Phgy 216 Study PDF

Phgy 216 Module 1 Key Topics Principles of Endocrinology Glands provide basic functions: digestive, rbc, reproductive, stress, growth,ANS, homeostasis Endocrine tissues secrete hormones A) Hydrophilic (thyroid, cataholmins epi/nor, amines and peptides that are unbound to plasma but BOUND TO CARRIER...

Phgy 216 Module 1 Key Topics Principles of Endocrinology Glands provide basic functions: digestive, rbc, reproductive, stress, growth,ANS, homeostasis Endocrine tissues secrete hormones A) Hydrophilic (thyroid, cataholmins epi/nor, amines and peptides that are unbound to plasma but BOUND TO CARRIER ) BINDS OUTSIDE B) Lipophilic (steroid bound to carrier) like cholesterol that need carrier) needs equilibrium BIND INSIDE CAmp: hormone lands on the surface, G-protein activating adenylyl then turns on worker protein CA: lands activating G-protein, wakes Phoilicisl C breaking pip, ca is released inside, with calciuln ( worker protein) Hypothalamic-Pituitary Axis Nervous control: rapid, brief hard wire targets Endocrine control: slow, long many targets Posterior Pituitary Gland: neurohyoplus ADH (Vaso water , Oxy pee) Anderter pituitary gland: anderhypolud TSH (thyroid ATCH adrenal, GH growth, LH ovulation, FSH egg, Prolactin (milk) 1.​ CRH: ATCH 2.​ TRH: TSH 3.​ PIH: Prolactin 4.​ GNRH: FSH, LH 5.​ GHIH: GH 6.​ GHRH: GH 7.​ PPH: Prolactim Thyroid Gland Located above trachea below larynx secretes thyroid hormone Made of follicular: ring like found in C secreting calcitonin within it contains Colloid (thyroglobulin) Two hormones 1. Tetraldothymine: 4 iodine molecules 90% 2. Triiodothyronine: 3 iodine 10% TRH secretes TSN: directly impacts thyroid gland as without it shrinks it or too much makes it bigger Synthesis of Thyroid Homomore 1.​ Thyroglobulin is made by folicar cell in ER transported by coliod (Exocytosis) 2.​ Iodine trapping: takin to follicular cells from blood via NA 3.​ Transfer to coilod: Iodine is moved to follicular lumen 4.​ Iodine organification: thyroperoix converts Iodine I to O makes MIT/DIT 5.​ Copleing: MIT/DIT form hormone T3 (1combo) /T4 (2DIT) Releases of thyroid Hormone 1.​ Engulf: follicular cells eat Thyroglobulin colloid by phagocytes 2.​ Digest: lysosomes fuse breaks down Thyroglobulin to release T3,T4,MIT, DIT 3.​ Release/Binding: T3,T4 are lipophilic, crossing plasma membrane that bind to thyroid-binding-globulin Actions: 1.​ Metabolic basis 2.​ Growth 3.​ Cardiovascular System 4.​ Intermediary 5.​ Sympathomimetic Hypothyroidism: low iodine, primary: autoimmune, secondary: hypothalamus/pituitary fails to secrete T3/4, symptoms: cold intolerance, weak HR, weight gain, slow BOTH CAN CAUSE GOITER: enlarged thyroid gland from increased TSH (not in secondary failure of thyroid gland) Hyperthyroidism: too much secretions, tumour on T3/4, grave’s symptoms: high HR, muscle weakness, mood swings, weight loss Adrenal Glands Responder of acute stress:medula and chronic: cortex Small on top of the kidneys two parts outer:cortex secretes steroid hormones Has 1.zona globlumarous: (mineral balance ex: aldosterone) Without mineraloids dies of circulatory shock 2. zona fasciculata: glucocorticoids: metabolism, stress, immune controlled HPA by ACTH 3. zona reticularis: androgens ex: sex hormone DHEA inner: medulla secretes cataholmies in response to stress: EPI HR BP + glycogen, NOR: F/F SNS Type: Hyperadrenalism: to much production ex: cushings Hyperaldosteronism: HBP, low potassium Hypersecretion: hirsutism Hypoadrenalism: fatigue, low BP, weight loss Fuel Metabolism Ana: synthesis of molecules Absorptive state/ fed insulin (beta) causes the uptake of glucose for energy that is diverted to fat with AA Activated glycogen, fat Inhibited neos delta cells (somatstain) Lowers bg Cata: breakdown of molecules Post absorptive/ fasted glycogen (alpha) broken-down to glucose fats used as FA god ketones, proteins Activated neos Inhibited glycogen Raises bg Diabetes Type 1: destruction of beta cells needs insulin injection Type 2: insulin resistance Hypoglycemia: Low bg Growth and Calcium Metabolism GH: secrets anterior pituitary, stimulates: protein synthesis, cell division, breakdown of fat. Stimulates chondrocytes in growth pates Controlled by 2 factors: 1. GHRH: stimulates it, 2. GHIH: inhibits Deficiency: dwarfish, less muscle mass Excess: gigantism, acromegaly Bone growth: 1. Osteoblasts: add bone layers to outer, 2. Epiphyseal: growth plates fusing after puberty TH, GH, SH promoted growth Calcium regulations: Plasma C levels: normal (2.2-2.6) regulated by 1.​ PTH: secreted by para glands to increase calcium release, enhances calcium reabsorption, makes VD active 2.​ Calction: secreted by thyroid (C cell) lowers blood calcium, promoted excretion 3.​ VD: converted by calcitriol, exchanges calcium and phosphate absorption Hypocalcemia: low blood calcium, spasms, tingling, cardiac issues Hypercalcemia: high blood calcium, fatigue, confusion, kidney stones Module 2 Key topics Introduction to reproductive systems Pineal Gland’s Role in Reproductive Hormones: Melatonin affects GnRH secretion, linking light exposure to reproductive cycles (e.g., seasonal breeding in animals and circadian effects in humans). Steroid Hormone Transport: Steroid hormones (e.g., testosterone and estrogen) bind to proteins like sex hormone-binding globulin (SHBG) for transport in blood. Depends on gamate and male, primary organ is the gonads (testes in male, ovaries in female), both have a reproductive track (allows the transport of gamate and secretions) Gamate produced by mitosis where diploid parent cells divide to produce haploid (sperm determines sex Y=boy /ova Y ) these cells combine to make chromosomes (46) Half sperm are X other Y Meiosis 1 pair of chromatids that = homologous that separate so each daughter gets 1 set of chromosome = 2 daughters cells and 1 set of chromosomes Meiosis 2 sister chromatids within chromosomes of each daughter separate are two cells 4 daughter cells and 1 set of chromosomes 1 set of chromatid Gonald sex: determined by Y in the 7th week by SRY which makes H Y antigen acting on gonads to become testes if Y