Endocrine
What are the *3 layers* of the Adrenal Cortex?
- Zona Glumerulosa - Zona Fasciculata - Zona Reticularis
What are some Developmental Aspects
1. Hormone-producing glands arise from all 3 germ layers 2. Most endocrine organs operate well until old age 3. Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function 4. Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants 5. Interference with glucocorticoids may help explain high cancer rates in certain areas
Type I DM
- 10% of cases - Some cases have autoimmune destruction of B cells, diagnosed about age 12 - Treated with diet, exercise, monitoring of blood glucose and periodic injections of insulin or insulin pump
What are *Parathyroid Glands*?
- 4-8 tiny glands embedded in posterior aspect of thyroid - Contain oxyphil cells (function unknown) and parathyroid cells that secrete *parathyroid hormone (PTH)* or parathormone - *PTH- most important hormone in Ca2+ homeostasis*
Type II DM
- 90% of cases - Insulin resistance- failure of tagged cells to respond to insulin - 3 major risk factors are heredity, age (40+) and obesity - Treated with weight loss program of diet and exercise - Oral medication improve insulin secretion or target cell sensitivity
*Hypersecretion of growth hormones*
- Acromegaly - Thickening of the bones and soft tissues - Problems in childhood or adolescence - Gigantism if over secretion - Dwarfism if *hyposecretion*
What is the *action of insulin on cells*?
- Activates tyrosine kinase enzyme receptor - Cascade --> increased glucose uptake - Triggers enzymes to: - Catalyze oxidation of glucose for ATP production- first priority - Polymerize glucose to form glycogen - Convert glucose to fat (particularly in adipose tissue)
What is *Thyroid Hormone* (TH)?
- Actually 2 related compounds - T4 (Thyroxine)- Has 2 tyrosine molecules + 4 bound iodine atoms - T3 (triiodothyronine)- Has 2 tyrosine + 3 bound iodine tons - Affect virtually every cell in the body
What is *Adrenogenital syndrome (AGS)*?
- Adrenal androgen hyper secretion *accompanies Cushing* - Causes: *enlargement of external sexual organs in children and early onset of puberty* - Masculinizing effects on women (deeper voice & beard growth)
What are symptoms of Addison's?
- Also involves deficits in mineralocorticoids - Decrease in glucose and Na+ levels - Weight loss, severe dehydration, and hypotension
What is *Toxic goiter* (Graves disease)?
- Antibodies mimic TSH - TH increases - Exophthalmos
What is the *Acute pathology* of Diabetes?
- Cells cannot absorb glucose, rely on fat and proteins (weight loss + weakness)
How is *aldosterone released triggered*?
- Decreasing blood volume and blood pressure - Rising blood levels of K+
What are symptoms of Cushing's?
- Depresses cartilage and bone formation - Inhibits inflammation - Depresses immune system - Disrupts cardiovascular, neural, and gastrointestinal function
What is *Hyperparathyroidism*?
- Due to a tumor - Bones soften and deform - Elevated Ca2+ depresses nervous system and contributes to formation of kidney stones
What is *Diabetes Mellitus* (DM)
- Due to hypo-secretion ( type 1) or hypo-activity (type 2) of insulin - Blood glucose levels remain high --> nausea --> higher blood glucose levels (flight or fight response) - *Glycosuria*- Glucose spilled into urine - Fats used for cellular fuel--> *lipidemia*; if severe--> *ketones* (ketone bodies) from fatty acid metabolism--> *ketonuria* and *ketoacidosis*
What *Factors* influence Insulin release?
- Elevated blood glucose levels- *primary stimulus* - Rising blood levels of amino acids and fatty acids - Release of acetylcholine by parasympathetic nerve fibers - Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids - *Somatostain*- Sympathetic nervous system
What do *Medullary chromatin cells* synthesize?
- Epinephrine (80%) - Noerpinepherine (20%)
What does the *placenta* secrete?
- Estrogen - Progesterone - Human chorionic gonadotropin (hCG)
What hormones do the *ovaries* produce?
- Estrogen and progesterone
What is *Hyperparathyroid*?
- Excess *PTH secretion* - Tumor in gland - Causes soft, fragile and deformed bones - increases blood Ca+2 - Renal calculi
What is *Cushing's syndrome*?
