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BIOL 1080
Jim Kirkland

BIOL*1080 Final Exam Notes Hormones and the Endocrine System In the body, hormones modulate: 1. Growth and development 2. Homeostasis 3. Reproduction (e.g. sperm) -and many other things in the physiome including aspects of the CCN (neurodevelopment and immunity) -have specific receptors (dependent on stimulus) Hormones come from secretory cells in: 1. Endocrine glands (e.g. pituitary, thyroid, parathyroid, adrenal and pineal glands) 2. Other organs with endocrine tissue that provides a secondary secretion function (e.g.hypothalamus, thymus, pancreas, ovaries, testes, heart, placenta, stomach, SI and kidneys) -Hormones diffuse into the bloodstream, and they are released in small amounts. • Lipid soluble hormones move through any cell’s plasma membrane because it’s a lipid bilayer • Water soluble hormones cannot pass through the lipid bilayer and cannot enter target cells; instead the hormone binds to a receptor on the plasma membrane of the target cell Hypothalamus: regulates physiological responses like body temperature and water balance -nerve cells in the hypothalamus synthesize and secrete hormones that travel through blood stream to anterior lobe, where they can stimulate or inhibit hormone secretion. Pituitary Gland: consists of anterior and posterior lobe • Anterior pituitary responds to releasing and inhibiting hormones from the hypothalamus by modifying its own synthesis and secretion of 6 hormones • Posterior lobe consists of neural tissue that releases hormones How does the Nervous System interact with the Endocrine System –to form the foundation of the CCN (from the organ to the person level)? 1. Some nerves release hormones directly into the bloodstream (neurohormones). BIOL*1080 Final Exam Notes 2. All primary endocrine glands and secondary endocrine tissue are innervated by neurons of the autonomic nervous system. Nerve signals, via local neurotransmitter release, can modulate hormone secretion. 3. Neurons in the CNS and PNS (along with astrocytes in the CNS) and astrocytes (like cells in the PNS) have receptors for many hormones. ie. insulin (hydrophilic) and estrogen (lipophilic) Pineal Gland: gland at centre of brain; it’s secretory cells produce the hormone melatonin -neurons of the retina, stimulated by light entering the eye, send impulses to the hypothalamus and ultimately the pineal gland, where they inhibit secretion of melatonin Hormones of the pancreas: • Pancreas has exocrine and endocrine functions • Diseases arise such as pancreatitis and cancer Single hormone organ axis: • Exocrine cells (acinar and duct cells) make up 95% • Islets(endocrine) make up 5% of pancreas • To maintain blood glucose levels, nerves communicate with alpha and beta cells Diabetes: when pancreas fails to produce enough insulin to regulate sugar metabolism, or when the body fails to use insulin effectively • Type 1 diabetes- a person’s own immune system attacks beta cells that produce insulin (beta cells die, need insulin injected) • Type 2 diabetes- decreased sensitivity to insulin (must inject insulin and are insulin sensitive) Risk Factors: • Runs in families • Obesity, low physical activity • Insulin shock: can occur with severe depletion of blood glucose which can occur when too much insulin is injected (can cause anxiety, sweating and disorientation but can lead to convulsions and unconsciousness when brain can no longer function, due to lack of glucose) Anabolic steroids are toxic because: • The effective dose is supraphysiological • The dose of the hormone/hormone agonist is not timed to mimic natural hormone production BIOL*1080 Final Exam Notes • Hormones are naturally released at low levels in complex, ultradian, circadian and infraradian rhythms The Local Support and Defense System First line of defense (chemical and physical surface barriers) - “keep the foreign organism or molecules out of the body in the first place” - includes epithelial barriers and washing away of pathogens (cleaning the human biome) Second line of defense (internal cellular and chemical defenses; active if surface barriers are penetrated) - “attack any foreign organism or molecule or cancer cell inside the body” - defensive cells (phagocytic cells, eosinophils, natural killer cells) - defensive proteins (interferons, complement system) - inflammation (widening of blood vessels and increased capillary permeability, leading to redness, heat, swelling and pain) - fever (abnormally high body temperature Third line of defense (immune response which destroys specific targets) - “destroy specific foreign organism or molecule or cancer cell inside the body” - Results in immune response destroying specific targets that are usually disease related Physical Barriers: tough outer layer of skin; mucous membranes lining digestive and respiratory passages Chemical Barriers: Sweat and oil on skin can reduce microbes; acidic lining of stomach destroys pathogens Defensive cells: • Phagocytes engulf pathogens, dead cells and damaged tissue by Phagocytosis • Eosinophils attack pathogens too large to be consumed by Phagocytosis • Natural killer cells roam the body in search of abnormal cells (and quickly kills them) Defensive Proteins: • Interferons slow viral reproduction