if androgen and if no androids X ovaries Wolffian Ducts: Placenta secretes (hCG) if testes are present, hCG makes testrone that stimulates this duct and secretes müllerian Müllerian Ducts: Wolffian degrade in absent of testrone these ducts develop Male reproductive Makes and delivers sperm Testes: The role is to promote spermatogenesis produced in semicoiler tubles. This is made possible as the scrotum which houses testes located outside the abdominal cavity inside the sac, is colder allowing for its role as it is very sensitive to temp. However in premature it doesn't drop to the outside resulting in sterility. What helps it gain heat is the cremaster and the dartos muscle which contract to push the testes toward the chest to gain heat. When too hot the muscles relax and push back down. Testosterone: within the ct and semicoiler tubules are leydig eggs once secreted some testosterone enters blood/circulates in distal cells. Most enter lumen of semicoiler tubles for sperm support. A)​ causes masculinization of reproductive tract/genilia B)​ Maintains reproductive tract in adulthood C)​ Develops sex drive  D)​ Causes voice to deepen E)​ Promotes bone growth Spermatogenesis Regulation: ​ Testosterone binds androgen receptors on Sertoli cells to maintain spermatogenesis. ​ Retinoic acid also plays a critical role in triggering meiosis during spermatogenesis. spermatogenesis: diploid are converted motile sperm haploid. A)​ Primordial germ cells called spermatogonia on the outer layer of the semicoiler tubules undergo mitotic division to create new germ cells. After each division round the danger cells remain on the edge with the other migration towards the lumen of the tuble. This cell undergoes mitotic division x2 to make 4 more primary spermatocytes that enter rest to prepare for meiosis. B)​ Meiosis: Each primary spermatocyte forms two secondary spermatocytes, each with 23 2 chromosomes. meiosis II, each 2nd spermatocyte results in two spermatids, each with 23 1 chromosomes. Then16 spermatids can be produced. C)​ Packaging: The final maturation of spermatids into spermatozoa (consists of head, acrosomal, midpiece atp tail). The cells are stripped down getting rid of of all non essentials spermatozoa Haploid1 spermatids Haploid1 primary spermatocyte Diploid2 secondary spermatocytes Haploid2 spermatogonia Diploid1 spermatogonium Diploid1 Sertoil cells: Makes up walls of seminiferous tubules and connected by tight junctions during spermatogenesis, developing sperm cells between the tight junctions allowing them to pass as they migrate near lumen. These sperm cells are engulfed by the sertoli cells as they head near the lumen then, the sperm head remains embedded until it matures. Functions as.. A)​ tight junctions form the blood-testis barrier. allows the Sertoli cells to control the intratubular environment. B)​ Nourish sperm cells. C)​ Absorb developing sperm cytoplasm/ removes defective germ cells. D)​ Secrete seminiferous tubule fluid to lumen flushing released sperm into the epididymis. E)​ Secrete androgen-binding protein, helps to concentrate testosterone in the lumen.  F)​ The site of action for testosterone and FSH for spermatogenesis. 5 hormones used: … A)​ FSH: Acts on the Sertoli cells to stimulate spermatogenesis and to secrete inhibin B)​ GnRH: Stimulates the anterior pituitary to release LH and FSH C)​ Inhibin: Released by Sertoli cells, feeds back to the anterior pituitary to decrease FSH release D)​ LH: Stimulates the Leydig cells to secrete testosterone E)​ Testosterone: Has a direct negative-feedback pathway at the level of both the hypothalamus and anterior pituitary Epididymis and Ductus Deferens After sperm production in the seminiferous tubules, they are taken by epididymis, (tightly coiled tube 5m). Sperm enter the epididymis; it's not motile, as its low pH. epididymal ducts of each testis form ductus deferens of each testis empties into the urethra. Sperm can be stored for months here. Male Accessory Sex Glands 3 that makes semen. 1.​ Seminal Vesicle: bulks up semen by supplying fructose for energy to ejaculated sperm, secrete prostaglandins for smooth muscle contractions in both reproductive tracts, to secrete fibrinogen 2.​ Prostate Gland: Called Cowper’s glands. A pair that empties into the urethra, on each side, before the urethra enters penis. It secretes clear substance during arousal helping to lubricate the urethra for sperm to pass. 3.​ Bulbourethral Glands: secretes alkaline fluid neutralizing acidic environment of vagina. It Secretes clotting enzymes acting on fibrinogen to produce fibrin, clots semen keeping it within the female Female reproductive A cycling egg, or ova, matures and is released. Oogenesis: ​ 1.​ Fetal Development: oogonia (germ cells) undergo mitotic division, forming primary oocytes by the 5th month of gestation (~6–7 million).Then Primary oocytes is arrested in prophase I of meiosis/surrounded by 1 layer of granulosa cells forming primordial follicles. 2.​ At Birth: Primary oocytes decrease to ~2 million through atresia (natural degeneration). 3.​ After Puberty: group of primary follicles begins to mature by FSH. Each month, 1 primary oocyte = meiosis I to form: A)​ A secondary oocyte (haploid, 23 chromosomes) surrounded by granulosa and theca cells, forming a secondary follicle. B)​ A polar body (non-functional, excess genetic material). 4. Ovulation: The secondary oocyte is released during ovulation/ arrested in metaphase II of meiosis. If fertilization occurs, the oocyte completes meiosis II, producing: fertilized ovum (zygote) with 23 chromosomes and a second polar body. 5. Follicle Progression: Primordial follicles → Primary follicles → Secondary follicles → Mature (Graafian) follicle.Then post ovulation, follicular cells form corpus luteum, secreting progesterone/estrogen. Oogonia Diploid1 Primary Oocyte Diploid2 Secondary Oocyte Haploid2 Polar Body Haploid2 Fertilized Ovum Haploid1 Second polar baby/sperm Haploid1 mature ovum haploid 2 Ovarian Cycle: cycle consists of two phases over 28-day period: 1.