- Excess cortical secretion - Causes: *Hyperglycemia, hypertension, weakness, edema* - Muscle and bone loss occurs with protein metabolism - Buffalo hump & moon face= fat deposition between shoulders or in face
What is *Hypoparathyroidism*?
- Following gland trauma or removal or dietary magnesium deficiency **results in tetany, respiratory paralysis and death**
More on *Hyperinsulinism*
- From excess insulin injection or pancreatic islet tumor - Causes hypoglycemia, weakness and hunger - triggers secretion of epinephrine, GH and glucagon (side effects- anxiety, sweating and increase HR) - Insulin shock- uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness
What are some Developmental Aspects part III
- GH levels decline with age- Accounts for muscle atrophy with age TH declines with age, contributing to lower basal metabolic rates - PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH
What is *Endemic goiter*?
- Goiter- enlarged thyroid gland - Dietary iodine deficiency no TH, no-feedback, *increase TSH*
What is *Congenital hypothyroidism?*
- Infant suffers abnormal bone development, thickened facial features, low temp, lethargy, brain damage
What is the *function to testosterone*?
- Initiates maturation of male reproductive organs - Causes appearance of male secondary sexual characteristics and sex drive - Necessary for normal sperm production - Maintains reproductive organs in functional state
What are *glucocorticoids*?
- Keep blood glucose levels relatively constant - Maintain blood pressure by increasing action of vasoconstrictors - *Cortisol (Hydrocortisone)*- Only one in significants amounts in humans - Cortisone - Corticosterone
Thymus
- Large in infants and children; *shrink as age* - *Thymulin, thymopoietins and thymosins*
What is *Myxedema (adult hypothyroidism)*?
- Low metabolic rate - Sluggishness - Sleepiness - Weight gain - Constipation - Dry skin and hair - Cold sensitivity - Increase blood pressure and tissue swelling
What are the effects of *Insulin*?
- Lowers blood glucose levels - Enhances membrane transport of glucose into fat and muscles cells - Inhibits glycogenolysis and gluconeogenesis - Participates in neuronal development and learning and memory - *Not needed for glucose uptake in liver, kidney or brain*
What do *Mineralocorticoids* regulate?
- Regulate electrolytes (primarily Na+ and K+) in ECF - *Importance of Na+*- Affects ECF volume, blood volume, blood pressure, levels of other ions - *Importance of K+*- Sets RMP of cells
*Cortisol*
- Released in response to ACTH, patterns of eating and activity and stress - Prime metabolic effect is gluconeogenesis- formation of glucose from fats and proteins- Promotes rises in blood glucose, fatty acids, and amino acids - "Saves" glucose for brain - Enhances vasoconstriction--> rise in blood pressure to quickly distribute nutrients to cells
What is the function of the *Adrenal Medulla*?
- Response is brief - Epinephrine stimulated metabolic activities, bronchial dilatation, and blood flow to skeletal muscles and heart - Norepinephrine influences peripheral vasoconstriction and blood pressure
What is *Chronic pathology* of Diabetes?
- Chronic hyperglycemia leads to neuropathy and cardiovascular damage from atherosclerosis **Retina and kidneys (common in type I), atherosclerosis leading to heart failure (common in typer II), and gangrene**
thyroid development: thyroid diverticulum arises from ___ and descends into ___
floor of primitive pharynx neck
what is the normal remnant of the thyroglossal duct?
foramen cecum
adrenal cortex is derived from what germ layer?
mesoderm
What is the major target of *glucagon*?
Liver
What does the *Zona Reticularis* release?
*Gonadocorticoids*
What does *hyper-secretion of TH* lead to?
*Graves' disease*
What do *Pinealocytes* secrete?
*Melatonin* derived from serotonin
What does the *Zona Glomerulosa* release?
*Mineralocorticoids*
What hormone does the *Skeleton (osteoblasts)* produce?
*Osteocalcin* - Prods pancreas to secrete more insulin; restrict fat storage; improves glucose handling; reduces body fat - Activated by insulin - Low levels of osteocalcin in type 2 diabetes- perhaps increasing levels may be new treatment
*Hyper-secretion* of Gonadocorticoids
- *Adrenogenital syndrome (masculinization* - Not noticeable in adult males - Females and prepubertal males: - Boys: reproductive organs mature; secondary sex characteristics emerge early - Females- Beard, masculine pattern of body hair; clitoris resembles small penis
What are *Pancreatic islets* (Islets of Langerhans)?
