Anatomy 2264 Exam IV PDF

Lower Order: Remember and Understand Define autonomic nervous system Autonomic Nervous System: - Controls involuntary responses - Contains the parasympathetic and sympathetic nervous system - Regulates the heart rate, respiration rate, maintain homeostasis List target tissue...

Lower Order: Remember and Understand Define autonomic nervous system Autonomic Nervous System: - Controls involuntary responses - Contains the parasympathetic and sympathetic nervous system - Regulates the heart rate, respiration rate, maintain homeostasis List target tissues for the ANS Target tissues for ANS: - Smooth muscle, cardiac muscle, glands, adipose tissue, Describe the anatomical organization of the sympathetic and parasympathetic nervous system The sympathetic nervous system is located along the spine- T1-L2 - sandwiched between PNS The parasympathetic nervous system is located on the cranial nerves of the brain AND the sacral region of the spinal cord Classify neurons of the sympathetic and parasympathetic divisions by their function/neurotransmitter The sympathetic nervous system: - “Fight or flight” response, speeding up heart rate, breathing rate - Epinephrine, norepinephrine - Preganglionic neuron in lateral horn of thoracolumbar spinal cord (T1-L2) - ACH (ACETYLCHOLINE) (nicotinic receptors) - is released from the preganglionic neurons - Synapse with postganglionic neurons in the sympathetic ganglia- go to target organs ** preganglionic shorter than post-ganglion Parasympathetic nervous system:  - “Rest and digest”/ “feed and breed” - Preganglionic neuron: originate in cranial nerves and the sacral region of the spinal cord (S2-S4) - Neurotransmitter Ach (ACETYLCHOLINE) (nicotinic receptors on the postganglionic neuron) - Receptor type: muscarinic receptors (M1, M2, M3) Division Neuron type Pregang Postgang receptors neurotransmitter neurotransmitter Sympathetic preganglioni ACh norepinephrine Nicotinic c (ACh) or Adrenergic (alpha and beta) postganglion Norepinephrine Adrenergic ic or ACh (alpha, beta) parasympathetic preganglioni ACH ACh Nicotinic c (ACh), muscarinic (M) postgang ACh M1, M2, M3 Summary: - Sympathetic division uses norepinephrine in postganglionic neurons - parasympathetic division uses ACH at both pre and post ganglion levels Sympathetic postganglionic neurons- adrenergic receptors (alpha, beta) Parasympathetic postganglionic neurons- muscarinic receptors (M)  Describe how messages that originate from the CNS ultimately reach their target tissues Through motor neurons and neurotransmitters - Upper and lower motor neuron to target tissue Classify receptors based upon their location within the ANS Sympathetic receptors: a) Adrenergic receptors: activated by norepinephrine or epinephrine i) Alpha receptors 1) Alpha 1- (a) Located on smooth muscle in blood vessels (vasoconstriction) the eye, and other target tissues- excitatory- increased BP, pupil dilation 2) Alpha 2 (a)Located on presynaptic nerve terminals- INHIBIT THE RELEASE OF NEUROTRANSMITTERS- (b) Inhibit norepinephrine release (negative feedback) platelet aggregation ii) Beta receptors 1) Beta 1 (a) Located in heart- increase heart rate, and conduction speed 2) Beta 2 (a) Relaxation of Smooth muscle in the lungs, blood vessels, and other tissues 3) Beta 3 (a) Found in adipose tissue where they facilitate lipolysis (b) Heat production b) Nicotinic receptors i) Found at ganglionic synapses of both sympathetic and parasympathetic division, where ACh is the neurotransmitter- located in the adrenal medulla Parasympathetic receptors - Primary neurotransmitter is acetylcholine (ACh) a) Cholinergic receptors- main receptors on target organs and are activated by ACh i) M1 receptors - found in the CNS 1) Excitatory GI secretion ii) M2 receptors: found in the heart 1) Inhibitory (decrease heart rate) iii) M3 receptors: smooth muscles and glands 1) Smooth muscle contraction, bladder contraction  b) Nicotinic receptors: found at ganglionic synapses of PNS- mediate transmission of signals at the NMJ i) Stimulates postganglionic neurons Define dual innervation and antagonistic control Dual Innervation: most organs and tissues in the body receive input from both brandes of AND: the sympathetic and parasympathetic NS - These two brandes hance opposing or complementary effects on the same organ or tissue, allowing for fine tuned regulation of physiological processes Example: - Heart: - Sympathetic: increased heart rate - Parasympathetic: decreased heart rate **not all organs have dual innervation: adrenal medulla is only innervated by Sympathetic fibers, and certain blood vessels mainly receive sympathetic input Antagonistic Control - Two branched of the ANS have OPPOSITE EFFECTS on a given organ or system allowing for balanced and dynamic regulation of physiological process - Heart rate: - Sympathetic stimulation: Increases heart rate (via beta-1 adrenergic receptors). - Parasympathetic stimulation: Decreases heart rate (via muscarinic receptors, particularly M₂). - - Dual innervation means that most organs receive input from both the sympathetic and parasympathetic systems. - Antagonistic control occurs when these two systems exert opposing effects on the same organ, allowing for fine control and balance of physiological functions. - Compare and contrast the fight or flight response with the rest and relax response Fight or Flight Response: - Sympathetic - Stress - Rapid response to danger - Less important regulations are pushed to the side Respiratory system: - Bronchodilation (opening of airways) via beta-2-adrenergic receptors, allowing more oxygen to reach lungs and blood Blood Vessels: Vasoconstriction in non-essential areas (e.g., digestive organs, skin) and vasodilation in skeletal muscles and heart to redirect blood flow to areas critical for action. Digestive System: Inhibition of digestive processes (decreased peristalsis, reduced secretion) to conserve energy and direct resources elsewhere. Adrenal Glands: Release of adrenaline (epinephrine) and noradrenaline (norepinephrine) from the adrenal medulla, which amplifies the effects of sympathetic stimulation. Rest and Digest: - Parasympathetic - Calm states, relaxation, recovery, rest - Conservation of energy Respiratory System: Bronchoconstriction (narrowing of airways) to maintain normal, relaxed breathing. Blood Vessels: Vasodilation in non-essential areas (like the digestive tract) to promote blood flow to the organs responsible for rest and digestion. Pupils: Pupil constriction (miosis), which is associated with a calm and relaxed state. Digestive System: Stimulated digestion with increased peristalsis and secretion of digestive enzymes to break down food and absorb nutrients. Adrenal Glands: Minimal to no release of adrenaline or noradrenaline, as the body is in a recovery state. Higher Order: Apply, Evaluate, Analyze Compare and contrast the somatic and autonomic nervous systems anatomically and functionally Anatomically: Somatic: Control: - voluntary