Introduction to Anatomy and Physiology II Bio 132 Professor Peter Smith D.P.T, ATC Smithpr@sunysuffolk.edu http://www2.sunysuffolk.edu/smithpr/ Spring 2013 Overview of Anatomy and Physiology • Anatomy – The study of the structure of body parts and their relationships to one another. • Physiology – the study of the function of the body’s structural machinery. • Understanding both the anatomy and physiology of the human body is critical to all health care providers. • You can’t diagnose disease (Pathology) if you don’t understand both the underline anatomy and physiology. Homeostasis • A great deal of energy is spent trying to maintain homeostasis. – the ability to maintain a relatively stable internal environment in an ever-changing world. • The internal environment of the body is in a dynamic state of equilibrium • Chemical, thermal, and neural factors interact to maintain homeostasis – As we age these mechanisms become less efficient. • Makes us more susceptible to disease and less resilient once we have one. Negative Feedback • In negative feedback systems, the output shuts off the original stimulus – This makes up 99% of the homeostatic feedback loops. • Examples include regulation of : body temperature, body pH, blood glucose levels, blood pressure, body calcium levels. – Prevents large fluctuations and keeps the internal environment relatively stable Negative Feedback Figure 1.5 Positive Feedback • In positive feedback systems, the output enhances or exaggerates the original stimulus. • Less than 1% of the feedback loops. Figure 1.6 Positive Feedback Endocrine System: Overview • Endocrine system – controlling system which influences metabolic activities of cells by means of hormones. • Hormones – chemical messenger secreted into bloodstream, stimulates response in another tissue or organ • Endocrine glands – produce hormones – pituitary, thyroid, parathyroid, adrenal, pineal, testes, ovaries and the hypothalamus. • Other tissues and organs that produce hormones include: adipose cells, cells in the walls of the small intestine, kidneys, and heart. Endocrine System Hormones • Hormones: – Regulate the metabolic function of other cells • Alter plasma membrane permeability ( insulin) • Stimulate protein synthesis (GH) • Activate or deactivate enzyme systems (GHRH,GHIH) • Induce secretory activity (Prolactin) • Stimulate mitosis (FSH) – Tend to have prolonged effects – Are classified as amino acid-based hormones, or steroids ( lipid based) • Eicosanoids – leukotrienes and prostaglandins Amino Acid Based Hormones • Most hormones belong to this class, including: – Glucagon, Insulin • are functional polypeptides – Specificity of hormone is determined by 3-D configuration. – Polar molecules: water soluble allowing them to be transported in the blood. – They exert their effects on extracellular receptors. Steroids (Lipid Based Hormones) • Steroids – derived from cholesterol – Non polar molecules: are hydrophobic therefore require a protein carrier to be transported in the blood. • Adrenocortical hormones • Aldosterone • Gonadal • Estrogen, Testosterone Hormone Action • Hormones alter target cell activity by one of two mechanisms – Second messengers involving: • Amino acid–based hormones cannot pass through the membrane. – They attach to a specific regulatory G protein on surface of cell membrane. – This sets off a series of steps that can activate or inhibit numerous functioning enzymes in the cell. – Direct gene activation involving steroid hormones • Since steroid based hormones are lipophillic they can diffuse through the cell membrane and enter the nucleus where they can alter gene expression. Amino Acid-Based Hormone Action: cAMP Second Messenger Figure 16.2a Amino Acid-Based Hormone Action: cAMP Second Messenger 1. Hormone (first messenger) binds to its receptor, which then binds to a G protein 2. The G protein is then activated as it binds GTP, displacing GDP 3. Activated G protein activates the effector enzyme adenylate cyclase 4. Adenylate cyclase generates cAMP (second messenger) from ATP – cAMP activates protein kinases, which then cause cellular effects Steroid Hormones Figure 16..3 Steroid Hormones 1. Steroid hormones and thyroid hormone are hydrophobic, therefore require a carrier protein to circulate in the blood. To exert their effects they separate from their carrier proteins and diffuse easily into their target cells. Once inside, they bind and activate a specific intracellular receptor The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein This interaction prompts DNA transcription to produce mRNA 2. 3. 4. 