BIOL*1080 Final Exam Notes • The complement system is a group of proteins whose activities enhance the body’s other defense mechanisms (destruction of pathogen, stimulation of inflammation, enhancement of Phagocytosis) o 50+ proteins made by liver o Present all the time o Does more than lysis of pathogens Protein based defense- lysis by complement (interferons) 1. Activated protein forms holes in the cell wall and membrane of the bacterium 2. The bacterium can no longer maintain a constant internal environment, water enters the cell 3. The bacterium bursts Defensive Processes: Inflammation (destroys invaders and restores damaged tissue) 1. Redness: blood flow carries defensive cells and chemicals to damaged tissues and removes toxins 2. Heat: increases the metabolic rate of cells in the injured area to speed healing 3. Swelling: fluid containing the defensive chemicals, blood-clotting factors, oxygen, nutrients and defensive cells seeps into the injured area 4. Pain: hampers movement, allowing the injured area to heal Outcome of Inflammation • Complement destroys bacteria • Phagocytes engulf bacteria • Inflammation can occur without thorn/dirt/microbes -bruises (acute), arthritis (chronic); usually worsens chronic disease Defensive processes: Fever • Infection, microbial toxins, mediators of inflammation and immune reactions can cause a fever • Fever of Unknown Origin - common in children and elderly (developing CCN) • Pyrogens: chemicals raise the “thermostat” in the brain to a higher set point causing fever Immune Response: • Immune system provides specific response and memory for defense (3 line)d • First, an immune response is directed at a particular pathogen and then acts to destroy it • Second, it has memory so if it remembers the pathogen it can act quickly to kill it o T cells and beta cells look for little particles to customize their attack o They’re responsible for the specifivity and memory of the immune response BIOL*1080 Final Exam Notes The LSDS does more than defending against invading microbes! (bigger concept than “immune system”) 1. Local tissue damage by processes that are not due to infectious microbes 2. Normal tissue turnover (cell senescence/ death and regeneration/remodeling) 3. Tissue repair and redevelopment in the latter stages of wound healing 4. Managing the appearance of transformed cell populations, self recognition -cancer is largely a disease of the LSDS *Like the CCN of which it is a part, the LSDS is always on, always doing multiple tasks. To view the Immune Response, as ‘waiting and watching’for invaders in the healthy adult ‐ is a naïve viewpoint… Systematic Lupus Erythematosus: a non-organ specific auto-immune disorder in which connective tissue is attacked -connective tissue is found throughout the body so almost any organ can be affected MHC markers: molecules embedded in the plasma membrane of a cell labelling it as “self” Autoimmunity: occurs when immune system attacks the tissues or organs of the body Vaccinations: procedure that introduces a harmless form of an antigen into the body to stimulate immune responses against the antigen Hay fever: a common allergy that occurs when allergen is inhaled, triggering an immune response in the respiratory system Q: What is the Local Support and Defense System? We know it is the 4th component of the CCN; we describe it as: • Maintenance and Support System • Adaptation and Repair System • Resident Defense System • Migrant Defense System To envision the LSDS: The parenchymal cells of glands or organs are the most prominent cell type in terms of function and (sometimes) mass. The parenchyma is the critical ‘functional’portion of the gland or organ. Traditionally, the parenchymal cells are: Liver – hepatocyte Skin‐ keratinocyte Skeletal Muscle – skeletal muscle cell/myocyte BIOL*1080 Final Exam Notes Heart – cardiomyocyte Kidney – tubule epithelial cells Lung – alveolar epithelial cells Brain – neurons (e.g. glial cells provide structure and functional support) Small intestine – enterocytes Adipose tissue (endocrine glands) ‐ adipocytes Glands – mixture of secretory cells The non‐parenchymal cells in tissues/organs form the Basic Logic Unit of the Local Support and Defense System The cell types are: 1. Afferent and efferent nerve endings 2. Capillary endothelial cells 3. Support and Defense cells of Lymphoid Origin (resident T‐cells, resident B‐Cells, NK and NKT cells) 4. Support and Defense Cells of Myeloid Origin (neutrophils, macrophages, dendritic cells and mast cells) 5. Fibroblast/Myofibroblast /Pericyte Cells 6. Stem Cells (in stem cell niche) *Called the stroma in the peripheral organs when extracellular matrix components (protein – carbohydrate network) are included - the stroma ‘supports’the functional portion of a gland or organ - the stroma could be the brains of the operation Pancreas and the LSDS • Duodenal papilla is the site of exocrine secretion, digestive enzymes move to the duodenum • Endocrine secretions move into the blood, insulin and glucagon The pancreas: • Alpha cells secrete glucagon • Beta cells secrete insulin • Delta cells secrete somatostatin • Exocrine pancreas (acinar and duct cells) - functionally all islets behave as a single unit - specific immune staining can find the CCN Diseases and disorders of