​ Follicular Phase (Days 1–14): Follicles develop to secondary/mature follicles by FSH and LH. The Granulosa cells (zona pellucia) layer of theca cells, surround oocytes secreting estrogen.The Estrogen stimulates thickening of the endometrial lining (uterine proliferative phase). These Rising estrogen levels = positive feedback loop, triggering surge of LH (stops estrogen, reintites meiosis, triggers local factors, differentiates follicles into luteal) leads to ovulation on Day 14. 2.​ Luteal Phase (Days 15–28): After ovulation, the remaining follicular cells form corpus luteum, secreting: A) Progesterone (uterine lining for implantation). B) Estrogen (uterine growth). However If not occuring, corpus luteum degenerates in corpus albicans (scar tissue), drops hormone levels/ onset of menstruation. Endometrial Proliferation: Estrogen increases spiral artery growth during the proliferative phase. Uterine Cycle three phases in response to the hormonal changes Two layers: myometrium: outer layer of smooth muscle and endometrium: highly vascularized with glands 1.​ Menstrual Phase (Days 1–5): functional layer of endometrium shedding due to the drop in estrogen/progesterone levels, release prostaglandins. Blood, mucus/ uterine lining expelled in vagina. 2.​ Proliferative Phase (Days 6–14): Estrogen, secreted by growing follicles, stimulating regrowth of endometrium glands until 3-5mm. These glands/ blood vessels proliferate for implantation. OVULATION HERE 3.​ Secretory Phase (Days 15–28): Progesterone from corpus luteum stimulating endometrial glands secreting nutrients, creating environment for a fertilized ovum. If no fertilization corpus luteum degenerates, progesterone/ estrogen levels fall, cycle restarts with menstruation. Endometriosis: a chronic inflammatory condition where endometrial tissue grows outside the uterus, typically on the ovaries, fallopian tubes, or pelvic lining. Less commonly, it can spread to other areas like the intestines, bladder, or diaphragm Hormonal Regulation of Reproductive Cycles 1.​ Follicle-Stimulating Hormone (FSH): early Stimulates maturation of ovarian follicles and promotes estrogen secretion by granulosa cells. 2.​ Luteinizing Hormone (LH): Surge in LH triggering ovulation.This Stimulates formation of corpus luteum/secretion of progesterone. SECONDARY FOLLICLES 3.​ Estrogen: Secreted by developing follicles, Stimulates endometrial thickening during the proliferative phase and negative feedback of FSH/ LH secretion initially, but high positive feedback to trigger the LH surge. 4.​ Progesterone: Secreted by the corpus luteum in luteal phase, Maintains the uterine lining in secretory phase. Prepares for implantation of embryo 5.​ Inhibin: inhibit production of LH and FSH in pituitary MenopauseOccurs between ages 45–55 when ovarian follicle reserves are depleted. A)​ Hormonal changes: reduction in estrogen/ progesterone levels.Increased FSH and LH as lack of negative feedback. B)​ Physiological effects: Osteoporosis due to increased osteoclast activity (bone resorption). C)​ Increased risk of cardiovascular diseases. D)​ Hot flashes, mood changes, and other symptoms of estrogen deficiency Sexual intercourse between Sexual reproduction needs the delivery of sperm to vagina by sex. The male penis becomes erect/ rigid for penetration, then ejaculation to deliver sperm to the female The Erection Process Erection occurs when blood fills (sponge vascular corpora cavernosa) in the penis. The arterioles supply penile vascular spaces for dilation during arousal, leads to increased flow/rigidity. Control by Erection Reflex: Initiated by thoughts/stimulation of mechanoreceptors in the glans penis. This reflex is a spinal response involving: A)​ Inhibition of Sympathetic Supply: Reduces vasoconstriction in penile arterioles. B)​ Activation of Parasympathetic Supply: vasodilation by nitric oxide (NO)-mediated mechanism. C)​ Parasympathetic Stimulation of Bulbourethral Glands: Secretes mucus for lubrication. Erectile Dysfunction (ED):inability to achieve/maintain erection. A Chronic ED is a sign of cardiovascular/metabolic conditions. Ejaculation is a spinal reflex mediated by the same stimuli as erection. It consists of two stages: A)​ Emission: Smooth muscles in the prostate, reproductive ducts, and seminal vesicles contract under sympathetic control. These contractions deliver semen components into the urethra. The bladder sphincter prevents urine from mixing/semen. B)​ Expulsion:The filling of the urethra with semen triggers the contraction of skeletal muscles at the penis’s base. These contractions increase pressure, forcibly expelling semen out of the penis. Male Sexual Response CycleDivided into four stages: 1.​ Excitement Phase: heightened sexual awareness and erection. 2.​ Plateau Phase: physiological responses + HR, bp,respiratory rate. 3.​ Orgasmic Phase: ejaculation/associated emotional release. 4.​ Resolution Phase:Involves the return of the body to pre-arousal state. Then refractory period follows ejaculation, which sexual stimulation cannot elicit another erection. Female Sexual Response Cycle Similar to the male cycle 4 stages: 1.​ Excitement Phase: stimulation of the clitoris/Activation of a spinal reflex for parasympathetic system, Arterioles dilate vagina/external= leading to vasocongestion. The clitoris, containing erectile tissue, becomes erect.This Increases blood flow to vaginal walls, forces fluid to vagina, forms lubrication by Bartholin’s gland secretions. 2.​ Plateau Phase: The uterus rises, lifts cervix/enlarges upper portion of the vagina = space for ejaculated semen, physiological responses + HR, bp,respiratory rate. 3.​ Orgasm Phase: Sympathetic impulses lead to rhythmic contractions of the pelvic/ vaginal musculature, contractions contribute to physical/ emotional release= peak of sexual pleasure. 4.