responses- controls skeletal muscle and conscious movememnt Neuron Structure - One neuron pathway- a single motor neuron that extends from the CNS directly to the target muscle Neurotransmitter - ACh No Ganglia and heavily myelinated Autonomic: Control: - Involuntary responses- internal organs- heart, digestive system - controls smooth muscle, cardiac muscle, adipose tissue Neuron Structure - Two neuron pathway- involves two neurons; a preganglionic neuron and postganglionic neuron Neurotransmitter - ACh and norepinephrine Ganglia - Autonomic ganglia- preganglionic and post ganglion with synapses occurring in ganglia outside the CNS Myelination - Lightly myelinated (preganglionic and unmyelinated (post ganglionic) neurons Predict how stimulating or inhibiting neurons/receptors in the autonomic nervous system would impact the fight or flight response and rest and digest functions Stimulating the sympathetic NS: - Increased secretion of norepinephrine at postganglionic synapses - Heart: increase heart rate and contractility through beta-1 adrenergic receptors - Lungs: more airflow (beta 2 adrenergic) - Pupils dilate - GI tract: decreased peristalsis and secretion through inhibition of parasympathetic control Inhibiting the sympathetic NS: - Leads to reduced release of norepinephrine and epinephrine thereby suppressing the fight or flight response - Heart: decreases HR - Constricted airways - Decrease in BP - Pupils constricted - Decreased sweating - Decreased release of epinephrine Stimulation of Parasympathetic NS: - Stimulating parasympathetic neurons leads to increased release of acetylcholine at postganglionic synapses, activating muscarinic receptors - Heart: decrease heart rate through M2 muscarinic receptors  - Lungs: bronchoconstriction via M3 muscarinic receptors in the smooth muscle of the airways - Blood vessels: vasodilation - Pupils: constriction - GI tract: increased peristalsis, increased digestive enzyme secretion, and GI motility via M3 receptors Inhibition of Parasympathetic NS - Reduce acetylcholine release, suppressing it normal effects - Heart rate increase - Bronchodilation- airways open - Slight vasoconstriction - Pupils dilate - GI: decreased digestive activity, leading to slower digestion - Urinary retention Receptor and its effects if stimulated/ inhibited Adrenergic receptors activation (sympathetic) 1. Alpha- 1- receptors a. Stimulation: cause vasoconstriction, pupil dilation, smooth muscle contraction b. Inhibition: leads to vasodilation, pupil constriction, and relaxation of smooth muscle 2. Beta 1 receptors: a. Simulation: increases heart rate, force of contraction b. Inhibition: decreased heart rate and force of contraction 3. Beta 2 receptors: a. Stimulation: causes bronchodilation, vasodilation in skeletal muscle, and glycogenolysis in the liver b. Inhibition: leads to bronchoconstriction, vasoconstriction, and reduced glucose metabolism Muscarinic receptor activation (parasympathetic) 1. M2 receptors (heart) a. stimulation : decreases heart rate by hyperpolarizing the sinoatrial node b. Inhibition: increases heart rate by removing parasympathetic tone 2. M3 receptors (smooth muscle and glands) a. Stimulation: promotes smooth muscle construction (GI tract, bladder) and glandular secretion (salivation, digestive enzymes)  b. Inhibition: relaxes smooth muscles and reduces glandular recreation, leading to constipation and dry mouth Explain why dual innervation and antagonistic control are required for normal body function Both Dual Innervation and antagonist control are essential mehcanims in the AND that help maintain homeostasis and ensure that the body’s internal environment functions optimally- these mechanisms involve both the sympathetic and parasympatehtic divisions of the ANS working together to regulate opposite effects on various organs and systems ; balance between action and rest, arousal and calm or stimulation and inhibition of certain bodily processes Dual Innervation: - Balanced regulation: - Ensures that organs can be quickly adjusted based on the body’s needs - Example: the heart receives both sympathetic input (increase HR) and parasympathetic (decrease HR) - This allows the body to shift quickly between states of high activity and low activity maintaining optimal performance in both situations Antagonistic COntrol: - The fact that the sympathetic and parasympathetic NS often produce opposite effects on the same organ or physiological process - This antagonism allows for precise control over physiological states by acting as a push-pull mechanism - Fine control of physiological process: - By exerting opposite effects on the same organ, the sympathetic and parasympathetic systems can finely adjust the activity of that organ - Example: - Sympathetic releases norepinephrine which increase heart rate - Parasympathetic releases ACh which decreases heart rate during rest or recovery - Endocrine System Part 1 Describe the major classes of hormones, their properties, and how they are regulated. 1. Peptide a. Polypeptide.protein messengers- release hormones, glucagan, insulin b. Synthesized as preprohormones- (inactive) c. Processed to become prohormones (smaller but still inactive) d. Cleaved to become hormones e. Example- insulin f. Do not require carrier proteins to travel through the blood stream g. Bind to cell surface receptors on plasma membrane, triggering second messenger systems- cAMP 2. Steroid a. Insoluble to water and plasma b. Made of cholesterol c. R groups change but cholesterol structure stays d. Sex steroids- estrogen, progesterone, testosterone e. Corticosteroids- cortisol, aldosterone 3. Amine a. From single amino acids- thyroid hormones, epinephrine, dopamine, norepinephrine b. Tyrosine and tryptophan- used by pineal gland to produce melatonin Classify different types of GPCRs according to the signal cascades they are involved in (class diagram) 1) G alpha (s)--> Describe the downstream signaling events that occur upon stimulation or inhibition of adrenergic receptors (class diagram) Downstream signaling events?- series of molecular processes that occur inside a cell AFTER a receptor on the cell’s surface (adrenergic receptor) has been activated - When a receptor (like an adreergic receptor) is activated by a signal (like adrenaline) it sets off a chain of reaections inside the cell- downstream signaling events- bc they occur AFTER the receptor activation and lead to a final effect- like raising heart rate ro relaxing muscles General Process of Downstream Signaling 1. Alpha-adrenergic receptor Give an example of a peptide, steroid, and amine hormone and how each can be regulated at the hormone or receptor level.’ Peptide: insulin (regulates blood glucose level), GH (stimulates growth and cell reproduction), ADH (regulates water balance in the body), oxytocin - Regulation: negative and positive feedback Steroid: Cholesterol; can pass the membrane- lipid soluble (not soluble with water and plasma) sex hormones- estrogen, testosterone - Require transport proteins Regulation: negative feedback - the hypothalamic, anterior pituitary axis (class drawing) Amine: from single amino acids- thyroid hormones, epinephrine , - Include tryptophan which derivatives include serotonin and melatonin Regulation:negative feedback, circadian rhythm Hormone class example Regulation at Regulation at hormone level receptor level peptide insulin Negative feedback Insulin resistance: by blood glucose receptors become levels- secretion less sensitive in increases with high conditions like type glucose and 2 diabetes decreased with low glucose steroid cortisol Negative feedback Glucocorticoid via Hypothalamus - receptor sensitivity- anterior pituitary can decrease in chronic stress or inflammation amine Thyroid hormones Negative feedback/ Thyroid hormone circadian rhythm resistance Describe a receptor tyrosine kinase A type of protein receptor on the surface of a cell that helps the cell respond to signals from the outside environment, such as growth factors or hormones - Span the cell membrane - Function: add a phosphate group to tyrosine ; turns on the receptor and starts a signaling cascade inside the cell How it works: - Binding of signal: - A signaling molecule- growth factor: binds to the extracellular part of the RTK on the cell surface (key and lock” - Receptor dimerization:  - When the signal molecule binds, the two RTK molecules come together - Autophosphorylation: - When the two RTKs bind together, the intracellular part of each receptor adds phosphate groups to tyrosine resides on the other receptor in the pair- auto phosphorylation- activates the receptors- like turning on a switch - Activation of intracellular signaling: - The phosphate groups on the tryosines act like “tags” that attract other proteins inside the cell- these proteins send signals to other parts of the cell, leading to various responses - Cell growth and division - Changes in cell shape - Cellular response Higher Order: Concepts to Analyze and Apply Compare and contrast the mechanism of action between lipid and water soluble hormones Lipid soluble hormones= need a carrier protein to move through water-based blood; can pass the membrane freely - Bind to intracellular receptors inside the target cell Mech of action: - lipid -soluble hormones travel in the bloodstream while bound to carrier proteins - They enter through the cell membrane (lipid bilayer) - Bind to intracellular receptors: hormone binds to a recepot in the cytoplasm or nucleus - The hormone receptor complex acts as a transcription factor- binding to specific regions of DNA to regulate gene expression; ON OR OFF Example: cortisol, (steroid hormone) binds to a receptor in the cytoplasm and the hormone receptor moves into the nucleus where it influences gene expression related to metboilism, stress response, and inflammation Water soluble hormones= do not need a carrier protein in the bloodstream - Bind to cell surface receptors because they cannot pass through the lipid bilayer of the cell membrane - Receptors on the cell surface are typically G-protein coupled receptors (GPCR) or RTKs Mech of action: - Water soluble hormones travel freely in the bloodstream to target cells - Since they cannot pass the cell membrane, water soluble hormones bind to specific receptors on the plasma membrane  - When the hormone binds ot its receptor, the receptor undergoes a conformational change and activities intracellular signaling pathways- cAMP, which amplifies the signal inside the cell - This causes a signaling cascade; on or off switch Ex- insulin=peptide hormone- binds to insulin receptors on the surface of target cells - This binding activates intracellular signaling pathways leading to the insertion of glucose transports into the cell membrane, allowing glucose to enter the cell Predict how changes in receptor expression and hormone half life impact the biological activity of a hormone Changes in a receptor expression and hormone half life impact the biological activity of a hormone: can affect how a hormone signals within the body and how strongly and for how long the hormone exerts its effects Changes in receptor expression - The expression of receptors on target cells determines how sensitive those cells are to a particular hormone - Upregulation - If the number of receptors for a hormone increases, the target cells will become more sensitive to that hormone; less hormone will be needed to produce a response OR the same amount of hormone will cause a stronger effect - Downregulation - If the number of receptors for a hormone decreased the target cells become less sensitive to that hormone this means that more hormone will be needed to achieve the same biological effect or the same amount of hormone will cause a weaker response Changes in Hormone Half-Life - The half-life is the amount of time it takes for the hormone to be cleared from the bloodstream- this affects how long a hormone remains active and how long it can produce biological effects Increased hormone half life - Effect on biological activity: if a hormones half-life increases (it stays in the bloodstream longer) the hormone will have a prolonged effect because it remains available to bind to its receptors for a longer period of time Decreased Hormone Half-life - If a hormones half-life decreased its biological activity will be shorter-lived - The hormone will need to be produced or released more frequently to maintain its effects (example- epinephrine “fight or flight” is short lived and only needs a short half life)  Compare and contrast the endocrine system to the nervous system Both play a role in maintaining homeostasis, regulating body functions,a nd enabling communication within the body Nervous System: - Runs off of electricity - Faster - Direct pathway - Precise locations - Reflex arcs; inhibition and excitation- regulation Endocrine system: - Comparatively slower - Chemical signaling- glands - Global - Negative and positive feedback Compare and contrast different g-protein receptor subtypes G-protein receptor subtypes: 1. Gs coupled a. Beta adrenergic receptors b. Gs GPCR coupled to Gs proteins, which activate adenylyl cyclase (AC) c. Activation of Gs leads to increase in cAMP i. cAMP acts as a second messenger, activating protein kinase A (PKA) which the phosphorylate target proteins, leading to various cellular responses d. Increase in heart rate e. Smooth muscle relaxation f. Metabolic regulation 2. Gai a. Muscarinic M2 receptors, alpha2 adrenergic receptors, dopamine D2 receptors b. G-protein activation: Gi GPCR couple to Gi or Go proteins which inhibit adenylyl cyclase (AC) decreasing cAMP, and activate other signaling pathways i. Inhibition of cAMP leads to reduced activation of PKA ii. Inhibition of neurotransmitter release iii. Decreased heart rate, smooth muscle contraction  c. Gaq i. Alpha 1 adrenergic receptors, ii. G protein activation: Gq GPCRs couple to Gq proteins which activate phospholipase iii. Smooth muscle