- *Alpha (a) cells*- produce *glucagon* (hyperglycemic hormone) - *B cells*- Produce *insulin* (hypoglycemic hormone)
What hormone does the *heart* produces?
- *Atrial natriuretic peptide (ANP)*- decrease blood Na+ concentration, therefore blood pressure and blood volume
What hormone does the *kidney* produce?
- *Erythropoietin*- Signals production of rbc - *Renin*- initiates the renin-angiotensin-aldosterone mechanism
What are the *Entetoendocrine cells* of the GI tract?
- *Gastrin*- Stimulates release of HCL - *Secretin*- Stimulates liver and pancreas - *Cholecystokinin*- stimulates pancreas, gallbladder and hepatopancreatic sphincter - *Serotonin*- Acts as paracrine
What *effects* does glucagon have?
- *Glycogenolysis*- breakdown of glycogen to glucose - *Gluconeogenesis*- Synthesis of glucose from lactic acid and non-carbohydrates - Release of glucose to blood
What happens to *Calcitonin at higher than normal doses*?
- *Inhibits osteoclast* activity and release of Ca2+ from bone matrix - *Stimulates Ca2+ uptake* and incorporation into bone matrix
What does the *Adipose Tissue* produce?
- *Leptin*- Appetite control; stimulates increased energy expenditure - *Resistin*- Insulin antagonist - *Adiponectin*- enhances sensitivity to insulin
How's TH regulated?
- *Negative feedback regulates TH release* - Rising TH levels provide negative feedback inhibition on release of TSH - Hypothalamic thyrotropin-releasing hormone (TRH) can *overcome negative feedback during pregnancy or exposure to cold*
What are the *3 cardial signs of DM*?
- *Polyuria*- Huge urine output (glucose acts as osmotic diuretic) - *Polydipsia*- Excessive thirst (From water loss due to polyuria) - *Polyphagia*- Excessive hunger and food consumption (Cells cannot take up glucose; are "starving"
What is the *mechanism of Aldosterone secretion*?
- *Renin-angiotensin-aldosteone mechanism*- decreased blood pressure stimulates kidneys to release renin--> triggers formation of angiotensin II potent stimulator of aldosterone release - *Plasma concentration of K+*- increase K+ directly influences zona glomerulosa cells to release aldosterone - *ACTH*- Causes small increases of aldosterone during stress - *Atrial natriuretic peptide (ANP)- Blocks renin and aldosterone secretion to decrease blood pressure
What does *hypo-secretion of Glucocorticoids* lead to?
*Addison's disease*
What is the *most potent* mineralocorticoids?
*Aldosterone*- stimulates Na+ reabsorption and water retention by kidneys; elimination of K+
What hormone does the *skin* produce?
*Cholecalciferol*- precursor of vit D
What does *hyposecretion of TH in infants* lead to?
*Cretinism*
What does *hypersecretion of Glucocorticoids* lead to?
*Cushing's syndrome/disease*
What does the *Zona Fasciculata* release?
*Glucocorticoids*
What happens in *hyper-secretion* of the adrenal medulla?
- Hyperglycemia - Increase metabolic rate - Rapid heartbeat - Palpitations - Hypertension - Intense nervousness - Sweating
What could happen by a homeostatic imbalance of PTH?
- Hyperparathyroidism - Hypoparathyroidism
What does *untreated ketoacidosis* leads to?
- Hyperpnea - Disrupted heart activity and O2 transport - Depression of nervous system--> coma and death possible
Functions of the *Thyroid Hormone*?
- Major metabolic hormone - Increases metabolic rate and heat production (calorigenic effect) - Regulation of tissue growth and development: *Development of skeletal and nervous systems; and reproductive capabilities* - Maintenance of blood pressure
What is the *function of estrogen*?
- Maturation of reproductive organs - Appearance of secondary sexual characteristics - With progesterone, causes breast development and cyclic changes in uterine mucosa
What are the functions of *Thymulin, thymopoietins, and thymosins*?
- May be involved in normal development of T lymphocytes in immune response - Classified as hormones; act as paracrines
What are *Gonadocorticods (Sex hormones*
- Most *weak androgens* (male sex hormones) converted to testosterone in tissue cells, some to estrogens - May contribute to: - Onset of puberty - Appearance to secondary sex characteristics - Sex drive in women - Estrogens in postmenopausal women
What does *hyposecretion of TH in adults* lead to?