​ Resolution Phase:Involves the return of the body to pre-arousal state. Fatigue Fertilization, pregnancy, lactation, parturition Fertilization Occurs in the ampulla of the oviduct within 24 hours of ovulation. A) Capacitation: Sperm undergo biochemical changes tract = removal of inhibitory proteins, enhancing motility/ allow penetration of the ovum. B) Acrosomal Reaction: Enzymes from the sperm’s acrosome break down the zona pellucida (glycoprotein layer surrounding the egg)= entry of the sperm. C) Cortical Reaction: Once one sperm fuses with the oocyte membrane, cortical granules release enzymes to harden the zona pellucida, preventing polyspermy D) Formation of the Zygote: The sperm nucleus merges with the egg’s nucleus, forming a diploid zygote (46 chromosomes). The zygote begins mitotic cleavage, forming a morula and then a blastocyst. Types of Twins A)​ Identical (Monozygotic) Twins: ​ Arise from the splitting of a single fertilized egg (zygote). ​ These twins are genetically identical and always share the same sex. ​ Early split (within 1-3 days): Each twin has its own amniotic sac and placenta. ​ Intermediate split (4-8 days): Twins share a placenta but have separate amniotic sacs. ​ Late split (9-12 days): Twins share both the placenta and the amniotic sac. ​ Very late split (beyond 12 days): Can result in conjoined twins. ​ 2.​ Fraternal (Dizygotic) Twins: ​ Arise when two separate eggs are fertilized by two separate sperm cells. ​ These twins are genetically different and can be the same or different sexes. ​ Each twin develops its own placenta and amniotic sac, though the placentas may fuse Early PregnancyBlastocyst Formation and Implantation: The blastocyst consists of: Trophoblast cells: Form the placenta, Inner cell mass: Develops into the embryo. The blastocyst adheres to the uterine wall (around day 6-7 post-fertilization). Trophoblast cells invade the endometrium, anchoring the blastocyst and forming the early placenta. 1.​ Hormonal Maintenance of Pregnancy: Human Chorionic Gonadotropin (hCG): Secreted by trophoblast cells, hCG prevents the degeneration of the corpus luteum. The corpus luteum continues producing progesterone and estrogen to maintain the uterine lining. Parturition Hormonal Feedback: CRH from the placenta triggers fetal cortisol, which in turn increases estrogen to promote uterine contractions. 2.​ Placental Hormones (after the first trimester):  1.​ Progesterone: Maintains uterine quiescence by inhibiting contractions. 2.​ Estrogen: Promotes uterine growth and increases blood flow. 3.​ Human Placental Lactogen (hPL): Modifies maternal metabolism to ensure a constant supply of glucose and nutrients for the fetus. Prepares the mammary glands for lactation. Fetal Development and Maternal Adaptations 1.​ Placental Functions: Acts as the interface for gas exchange, nutrient delivery, and waste elimination.Transfers maternal antibodies (primarily IgG) to provide passive immunity. 2.​ Maternal Physiological Changes: Cardiovascular: Increased blood volume and cardiac output. Respiratory: Enhanced tidal volume and oxygen consumption.Renal: Increased glomerular filtration rate to eliminate fetal waste products. Parturition (Childbirth) A)​ Hormonal Regulation: Late in pregnancy, fetal cortisol stimulates the placenta to increase estrogen production, enhancing uterine excitability. B)​ Oxytocin from the posterior pituitary initiates and strengthens uterine contractions. It stimulates myoepithelial cell contraction, ejecting milk. C)​ Prostaglandins soften the cervix and increase contractility of the myometrium. ​ Stages of Labor: ​ 1.​ Dilation Stage: Begins with regular uterine contractions. The cervix dilates to approximately 10 cm. Amniotic sac may rupture (“water breaking”). ​ 2.​ Expulsion Stage: Intense contractions push the baby through the birth canal. The baby is delivered during this stage. ​ 3.​ Placental Stage: The placenta and associated membranes are expelled. Continued uterine contractions minimize blood loss and facilitate uterine involution. Lactation 1.​ Preparation During Pregnancy: Estrogen stimulates the growth of milk ducts. Progesterone promotes the development of alveoli but inhibits milk secretion. 2.​ Milk Secretion Post-Birth: After delivery, the drop in estrogen and progesterone allows prolactin to stimulate milk production. 3.​ Let-Down Reflex: Suckling triggers the release of oxytocin, causing contraction of myoepithelial cells around alveoli to eject milk. 4.​ Milk Composition: Contains essential nutrients (carbohydrates, fats, proteins) and immune components (antibodies, lysozymes). Colostrum (produced in the first few days post-birth): Rich in antibodies and growth factors to protect the newborn. Clinical Consideration A)​ Complications in Fertilization: Ectopic Pregnancy: Fertilized egg implants outside the uterus, often in the oviduct, posing risks to the mother. B)​ Gestational Issues: Pre-eclampsia: Hypertension during pregnancy due to placental dysfunction. C)​ Post-Partum: Postpartum Hemorrhage: Excessive bleeding after delivery due to uterine atony. Or Lactational Amenorrhea: Suppression of ovulation during breastfeeding due to high prolactin levels. Developmental Physiology ​ XX individuals with congenital adrenal hyperplasia (CAH) develop ambiguous genitalia due to excess androgens. ​ Testosterone Conversion to DHT: 5α-reductase deficiency can lead to male pseudohermaphroditism (undervirilization despite XY chromosomes). Module 3 Introduction into Respiratory System The respiratory system is crucial for the survival of all cells by facilitating gas exchange. This is essential to support cellular respiration—the process that produces ATP (adenosine triphosphate) for energy. Oxygen is taken in from the atmosphere, and carbon dioxide (a metabolic waste product) is expelled from the body. There are two types of respiration: 1.​ Internal respiration – Oxygen use and carbon dioxide production inside cells (metabolism). 2.​ External respiration – The process of bringing oxygen into the body, transporting it to tissues, and removing carbon dioxide. This module focuses on external respiration, broken down into four steps: A)​ Ventilation: Air is moved between the atmosphere and alveoli. B)​ Exchange of Gases: Oxygen diffuses from alveoli into pulmonary capillaries; carbon dioxide moves in the opposite direction. C)​ Transport of Gases: Oxygen is carried to tissues through the blood, while carbon dioxide is returned to the lungs.  