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Exocrine
secretes through a duct
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Endocrine
secretes through fenestrated capillaries
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Autocrine
target cell is cell that secreted hormone
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paracrine
target cell is nearby distinct cell type
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juxtacrine
receptor/ligand interaction, not endocrine/secretion
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endocrine cords
rounded, few junctional complexes, do not surround lumen (epithelioid)
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endocrine follicles
spherical, surround central lumen, single layer with polarity and junctional complexes
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Four types of secretory product
proteins - anterior pituitary (high RER and Golgi), amines - adrenal medulla (similar, but less RER), steroids - ovary (high SER and lipid droplets), and eicosanoids - mast cells (similar to steroid)
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Thyroid
Bilobed with connecting isthmus, ventral to trachea/inferior to thyroid cartilage, produces T3 (tri-iodothyronine) and T4 (thyroxine) which elevate the basal metabolic rate, has follicles and C cells
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Thyroid follicles - protein colloid, simple epithelium, thin connective tissue connects to capillary, can be squamous to columnar, height corresponds to activity level. Have much RER, Golgi, lysosomes, and mitos, but few secretory droplets.
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Iodothyroglobulin Synthesis
In response to TSH, thryoglobulin (125 Tyrosine residues) made in RER, then glycosylated in Golgi, then exocytosed. Iodide pump brings in iodide from basal, then transcytosed and oxidized to iodine. Immediately, thyroglobulin is iodinated to completion and stored as iodothyroglubulin
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Iodothyroglobulin Processing
TSH stimulates, thyroid cells endocytose iodothyroglobulin and form phagosomes. Then form secondary lysosomes. Then cleaved to T3/T4. T3 is converted to T4 in target cell.
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Cretinism
Thyroid hormone deficiency during fetal development (thyroid hormone and growth hormone are synergistic). Defects in CNS development and stunted growth
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Myxedema
Hypothyroidism = mental/physical sluggishness, cold intolerance, loss of appetite, weight gain.
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Hyperthyroidism
sleeplessness, heat intolerance, increased appetite, weight loss
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Graves' disease
autoimmune disorder, Abs made to TSH receptor and mimic TSH action. increased hormone production, mimics hyperthyroidism
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Goiter
enlarged thyroid, lack of iodine in diet or defects in T3/T4 production. Gland is not neoplasmic or overactive
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Calcitonin
Produces in Thyroidal C cells (never tough follicle lumen, sit next to capillary) in response to high blood calcium. Stimulates osteoblasts and inhibits osteoclasts to increase bone formation
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Parathyroid gland
two pairs on dorsal surface of thyroid gland. Made of chief cells and oxiphyl cells (no known function, lots of mitos, increase in number with age, larger than chief cells)
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Chief cells
Main cells in parathyroid, secrete parathormone in response to low blood calcium concetration.
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Parathormone
In bone - inhibits osteoblasts and stimulates osteoclasts. In kidney - stimulates phsosphate excretion and inhibits calcium excretion. In intestine - stimulates calcium absorption while using active metabolites of vitamin D.
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Hypoparathyroidsim
low blood calcium, increased excitability of the nervous system, convulsions, and muscle tetany
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Hyperparathyroidism
high blood calcium, fragile bones, calcium deposits in kidney tubules and blood vessels
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Adrenal Glands
suprarenal glands, superior poles of the kidney. Cortex (develops from mesoderm) and Medulla (develops from neural crest, similar to sympathetic ganglia)
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Adrenal Medulla blood supply
two sources, 1) medullary arteries pass through cortex to medullary sinusoids (arterial) 2) cortical arteries -> capillaries in cortex (sinusoids) -> receive adrenal cortex hormones -> medullary sinusoids (venous) -> drained by veins
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Adrenal Cortex
from inside to outside = zona reticularis, xona fasiculata, and zona glomerulosa
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Zona Glomerulosa
Outermost adrenal cortex, arched cords (high SER, golgi, and mito). secrete mineralcorticoids = aldosterone. under renal control
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Angiotensin II
In response to low blood pressure, kidney secretes renin, which converts circulating angiotensinogen to angiotensin I, which is then converted to Angiotensin II.
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Aldosterone
targets kidney, salivary, and sweat glands. release stimulated by angiotensin II (from kidney). stimulates kidney distal convoluted tubule to absorb sodium. sodium/water is retained, and potassium is excreted (Na/K ATPase)
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Zona Fasciculata
central adrenal cortex, large, polyhedral, pale staining cells in two cell wide columns with a sinusoidal capillary. secrete glucocorticoids = cortisol, under control of pituitary gland (ACTH).
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Cortisol
glucocorticoid released from zona fasciculata (Adrenal cortex) in response to stress. Stimulated by ACTH from pituitary gland. regulats carb/protein metabolism. stimulated anabolic activity in liver, and catabolic activity in adipose/muscle. fats, sugars, and AAs used to glycogenolysis, gluconeogenesis, and enzyme synth. (PNMT methylates norepinephrine to epinephrine) overexposure depressed immune system.