- Myxedema - Goiter (due to lack of iodine)
What happens in *hypo-secretion* of the adrenal medulla?
- Not problematic - Adrenal catecholamines are *not essential to life*
What are some Developmental Aspects part II
- Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur - Testosteron also diminishes with age, but effect is not usually seen until very old age
What are the *Adrenal (Suprarenal) Glands*?
- Paired, pyramid-shaped organs atop kidney - Structurally and functionally are 2 glands in one *Adrenal medulla*- Nervous tissue; part of sympathetic nervous system *Adrenal Cortex*- 3 layers of glandular tissue that synthesize and secrete corticosteroids
What are *Acinar cells*?
- Produce enzyme-rich juice for digestion
What is *Calcitonin*?
- Produced by *Parafollicular (C) cells* - No known physiological role in humans - *Antagonist* to parathyroid hormone (PTH)
Where is the *Pineal Gland*?
- Small gland hanging from roof of third ventricle
What are the functions of the *parathyroid hormone*?
- Stimulates *osteoclasts* to digest bone matrix and release Ca2+ to blood - Enhances *reabsorption of Ca2+* and secretion of phosphate by kidneys - Promotes *activation of vitamin D* (by kidneys); increases absorption of Ca2+ by intestinal mucosa ***Negative feedback control: rising Ca2+ in blood inhibits PTH release***
What is *Hypoparathyroid*?
- Surgical excision during thyroid surgery - Fatal tetany 3-4 days
Transport of TH
- T4 and T3 transported by thyroxine-binding globulins (TBGs) - Both bind to target receptors, but T3 is 10x more active than T4 - Peripheral tissues convert T4 to T3
How is the *Synthesis of Thyroid Hormone*?
- Thyroid gland stores hormone extracellularly - Thyroglobulin synthesized and discharged into follicle lumen - Iodides (I-) activist taken into cell and released into lumen - Iodide oxidized to iodine (I2) - Iodine attached to tyrosine, mediated by peroxidase enzymes - Iodine tyrosine link together to form T3 and T4 - Colloid is endocytose and combine with lysosome - T3 and T4 are cleaved and diffuse into bloodstream
What can *Melatonin* affect?
- Timing of sexual maturation and puberty - Day/night cycles - Physiological processes that show rhythmic variations (body temp, sleep, appetite) - Production of antioxidant and detoxification molecules in cells
Where is the *Pancreas*?
- Triangular gland partially behind stomach
The *Thyroid Gland*
- Two lateral lobes connected by median mass called *isthmus* - Composed of follicles that produce glycoprotein *thyroglobulin* - Collid (thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone - *Parafollicular cells* produce the hormone *calcitonin*
What are the effects of *epinephrine and nor-epinephrine*
- Vasoconstriction - Increased heart rate - Increased blood glucose levels - Blood diverted to brain, heart, and skeletal muscle
zona reticularis: primary regulatory control and secretory products
ACTH, CRH sex hormones (e.g. androgens)
What can *Hyperinsulinism* cause?
Causes *hypoglycemia* - Low blood glucose levels - Anxiety - Nervousness - Disorientation - Unconsciousness - Even death **Treated by sugar ingestion**
What is *Aldosteronism*?
Hyper-secretion due to adrenal tumors - Hypertension and edema due to excessive Na+ - Excretion of K+ leading to abnormal function of neuron and muscle
What is *Hyperinsulinism*?
Excessive insulin secretion
What kind of cells do the pancreas has?
Has both exocrine and endocrine cells *Acinar cells*- exocrine *Pancreatic islets*- endocrine
What does glucagon causes?
Increased blood glucose levels
What hormone is produced by the *Testes*?
Testosterone
adrenal medulla embryologic dericative
neural crest
thyroglossal duct cyst
presents as anterior midline neck mass that moves with swallowing or protrusion of tongue (vs. persistent cervical sinus leading to branchial cleft cyst in lateral neck)
zona glomerulosa: primary regulatory control and secretory products
renin-angiotensin aldosterone
the thyroid, in development, is connected to tongue by ___. what is the fate of this structure?
thyroglossal duct normally disappears but may persist as pyramidal lobe of thyroid
most common ectopic thyroid tissue site
tongue
adrenal cortex: layers from innermost to outer
zona reticularis zona fasciculata zona glomerulosa