D)​ Tissue Exchange: Oxygen diffuses from blood to tissues, while carbon dioxide enters the blood from tissues. Functions of the Respiratory System ​ Enables speech by air passing over the vocal cords. ​ Defends against inhaled foreign matter through mucus, cilia, and immune cells. ​ Plays a role in parturition (childbirth) and defecation by aiding abdominal pressure. ​ Acts as a blood reservoir to balance the outputs of the heart. ​ Helps maintain acid-base balance, which affects blood pH levels. Anatomy of the Respiratory System The respiratory system consists of the lungs, chest wall, and pleural space. 1. The Upper Tract ​ Nose and nasal cavities: Filter, moisten, and warm incoming air. ​ Pharynx: Common passage for air and food. ​ Larynx: Contains vocal cords and prevents food from entering the airways via the epiglottis. 2. The Lower Tract ​ Trachea: Reinforced by cartilage rings to prevent collapse. ​ Bronchi: The trachea branches into the right and left bronchi, each leading to a lung. ​ Bronchioles: Smaller airways that branch repeatedly. The smallest, respiratory bronchioles, allow some gas exchange due to their thin walls ​ Alveoli: Small air sacs where most gas exchange occurs, surrounded by capillaries. The Branching Airways ​ The airway branches resemble a tracheobronchial tree, with increasing cross-sectional area as branches get smaller. ​ Convective flow (requires energy) transitions to diffusive flow (passive) at the respiratory bronchioles, facilitating air movement into the alveoli. Muscles of Respiration ​ 1.​ Muscles of Inspiration (breathing in): ​ Diaphragm: Descends and enlarges the thoracic cavity. ​ External intercostal muscles: Lift the ribs, further expanding the cavity. ​ 2.​ Muscles of Expiration (breathing out): ​ At rest, expiration is passive due to lung elastic recoil. ​ During active expiration (e.g., exercise), internal intercostals and abdominal muscles contract to decrease thoracic volume and increase airflow out of the lungs. The Pleural Space ​ The lungs are encased by the visceral pleura (lung membrane), while the parietal pleura lines the inside of the chest wall. ​ The pleural space contains pleural fluid that reduces friction during lung expansion and contraction. Respiratory Pressures and Flow: Respiration relies on pressure gradients for air movement: 1.​ Air flows into the lungs when alveolar pressure drops below atmospheric pressure. 2.​ Air flows out when alveolar pressure exceeds atmospheric pressure. Two key processes drive respiration: 1.​ Pressure gradient generation: Respiratory muscles create a pressure difference to overcome airway resistance and inflate the lungs. 2.​ Gas diffusion: Oxygen and carbon dioxide diffuse across the alveolar-capillary barrier based on their concentration gradients. Mechanisms of Breathing ​ Respiration depends on the creation and maintenance of a pressure gradient. In this section, flow is represented by V, and the airflow formula is: ​ Air flows into the alveoli when alveolar pressure is lower than atmospheric pressure. ​ Conversely, air flows out when alveolar pressure is greater than atmospheric pressure. ​ Respiratory mechanics refers to how these pressures are generated and regulated. Pressures in the Respiratory System ​ 1.​ Atmospheric Pressure (PB): barometric pressure, pressure exerted by the air in the atmosphere and At sea level, this is 760 mm Hg (or 0 cm H₂O in respiratory terms). 2.​ Alveolar Pressure (PA):The pressure inside the alveoli and At the end of inspiration or expiration, this equals atmospheric pressure (0 cm H₂O). 3.​ Pleural Pressure (Ppl): Pressure in the pleural space.It is negative relative to atmospheric pressure (around -5 cm H₂O) because the lungs naturally want to collapse while the chest wall wants to expand. 4.​ Transpulmonary Pressure (Ptp):The difference between alveolar pressure and pleural pressure. Also called lung recoil pressure, this helps keep the lungs inflated. Elastic Recoil of the Lungs The lungs have a natural tendency to collapse due to elastic recoil, which arises from: 1.​ Elastin fibers in the lung tissue: These fibers stretch during inhalation and recoil during exhalation. 2.​ Surface tension inside the alveoli: A liquid film lines the alveoli, and the water molecules exert surface tension, promoting alveolar collapse. Alveolar Stability Despite the strong collapsing forces of surface tension, alveoli do not collapse due to: 1.​ Pulmonary Surfactant: Produced by type II alveolar cells, surfactant is a mixture of lipids and proteins. ​ Surfactant reduces surface tension by disrupting water molecule interactions, Increases lung compliance ​ Prevents smaller alveoli from collapsing by reducing their surface tension more than in larger alveoli. 2.​ Alveolar Interdependence: Alveoli are interconnected by elastic fibers. ​ When one alveolus begins to collapse, the surrounding alveoli are stretched and recoil outward, pulling on the collapsing alveolus to keep it open. Law of Laplace The law of Laplace explains how surface tension affects alveolar stability. It states: 1.​ Smaller alveoli have greater collapsing pressure if surface tension is the same. 2.​ Pulmonary surfactant reduces surface tension in smaller alveoli more than in larger ones, helping balance the collapsing pressures. ​ ​ P = Collapsing pressure in the alveolus ​ ​ T = Surface tension ​ ​ r = Radius of the alveolus Changes in Pressure During Breathing Airflow depends on how alveolar pressure changes relative to atmospheric pressure. These changes are driven by pleural pressure and lung recoil: 1. Inhalation: The inspiratory muscles (diaphragm and external intercostals) contract, expanding the thoracic cavity. ​ This lowers pleural pressure, which reduces alveolar pressure. ​ Air flows into the lungs down the pressure gradient. ​ Inhalation ends when alveolar pressure equals atmospheric pressure. 