contraction iv. Cell proliferation and differentiation d. The alpha 1 adrenergic receptor responds to norepinephrine by i. Activating PLCB, leading IP3 and DAG production resulting in calcium release and smooth muscle contraction causing vasoconstriction Compare and contrast GPCRs and RTKs GPCRs vs RTKs GPCRs: - Have 7 transmembrane loops that span the cell membrane- single polypeptide chains - When a ligand binds to the extracellular domain of the GPCR, it undergoes a conformational change, activating an intracellular G-protein - When ligand binds to the GPCR, the receptor undergoes a conformational change that activates ana associated G-protein ** signaling pathways: cAMP production, PLC levels (intracellular calcium levels) - Gas→ cAMP→ PKA (protein kinase A) - Gai→ decreased cAMP→ inhibition of PKA - Qaq→PLC→IP3/DAG→PKC→Ca++ signaling Duration: - Fast and transient signaling response- short lived effects due to rapid dissension and internalization of the receptor G-protein signaling termination RTKs - Single pass transmembrane proteins with large extracellular ligand-binding domain and a cytoplasmic kinase domain - They have a single polypeptide chain with an intracellular region that contains tyrosine kinase activity  - Activation: ligand binding induces dimerization of the receptor, leading to autophosphorylation of tyrosine residues on the intracellular domain - Activate tyrosine kinase signaling pathways through phosphorylation of specific tyrosine residues - Lead to long term effects: cell differentiation, growth, survival, metabolism Duration: - Slower, but longer lasting - Results in changes to gene expression, cell growth, differentiation, and survival over a longer period of time GPCR: - Beta adrenergic receptors (epinephrine/norepinephrine signaling) - Muscarinic acetylcholine receptors (Parasympathetic NS) - Dopamine receptors - Serotonin receptors - Olfactory receptors - Vision RTKs - Insulin receptors - Epidural growth factor receptor - Vascular endothelial growth factor receipts  Lower Level: Knowledge and Comprehension: Do you know the general classifications of hormonal regulation? Endocrine Regulation: endocrine glands secrete hormone directly into bloodstream: transported to target organs or tissues, where they exert their effects Paracrine Regulation: paracrine signaling involves the release of hormones or signaling molecule that affect nearby cells- these molecules are not released into the bloodstream but act on neighboring cells or tissues Autocrine regulation: - Hormone or signaling molecule being released by a cell that acts on itself or on the same type of cell that produced it - cytokines that are produced by immune cells and act on the same cells to regulate their immune response Neuroendocrine regulation: neurocrine signaling: when hormones or neurotransmitters are released by neurons and affect target cells including other neurons, muscles, or glands Positive and Negative Feedback loops: Negative feedback: -most common form of hormonal regulation, where the output of a system inhibits further hormone secretion. When a physiological parameter such as blood glucose or body temp reaches a set point, the system stops releasing the hormone to prevent overcorrection -example: thyroid hormone: controlled by negative feedback; when thyroid hormone levels are high, they inhibit the release of TRH from the hypothalamus and TSH (thyroid-stimulating hormone) from the pituitary, which in turn reduces thyroid hormone production Positive Feedback: - The release of a hormone stimulates further release of the hormone, creating a cascade effect- positive feedback is less common and typically occurs in processes that need to completed rapidly - Example: Oxytocin during labor- open the cervix which causes contractions which stimulate more oxytocin release leading to stronger contractions and eventual birth Can you define permissiveness? Permissiveness: where the presence of one hormone (thyroid hormone) enhances the action of another hormone, allowing it to exert its full effect. Thyroid hormones T3 and T4 play a key permissive role in the body, meaning they don't directly cause a specific physiological response but make other hormones more effective or enable their action Thyroid hormones are known to amplify the effects of other hormones on various tissues and organs 1. Thyroid hormones and growth hormones: a. T3 enhances the effectiveness of growth hormone in stimulating growth and development b. Thyroid hormones increase the number and sensitivity of growth hormone receptors on cells, allowing GH to exert its full effects on growth, protein synthesis, and bone development 2. Thyroid hormones and epinephrine (adrenaline) a. Thyroid hormones also have permissive effect on epinephrine i. Thyroid hormone increases the number of adrenergic receptors (beta-adrenergic receptors) on target cells heart, muscle, adipose tissue) ii. This allows epinephrine to exert stronger effects like increasing heart rate and promoting lipolysis (fat breakdown) 3. Thyroid hormones and indulin a. Thyroid hormones enhance the action of insulin in promoting glucose uptake and glycogen synthesis in various tissues in the muscle and liver Can you describe the hierarchical control of hypothalamic-pituitary axes? The regulation of various endocrine functions through a system where hypothalamus and pituitary gland plat central roles in coordinating the release of hormones that control other endocrine glands  ***hypothalamus controls the anterior pituitary, which in turn regulates the function of peripheral endocrine glands - This ensures right control and coordination of key physiological processes such as metabolism stress response, reproduction, and growth The hypothalamus releases releasing hormones (or inhibiting hormones) that control the release of hormones from the anterior pituitary, which then stimulates the release of hormones form the peripheral endocrine glands Example: 1. Hypothalamus: the hypothalamus releases TRH into the blood a. TRH is a releasing hormone that stimulates the anterior pituitary to release thyroid stimulating hormones (TSH) 2. Anterior pituitary: in response to TRH, the anterior pituitary releases TSH into the bloodstream. TSH acts on the thyroid gland to stimulate the production and release of thyroid hormones (T3 and T4) 3. Thyroid Gland a. The thyroid gland released T3 and T4 which regulate the metabolic processes throughout the body, including energy metabolism, growth, and development 4. Negative feedback: a. Levels of T3 and T4 in the bloodstream act ont he hypothalamus and anterior pituitary to inhibit the release of TRH and TSH, respectively b. This negative feedback loops helps maintain the appropriate levels of thyroid hormones in the body Can you define a releasing, tropic, and effector hormone? Releasing, Tropic, and effector hormone: Releasing hormone: a hormone secreted by hypothalamus that stimulates the release of another hormone from the anterior pituitary