
What does ACTH do?
Stimulates Fasciculata and reticularis through melanocortin 2 receptors (adenylyl cyclase and cAMP)
Difference between idiopathic adrenocortical atrophy and trophic atrophy secondary to pituitary lesion with decrease in ACTH stimulation?
Idiopathic adrenocortical atrophy affects all layers of cortex, whereas trophic atrophy only affects inner two layers of cortex, so no electrolyte disturbances
Layers affected by nodular hyperplasia of adrenal cortex
G and F
Layers affected by diffuse adrenal cortical hyperplasia; cause?
Corticotroph adenoma, causes hyperplasia of Fasciculata and reticularis
Associated lesion with adrenal cortical carcinoma; most common in who?
Extension into caudal vena cava; Cattle*, occurs in dogs but adenoma more common
Most common adrenal tumor in ferrets
Cortical carcinoma, usually in left adrenal
Clinical signs with ferret adrenal tumor; pathogenesis
PU/PD, vulvar enlargement, alopecia; overproduction of estrogenic steroids (estradiol-17beta)
Associated lesion in ferrets with adrenal tumors
Insulin-producing islet cell tumors
Predisposing factors for ferret adrenal tumors
Female, early gonadectomy (elevated LH secretion due to lack of negative feedback)
Role of adrenal medulla; IHCs for medulla
Synthesis of catecholamines- NE and Ep; Chromogranin A
Catecholamine pathway
Tyrosine–>Dopamine–>norepinephrine–>epinephrine
Tumor that commonly accompanies pheochromocytoma
C cell thyroid adenoma
Key histo with pheochromocytoma
Fine granular cytoplasm, neuroendocrine appearance, muddy brown cytoplasm
Clinical signs with pheochromocytoma
Tachycardia, edema, cardiac hypertrophy, arteriolar sclerosis and medial hyperplasia
Apicomplexan that commonly localizes to adrenal cortex
Toxoplasma gondii
How is PTH regulated? Role of phosphorus?
When blood Ca is high, PTH release inhibited, when low, PTH released; Hyperphosphatemia decreases Ca, stimulating parathyroids
Major inhibitors of PTH synthesis and release?
Calcium and calcitriol
Actions of PTH
Stimulate calcitriol production in kidney
Increase reabsorption of Ca in kidney, and excretion of phosphorus
Mobilize Ca (and phos) from bone
Upregulates RANKL on osteoblasts (stimulate differentiation of osteoclasts)
RANKL is on which cell? RANK is on which cell? Osteoprotegerin is what?
Osteoblasts; osteoclasts; soluble decoy receptor to regulate resorption
Vitamin D activation pathway
Cholecalciferol from diet and skin–>In hepatocyte ER, cholecalciferol-25-hydroxylase converts to 25-hydroxycholecalciferol–> in kidney PCT mitochondria, 1 alpha hydroxylase converts to calcitriol (rate-limiting)
PTH role in vitamin D activation
PTH stimulates 1 alpha hydroxylase, increasing production of calcitriol
What other factors influence calcitriol?
Phosphate- inhibits 1 alpha hydroxylase
FGF23 inhibits 1 alpha hydroxylase
Calcitriol’s main role; how
Increase absorption of Ca and phosphate from intestine; increases calcium binding protein on luminal enterocyte
Other roles of calcitriol (in bone)
Upregulates RANKL on osteoblasts (stimulating differentiation of osteoclasts)
Stimulates release of FGF23 by osteocytes
Roles of FGF23
Inhibits 1 alpha hydroxylase
Inhibits PTH secretion
Increases renal phosphate excretion
Calcitonin’s role in Ca regulation; what stimulates its release?
Lowers plasma Ca; concentration of Ca in plasma and ECF stimulates C cells (same receptor as Chief cells)
What causes C cell hyperplasia?
Long-standing hypercalcemia
Actions of calcitonin
Inhibit osteoclastic bone resorption
Prevents postprandial hypercalcemia and excessive loss during pregnancy
What causes diffuse parathyroid hyperplasia?