2. Exhalation: The inspiratory muscles relax, causing pleural pressure and alveolar pressure to rise. ​ Air flows out until alveolar pressure equals atmospheric pressure. ​ In healthy individuals at rest, exhalation is passive, relying on elastic recoil rather than muscle contraction. Active Exhalation During activities like exercise, active expiration is necessary to meet increased ventilation demands: ​ Expiratory muscles (internal intercostals and abdominal muscles) contract to force air out. ​ This increases pleural and alveolar pressure, leading to faster and more forceful exhalation. ​ As pleural pressure increases, airway compression can occur at a point where internal airway pressure equals pleural pressure (the equal pressure point). ​ Beyond this point, further increases in pressure do not enhance airflow due to airway collapse. Pressure-Volume Relationship The relationship between lung pressure and volume changes is illustrated through pressure-volume curves for: ​ 1.​ Lung pressure (PL): Increases as lung volume rises. ​ 2.​ Chest wall pressure (PW): Acts like a spring, generating negative (inflating) pressures at lower lung volumes and positive (collapsing) pressures at high volumes. ​ 3.​ Respiratory system pressure (Prs): The combined effect of lung and chest wall pressures. Lung Compliance Compliance refers to how easily the lungs stretch. It is the slope of the pressure-volume curve and is highest at functional residual capacity (FRC), where breathing requires minimal effort. ​ High compliance: Easier to inflate the lungs with less pressure. ​ Low compliance: More pressure is needed to inflate the lungs, as seen in conditions like emphysema. Dynamics of Flow Poiseuille’s Law: Where: ​ ​ R = Resistance ​ ​ η = Viscosity of the air ​ ​ l = Length of the airway ​ ​ r = Radius of the airway ​ The airway radius is the primary determinant of resistance since it is raised to the fourth power. ​ A slight decrease in airway radius can lead to a significant increase in resistance. Airway Resistance In healthy individuals, airway resistance is typically low because: ​ Airways in the conducting zone have large radii. ​ The small pressure gradient (1-2 cm H₂O) generated during breathing is sufficient to drive airflow ​ However, airway resistance becomes significant during pathological conditions or high ventilatory demands (e.g., during exercise). Bronchoconstriction and Bronchodilation 1. Bronchoconstriction: refers to a decrease in airway radius, which increases airway resistance. ​ Occurs due to parasympathetic stimulation, which dominates during rest when oxygen demand is low. ​ Smooth muscle contraction in the bronchioles reduces the airway radius, increasing resistance. ​ Local chemical control also triggers bronchoconstriction in response to low CO₂ levels. ​ Histamine release (e.g., during allergic reactions).  ​ Excess mucus. ​ Airway wall edema (swelling). ​ Airway collapse. ​ Allergic spasms caused by substances like slow-reactive substance of anaphylaxis (SRS-A). 2. Bronchodilation: increase in airway radius, which decreases airway resistance. ​ Occurs due to sympathetic stimulation during periods of increased oxygen demand (e.g., exercise). ​ Direct innervation: Sympathetic nerves release norepinephrine, activating β2-adrenergic receptors on bronchial smooth muscle cells, causing relaxation and increased airway radius. ​ Indirect innervation: The adrenal medulla releases epinephrine, which circulates to the airway smooth muscle, enhancing bronchodilation. ​ Increased CO₂ levels can also stimulate bronchodilation to enhance ventilation and remove excess CO₂. Airway Resistance and Chronic Pulmonary Diseases ​ Chronic lung diseases often involve narrowing of the lower airways, which increases resistance and makes breathing difficult. ​ These diseases can be classified as obstructive or restrictive. Obstructive Lung Diseases 1. Asthma ​ A chronic inflammatory disease that causes difficulty breathing. ​ Symptoms include shortness of breath, chest tightness, coughing, and wheezing. ​ ​ Airways are impaired in three ways: ​ 1.​ Thickening of airway walls due to histamine-induced swelling (edema). ​ 2.​ Thick mucus secretion, which physically blocks the airways. ​ 3.​ Smooth muscle spasms, causing airway constriction. 2. Chronic Obstructive Pulmonary Disease (COPD) ​ COPD is a term that includes chronic bronchitis and emphysema. ​ It is primarily caused by long-term cigarette smoking and is one of the leading causes of death in Canada.  3.​ Chronic Bronchitis: ​ A long-term inflammation of the lower airways. ​ Caused by chronic exposure to irritants (e.g., cigarette smoke, air pollution). ​ The airways narrow due to swelling (edema) and mucus overproduction. 4.​ Emphysema: ​ An irreversible condition characterized by the breakdown of alveolar tissue and collapse of smaller airways. ​ Chronic exposure to cigarette smoke causes alveolar macrophages to release enzymes (e.g., trypsin), which destroy lung tissue. ​ This reduces the surface area available for gas exchange and impairs airflow. Restrictive Lung Diseases In restrictive diseases, the total lung capacity is reduced because the lungs cannot fully expand. Unlike obstructive diseases, airflow is not blocked, but lung volumes are lower. This may result from: ​ Fibrosis (scarring of lung tissue). ​ Conditions that restrict lung expansion (e.g., pleural disease). Impact of Pulmonary Diseases on Breathing Patients with obstructive diseases often experience difficulty exhaling due to increased airway resistance. This can lead to breath stacking: ​ Incomplete exhalation results in higher residual lung volumes. ​ Subsequent breaths begin at elevated lung volumes, which initially reduces resistance. ​ Over time, dynamic hyperinflation occurs, making it difficult to breathe both in and out ​ Patients often report the sensation of not getting enough air in, even though the primary problem is with exhalation. This leads to dyspnea (shortness of breath). Lung Volumes Introduction to Lung Volumes Lung volumes and capacities are measured using a spirometer, which generates a spirogram. Spirometry can determine the following key lung volumes and capacities: Lung Volumes ​ 1.​ Tidal Volume (VT): The amount of air entering or leaving the lungs in a single breath. At rest, this is typically around 500 mL. ​ 2.