the pancreas Pancreatitis – acute, chronic (alcohol-especially binge drinking, anabolic steroid use) BIOL*1080 Final Exam Notes Diabetes – Type 1, Type 2 Exocrine Pancreas Insufficiency Cystic Fibrosis (one cause of Exocrine Pancreas Insufficiency)-take pills with digestive enzymes Pancreatic Cancer Pancreatic Steatosis- fatty pancreas Migration & Memory in the Local Support and Defense System Continuous production and movement of cells into the blood: • Stem cells are undifferentiated cells in the red bone marrow that give rise to all the formed elements • Stem cells divide and become specialized • Mature formed elements are specialized for specific functions • Move to bloodstream, then tissues • Neutrophil to phagocytes, monocyte to macrophage and lymphocyte to B-cells, T-cells and NK-cells - white blood cells are the migratory cells of the LSDS White blood cells migrate into and out from peripheral tissues: 1. White blood cells exit a capillary by squeezing between the cells of the vessel walls and by migrating into tissues 2. Platelets and red blood cells do not migrate Phagocytosis (Attack!) 1. Threat- an invader enters the body 2. Detection- a macrophage encounters, engulfs, and digests the invader(antigen i.e. bacterium) -the macrophage places a piece of the invader on its surface with the self marker 3. Alert- the macrophage presents the antigen to a helper T-cell and secretes a chemical that activates the helper T-cell (cytokine) Effector helper T-cell can activate: -antibody mediated response from a B-cell -cell mediated response from a T-cell (cytotoxicity) Cell-based immunity and Antibody-based immunity route of attack: 1. Threat: Foreign cell or molecule enters the body 2. Detection: Macrophage detects foreign cell or molecule and engulfs it 3. Alert: Macrophage presents antigen to and activates the helper T-cells 4. Alarm: Helper T cell activates both lines of defense to fight that specific antigen BIOL*1080 Final Exam Notes Antibody-based immunity route of attack: 5. Specific Defenses: B- cells are activated and divide to form plasma cells that secrete antibodies specific to the antigen 6. Defense:Antibodies specific to antigen eliminate the antigen 7. Memory formed when helper T-cells, cytotoxic T-cells, and B-cells were activated to provide swift response if the antigen is detected again 8. Withdrawal of forces: suppressor T-cells shut down immune response to that antigen Cell-based immunity (T-lymphocyte) route of attack 5. Specific Defenses: T cells divide to form cytotoxic T-cells that attack cells with the specific antigen 6. Defense: Cytotoxic T-cells cause cells with the antigen to burst 7. Memory formed when helper T-cells, cytotoxic T-cells, and B-cells were activated to provide swift response if the antigen is detected again 8. Withdrawal of forces: suppressor T-cells shut down immune response to that antigen Q:After the carnage is over, and the debris cleaned up and the local cells repaired….what is left in the tissue, in the bone marrow and in the thymus? A: Memory: in the form of the Memory Helper T Cells, the Memory Cytotoxic T Cells and the Memory B Cells populations ‐‐‐AND in the form of sensory (interoceptive) memory in the CNS. In bone marrow, thymus etc. there is memory in the cells of the LSDS Three applications of the concept: 1. Second bout of same disease (good) 2. Vaccination 3. Development of allergy or autoimmunity (harmful dysfunction of the LSDS or CCN) -on second exposure to an antigen, the immune response is faster and stronger Cancer: characterized by the uncontrollable growth and spreading of abnormal cells Cancer Risks: • Tobacco, poor diet, physical inactivity • Carcinogens (cancer causing agents), e.g. tar in cigarettes • Oncogenes (cancer causing genes present on chromosomes • Proto-oncogenes (genes that can become oncogenes under certain conditions) The Cardiovascular Lymphatic System The Components of the Cardiovascular ‐ Lymphatic System I. Fluids a. blood BIOL*1080 Final Exam Notes b. lymph (similar to plasma) c. cerebrospinal fluid (CSF and EF = white blood cells; no red blood cells, no platelets) d. extracellular fluid II. Vessels a. blood vessels b. lymph vessels c. cerebrospinal fluid vessels III. Organs a. heart b. kidney (controls blood pressure and volume, produces EPO to O2 carrying capacity) c. spleen, thymus, tonsils d. Lymph nodes (no dedicated pump) IV. Innervation a. sympathetic b. parasympathetic c. sensory V. Stem Cell Pool a. bone marrow b. other Lymphatic System: consists of lymph (fluid identical to interstitial fluid that bathes the body’s cells), lymphatic vessels (through which the lymph flows) and of various lymphoid tissues and organs scattered throughout the body Cells circulating in the blood: • Plasma is a medium for transporting materials in the blood (55%) • The formed elements consist of the red blood cells, white blood cells and platelets (45%) -platelets are cell fragments essential for blood clotting (p+w= 1%) -white blood cells defend the body against disease -red blood cells transport oxygen (99%) • During infection, the number of white blood cells increases dramatically Blood Clotting: 1. Injured cells in the walls of the vessels and platelets release clotting factors 2. Clotting factors convert an inactivate blood protein