Endocrine Student Notes PDF

QUESTIONS & REVIEW A & P: Pathophysiology: Hormones DI & SIADH Hypothalamus Hyperthyroidism & thyroid Storm Pituitary (Ant/Post) Cushing’s & adrenal insufficiency Adrenals (Cortex/Medulla) DKA/HH...

QUESTIONS & REVIEW A & P: Pathophysiology: Hormones DI & SIADH Hypothalamus Hyperthyroidism & thyroid Storm Pituitary (Ant/Post) Cushing’s & adrenal insufficiency Adrenals (Cortex/Medulla) DKA/HHS Thyroid Parathyroid Pineal GROUP WORK: Endocrine Case QUESTIONS & REVIEW & GROUPS  HORMONES Chemical substance produced by specialized cells Transported to distant cells on which they exert regulatory effects Structural categories: water-soluble or lipid-soluble Classified as: Peptide Hormone: Water-soluble polypeptide chains that bind onto effector cell receptors inducing a cascade effect Amino Acid Hormone: Water-soluble substance derived from tyrosine and tryptophan which undergo enzymatic conversion and like peptide hormones bind to receptors on effector cell membranes. Ends with “in” or “ine” Steroid Hormone: Lipid-soluble substance which crosses the effector cell membrane to bind to a cytoplasmic receptor which allows passage into the nucleus, binding to DNA & initiating transcription Ends with “ol” or “one” HORMONE REGULATION Hormone secretion patterns: Diurnal Pulsatile & Circadian Levels of circulating substrates Feedback systems: Negative & positive Endocrine / Hormonal factors Chemical / Humoral factors Neural control  HORMONE RECEPTORS The sensitivity of a cell to a hormone is determined by the number of non-mutated receptors it has on its plasma membrane or within its cytoplasm specific for that hormone. The number of receptors and their hormone affinity can increase (up-regulation) or decrease (down-regulate) within hours, changing a cell’s sensitivity to hormone in response to the level of circulating hormone or conditions like pH & body temperature. diet PH temp R mutations drugs may all updown regulateRs HORMONE SIGNAL TRANSDUCTION Hormones are the FIRST MESSENGERS carrying external messages to a responding cell’s interior. Water-soluble hormones attach to plasma membrane receptors: - G-protein linked receptors - Ion channel receptors - Enzyme-linked receptors Lipid-soluble hormones attach to: - Plasma membrane receptors - Cytoplasmic receptors - Nuclear membrane receptors SIGNAL TRANSDUCTION: G-PROTEIN LINKED RECEPTORS Hormones, the first messengers, attachment to a G-protein linked plasma membrane receptor: 1. G- protein is activated 2. Activated G-protein reacts with guanosine triphosphate (GTP) 3. GTP activates the plasma membrane adenylyl cyclase enzyme 4. Adenylyl Cyclase catalyzes ATP→CAMP, a second messenger 5. cAMP activates protein kinase (PKA) 6. PKA activates several intracellular enzymes that act in metabolic I pathways that lead to entrance into the nucleus. 7. Affected transcription results in the synthesis of proteins which will produce the target cell’s response. cascade SIGNAL TRANSDUCTION: ION CHANNEL RECEPTORS Hormones / neurotransmitters open ion channels by direct attachment or by attachment to g-protein linked channels. - Changes membrane potential SIGNAL TRANSDUCTION: ENZYME LINKED RECEPTORS Hormone attachment to an enzyme-linked receptor leads to the activation of several enzyme systems within the cells. 🡨 🡨 Example: 1. Leptin, the first messenger, attaches to a plasma membrane enzyme receptor 2. Janus kinase 2 (JAK2), a second messenger is phosphorylated & activated 3. Signal transduction & activator (STAT) proteins are phosphorylated & activated to activate the transcription of genes for protein synthesis. 4. Other enzyme systems that produce the hormone’s effects are simultaneously activated by the second messenger. SIGNAL TRANSMISSION OF LIPID SOLUBLE HORMONES cytoplasmic complex 1 H man Xs Ito 99signal  HYPOTHALAMUS The hypothalamus is located below the thalamus, above the midbrain in the ventral diencephalon, connected to the pituitary gland. Comprised of nuclei, clusters of neuron cell bodies connected by their axons, linking the nervous & endocrine systems Nuclei produce hormones or hormone stimulating/inhibiting factors which will be transported or transmitted to the pituitary gland HYPOTHALAMIC FUNCTION The hypothalamus maintains homeostasis within an organism. - Temperature regulation - Food & water intake (satiety, hunger & thirst centers) - Sexual behavior & reproduction - Daily cycles (direct pathway from eyes) - Emotional & stress responses - Metabolism - Growth Anyhypothalamic injurycan disrupt temp PITUITARY GLAND (HYPOPHYSIS) accessedvia noseduring The pituitary gland is a pea-sized gland attached to the hypothalamus at the base of the brain. surgery It receives hormones for storage & release from the hypothalamus as well as hormone stimulatory and inhibitory factors which promote or inhibit hormone synthesis and release. Often referred to as the master gland whose hormones control almost every other endocrine gland’s activity. Partitioned into an ANTERIOR portion and a POSTERIOR portion mostlyunmyelinated secretory neurons THE POSTERIOR PITUITARY (NEUROHYPOPHYSIS) The posterior pituitary gland receives peptide hormones produced in the nuclei of the hypothalamus. - Oxytocin & Antidiuretic hormone (ADH or arginine-vasopressin) are synthesized and packaged in vesicles with carrier proteins. - Vesicles moved down the axons of the pituitary stalk for storage in the posterior pituitary gland. - Glutamate and GABA neurotransmitters stimulate or inhibit the hormones’ split from their carrier proteins and release from vesicles into the circulation. POSTERIOR PITUITARY HORMONES Oxytocin ADH ANTIDIURETIC HORMONE Antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates water reabsorption in the final collecting tubules of the renal nephron ADH Secretion from the posterior pituitary is triggered by an increased serum osmolarity sensed by osmoreceptors in the hypothalamus. Circulating ADH binds to V1 receptors in smooth muscle to cause vasoconstriction with resultant increased arterial BP. ADH binds to v2 receptors in the renal distal convoluted tubules stimulating aquaporin channel’s translocation from the cytoplasm to the apical membrane. Water passes out of the tubules and collecting ducts so that it can be reabsorbed into the blood Blood osmolarity is maintained  HYPOTHALAMIC - PITUITARY ALTERATIONS Arginine rasoness t Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Diabetes Insipidus (DI) Circulating ADH levels are high without appropriate feedback to the Disorder Deficient circulating ADH without appropriate feedback hypothalamus - Hypothalamic/Pituitary disruption Ismul - Polyuria - Polydipsia urine r300 - Ectopic source of ADH by tumor cells - Neurogenic DI caused by inadequate ADH - Nephrotic mutations in AVP genes with chronic V2 receptor activation - Nephrogenic DI caused by renal tubular collecting duct insensitivity to ADH Water retention with dilutional hyponatremia NOedema - Dipsogenic DI caused by excessive water intake with - Acute ↓Na+ 130-140 = Thirst, ↓ taste, DOE, fatigue, ↓mentation 120-130 = Vomiting, abdominal cramps dilution below the ADH threshold 110-115 = Confusion, muscle twitching, seizure Excessive water loss leads to ↑serum osmolality, - No edema sodium problemshypoNat hypo osmolar urine It + - Serum osmolality