​ Inspiratory Reserve Volume (IRV): The maximum volume of air that can be inhaled above the normal tidal volume. At rest, this is around 3000 mL. ​ 3.​ Expiratory Reserve Volume (ERV): The maximum volume of air that can be exhaled after a normal tidal exhalation.Typically around 1000 mL. ​ 4.​ Residual Volume (RV):The volume of air remaining in the lungs after maximal exhalation.About 1200 mL and cannot be directly measured by spirometry. Lung CapacitiesLung capacities are combinations of two or more lung volumes: ​ 1.​ Inspiratory Capacity (IC):The maximum amount of air that can be inhaled starting from the end of a normal exhalation.IC = VT + IRV (~3500 mL). ​ 2.​ Functional Residual Capacity (FRC):The volume of air remaining in the lungs at the end of a normal exhalation.FRC = ERV + RV (~2200 mL). ​ 3.​ Vital Capacity (VC):The maximum amount of air that can be exhaled after a maximal inhalation.VC = IRV + VT + ERV (~4500 mL). ​ 4.​ Total Lung Capacity (TLC):The maximum volume of air the lungs can hold. TLC = VC + RV (~5700 mL). ​ 5.​ Forced Expiratory Volume in One Second (FEV₁):The amount of air expelled in the first second of a forced exhalation. Typically, FEV₁ is about 80% of the forced vital capacity (FVC). Lung Volumes and Respiratory Dysfunction Dysfunction is generally classified into two categories: 1.​ Obstructive Lung Disease ​ Characterized by increased airway resistance and difficulty exhaling. ​ FEV₁ is reduced due to airflow obstruction. ​ FRC and RV are higher than normal, while VC is lower because of incomplete exhalation. ​ This condition leads to breath stacking and dynamic hyperinflation, further reducing lung efficiency. 2.​ Restrictive Lung Disease ​ Characterized by reduced lung volumes due to an inability to fully expand the lungs. ​ FEV₁ may be reduced, but the FEV₁/FVC ratio remains normal because airflow is not obstructed. ​ The lungs are physically restricted, often due to conditions like pulmonary fibrosis or pleural disease. Ventilation The minute ventilation refers to the total amount of air breathed per minute and is calculated as: Where: ​ ​ VT = Tidal volume ​ ​ f = Respiratory frequency (breaths per minute) At rest: ​ ​ VT = 500 mL ​ ​ f = 12 breaths/min ​ ​ Minute ventilation (VE) = 500 mL × 12 = 6 L/min ​ However, minute ventilation does not represent the air available for gas exchange due to the presence of anatomical dead space (~150 mL), where no gas exchange occurs. Expiratory Flow and Lung Function During pulmonary function tests, expiratory flow data is often more informative than inspiratory data because airflow limitations are more pronounced during exhalation. Experiment Demonstration: 1.​ Exhale completely and then inhale as fast as possible to full lung capacity. 2.​ Now, inhale fully and exhale as fast as possible to residual volume. Work of Breathing Breathing requires energy to overcome: ​ 1.​ Elastic forces (e.g., lung recoil). ​ 2.​ Airway resistance. Gas Exchange Gas exchange is essential for supplying oxygen to the tissues and removing carbon dioxide from the body. It occurs at two primary sites: 1.​ Pulmonary capillaries in the lungs, where oxygen enters the blood and carbon dioxide is expelled. 2.​ Systemic capillaries, where oxygen is delivered to tissues and carbon dioxide is absorbed into the blood. Partial Pressure of Gases The movement of oxygen and carbon dioxide is driven by partial pressure gradients. According to Dalton’s Law, each gas in a mixture exerts its own pressure independently of the other gases. ​ For example, at sea level, atmospheric pressure is 760 mm Hg: Oxygen makes up 21% of the atmosphere, so its partial pressure (PO₂) Partial pressures in the body vary depending on location: ​ Alveolar PO₂ is around 100 mm Hg due to mixing with expired air. ​ Pulmonary capillary PO₂ is initially low (~40 mm Hg) but rises as oxygen diffuses into the blood. Gas Exchange in the Lungs In the alveoli, gas exchange occurs by diffusion: 1.​ Oxygen diffuses from the alveoli (PO₂ ~100 mm Hg) into the pulmonary capillaries (PO₂ ~40 mm Hg). 2.​ Carbon dioxide diffuses from the pulmonary capillaries (PCO₂ ~46 mm Hg) into the alveoli (PCO₂ ~40 mm Hg). 3.​ These gradients ensure a continuous exchange of gases during both inhalation and exhalation. Gas Exchange in Systemic Tissues The process is reversed in the systemic tissues: 1.​ Oxygen diffuses from the blood (PO₂ ~100 mm Hg) into the tissues, where PO₂ is much lower (~40 mm Hg). 2.​ Carbon dioxide moves from the tissues (PCO₂ ~46 mm Hg) into the blood, where PCO₂ is lower (~40 mm Hg). 3.​ This diffusion continues until equilibrium is reached. Factors Affecting Gas Exchange Several factors influence the efficiency of gas exchange: ​ 1.​ Partial Pressure Differences: ​ A greater pressure gradient increases the rate of diffusion. ​ High altitude, where atmospheric PO₂ is lower, reduces the gradient and slows oxygen diffusion. ​ 2.​ Surface Area: ​ A larger alveolar surface area allows more gas exchange. ​ Diseases like emphysema reduce surface area, impairing oxygen transfer. ​ 3.​ Diffusion Distance: ​ Thin alveolar-capillary membranes promote rapid diffusion. ​ Conditions like pulmonary edema increase diffusion distance, slowing gas exchange. ​ 4.​ Ventilation-Perfusion Matching: ​ Efficient gas exchange requires proper matching of ventilation (airflow) and perfusion (blood flow). ​ Mismatches (e.g., in chronic lung diseases) lead to impaired gas exchange. Gas transport Once oxygen and carbon dioxide have been exchanged in the lungs, they must be transported to and from the tissues. The blood has specialized mechanisms to efficiently transport both gases: ​ Oxygen is carried by hemoglobin in red blood cells. ​ Carbon dioxide is transported through multiple pathways, including in dissolved form, bound to hemoglobin, and as bicarbonate ions. Oxygen Transport Oxygen is transported in two forms: 1.​ Dissolved in plasma (~1.5% of oxygen): Limited due to the low solubility of oxygen in blood. 2.