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Zona Reticularis
inner adrenal cortex, cells in anastomosing cords (web) separated by fenestrated capillaries. source of weak androgens. regulated by ACTH from pituitary.
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Adrenal Medulla
large, palely staining epitheliod cells (chromaffin cells = sympathetic neurons with rudimentary dendrites and no axons). secretes epinephrine/norepinephrine, controlled by preganglionic sympathetic neurons.
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Epinephrine
increases heart rate/cardiac output without increasing blood pressure, also increases basal metabolic rate. producing cells lie in regions fed by cortex blood.
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Conn's syndrome
zona glomerulosa (outer adrenal cortex) overproduces aldosterone. high blood pressure/increased potassium excretion
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Cushing's syndrome
zona fasciculata (central adrenal cortex) overproduce cortisol. can be adrenal tumor, but most often excessive ACTH from pituitary (adenoma), rapid weight gain (trunk and face, central obesity) and excessive sweating
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Norepinephrine
increases blood pressure by vasoconstricting peripheral ateries, without affecting heart rate/cardiac output (made from larger, denser granulate in cells)
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Addison's disease
adrenal insufficiency. low aldosteron/cortisol (autoimmune damage), weight loss, muscle weakness, fatigue, low BP
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Pheochromocytomas
tumors of adrenal medulla which produce excess adrenaline. high heart rate, excessive sweating, headaches, and anxiety.
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Endocrine Pancreas
islets of Langerhans, 70% beta (insulin), 20% alpha (glucagon), 5% delta (somatostatin), gamma make 36 amino acid pancreatic polypeptide (inhibits bile secretion from gall bladder)
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Somatostatin
inhibits growth hormone from pituitary, supressed both insulin/glucagon (paracrine) supresses pancreatic exocrine secretions
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Major Divisions of Pituitary Gland (Hypophysis)
Adenohypophysis (Anterior Pituitary) & Neurohypophysis (Posterior Pituitary)
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Subdivisions of Adenohypophysis
Pars Distalis, Pars Intermedia, and Pars Tuberalis
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Subdivisions of Neurohypophysis
Pars Nervosa, Infundibulum (Median eminence & Infundibulum stem)
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Adenohypophysis
outgrowth of oral cavity, glandular epithelium, pars distills is major lobe, epitheloid cords, fenestrated capillaries, and reticular connective tissue
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Neurohypophysis
outgrowth of brain (neural secretory tissue), pars nervosa is major lobe, unmyelinated axons of hypothalamic neurons, pituicytes (glial cells), blood vessels, and stored neurosecretory material (herring bodies)
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Pituitary Portal System
superior hypophesial ateries -> primary capillary plexus in the infundibulum -> pituitary portal veins -> secondary capillary plexus in the adenohypophysis -> hypophyseal veins -> pars distalis
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Pars tuberalis blood supply
superior hypophyseal arteries and primary capillary plexus
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Pars nervosa blood supply
direct blood supply from inferior hypophyseal arteries -> capillary plexus then drain into dural venous sinus
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Portal system
blood supply entering and leaving capillary as same category
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Cell types of Adenohypophysis
Chromophobes, Chromophils, which are Acidophils - eosin/pink (somatotrophs and mammotrophs) and Basophils - hematoxilin/blue (gonadotrophs, thyrotrophs, and corticotrophs)
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hypothalamohypophyseal tract
the axonal connection between the paraventricular and supraoptic nuclei of the hypothalamus and the pars nervosa to the hypophysis
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Hormones secreted by the adenohypophysis
ACTH, GH (STH), FSH, LH, PRL
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Hormones secreted by the neurohypophysis
oxytocin, vasopressin (ADH)
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ACTH
adrenocorticotropic hormone. stimulates the zona fasciculata (the central adrenal cortex) to produce glucocorticoids (cortisol). Stimulated by CRH (corticotroph releasing hormone) from hypothalamus
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GH
growth hormone, somatotropin (STH). stimulated liver to produce somatomedin (stimulates bone growth and metabolism in most cells), Stimulated by SRH (somatotroph releasing hormone) from hypothalamus
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TSH
thyroid stimulating hormone. stimulates thyroid to produce T3/T4, which increase basal metabolic rate. Stimulated by TRH (thyrotroph releasing hormone) by hypothalamus
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FSH
follicle stimulating hormone. In females, stimulates ovary to produce estrogen (for oocyte/uterine growth). In males, stimulates Sertoli cells (testes) to produce androgen binding protein (spermatogenesis). Stimulated by GnRH (gonadotroph releasing hormone) from hypothalamus
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LH
leutinizing hormone. In females stimulates ovulation, corpus luteum formation, and progesterone production. In males, stimulates Leydig cells to secrete testosterone (spermatogenesis) stimulated by GnRH (gonadotroph releasing hormone) from hypothalamus
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PRL
Prolactin or mammotropin. stimulates mammary glands to produce milk, may stimulate oligodendrocyte precursor cells in CNS, high levels cause infertility in men. Inhibited by PIH (prolactin inhibiting hormone) from hypothalamus
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Oxytocin
In women, stimulates smooth muscle contraction ar birth, mammary function, and maternal bonding. In men, facilitates sperm transport and social behavior. most is produced in paraventricular nucleus. bound non convalently to transport proteins, neurophysins and ATP.