Chronic renal failure, dietary imbalances
Key histo with parathyroid adenoma; who is predisposed?
Karyomegaly and anisokaryosis, fibrous capsule, compressed rim of normal tissue; keeshonds
Associated lesion with primary hyperparathyroidism
Hyperostotic fibrous osteodystrophy
Where does thyroid carcinoma often metastasize to first?
Pulmonary, then lymph nodes, because drains directly into brachiocephalic trunk
Thyroid hormone synthesis pathway
Tyrosine–>incorporated into thyroglobulin protein–>thyroperoxidase oxidizes iodide into iodine–> iodine bound to tyrosine–>thyroxine (T4) and triiodothyronine (T3)
How is iodine transported to follicular lumen?
Cotransported into follicular cell as iodide via NIS, then passively transported via pendrin into lumen
What happens to follicles with sustained TSH?
Follicular cells become more columnar, lumina become smaller, increased endocytosis of colloid
What happens to follicles with decreased TSH?
Follicular cells become flattened/cuboidal, follicles become enlarged and distended, decreased endocytosis of colloid
Most common two causes of hypothyroidism in dogs
Lymphocytic thyroiditis and idiopathic follicular collapse
What causes lymphocytic thyroiditis?
Autoantibodies against thyroglobulin, thyroperoxidase, the TSH receptor, or other
How does excess iodide cause goiter?
Interferes with fusion of lysosomes and colloid droplets
Plants that cause goiter; toxic principle?
White clover (trifolium)
Couch grass (cynoden)
Linseed meal
Brassica; Goitrin inhibits organification of iodine
Cats with hyperthyroidism often have what concurrent histo finding?
Diffuse chief cell hypertrophy and hyperplasia in the parathyroid
Most common type of thyroid adenoma?
Follicular adenoma
Most common thyroid tumor in the dog? Cat?
Follicular cell carcinoma; adenoma
Breeds predisposed to thyroid carcinoma
Beagles, boxers, huskies, goldens
Who gets C cell (parafollicular) thyroid tumors?
Guernsey Bulls and rats get carcinomas, most common thyroid tumor in horses
Key histo with C cell carcinoma
Amyloid (A Cal), neuroendocrine appearance
What is a predisposing factor to C cell tumors, especially in which species?
High calcium diets; cattle
Who is predisposed to pheochromocytomas?
Clouded leopards
Diagnostic test on necropsy floor for pheochromocytomas?
Zenkers solution- turn brown-yellow
TEM of pheochromocytomas
Wonky granules with wide submembranous space- NE
Less dense core with narrow submembranous space- Epinephrine
Key histo with chemodectoma?
Variable numbers of karyomegalic or hypertrophied giant cells; positive for chromogranin A and Churukian Schenk
Difference between pheochromocytoma and chemodectoma?
Pheochromocytoma is derived from chromaffin cells
Chemodectoma is derived from nonchromaffin, extraadrenal paraganglia, no chromaffin granules
Which chemodectoma has the worst prognosis? Who is predisposed?
Carotid body tumors; brachycephalic breeds (chronic hypoxia)
Predominant exocrine stimulus; inhibitors?
Insulin; glucagon, somatostatin
Role of insulin
decreases serum glucose by stimulating uptake and glycogenesis, anabolic effects, cell growth
Role of glucagon
Promotes glycogenolysis, gluconeogenesis, lipolysis
What inhibits glucagon release?
Amylin (co-secreted with insulin) and somatostatin
Role of somatostatin
Inhibits release of glucagon, insulin, pancreatic polypeptide (regulates magnitude of responses)
Species differences in distribution of islets
Dogs- more in tail
Cats- large irregular shape
Ruminants- large and small islets
Cause of islet amyloidosis in cats
Associated with diabetes- may be pre-diabetic, caused by IAPP (amylin)
Islet amyloid with potassium permanganate
Retains congophilia
What is islet inflammation associated with in rats?
lymphocytic thyroiditis
What are glucagonomas associated with in dogs?
Superficial necrolytic dermatitis