gland - Function: releasing hormones regulate the secretion of tropic hormones from the anterior pituitary which in turn regulate the activity of peripheral endocrine glands (thyroid, adrenal glands) - Examples: TRH (thyrotropin-releasing hormone, TSH (thyroid-stimulating hormone, GH, GHRH - growth hormone and growth hormone releasing hormone Tropic Hormone: a hormone released by the anterior pituitary that stimulates the release of effector hormones form the peripheral endocrine glands  - Function: tropic hormones act as “intermediate” messengers, directing other glands to release their specific hormones - Regulated by releasing hormones from the hypothalamus and are key to maintaining physical processes such as growth, metabolism , and reproduction - Examples: TSH, GH Effector Hormone: - Effector hormone is a hormone produced and secreted by a peripheral endocrine gland in response to stimulation by a tropic hormone - Effector hormones exert endocrine gland in response to stimulation by a tropic hormone- effector hormones exert their effects on target tissues or organs - Function: the final mediators of the hormonal cascade - Typically regulate long-term functions such as metabolism, growth, reproduction, and stress response *** effector hormones Exert negative feedback on the hypothalamus and AP to regulate their own levels and maintain homeostasis - Do you know the various levels of negative feedback loops? 1. Ultra short a. Releasing hormone on hypothalamus: can cause inhibition of that same releasing hormone from being secreted further 2. Short loop a. Tropic hormone on hypothalamus b. When the anterior pituitary hormone itself acts to inhibit the secretion of hypothalamic releasing hormones 3. Long loop a. When the effector hormone (released from the peripheral endocrine gland) acts on both the hypothalamus and anterior pituitary to inhibit the release of their respective hormones b. The final hormone in a signaling cascade (the effector hormone) provides feedback to both the hypothalamus and anterior pituitary, reducing the secretion of the releasing hormone and tropic hormone, respectively Can you give examples of positive feedback loops? Birth, blood clotting, lactation,  ` Do you know how growth hormone secretion is regulated? Growth hormone secretion is regulated through hormones released by the hypothalamus Complex interaction of signals from the hypothalamus, the anterior pituitary, and other hormones, with both stimulatory and inhibitory factors at play Feedback loop that maintains GH levels within an optimal range, ensuring proper growth and metabolism The hypothalamus plays a central role in regulating the secretion of GH by releasing specific releasing hormones and inhibitory hormones - GHRH: the hypothalamus secretes GHRH which stimulates the anterior pituitary to release GH - GHIH- inhibits growth hormone: hypothalamus releases somatostatin, which inhibits GH secretion from the anterior pituitary Anterior Pituitary: site of GH production and secretion - Responds to GHRH and somatostatin which inhibits GH secretion Negative feedback as well Can you describe the direct and indirect effects of growth hormone? Direct effects of growth hormone:Primarily due to its interaction with GH receptors on the surface of various tissues, leading to various biological responses 1. Increased protein synthesis: a. GH stimulates protein synthesis in many tissues, particularly in muscle, by enhancing the translation of messenger RNA (mRNA) into proteins 2. Lipolysis (fat breakdown) i. GH promotes the breakdown of stored fat (lipolysis) in adipose tissue ii. It does this by stimulating the release of free fatty acids from dat cells which can be used as an energy source 3. Carbohydrate metabolism a. GH has an anti-insulin effect (insulin resistance) it reduces the effectiveness of insulin, causing an increase in blood glucose levels by decreasing glucose uptake into cells b. This effect is thought to be adaptive, providing more energy substrates for growth and metabolism c. Over time, this can contribute to insulin resistance, which is observed in individuals with prolonged excess GH  4. Bone growth a. GH firstly influences bone metabolism by acting on bone cells to increase bone turnover, including the mineralization of bone and the formation of the extracellular matrix Indirect effects of Growth hormone: 0 the indirect effects of GH are primarily mediated by IGF-1 a protein that is predominantly produced in the liver and in other tissues in response to GH IGF-1 acts as the major mediator of GH’s growth-promoting effects, particularly on bone and cartilage 1. Promoting linear growth (bone growth) a. One of the most important indirect effects of GH is through the stimulation of IGF-1 in bone and cartilage, particular in the growth plates of long bones b. IGF-1 promotes the proliferation of chondrocytes (cartilage cells) in the growth plate, leading to the lengthening of bones i. This contributes to height growth during childhood and adolescence 2. Cellular growth and tissue repair 3. Cartilage formation 4. Insulin like metabolic effects 5. Maintenance of bone mineral density Can you describe the anatomy of the thyroid gland? “Butterfly shape” Location: in the neck, just below the larynx (voice box) and in front of the trachea (windpipe) - It is positioned on either side of the trachea, and the gland often has a characteric butterfly shape Colloid - Surrounded follicular cells (functional unit of the thyroid gland) - Consists of thyroid endothelial cells that surround a central colloid- filled cavity - Secrete T3 (triiodothyronine) and T4 (Thyroxine) Parafollicular cells= produce calcitonin (lowers calcium)  Do you know how thyroid hormone is regulated, synthesized, and secreted? Regulated: - Thyroid hormone is regulated by the hypothalamus/pituitary peripheral gland axis (Hypothalamic-pituitary-thyroid HPT axis) 1. Hypothalamus a. The hypothalamus regulated thyroid hormone production through the release of TRH (thyrotropin-releasing-hormone) 2. Pituitary gland a. TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH) known as thyropin b. TSH binds to TSH recepots on thyroid follicular cells and activates the synthesis and release of thyroid hormones (T3 and T4) from the thyroid gland 3. Thyroid gland a. In response to TSH, the thyroid gland synthesises and secretes T3 and T4 which are released into the bloodstream Synthesized: - Thyroid hormone is synthesized within the thyroid follicles which are the functional units of the thyroid gland in steps: 1. Iodine is a key component of thyroid hormones. The thyroid gland actively takes up iodine from the blood stream through a sodium-iodine symporter NIS located on the basolateral membrane of thyroid follicular cells a. The iodine is transported into the thyroid follicular cells from the blood where it is used for the synthesis of thyroid hormones b. The iodine concentration inside th thyroid gland is MUCH HIGHER THAN IN THE BLOOD allowing