5. – – The mRNA is translated into proteins, which bring about a cellular effect. What’s the significance of having both lipid and amino acid based hormones. Nervous / Endocrine System Interrelationship • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms. • Nervous system is fast acting/short duration while the endocrine is slow starting/long lasting. • The nervous system can override normal endocrine controls. – For example, control of blood glucose levels are normally maintained by the endocrine system. • Under stress when the body needs more glucose the hypothalamus and the sympathetic nervous system are activated to supply ample glucose. Communication by the Nervous and Endocrine Systems Endocrine vs. Exocrine Glands • Exocrine glands – Ducts carry secretion to a surface or organ cavity which exert extracellular effects. • (food digestion) Amylase is released to hydrolyze polysaccharides into di and monosaccharides • Endocrine glands – no ducts, release hormones into tissue fluids such as the blood. • Rich blood supply to distribute hormones. • intracellular effects, alter target cell metabolism Control of Hormone Release • Blood levels of hormones: – Are controlled by negative feedback systems – Vary only within a narrow desirable range • Hormones are synthesized and released in response to three basic mechanisms. • Humoral: changes and substances in the blood (glucose or K+) • Neural: stimulation from the nervous system via neurotransmitters. • Hormonal stimuli: organ or gland releases a hormone that stimulates the release of another hormone from another glands or organ. Endocrine Organs Hypothalamus • Controls many endocrine glands: – regulates the endocrine system through it’s direct connection to the pituitary gland • The hypothalamus controls basic functions such as: – body temperature, blood pressure, growth and development ,reproduction, electrolyte balance and water regulation. • It accomplishes this by producing both releasing and inhibiting hormones that influence the anterior pituitary gland. • Produces ADH and Oxytocin which are transported to the posterior pituitary where they will ultimately be released. Pituitary Gland (Hypophysis) • Suspended from hypothalamus by the pituitary stalk (infundibulum) – housed in sella turcica of sphenoid bone • Adenohypophysis (anterior pituitary) – arises from glandular tissue • Neurohypophysis (Posterior Pituitary) – arises from brain (neural tissue) Histology of Pituitary Gland Neurohypophysis Posterior Pituitary • Neurohypophysis – posterior lobe (neural tissue) and the infundibulum – Receives hormones from the hypothalamus. – Hormones are stored, and released • Oxytocin and ADH Oxytocin • Oxytocin is a strong stimulant of uterine contraction – During labor increasing levels leads to increased intensity of uterine contractions. • Regulated by a positive feedback mechanism – PITOCIN is a synthetic form used to induce labor • Oxytocin triggers milk ejection (“letdown” reflex) in women producing milk. – Baby suckling of breast causes ejection of milk. – It’s considered the pair bonding hormone Oxytocin Antidiuretic Hormone • AKA. Vasopressin is released in response to low blood pressure, dehydration and high solute concentration in the hypothalamus. • ADH helps to prevent dehydration by: – ADH stimulates thirst – ADH targets aquaporins in the kidney to increase water permeability. • This will increase blood volume which increases BP – Causes small arteries to constrict thus increasing BP – Reduces secretory activity of sweat glands preventing additional water loss Antidiuretic Hormone (ADH) • Alcohol inhibits ADH release and causes many unwanted trips to the bathroom. – Hang over symptoms primarily result of dehydration . • Diabetes insipidus is a condition where there is a hyposecretion of ADH – What effect will this have on urinary output and hydration status? Anterior Pituitary-Hypothalamic Connection: Figure 16.5 Anterior Pituitary • Adenohypophysis – anterior lobe, made up of glandular tissue derived from the oral mucosa during embryologic development. – Synthesizes and secretes a 6 major hormones • There is a vascular connection via the hypophyseal portal system – The vascular anatomical connection provides an a means of delivering hypothalamic hormones directly to the anterior pituitary. – Hypothalamic hormones avoid general circulation allowing smaller amounts of hormones to be delivered in a fraction of the time. Activity of the Adenophypophysis • The hypothalamus sends a chemical stimulus to the anterior pituitary in the form of releasing hormones : – Releasing hormones stimulate the synthesis and release of hormones from the anterior pituitary. • example TRH (Thyrotropin