Introduction to Pathophysiology and Cellular Basis of Disease Part 5

ENDOCRINE ● Intro ○ Wireless ○ Endocrine gland - any gland or anything that releases chemical messenger (hormone) directly into bloodstream (endocrine release) ■ Hormone → once released into bloodstream, binds TO EVERY RECEPTOR THAT HAS AFFINITY FOR IT IN BODY ● Wide ranging effects on the body and ■ ● ○ Binding of hormone with receptor triggers one of the intracellular events: ○ Alters channel permeability by acting on pre-existing channel-forming proteins ■ Ex. cortisol. Changes brain permeability. Mental agility goes up in stressful situations ○ Acts through second-messenger system to alter activity of pre-existing proteins ■ Turn on/off enzymes ■ Ex. insulin. Binds to fat receptors. Turns on activity of enzymes needed to turn glucose into fat ○ Activates specific genes to cause formation of new proteins ■ Ex. puberty. Rise in estrogen/testosterone → increase growth of tissue ○ → Causes physiologic response Central vs peripheral endocrine gland structures ■ Central endocrine gland - part of CNS ● Parts of brain that release hormone that releases into bloodstream ○ Hypothalamus ○ Pineal gland ○ Pituitary gland ■ Peripheral - anything else ● ● Dedicated endocrine structures (endocrine glands that don’t have any other function besides endocrine release) ○ Thyroid hormone ○ Parathyroid hormone ○ Adrenal glands ● Mixed endocrine structures (organs of body that have other jobs as well as hormone release) ○ Kidneys - filter blood to produce urine and also releases EPO ○ Reproductive organs - produce gametes and releases hormones Chemical types of hormones and significance ○ 3 types of hormones ■ Peptide and protein hormones ● Chains of amino acids ■ Amino acid derived hormones ● Single amino acid gets modified and becomes hormone ■ Steroids hormones ● Derived from cholesterol → cholesterol converted to PREGNENOLONE → converted to other steroid hormone ○ Distinction between water-soluble and lipid-soluble hormones impact: ■ Hormone synthesis ● Don’t make steroid hormones in large amounts bc hard to store ■ Hormone storage ● Steroids hard to store ■ Hormone transport ● Lipids have trouble moving in bloodstream ○ Need binding protein (ex. albumin) to move ■ Lipid crosses plasma membrane FREELY ● ONLY LIPID HORMONES WILL AFFECT GENE EXPRESSION ● Water soluble MOVE FREELY IN BLOODSTREAM ○ Cannot cross membrane. Needs to bind to membrane receptor ■ Hormone interaction with target ■ All peptide derived hormone = WATER SOLUBLE EXCEPT THYROID (fat soluble) ● Lipid soluble = all steroids ● ○ Hormone subtypes ○ ■ ■ Synthesized by hypothalamus. Released by post pituitary ● Stored in intracellular vesicles, released when needed ADH has two names ● “Vasopressin” → “Pressin” bc of its pressor effects as vasoconstrictor ○ Binds to B1 rec on blood vessels ● ALSO ADH → ○ Binds to B2 on kidneys and causes increased water reabsorption ○ ■ ■ Very similar hormones Released by adrenal medulla. Acts as hormone and NT depends on how its released ■ Only T3 is active form of hormone ● T4 ‘s extra iodine must be removed to be active Structure evens out distribution of electrons → causes overall structure to be NONPOLAR → LIPID SOLUBLE even though amino acid derived ● Tend to cross membrane and change gene expression → codes for proteins that consume lots of energy → RELATED TO INCREASED METABOLIC RATE ○ ■ ○ Hyperthyroidism = anxiety inducing ○ ■ Steroid hormone synthesis ● ● Derive from cholesterol. Dietary or liver synthesized ○ Cholesterol is fat. Packaged in lipoprotein (LDL) to move through blood and bind to endocrine cells via LDL receptor. LDL gets internalized and broken down to cholesterol → pregnenolone → depends on what gland this is → produces aldosterone, cortisol, estradiol, testosterone ■ Each step requires ENZYME TO CONVERT ○ ■ Peptide can’t cross membrane. Triggers second messenger. Either: ● cAMP ● Ca++ ○ Initiate cascade of events to create cell response ○ ■ ● Steroids go straight to nucleus for gene expression ● Ex. thyroid hormone → enters nucleus → triggers production of protein (Na/K ATP pumps) → increase metabolism Control of hormonal