efficient production of thyroid hormones c. Once inside the colloid, iodine is oxidized by the enzyme thyroid peroxidase and then imported into tyrosine resides of thyroglobulin. This forms MIT and DIT d. MIT and DIT molecules within the thyroglobulin molecule are then coupled by thyroid peroxidase (TPO) to form the thyroid hormones i. T3 formed by the coupling of one MIT and one DIT ii. T4 formed by the coupling of two DIT molecules e. The iodinated thyroglobulin (containing T3 and T4) is stored in the colloid of the thyroid follicles until the thyroid hormones are needed. ****From notes: adding iodine to thyroglobulin that is stored in the colloid\ Secreted: - Once T3 and T4 are synthesized and stored in the form of iodinated thyroglobulin, the thyroid gland can release these hormones into the blood stream when needed 1. Endocytosis of thyroglobulin a. When thyroid hormone secretion si stimulated by TSH, thyroglobulin stored in the colloid is taken up the thyroid follicular cells through endocytosis i. The thyroid cells engulf the colloid, forming vessels that bring the thyroglobulin into the cytoplasm 2. Step 2: Lysosomal Cleavage a. The vesicles fuse with lysosomes, where proteases break down the thyroglobulin, releasing the free T3 and T4 molecules. b. T4 (thyroxine) is released in much greater quantities than T3, but T3 is the more active form of the hormone. 3. Step 3: Release into the Bloodstream a. T3 and T4 are then released into the bloodstream, where they bind to plasma proteins like thyroxine-binding globulin (TBG), albumin, and transthyretin. These proteins serve to transport the thyroid hormones in the blood and maintain a reservoir of hormones for when they are needed. b. T4 is released in larger amounts, but much of it is converted into the more active T3 in peripheral tissues like the liver, kidneys, and muscle. Can you describe the cellular and systemic effects of thyroid hormone? Cellular effects of the thyroid hormone: - Thyroid hormones primarily ecert their effects by binding to specific receptors in the nucleus of target cells, where they influence gene expression 1. Gene expression and protein synthesis a. T3 is the most biologically active thyroid hormone, and it binds to thyroid hormone receptors TRs in the nucleus  b. These receptors then bing to specific DNA sequences known as thyroid hormone response elements (TREs), which regulate the transcription of genes involved in metabolic processes c. T3 and T4 regulate the synthesis of enzymes that control energy production, lipid and carbohydrate metabolism, and protein turnover d. T3 upregulates genes that increase the activity of mitochondrial enzymes involved in oxidase phosphorylation, leading to increased ATP production 2. Increased basal metabolic rate (BMR) a. One of the most important cellular effects of thyroid hormones is the increase in basal metabolic rate (BMR) b. Thyroid hormone stimulate the mitochondria to produce more ATP which increases the energy expenditure of cells and overall body metabolism c. They also increase the expression of uncoupling proteins in mitochondria, which dissipate energy as heat rather than storing it, or thermogenesis 3. Protein and lipid metabolism a. Protein synthesis and breakdown b. Lipolysis: breakdown of stored fat 4. Glycogen breakdown 5. Gluconeogenesis- creating glucose energy from non carb sources 6. Increased transcription of Na/K ATPase: increase oxygen consumption 7. Enhanced cholesterol synthesis a. LDL (low density lipoproteins) regulation (uptake) energy regulation Systemic Effects of Thyroid Hormones: at the systemic level, thyroid hormones regulate a wide variety of physiological processes including growth and development, cardiovascular function, respiratory function, neurological function, and reproductive health 1. Cardiovascular system a. Increased heart rate and cardiac output: thyroid hormones increase heart rate and contractility (positive inotropic effect) by increasing the expression of adrenergic receptors in the heart, enhancing sensitivity to catecholamines (such as norepinephrine and epinephrine) this leads to increased cardiac output and enhances delivery of oxygen and nutrients to tissues b. Vascular Tone: Thyroid hormones cause vasodilation in many tissues, reducing peripheral vascular resistance and thus contributing to a lower diastolic blood pressure. However, the systolic blood pressure may remain elevated due to the increased cardiac output. **from notes: - Increase BMR (basal metabolic rate) and heat production  - calorigenic effect through glycogen breakdown, gluconeogenesis - Synthesis of adrenergic receptors - Permissiveness - Regulator of tissue growth and development - Required for skeletal and CNS development/maturation Upper Level: Apply, Evaluate, and Analyze Can you compare and contrast different types of regulation? Can you predict the effects of disease in various endocrine tissues? Hypothyroidism (Underactive thyroid) - Causes - Iodine deficiency - Thyroidectomy - Oituitray or hypothalamic dysfunction - Effects - Metabolic slowing - Fatigue - Weight gain - Cold intolerance - Constipation - Bradycardia - Depression - goiter Hyperthyroidism (overactive thyroid) - Causes: - grave’ s disease - Effects: - Increased metabolic rate: elevated levels of thyroid hormones increase BMR, causing weight loss, heat intolerance, and increased sweating - nervousness/anxiety - Hyperactivity: mental and physical hyperactivity can occur - Muscle weakness - Osteoporosis Cushing's Syndrome (Excess Cortisol)  Causes: ○ Pituitary adenoma (Cushing's disease) causing overproduction of ACTH. ○ Adrenal adenoma or carcinoma causing overproduction of cortisol. ○ Exogenous corticosteroid use (e.g., prednisone). Effects: ○ Central Obesity: Fat redistribution leads to moon face, buffalo hump, and abdominal fat deposition. ○ Hyperglycemia: Elevated cortisol leads to insulin resistance and high blood sugar. ○ Hypertension: Cortisol increases blood pressure by promoting sodium retention. ○ Skin Changes: Thin, fragile skin, easy bruising, striae (stretch marks). ○ Osteoporosis: Chronic elevated cortisol leads to bone loss and increased fracture risk. 3. Pancreatic Disorders Diabetes Mellitus Type 1 (Insulin-Dependent Diabetes) Causes: ○ Autoimmune destruction of pancreatic beta cells, leading to insulin deficiency. Effects: ○ Hyperglycemia: Lack of insulin leads to high blood sugar levels. ○ Polydipsia (excessive thirst) and polyuria (excessive urination) due to the kidneys trying to excrete excess glucose. ○ Fatigue: Inability to use glucose for energy results in fatigue and weakness. ○ Weight Loss: Despite high blood sugar levels, lack of insulin leads to the breakdown of fat and muscle. ○ Ketoacidosis: In the absence of insulin, the body breaks down fats for energy, leading to the production of ketone bodies (which can lead to diabetic ketoacidosis). Diabetes Mellitus Type 2 (Insulin Resistance) Causes: ○ Insulin resistance (cells do not respond properly to insulin). ○ Beta cell dysfunction leading to inadequate insulin production.  ○ Risk factors include obesity, sedentary lifestyle, and genetic predisposition. Effects: ○ Hyperglycemia: Due to impaired insulin action and inadequate insulin production. ○ Polydipsia and Polyuria: Excessive thirst and urination due to hyperglycemia. ○ Fatigue and Weight Gain: Insulin resistance prevents effective use of glucose, leading to fatigue and potential weight gain. ○ Increased Risk of Cardiovascular Disease: Elevated blood sugar and insulin resistance contribute to hypertension, dyslipidemia, and atherosclerosis. 5. Pituitary Gland Disorders Pituitary Adenomas Causes: ○ Benign tumors in the pituitary gland leading to either overproduction or underproduction of pituitary hormones. Effects (depending on the hormone affected): ○ Prolactin excess: Causes galactorrhea (inappropriate milk production) and amenorrhea in women, and can cause erectile dysfunction in men. ○ Growth hormone (GH) excess: Causes gigantism in children (excessive growth) and acromegaly in adults (enlargement of bones, especially in the hands, feet, and face). ○ ACTH excess: Leads to Cushing's disease, with symptoms like obesity, hypertension, and hyperglycemia. Could you hypothesize the effects of hormonal drugs? Hormonal drugs can mimic, enhance, or inhibit action of natural hormones in the body - Depends on their mechanism of action and the hormone they target Absolutely! Hormonal drugs can either mimic, enhance, or inhibit the actions of natural hormones in the body. They are widely used in the treatment of various endocrine and non-endocrine conditions, ranging from hormone replacement therapy (HRT) to drugs that modify metabolic or reproductive function. The effects of these drugs depend on their mechanism of action, the hormone they target, and the specific tissues or organs they affect. Here’s a breakdown of the hypothesized effects of various types of hormonal drugs: 1. Thyroid Hormones (Levothyroxine, Liothyronine) Mechanism of Action: These drugs provide synthetic thyroid hormones (typically T4 or T3) to replace or supplement the natural thyroid hormones in cases of hypothyroidism. Hypothesized Effects: Hypothyroidism (Underactive Thyroid): ○ Increase Basal Metabolic Rate (BMR): Synthetic thyroid hormone boosts cellular metabolism, leading to increased energy and fat loss. ○ Improved Cognitive Function: Reduces the brain fog, depression, and fatigue often seen in hypothyroidism. ○ Restoration of Normal Thermoregulation: The body becomes more capable of maintaining normal temperature, reducing cold intolerance. Can you interpret disruption of negative feedback loops at varying levels? Disruption of negative feedback loops at various levels of the endocrine system can have significant physiological consequences - Negative feedback loops are essential for maintaining homeostasis, ensuring that hormone levels and physiological process stat within an optimal range - When these loops are disrupted at any point- whether at the hypothalamic, pituitary, or target gland level- it can lead to hyperfunction or hypofunction of the endocrine glands - To interpret the effects of discussions in negative feedback it is important to consider the three main levels 1. Hypothalamic level (regulation of hormone secretion by the hypothalamus)  a. At the hypothalamic level, the hypothalamus senses changes in hormone levels or physiological condition and released releasing hormones that stimulate or inhibit the secretion of hormones from the pituitary gland - disrupting this can interfere with the entire hormonal cascade that regulates endocrine function b. EXAMPLE: Hypothalamic-pituitary-thyroid axis i. Disruption at the Hypothalamic Level: ii. If the hypothalamus is unable to detect or respond appropriately to the levels of thyroid hormones (e.g., due to damage or a genetic mutation in TRH production), it might continue to produce TRH despite elevated thyroid hormone levels. iii. As a result, TSH levels would remain high, leading to overstimulation of the thyroid gland, which could cause hyperthyroidism (e.g., Graves' disease). iv. Conversely, if the hypothalamus fails to produce sufficient TRH in response to low thyroid hormones (due to hypothalamic dysfunction), this could lead to hypothyroidism despite normal TSH levels. 2. Pituitary Level (Regulation of Hormone Secretion by the Pituitary Gland) The pituitary gland is often referred to as the "master gland" because it regulates the release of many hormones that control other endocrine glands (like the thyroid, adrenal glands, and gonads). Disruption at the pituitary level affects the downstream glands and their hormone production. Example: Hypothalamic-Pituitary-Adrenal Axis (HPA Axis) - Normal Feedback Loop: The hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal cortex to secrete cortisol. High levels of cortisol provide negative feedback to both the hypothalamus and the pituitary, inhibiting the release of CRH and ACTH. - Disruption at the Pituitary Level: - If the pituitary is damaged (e.g., due to a tumor or injury), it might fail to release adequate ACTH, leading to insufficient cortisol production from the adrenal glands. This condition is known as secondary adrenal insufficiency. - On the other hand, a pituitary adenoma (tumor) could cause the excessive release of ACTH, resulting in Cushing’s disease,  with symptoms such as weight gain, hypertension, hyperglycemia, and osteoporosis. - Disruption of Negative Feedback: - If the negative feedback loop is not functioning properly (e.g., due to a pituitary tumor secreting excess ACTH), cortisol levels might become excessively elevated, overriding normal regulatory mechanisms and causing Cushing's syndrome. - In contrast, if the pituitary fails to respond to cortisol levels and continues to release ACTH in excess, this will lead to excessive stimulation of the adrenal glands, causing hypercortisolism. Disruption of negative feedback loops at various levels of the endocrine system can have significant physiological consequences. Negative feedback loops are essential for maintaining homeostasis, ensuring that hormone levels and physiological processes stay within an optimal range. When these loops are disrupted at any point—whether at the hypothalamic, pituitary, or target gland level—it can lead to either hyperfunction (excessive hormone secretion) or hypofunction (insufficient hormone secretion) of the endocrine glands. To interpret the effects of disruptions in negative feedback, it's important to consider the three main levels at which negative feedback occurs in the endocrine system: 1. Hypothalamic Level (Regulation of Hormone Secretion by the Hypothalamus) At the hypothalamic level, the hypothalamus senses changes in hormone levels or physiological conditions and releases releasing hormones that stimulate or inhibit the secretion of hormones from the pituitary gland. Disruption here can interfere with the entire hormonal cascade that regulates endocrine function. Example: Hypothalamic-Pituitary-Thyroid Axis Normal Feedback Loop: The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary gland to release thyroid-stimulating hormone (TSH). TSH then stimulates the thyroid gland to release T3 and T4. High levels of thyroid hormones (T3 and T4) then provide negative feedback to the hypothalamus and pituitary, inhibiting the release of TRH and TSH. Disruption at the Hypothalamic Level: ○ If the hypothalamus is unable to detect or respond appropriately to the levels of thyroid hormones (e.g., due to damage or a genetic mutation  in TRH production), it might continue to produce TRH despite elevated thyroid hormone levels. ○ As a result, TSH levels would remain high, leading to overstimulation of the thyroid gland, which could cause hyperthyroidism (e.g., Graves' disease). ○ Conversely, if the hypothalamus fails to produce sufficient TRH in response to low thyroid hormones (due to hypothalamic dysfunction), this could lead to hypothyroidism despite normal TSH levels. 