to prothrombin activator 3. Prothrombin activator converts prothrombin to thrombin 4. Thrombin converts fibrionogen to fibrin 5. Fibrin network traps red blood cells and platelets, forming a blood clot Fibrin Clot: a clot produced when the protein fibrin makes a web that traps blood BIOL*1080 Final Exam Notes Platelet Plug: formed when platelets cling to cables of collagen (protein fibre on torn blood vessel surface) Coagulation disorders I: Platelet Dysfunction • Collagen causes platelet aggregation • Aspirin inhibits platelet aggregation (and long term use can cause GI bleeding Coagulation disorders II: Fibrin Dysfunction • Genetic disorders: hemophilia (no clotting) • Blood thinners prevent clotting that could cause a heart attack or stroke Blood Vessels & Blood Flow -The inner lining of the blood vessel called the epithelium provides a smooth surface, that minimizes friction, so blood can flow easily Coronary Circulation: an extensive network of vessels that service the tissues of the heart -first two arteries that branch off the aorta are the coronary arteries -blood passes through the capillary beds for nourishment -blood enters cardiac veins and eventually flows into the right atrium Electrocardiogram: an image of the electrical activities of the heart generated by a recording device Hemoglobin: the oxygen binding pigment that’s responsible for the cells’red colour Spygmomanometer: device that measure blood pressure (cuff and device that can read pressure) Diseases and disorders of the fluids of the circulatory system • Anemia – various types o iron deficiency (also some vitamins) o hemolytic- toxins, disease o not enough red blood cells • Coagulation disorders ‐ platelet/clotting factors o genetic or drug induced o internal or external bleeding to death • Leukemias (many types) • White Blood Cell Deficiencies – Immuno deficiencies • Dehydration/Hemoconcentration • Blood loss -hemodilation (too much water) Leukemia patients BIOL*1080 Final Exam Notes -have more white blood cells (stained smears) -almost one third of centrifuged blood is white blood cells V. Stem Cell Pool Periods of acute oxygen deficit: - Training for a marathon, anemic due to Iron deficiency etc. Not a full homeostatic system - Dangerous because red blood cells cannot be brought down in system, only brought up White blood cell deficiencies Ex) SCID- severe immunodeficiency in which T & B cells are decimated because of genetic deficiency blocking a certain gene • Can be treated by gene therapy • If cell isn’t inserted properly it can grow irregularly (leukemia) • HIV affects T helper cells • Cancers can develop due to a lack of T cell activity II. Vessels- the blood vessels conduct the blood in continuous loops • Arteries and arterioles have more smooth musvle than their venous counterparts • Veins and venules are at a lower pressure • Veins have a larger lumen with a thinner wall than arteries Blood flow- general circuit • 2 distinct loops of circulation within 4 chambers of the heart • (Pulmonary circuit) Pulmonary veins to left atrium through left ventricle through aorta (systemic circuit) right atrium (vena cavae), right ventricle through pulmonary arteries Blood flow- continuous loops in parallel • Heart has own blood supply • Right heart loop (pulmonary), left heart loop (systemic) • 60% of blood in systemic veins and venules (transport back from tissues) • 15% in systemic arteries and arterioles (transport to tissues) • 12% in pulmonary blood vessels • 8% in heart • 5% in capillaries (they deliver nutrients, chemical messengers and migrant cells) - Brain gets freshest blood - Heart pumps blood back into own tissues - Liver has 2 incoming blood supplies BIOL*1080 Final Exam Notes The lymphatic vessels collect material from the extracellular fluid at capillary beds and form lymph, and move lymph back to the major veins of the blood system- the lymphatic system is NOT a continuous loop • Lymphatic capillaries have a blunt, closed end • Dietary lymph carries nutrients from food • Note that cerebrospinal fluid drains back into the CNS circulation and into the lymphatic system at various points outside the brain What do lymphatic capillaries, veins and ducts look like? 1. Leaky (out) o Required for movement of metabolites/ signalling molecules o Pressure gradient (from blood capillary to lymphatic capillary) 2. Leaky (in) o Openings are even larger than in blood capillaries 3. Many valves 4. T & B cell surveillance of lymph Arterioles – main site of blood flow and blood pressure regulation Capillaries – nutrient, waste, fluid exchange at local level Venules – main site of lymphocytes crossing from blood to lymph nodes Blood vessels differ by velocity and surface area: High velocity and small surface area = direct, rapid conductance of blood Low velocity and large surface area = optimal exchange Organ specific control of blood flow 1. Resting blood flow (Cardiac output= 5L/min) 2. Exercise blood flow (Cardiac output= 25L/min) o More blood to skeletal muscle (1L/min to 20L/min), heart, skin o Less blood to GI tract (1.25L/min to 1.05 L/min) and kidneys Blood return improved by: 1. Values that prevent backflow 2. Contractions of surround skeletal muscle 3. Breathing causes pressure changes that draw blood upwards • Relaxed calf muscle: Skeletal muscles relax, and blood fills the valves and closes them • Contracted calf muscle: Muscle contraction squeezes the vein, pushing blood through the open valve into the heart BIOL*1080 Final Exam Notes Diseases and disorders of the vessels of the circulatory system • Arteries ‐ aneurysms, atherosclerosis • Veins – varicose veins, deep vein thrombosis • Lymphatic Vessels – lymphedema • Cerebrospinal Fluid ‐ hydrocephalus o Excess CSF leads to increased cranial pressure o Hydrocephalus: child with a ventricular cannula shunted to abdominal cavity o Cannula drains CSF Failure of the CCN with aging: • Deep vein thrombosis= clot formation in blood vein • Lymphedema= failure of lymph return (diabetes) • Varicose veins= failure of valves Circulatory System (Network)Analysis Organ Function: Heart – Pump Blood Kidney – filter and adjust volume and content of blood plasma, indirectly control blood pressure Spleen – filter and remove old red cells and platelets, site of maturation of white blood cells Thymus – site of maturation of white blood cells, major site of antigen presentation and memory formation in B cell populations Tonsils (4 types) – site of storage and maturation of white blood cells The Heart as a Muscular Pump • The heart is made of cardiac muscle tissue called myocardium • generates the force needed to circulate blood; it beats 72 times each minute Neural input: involuntary, autonomic (calcium waves) Neural conduction: gap junctions= very fast; contract as a unit i.e. no fibre recruitment like skeletal muscle (in a wave like action) Metabolism: VERY high oxidative capacity (lots of mitochondria) – fatigue resistant • heart has 4 chambers (2 atria and 2 ventricles) • right atrium, right ventricle to lungs • left atrium, left ventricle, to body • The right side of the heart (pulmonary circuit) with right atrium and ventricle – Contains blood rich in carbon dioxide -Returns from the tissues -Flows out to the lungs • The left side of the heart (systemic circuit) with left atrium and ventricle BIOL*1080 Final Exam Notes – Contains blood rich in oxygen -Returns from the lungs -Flows out to the tissues Controlling direction of blood flow with valves: • “Lub” sound from entering ventricle; in atrioventricular valves between each atrium and ventricle (tricuspid, mitral) • “Dub” sound from leacing ventricle; semilunar valves between each ventricle and artery (pulmonary, aortic) Just as in large veins, there can be problems with heart valves. Example: • Stenosis – narrowing of a valve. -May be congenital, due to calcification, or scarring from rheumatic fever. -can cause fatigue and shortness of breath, exercise intolerance, or in more serious cases heart failure, fluid buildup in lungs (pulmonary edema and hypertension) and death. Tends to occur in: • Aortic valve: between left ventricle and aorta • Mitral valve: between right atria and ventricle Artificial Heart Valves Issues: • durability – supposed to last 20+ years • clot formation – requires consistent anticoagulant therapy (blood thinners) • getting stuck • resistance to flow; ; vulnerability to backflow and regurgitation Biological values are an alternative (usually porcine, or pig) -referred to as xenotransplantation (between species) – requires immunosupression therapy Cardiac Cycle: - Atrial Systole: Both atria contract and force blood into ventricles - Ventricular Systole: Both ventricles contract o Right ventricle forces blood into the pulmonary trunk o Left ventricle forces blood into the aorta - Early Diastole:Atria and ventricles are relaxed and fill passively - Later Diastole: Ventricles are still relaxing and filling passively • Contraction is called systole • Relaxation is called diastole Blood Pressure: is the force exerted by the blood against the walls of the vessels BIOL*1080 Final Exam Notes -Systolic pressure is the highest pressure in the artery during each heartbeat (110-120mm Hg) -Diastolic pressure is the lowest pressure (70-80mm Hg) Enlargement of the Heart is anAdaptation: Hypertrophy – a sign of being “overworked”. The heart muscle will respond and hypertrophy just like your skeletal muscle would respond to weight‐lifting. Bad: Causes include high blood pressure (hypertension) and narrowing of aortic valve … the heart has to work harder to overcome these Good:Athletes heart – an appropriate adaptation. Occurs in both endurance athletes and weightlifters. Sinoatrial Node: a cluster of specialized cardiac muscle cells that sets tempo of heartbeat; located in right atrium near the junction of the superior vena cava Electrical aspects of the heart: • Initiates contraction at SAnode • Atria contract, signal reaches AV node • Signal connected to Purkinje fibres, atria fully contracted • Ventricles contract Electrical signal is propagated by: • Nodes (SAnode,AV node) • Nerves (bundle of His, bundle branches, Purkinje fibres) • Intercalated disks (gap junctions, connexions) Synoptium: wave is final step in strong ventricular contraction that moves blood around Some examples of miscommunication, usually some kind of arrhythmia: • abnormal SAnode firing (tachycardia, bradycardia) • blocks e.g. at theAV node, vary in terms of degree of block e.g. can slow down or even prevent signal propagation from atria to ventricles. Ventricles now contract