Releasing Hormone) causes the production and release of TSH( Thyroid Stimulating Hormone) – Inhibiting hormones shut off the synthesis and release of hormones. – PIL( Prolactin inhibiting Hormone) • inhibits the synthesis and release of Prolactin Metabolic Action of Growth Hormone • Releasing hormone (GHRH) from the hypothalamus stimulates GH release in response to low blood sugar, increased levels of stress i.e. exercise and increases in levels of some amino acids. • GH: causes cells in the liver, muscle, cartilage, bones and other tissues to release (IGF’s): • Insulin like growth factors. (Anabolic) – Skeletal muscle: increase uptake of A.A to build more protein and inhibits protein catabolism. – Facilitates bone and cartilage growth by absorbing building blocks such as sulfur.( i.e. glucoseamine sulfate, Chondroitin sulfate) – Promotes sodium, potassium and chloride retention by the kidneys and enhances calcium absorption by the small intestine. Metabolic Action of Growth Hormone • Anti-insulin effects include – Liver: reduces the formation of glycogen and promotes lipolysis of adipose cells. (the hydrolysis triglycerides for energy). • Decreased rate of glycogen production in the liver makes more available for structures rely on sugar exclusively. (brain) – :Growth hormone–inhibiting hormone (GHIH) inhibits GH release Gigantism • Excessive growth hormone before the growth plates fuse. – Good for basketball – Bad for horse racing. Acromegaly • To much GH usually after the growth plates have fused. – Results in great wrestlers. • Beware the Pituitary Tumor. Dwarfism • Hyposecretion of GH • May require GH replacement therapy Thyroid Gland • The largest endocrine gland, located in the anterior neck, consists of two lateral lobes connected by a median tissue mass called the isthmus • Its rich blood supply reflect its importance. Thyroid Stimulating Hormone • Triggered by hypothalamic secretion of thyrotropinreleasing hormone (TRH ) • TSH stimulates the normal development and secretory activity of the thyroid gland (Thyroxin) • Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH Thyroid Gland • Thyroid follicles – lined with simple cuboidal epithelial (follicular cells) that secretes two hormones, T3 and T4 • T4 : 98% and relatively inactive. • T3 :cells convert T4 into this form which is much more active. – Colloid: incorporates iodine and thryoglobulin to produce thyroid hormone – thyroid hormone is stimulated by conditions that increase the bodies need for ATP. • A ↓in body temperature, hypoglycemia, high altitude and pregnancy all increased thyroid hormone Synthesis of Thyroid Hormone Figure 16.8 Thyroid Hormone • Thyroid hormone (TH) action is like turning up the thermostat. • TH causes: – body’s metabolic rate and O2 consumption – Calorigenic effect - heat production with increased ATP consumption. – heart rate, contraction strength blood pressure and respiratory rate » by enhancing norepinephrine and epinephrine actions. • stimulates many things necessary for growth and devolvement. • in appetite and breaking down of CHO, lipids and proteins for energy Endemic goiter • Goiter = enlarged thyroid gland – results from dietary iodine deficiency. – Can’t produce TH, – no feedback to Pituitary TSH – This causes hypertrophy of the thyroid gland. Toxic goiter (Graves disease) • Antibodies mimic TSH causing ’d TH to be released, • Excessive Thyroxin levels – – – – – elevated metabolism heart rate weight loss nervousness exophthalmos (bulging eyes) – ANS induced sweating. Thyroid Histology Calcitonin • Parafollicular cells produce calcitonin: – blood Ca2+ and promotes Ca2+ deposition in bone. • Calcitonin: – Inhibits osteoclast activity (breaks down bone releasing calcium from the bone matrix) – Stimulates calcium uptake and incorporation into the bone matrix by increasing osteoblast activity. • Regulated by a blood (calcium ion concentration in the blood) negative feedback mechanism • Antagonist to parathyroid hormone (PTH) Parathyroid Glands • Tiny glands embedded in the posterior aspect of the thyroid – Chief (principal) cells secrete PTH (parathyroid hormone) – PTH regulates calcium balance in the blood Effects of Parathyroid Hormone Figure 16.11 Adrenal Cortex Figure 16.12a Adrenal (Suprarenal) Glands • Adrenal glands – paired, pyramid-shaped organs on top of the kidneys structurally and functionally they are two glands in one. • Adrenal Cortex releases a variety of hormones that allow the body to deal stress blood pressure changes with development of secondary sex characteristics. • Adrenal medulla – nervous tissue that is the hormonal branch of the sympathetic nervous system (fight/flight) Adrenal Cortex • Different corticosteroids are produced in each of the three layers – Zona glomerulosa – mineralocorticoids (chiefly aldosterone) – Zona fasciculata – glucocorticoids (chiefly cortisol) – Zona reticularis – gonadocorticoids (chiefly androgens) testosterone in males and estrogen in females Adrenocorticotropic Hormone (ACTH) (Corticotropin) • Produced by the Anterior Pituitary. – Triggered by hypothalamic corticotropinreleasing hormone (CRH) – Stimulates the adrenal cortex to release corticosteroids and mineralocorticoids. • ACTH is stimulated by – fever, – hypoglycemia, – various stressors Mineralocorticoids • Regulate the electrolyte concentrations of extracellular fluids – Aldosterone – most important mineralocorticoid – Maintains Na+ balance by reducing excretion of Na+ from the body while increasing K+ excretion. Aldosterone secretion is stimulated by: – Rising blood levels of K+ – Low blood Na+ – Decreasing blood volume or pressure Glucocorticoids (Cortisol) • Stress on body causes hypothalamus to release CRHACTH targets adrenal cortex to release Cortisol: Cortisol – targets liver and muscle cells: – Increases levels of the following in the blood to ensure there is enough available fuel to deal with stress. • glucose • fatty acids • amino acids – Gluconeogenesis (formation of glucose from noncarbohydrates) • Inhibit inflammation • Depressed the immune system Cushing Disease • Cushing Disease :hyper secretion of ACTH or Cortisol – Results in moon face hunch back appearance. – Muscle wasting – Hyperglycemia • Depress cartilage and bone formation • Promote diseases of the cardiovascular, nervous and gastrointestinal systems. • Increased blood pressure • Often medically induced as a result of patient given high dose corticosteroids – For treatment of inflammatory, autoimmune and allergic medical condition. Cushing Disease Cushing Disease Adrenal Medulla • The adrenal medulla functions as an extension of the sympathetic nervous system. • Under periods of stress a neuron from the hypothalamus directly stimulates as the adrenal medulla. • Since this is a direct neural connection the adrenal medulla can release the catecholamines (epinephrine and norepinephrine) immediately. – Catecholamines are the hormonal portion of the SNS • Functionally their effects on the body are the same. Stress and the Adrenal Gland Figure 16.15 Addison's Disease • Results from a hyposecretion of ACTH or an autoimmune disease that damages the adrenals. • Results in decreased glucocorticoids and mineralocorticoid release. • Results in hypotension and hypoglycemia • Corticosteroid replacement therapy A patient 16 y/o male with complaints of tunnel vision and HA comes into your office. He is 6ft 11inches in height and weighs 295 lbs. The patients parents are both over 6 feet. What is a possible diagnosis for his condition. A. A tumor causing increased thyroid function. B. Genetic ( follow up with ophthalmologist for tunnel vision.) C. A hyperactive pancreas D. A pituitary tumor E. Under active hypothalamic secretions Clinical Question What actions would be appropriate. • A) Order a head CT to observe any anomalies in the cranium. • B) Blood work to look at levels of GH, LH, insulin, ETC • C) Send him to an ophthalmologist for further examination. • D) Set him up with your 6ft 2 sister and tell him not to walk into any walls. • E) All of the above. A 48 female presents to the doctor with the following complaints. She reports excessive fatigue recent weight gain and depression. She has recently been loosing her hair and has become very forgetful. • Is this an endocrine problem? • If so what hormone might explain these symptoms. A patient was in a car accident five years ago. Since then he has been in chronic pain managed by opiate painkillers. The patient reports that the medication is no longer working. The doctor responds by increasing the dose. Why did the patient require a higher dose of medication to get the same therapeutic effect? Hormones and Target Cell Sensitivity • • Cells respond to hormonal levels of stimulation differently. When signaling is low the target cell will make more receptors. When stimulation is high the cell will reduce the number of receptors. What is the clinical applications to the cells intrinsic homeostatic mechanisms? Endocrine Screen • • • • • Hyperglycemia / Hypoglycemia Poly /glucosurea Temp. intolerance (hot vs. cold) Changes in heart rate / palpitations Changes in physical features – Skin changes, excessive abnormal hair growth, Body Fat distribution • • • • • Deep Rapid Breathing Changes in Body WT. Fatigue /weakness Goiter Irradiation exposure