2. Pituitary Level (Regulation of Hormone Secretion by the Pituitary Gland) The pituitary gland is often referred to as the "master gland" because it regulates the release of many hormones that control other endocrine glands (like the thyroid, adrenal glands, and gonads). Disruption at the pituitary level affects the downstream glands and their hormone production. Example: Hypothalamic-Pituitary-Adrenal Axis (HPA Axis) Normal Feedback Loop: The hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal cortex to secrete cortisol. High levels of cortisol provide negative feedback to both the hypothalamus and the pituitary, inhibiting the release of CRH and ACTH. Disruption at the Pituitary Level: ○ If the pituitary is damaged (e.g., due to a tumor or injury), it might fail to release adequate ACTH, leading to insufficient cortisol production from the adrenal glands. This condition is known as secondary adrenal insufficiency. ○ On the other hand, a pituitary adenoma (tumor) could cause the excessive release of ACTH, resulting in Cushing’s disease, with symptoms such as weight gain, hypertension, hyperglycemia, and osteoporosis. Disruption of Negative Feedback: ○ If the negative feedback loop is not functioning properly (e.g., due to a pituitary tumor secreting excess ACTH), cortisol levels might become excessively elevated, overriding normal regulatory mechanisms and causing Cushing's syndrome.  ○ In contrast, if the pituitary fails to respond to cortisol levels and continues to release ACTH in excess, this will lead to excessive stimulation of the adrenal glands, causing hypercortisolism. 3. Target Gland Level (Regulation of Hormone Secretion by Target Glands) At the target gland level, the gland (e.g., thyroid, adrenal glands, gonads) secretes hormones in response to signals from the pituitary or hypothalamus. Disruptions in negative feedback at this level can cause overproduction or underproduction of hormones and affect the target tissues. Example: Gonadal Axis - Normal Feedback Loop: In the male reproductive system, gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones stimulate the testes to produce testosterone. High levels of testosterone provide negative feedback to both the hypothalamus and pituitary to reduce the release of GnRH, LH, and FSH. - Disruption at the Target Gland Level: - Primary Hypogonadism (testicular failure) can occur when the testes are damaged and fail to produce sufficient testosterone. Despite the absence of testosterone, the hypothalamus and pituitary may continue to release high levels of GnRH, LH, and FSH in an attempt to stimulate the testes. - Secondary Hypogonadism occurs when there is insufficient secretion of LH and FSH from the pituitary, leading to low levels of testosterone. The feedback loop still works, but the pituitary fails to respond appropriately. - Disruption of Negative Feedback: - In cases of testosterone overproduction (e.g., testicular tumors or androgen-secreting tumors), the feedback mechanism can fail, leading to excessive testosterone levels. The high levels of testosterone may not effectively inhibit GnRH, LH, and FSH production due to tumor-driven hormone secretion. - This disruption can lead to symptoms like accelerated growth in adolescence (precocious puberty) or virilization (development of male characteristics in women or prepubertal children). General Impacts of Disruption in Negative Feedback Loops at Various Levels: 1. Hyperfunction (Overproduction of Hormones) When feedback regulation is disrupted and there is reduced inhibition or no inhibition at all, it can lead to overproduction of hormones, causing hyperfunction in the target glands. Example: A tumor in the pituitary gland (like a prolactinoma) might result in excessive secretion of prolactin, causing galactorrhea (milk production) and amenorrhea (lack of menstruation) in women. In men, it may cause sexual dysfunction. Example: A disruption in the thyroid feedback loop (e.g., Graves’ disease) could lead to hyperthyroidism, with symptoms like tachycardia, weight loss, and increased sweating. 2. Hypofunction (Underproduction of Hormones) When feedback mechanisms fail to promote adequate hormone production, or there is a failure at the target gland to produce sufficient hormones, it can result in hypofunction of the endocrine system. Example: Primary hypothyroidism occurs when the thyroid gland is unable to produce sufficient thyroid hormones, despite normal or high levels of TSH (due to inadequate feedback regulation). This leads to symptoms like fatigue, weight gain, constipation, and cold intolerance. Example: In Addison's disease (primary adrenal insufficiency), the adrenal glands fail to produce adequate cortisol, and the feedback loop to the pituitary and hypothalamus may become disrupted, leading to increased ACTH levels but low cortisol levels, causing fatigue, hyponatremia, and hypotension. 3. Autoregulatory Disruption Some disruptions in feedback can result from the target gland itself, as in cases where gland function is impaired by disease (e.g., autoimmune diseases, infections, or tumors). 4. Long-Term Consequences - Long-term disruptions in negative feedback can result in compensatory mechanisms where the hypothalamus, pituitary, or target glands attempt to restore balance, but the feedback system is still impaired. This  can lead to chronic disease states such as diabetes, hypothyroidism, or Cushing’s syndrome, where compensatory mechanisms exacerbate symptoms rather than resolve them. - Can you explain the symptoms of hypo and hyper growth hormone and thyroid hormone secretion? 1. Growth Hormone: a. Hyposecretion of GH i. Short stature, delayed puberty, reduced muscle mass b. Hypersecretion of GH i. Giantism, acromegaly 2. Thyroid hormone: a. Hypothyroidism i. Fatigue, coldness, dry skin, weight gain, constipation, slow heart rate- bradycardia, depression b. Hyperthyroidism i. Weih loss, high metabolism, nervousness, -