independently (bundle of His, 40 bpm) • most serious are fibrillations, when cells depolarize independently (occurs during many heart attacks) Hormonal control of heart rate and contraction strength • Epinephrine (80%) and norepinephrine (20%) • Epinephrine increases contraction strength • Norepinephrine increases rate • Released by sympathetic factors; secreted and are circulated in the blood stream BIOL*1080 Final Exam Notes Controlling the Heart’s Contractions • Nervous and endocrine signals control the strength and rate of contraction of the heart e.g. from rest to exercise: heart rate increases to nearly 200 bpm cardiac output increases from 5 to 25 L/min (40 in elite athletes!) • Sympathetic innervation (NE): increases heart rate • Parasympathetic innervation (ACh): decreases heart rate • Epinephrine: increases strength of each contraction Blood supply to heart: 1. Arteries bring oxygen and fuel to muscle 2. Coronary arteries are an important site for atherosclerosis -heart attack occurs because of atherosclerotic plaque Types of CVD; The four most common types include: 1. Atherosclerosis o Anarrowing of the arteries due to calcified fatty deposits (plaque) and thickening of the wall o Triggered by damage to arterial wall (inflammation) o Can lead to heart attack or stroke 2. Coronary Heart disease o When atherosclerosis occurs in the arteries of the heart muscle, it is called coronary artery/heart disease o Complete blockage causes a heart attack 3. Stroke (occurs when there is reduced blood flow to the brain) 4. Hypertension /High blood pressure o causes the heart muscle to thicken, and the heart to enlarge -Heart attack can occur because of blockage, necrosis or fibrillation Factors: –Hypertension, inflammatory mediators (Creactive peptide) – Diet (sat/trans fats, cholesterol), therefore elevated blood lipids and physical inactivity – Smoking, physical inactivity, obesity/diabetes – Age, genetics Angioplasty: • Acatheter and balloon are threaded into the coronary artery to the point of blockage • The balloon is inserted into blocked are and inflated • Plaque is pushed to artery walls and held there by stent Atherectomy: scraping or lasering the deposits away BIOL*1080 Final Exam Notes - For bypass surgery or a coronary artery bypass graft, you use a saphenous vein from leg in the heart -to treat scar tissue you can take a low des of aspirin, a statin drug or 1/3 of a dose of 3 types of blood pressure drugs Digestive System The gastrointestinal tract is a very large organ system with multiple overlapping functions. It has multiple ‘peripheral clocks’. The central (brain) and peripheral clocks of the human physiome are set by zeitgebers, cues from the environment as to how to synchronize activities of the system. Sunlight, ie. the solar day‐ night cycle, is the evolutionary zietgebar for our sleep‐wake cycle. Moonlight, ie. the lunar cycle, likely is the zeitgebar for the menstrual cycle. The physiome detects that light through the specialized sensory organ (the eyes), sends the information it to visual processing centers in the brain where it is analyzed and then relays that information eventually to the central clock in the brain. Information from the central clock is then sent to peripheral clocks in a variety organs and tissues. If ‘light’is the primary zeitgeber of the physiome then the second major zeitgeber is ‘eating/food consumption’. 6 muscular sphincters (valves) partially segregate function in the tube 1. Upper esophageal sphincter (SNS- voluntary secretions, motility) 2. Lower esophageal sphincter (ANS- involuntary secretions, motility) 3. Pyloric sphincter (ANS- involuntary) 4. Ileocecal valve (ANS- involuntary) 5. Internal anal sphincter (ANS- involuntary) 6. External anal sphincter (SNS- voluntary) Four Basic Processes: Motility, Secretion, Digestion,Absorption (and Excretion) *These processes go on at all times, ie. in the presence, and absence, of what we think of as ‘food’in the tube. (during sleep etc.) The GI tube has: Intestinal Epithelium- this single layer (and mucus) separates inside and outside of the body The GI ‘tube’has unique properties… • It is about 28 ft. long – thus it has to be folded extensively in the abdominal cavity • It has a luminal surface area of between 200‐400 square meters BIOL*1080 Final Exam Notes o thus the invagination depth/ villus‐microvillus height and densities of the mucosal layer are extensive in certain zones • Has a highly variable ‘transit time’for an ingested meal with a marker (30‐80 hours) of which around 5‐ 8 hours is for normal passage through the stomach and small intestine. • Senses and expels noxious substances – diarrhea and vomiting • Continuously interacts with the resident gut microbiome consisting of bacteria, archaea, and small eucaryotes and protect against pathogenic microbes that enter/reside in the tract. o Is a subset of the total human microme o Individually unique, like a finger print o Communicates and acts like an organ (ie. Brain, has full nervous circuits) Abdominal breathing vs. Clavicular breathing (effect on GI tract) -encourages GI function -encourages venous blood return Motility: Peristalsis vs. Segmentation Peristalsis: muscle contraction that moves food along the esophagus and rest of GI tract • esophagus, one