​ Bound to hemoglobin (Hb) (~98.5% of oxygen): Each hemoglobin molecule can bind up to four oxygen molecules. ​ Oxygen binding to hemoglobin is reversible and depends on the partial pressure of oxygen (PO₂). Oxygen Dissociation Curve The oxygen dissociation curve shows the relationship between PO₂ and hemoglobin saturation. It is sigmoidal (S-shaped) due to cooperative binding—when one oxygen molecule binds to hemoglobin, the affinity for additional oxygen increases. ​ 1.​ Plateau region (PO₂ ~60-100 mm Hg): ​ Hemoglobin saturation remains high (~90-100%) even with slight decreases in PO₂. ​ This ensures adequate oxygen delivery under normal conditions and at moderate altitudes. ​ 2.​ Steep region (PO₂ ~20-60 mm Hg):  ​ In tissues where PO₂ is low, oxygen readily dissociates from hemoglobin, allowing efficient oxygen delivery. Factors Affecting the Oxygen Dissociation Curve ​ 1.​ Right Shift (reduced affinity for oxygen) – Enhances oxygen unloading in tissues: ​ Increased CO₂ (Bohr effect) ​ Increased H⁺ (lower pH) ​ Increased temperature ​ Increased 2,3-BPG (produced during hypoxia) ​ 2.​ Left Shift (increased affinity for oxygen) – Reduces oxygen release: ​ Decreased CO₂ ​ Increased pH (alkalosis) ​ Lower temperature Carbon Dioxide Transport Carbon dioxide is transported in three forms: 1.​ Dissolved in plasma (~10%):Carbon dioxide is more soluble in blood than oxygen, but only a small amount is transported in dissolved form. 2.​ Bound to hemoglobin (~20%): CO₂ binds to hemoglobin at a different site than oxygen, forming carbaminohemoglobin. This binding is influenced by oxygen levels (explained by the Haldane effect). 3.​ As bicarbonate ions (HCO₃⁻) (~70%): In red blood cells, CO₂ reacts with water to form carbonic acid (H₂CO₃), which quickly dissociates into HCO₃⁻ and H⁺: ​ The enzyme carbonic anhydrase catalyzes this reaction. ​ Bicarbonate is transported out of red blood cells in exchange for chloride ions (chloride shift). The Chloride (Hamburger) Shift ​ To maintain electrical balance, when HCO₃⁻ leaves red blood cells, Cl⁻ ions enter ​ This process ensures efficient transport of carbon dioxide in the blood. The Haldane Effect ​ Oxygen binding to hemoglobin reduces hemoglobin’s ability to bind CO₂ and H⁺. ​ Conversely, when oxygen levels are low (e.g., in tissues), hemoglobin binds more CO₂ and H⁺, enhancing CO₂ transport. Abnormalities in Gas Transport Disruptions in oxygen or carbon dioxide transport can lead to clinical conditions: 1.​ Hypoxemia – Low arterial oxygen levels (low PO₂). 2.​ Hypercapnia – Excess carbon dioxide in the blood (high PCO₂), often due to inadequate ventilation. 3.​ Respiratory Acidosis – Occurs when CO₂ accumulation lowers blood pH. 4.​ Respiratory Alkalosis – Caused by excessive CO₂ loss, leading to elevated pH. Control of ventilation Breathing is an automatic process regulated by the respiratory control centers in the brain. This control ensures that oxygen and carbon dioxide levels in the body remain within normal ranges. Ventilation is adjusted based on both mechanical and chemical signals. Central Control of Breathing The medulla oblongata and pons in the brainstem are responsible for generating and regulating the breathing rhythm. 1.​ Medullary Respiratory Centers: ​ The dorsal respiratory group (DRG) primarily controls inspiration by stimulating the diaphragm and external intercostal muscles. ​ The ventral respiratory group (VRG) is involved in both inspiration and active expiration, particularly during increased ventilation demands (e.g., exercise). ​ 2.​ Pontine Respiratory Centers: ​ The pneumotaxic center and apneustic center in the pons fine-tune the respiratory rhythm and depth of breathing. Mechanical Control of Breathing Mechanical factors that influence ventilation include: ​ 1.​ Lung stretch receptors: ​ These receptors prevent over-inflation of the lungs through the Hering-Breuer reflex, which inhibits inspiration when the lungs expand excessively. ​ 2.​ Muscle and joint receptors: ​ During physical activity, these receptors provide feedback to increase ventilation to meet the body’s oxygen demands. Chemical Control of Breathing Chemical control is the primary mechanism for adjusting ventilation based on levels of oxygen, carbon dioxide, and hydrogen ions in the blood and cerebrospinal fluid (CSF). 1. Peripheral Chemoreceptors ​ Located in the carotid and aortic bodies, these chemoreceptors detect changes in arterial PO₂, PCO₂, and pH. ​ Decreased arterial PO₂ stimulates peripheral chemoreceptors, but this response only becomes significant when PO₂ falls below 60 mm Hg. 2. Central Chemoreceptors ​ Located in the medulla, these receptors are sensitive to changes in PCO₂ and H⁺ levels in the CSF. ​ Increased arterial PCO₂ (hypercapnia) causes CO₂ to cross the blood-brain barrier, where it forms carbonic acid and dissociates into H⁺ and bicarbonate. The increase in H⁺ stimulates central chemoreceptors to increase ventilation. Effects of Oxygen, Carbon Dioxide, and pH on Ventilation ​ 1.​ Increased PCO₂ is the most potent stimulus for ventilation. Even small increases in PCO₂ lead to significant increases in respiratory rate and depth. ​ 2.​ Low PO₂ primarily affects peripheral chemoreceptors and plays a minor role in ventilation control unless PO₂ drops significantly. ​ 3.​ Acidosis (low pH) stimulates both central and peripheral chemoreceptors to increase ventilation to expel CO₂ and restore pH balance. Effects of Exercise on Ventilation During exercise, ventilation increases to meet the heightened oxygen demands and to eliminate excess CO₂. Interestingly, the increase in ventilation is not driven solely by chemical changes: 1.​ Neural input from higher brain centers and muscle receptors initiates increased ventilation even before blood gas levels change. 2.​ The body’s ventilation stabilizes to match the metabolic rate during sustained exercise. Ventilation Summary Control of ventilation involves both central and peripheral mechanisms: 1.​ Medullary and pontine centers generate and regulate the respiratory rhythm. 2.​ Peripheral chemoreceptors respond to low oxygen and high hydrogen ion levels. 3.​ Central chemoreceptors are sensitive to carbon dioxide and pH changes. 4.​ During exercise, neural input and muscle receptors help regulate ventilation.