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Vasopressin
ADH (antidiuretic hormone). most is produces in supraoptic nucleus. bound non convalently to transport proteins, neurophysins and ATP.
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Structure of bone
Epiphysis, Metaphysis, and Diaphysis
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Three main sources of blood supply
nutrient artieries, perisoteum arteries, and metaphyseal complex
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Functional organization of bone
Compact (cortical) bone and spongy (trabecular, cancellous) bone
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Osteoprogenitor cells
differentiate into osteoblasts (mesychymal stem cells or multipotent marrow stromal cells)
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Osteoblasts
secrete extracellular matrix of bone (osteoid) when active, cuboidal/columnar, squamous when inactive. found on all surfaces of bone
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Osteocytes
stellate cells that are surrounded by and maintain the bone matrix. come from osteoblasts. most numerous of bone cells. communicate the mechanical load and strain in the bone to guide formation/degradation.
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Osteoclasts
bone-destroying cells. active when bone is being resorbed. derived from monocytes, but are multinucleated (2-50 monocytes). Can be on the inner surface (endosteal) or outer surface (periosteal).
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Volkmann's canals
perpendicular canals to supply blood to the osteocytes
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Haversian canals
center of an osteon, supplies blood to chondrocytes Require 3-4 months to complete
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endochondral ossification
bone replacing tissue within cartilage. hyaline cartilage forms in developing embryo, mesynchymal cells differentiate into osteoprogenitor cells, and then go to osteoblasts and secrete osteoid (unmineralized, organic part of bone). The osteoid becomes mineralized, forming the bony collar that surrounds the future diaphysis. chondrocytes are cut off and mineralize as they die.
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Osteoid
collagen I, glycosaminoglycans, proteoglycans. glycoprotein called osteocalcin binds calcium. Osteoblasta also accumulate calcium and phosphate ions to deposit hydroxapatite (mineralization)
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Initiation of marrow cavity
osteogenic bud tunnels into diaphysis of calcified cartilage. It's chondroclasts followed by angiogenic bud, osteoprogenitor cells, osteoblasts, and nerves. The middle becomes the primary ossification center. Cartilage is destroyed and replaced by bony trabeculae. Cavity fills with reticular CT (III) and hematopoietic tissue from fetal liver.
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secondary ossification center
osteogenic buds invade epiphyses, at birth. The intervening hyaline cartilage becomes epiphyseal plate (growth plate).
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intramembranous ossification
flat bones do not require cartilage model. mesynchymal cells between the skin and brain condense to form thickened sheets (membranes) of cells and ECM. responding to growth factors, some differentiate into osteoprogenitor cells and then into osteoblasts, which secrete osteoid. The osteoid becomes mineralized and then strips (plates) of bones form.
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Bone length growth
- Epiphyseal plate - zone of resting cartilage (nearest epiphysis, random chondrocytes), then zones of proliferation (chondrocytes division/alignment), hypertrophying (chondrocyte enlargement), and calcifying cartilage (chondrocytes die/matric minerialized), then ossification zone (calcified cartilage is resorbed by chondroclasts and bone is deposited).
- Proliferation/hypertrophying contribute to bone growth.
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Bone width growth
appostional growth, osteoblasts from the periosteum (dense irregular CT) add new layers of bone. Osteocytes keep contact with filopodia within canaliculi.
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Filopodia
Exchanges nutrients/waste in between osteocytes trapped in bony matrix.
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Lamella
distance between two rows of osteocytes. A chain of osteocytes can only communication between 8-10 lamellae.
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Circumferential lamellae
rows around endosteum and periosteum of long bones. don't need haversian canals.
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Bone maturation
Primary, woven bone (initial, unorganized) is destroyed and replaced by secondary bone (repeated many times). Secondary bone is stronger from greater mineralization/regularly arranged collagen.
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Bone remodeling
1) incorporate new blood vessels, initiated by osteoclasts which secrete enzymes to tunnel through bone. Blood vessels follow, first perpendicular (Volksmann's canals), then parallel (Haversian).
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bone repair
fractued, unsalvageable fragments are resorbed by macrophages. a callus from periosteum/endosteum unites the salvageable fragments. If stabalized, little callus forms and growth = intramembraneous ossification (primary bone healing). else, hyaline and then endochondral ossification (secondary bone healing).
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estrogen
causes calcium deposition in bone. antagonizes PTH
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