way; can be reversible (food poisoning, vomiting) • Multiple layers of smooth muscle (moves in both directions) Segmentation: small intestine, movement in both directions- allows great mixing • Gap junctions, pacemaker cells Stomach is a muscular sac that: 1. Stores food and regulates the release of food to the small intestine 2. Liquefies food (food is churned and mixed with secretions, takes 2-6 hours) 3. Carries out the original chemical digestion of protein Small intestine: its functions include chemical digestion and absorption Bile: keeps fats separated into small droplets that disperse into liquid making digestion more efficient (produced in liver, stored in gall bladder, acts in small intestine) Role of Liver and Pancreas in digestion: -pancreas produces several digestive enzymes that cat in the small intestine - liver produces bile, which is stored in the gall bladder before being released into the small intestine -both nerves and hormones play a role in orchestrating the release of digestive secretions, timing the release of each to the presence of food at each stop BIOL*1080 Final Exam Notes Hepatic portal veins: carry blood from the capillary network of the villi of the small intestine to the capillary beds of the liver Salivary glands: release saliva into the mouth; moistens food so it can go through GI tract easily Diseases and disorders of motility in the GI tract • GERD – Gastroesophageal reflux disease (poor closing of upper esophageal sphincter) • Gastroparesis (poor closing of lower esophageal sphincter); nausea, vomiting, loss of appetite, things sit still in stomach • SBBOS ‐ Small bowel bacterial overgrowth syndrome; nausea, bloating, flatulence • Chronic constipation- complex and multifactorial Secretion- Into the lumen from glands: saliva from salivary glands, acid from gastric glands (stomach, bicarbonate from Brunner’s glands (small intestine), pancreatic juice from the exocrine pancreas, bile from the liver From individual cells in the epithelium: mucus secretion from Goblet Cells, defensins from Paneth cells, secretory IgA from specialized epithelial cells. - gut epithelial cells also secrete paracrine messengers to neighboring cells via the extracellular fluid in the tissue and secrete hormones to enter thebloodstream and travel to distal sites! -secretion is happening in every direction -huge amounts of water and electrolytes -tiny amounts of hormones/ neurohormones Bulk fluid secretion and blood flow -urine/sweat output drives thirst -no proven benefit to drinking water except that it decreases thirst (except during or after strong exertion) Diseases and disorders of secretion in the GI tract Cystic Fibrosis (CFTR/Cl- pump) Inflammatory and secretory diarrhea (CFTR/Cl- pump) Achlorhydria- low acid production, or excess antacid use causes poor digestion and an increase in bacteria Xerostomia- dry mouth, lack of saliva Second brain (Enteric Nervous System) • Has reflex loops that do not require CNS (sphincter, opening) • Does not happen in any other tissue BIOL*1080 Final Exam Notes • Can also contol the 1 brain • Has diffuse neural networks (unlike solid CNS) Before we start to eat ‐ there are some preconditions which determine, in part, the outcome of the food and of the ‘meal eating experience’. I. Motivation to Eat Hedonic Hunger Homeostatic Hunger II. Nutritional Status Deficiency of Nutrients and/or Energy Adequacy of Nutrients and /or Energy Excess of Nutrients and/or Energy Within about 48 hr, food consumed to support growth, maintenance and repair of the body is “processed”. During this time you must convert polymers and complex macromolecules into useable units and distribute them throughout the body. • amino acids (protein) • monosaccharides (carbohydrate) • fatty acids (fat or lipids) • vitamins • minerals - Essential, conditionally essential, non-essential nutrient chemicals in food - Deficiency in diet- nutritional deficiency disease The Cephalic Phase of Digestion andAbsorption: • Chemical and mechanical digestion begins in the mouth • Chewing: mastication -all senses involved in preparing to eat -large areas of our brain light up when preparing to eat (brain imaging) • Salivary secretion is under autonomic control (stim by SNS and PNS) ‐ softens and lubricates food and provides enzymes: amylase and some lipase The tongue contains “taste buds” or papillae that are able to detect bitter, sweet, salty, sour and savory (umami) • Contrary to popular belief there is no regional segregation for these flavours Together with receptors in the nasal cavity the tongue transmits ‘flavour and smell information” to the CNS BIOL*1080 Final Exam Notes • stimulate salivary glands to begin digestion Taste: sweet(=sucrose), sour(=HCl/acid), salty(=NaCl), bitter(=quinine), savoury(=L-theanine) Gastric glands: gastric pits in the lining of the stomach containing various secretory cells Gastric juice: a mixture of HCl and pepsin which begins the chemical digestion of proteins The gastric phase of digestion and absorption Secretory cells of the gastric mucosa: -parietal cells secrete gastric acid (HCl) to activate pepsin -chief cells secrete pepsin(ogen) to digest protein, gastric lipase to digest fat • complexity in gastric epithelium cells exists in invaginations (below surface) • disrupted by