secretion ○ NEGATIVE FEEDBACK REGULATION ■ ■ How much hormone is present in bloodstream directs if more hormone is needed to be produced HIERARCHICAL CONTROL ● Hormone 1 binds to endocrine gland 2 → releases hormone 2 that binds to endocrine gland 3 → releases hormone 3 that binds to target tissue ○ Hormone 3 communicates with endocrine gland 2 and 1 to stop production when it’s no longer needed ● Ex. hypothalamus (gland 1) → anterior pituitary (gland 2) → peripheral glands like thyroid (gland 3) ○ Thyroid hormone released by gland 3 communicates up ● ○ Anterior pituitary is TRUE ENDOCRINE GLAND ■ Posterior is just extension of hypothalamus ● ○ HYPOTHALAMUS → POSTERIOR PITUITARY → release of VASOPRESSIN and OXYTOCIN ■ Capillaries go from hypo straight to posterior ○ ANTERIOR ■ Hypo releases hormone into blood vessels of connecting stalk → hormone travels to anterior pituitary → anterior pituitary releases its own hormone: ● TSH (thyroid stimulating hormone) ● ACTH ( ● PROLACTIN (promote breast milk) ● GROWTH HORMONE ● ● LH/FSH ■ ■ ● KNOW what hypo releases and what anterior releases Regulation of GH Release ● ○ Hypothalamus releases two hormones that control the somatotrophs to synthesize and release Growth Hormone (GH) ■ ■ Somatostatin inhibits the release of GH, GHRH stimulates the release of GH ● ○ ○ ○ Growth hormone released during NONREM SLEEP Circadian/diurnal pattern – controlled by our brain and body’s 24-hour clock; release of GH differs during the day vs. night • GH released in pulses, with bigger and more frequent pulses (more GH release) during sleeping hours o ■ Anything that disrupts quality/quantity of sleep affects release of GH à affects overall body and health ● ○ ○ Thyroid gland ■ ● ● In each lobe, parathyroid gland ○ Important in regulation of calcium Thyroid gland → controls thyroid ● In follicular cell → colloid ■ Follicular cells synthesize thyroid hormone ● Thyroid hormone stored in colloid ○ Thyroid hormone released in blood capillaries ■ Parafollicular cell (C Cell) → release calcitonin ● Regulates calcium in body ■ T3 and T4 cause: ● Metabolic rate and symp activity ● Regulates series of genes that when expressed, consumes more energy à drives higher metabolism o ● T3 enters cell (T4 gets turned into T3 via enzyme) o ○ T3 binds to thyroid hormone receptor that sits on promoter region of gene sequences that control a lot of energyconsuming elements § ■ Na+/K+ pump § ■ Gluconeogenic enzymes – making more glucose § ■ Respiratory enzymes – for cellular respiration § ■ Myosin heavy chain – powers muscle contraction § ■ B-adrenergic receptors – sympathetic activity in the body Adrenal gland ■ • Adrenal glands sit on top of our kidneys • ● First major zone = inner region of adrenal gland = adrenal medulla ○ Produces catecholamines; mostly Epi, some NE o ○ Part of sympathetic NS • ● Second major zone = outer region of adrenal gland = adrenal cortex o ○ ○ ○ Produces all steroid hormones; sex hormones, glucocorticoids, and mineralcorticoids ● ■ ● ■ Mineral-corticoids are produced through glomerulosa cells only o ○ Enzyme needed to convert corticosterone (a glucocorticoid) to aldosterone (a mineral-corticoid) is only found in these cells • ● Three zones in the adrenal cortex – zona glomerulosa (outer layer), zona fasciculata (middle layer), and zona reticularis (innermost layer) o ○ Gluco-corticoids are synthesized in the zona fasciculata o ○ Mineral-corticoids are synthesized in the zona glomerulosa Cortisol = stress response o ● Elevates blood glucose levels § ○ ● ● ● ● ● ○ Pancreas ■ Break down muscle à free amino acids à triggers liver à break down glycogen + produce glucose à mobilize energy ○ Prevents insulin from bringing glucose into cells (which would drop blood glucose) § ○ Break down bone à release calcium à more muscle contraction • ■ Increase calcium secretion (counter-balance calcium release) o Sodium retention, potassium loss o Vasoconstriction à NE can better control BP o Anti-inflammatory à suppress immune responses o Increase excitability of the brain à think fast, alert/agile ○ CORTISOL LEVELS LOWEST IN EVENING. Highest just before waking ○ Helps you wake up