alcohol, aspirin etc. The small intestine phase of digestion and absorption Duodenum: short, very dense villi and microvilli, lots of SA Jejunum: longer (less SA/ft of intestine because concentration of nutrients is decreasing) Ileum: longest, smallest density of SA The accessory organs of the small intestine: 1. liver makes bile components (detergents and bicarbonate) 2. gall bladder stores and secretes bile -could lose gall bladder form a systems bio perspective 3. pancreas makes digestive enzymes and carbonate -exocrine pancreas uses a duct, endocrine pancreas is ductless Villi (10x), microvilli(20x): projections that increase the surface area and absorption of the small intestine 1. Nutrients have to cross 2 membranes (apical and basolateral) 2. Most absorption at top layer of stomach (surface epithelium) 3. Water soluble nutrients to the liver and fat soluble nutrients stay Secretions into the lumen of the small intestine upon the opening of the pyloric sphincter and food (chyme) entering the upper duodenum 1. Bicarbonate ‐ from cells in the intestinal epithelium and in pancreatic secretions 2. Digestive enzymes – from the pancreas 3. Bile acids (as bile fluid) – from the liver/gallbladder -for bile acids/fat detergents to be absorbed, nutrient chemicals must be solubilised in the water based lumen contents BIOL*1080 Final Exam Notes Digestive enzymes anchored on the luminal surface of small intestine epithelial cells 1. Disaccharidases 2. Amino peptidases NutrientAbsorption: Carbohydrate digestion- Polysacchrides and disaccharides move to blood, then liver Protein digestion- Proteases and peptidases move to blood, then liver Fat digestion- Lipases move to thoracic duct (lymph) Vitamins & Minerals- Various transporters, mostly small intestines Q: Is there some sort of paracellular absorption? (between cells) A:Yes, a small amount is normal (more= food allergies?) The Large Intestinal Phase of Digestion andAbsorption Q: What comes in from the Ileum (ileocecal valve)? A: Ileal chyme (a chemical and particle‐rich liquid) • Any unabsorbed nutrients • Hormones and chemical messengers • Soluble fibre (prebiotic) (ex. From oats- support bacterium health in colon) • Insoluble fibre (bulking agent) • Microbes (probiotics and other) (probiotic= living bacteria that improves population) • Cellular debris • Excretion products from the liver (bile pigments, feces colour) What happens in the large intestine (cecum plus colon)? 1. The colonic epithelium absorbs water and simple ions like sodium, potassium, magnesium and calcium. (i.e. electrolytes) 2. The resident microbes digest and absorb what chemicals they can (prebiotics) in a process called fermentation. They produce short‐chain fatty acids as end‐products of fermentation. 3. The resident microbes produce some vitamins (vitamin K, some B vitamins) as a by‐product of their metabolism. Some of their end‐products can have hormone like activity. 4. The resident microbes produce gases during their digestion and consumption of the ileal chyme. (Carbon dioxide, methane, hydrogen sulfide). 5. Newly arriving live microbes (probiotic or other) seek to get a foothold in the microbial ecosystem and multiply. (microbes compete and co-operate) Large Intestine: 1. Absorbs water from indigestible food residue to adjust consistency of feces BIOL*1080 Final Exam Notes 2. Stores the feces 3. Eliminates feces from the body Gastric Bypass Surgery – More Than Just Reducing the Stomach? Several different types of bariatric (weight loss) surgery, but the most common are: Roux‐en Y Procedure: a small pouch is created in the upper stomach and attached directly to the small intestine, bypass most of the stomach and the duodenum (major surgery) Lap Banding Procedure: a silicone band containing saline is placed around the upper stomach. It is placed under the skin and is easily inflated, allowing adjustment. (reversible) BOTH procedures results in 40‐50% weight loss within a year of surgery due only to smaller/restricted stomach? Hormonal ChangesAssociated with Gastric Bypass Surgery • increased PYY levels • decreased ghrelin levels – this also occurs with gastric banding, but possibly to a lesser extent Changes in key appetite regulating hormones might contribute to the success of gastric bypass surgery • There are metabolic improvements immediately after surgery (before weight loss) Humans and Microbes The human microbiome: the group of microorganisms aggregating on the human host Quorum sensing and chemical signalling in bacteria: - bacteria use quorum sensing to track population density to coordinate gene expression - use it form biofilm formation, virulence and antibiotic resistance - bacteria secrete small molecules that can inform the bacteria when it reaches a population set point - bacteria have receptors that receives signal when populations are ata good level, so they can function in tandem Bacteria biofilms and antibiotic strategies: - a biofilm is a group of organisms that stick to a cell’s surface - can make disease specific anti-quorom sensing molecules (receptor antagonists) The Energy Distribution System The energy value of foods: • Proteins and carbohydrates 4kcal/g • Fats 9 kcal/g • Ethanol 7 kcal/g BIOL*1080 Final Exam No
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