Applied Homeostasis Lecture Notes PDF

MBBS-1 APPLIED HOMEOSTASIS Department of Physiology Faculty of Medicine  Desired Learning Outcomes On completion of this topic, you should be able to: 1.Explain homeostasis at the cellular level. 2.Differentiate between homeostasis and allostasis. 3.Explain — adaptation, acclimati...

MBBS-1 APPLIED HOMEOSTASIS Department of Physiology Faculty of Medicine  Desired Learning Outcomes On completion of this topic, you should be able to: 1.Explain homeostasis at the cellular level. 2.Differentiate between homeostasis and allostasis. 3.Explain — adaptation, acclimatization, biological clock, apoptosis. 4. State the effects of increased demand or stress on a normal cell.  INTRO: THE CELL Cell – termed coined by Robert Hooke – 1665 Cell Theory – Schleiden and Schwann -1839 – Cell is the structural and functional unit of all living organisms – All life forms are made from one or more cells -Cells arise only from pre-existing cells -Cells is the smallest form of life as the structural basis of living organisms “ The basic living unit of the body is the cell”  THE CELL Entire body – 100 trillion cells Each cell is specially adapted to perform one or few specific functions Cells differ markedly from one another Cells have basic functional characteristics – e.g: metabolism Cells deliver end products to the surrounding medium All cells have the ability to reproduce additional cells of their own kind  THE CELL Collections of CELL with similar function – Tissues Organ – contains many types of tissues System – consists of several organs The proper functioning of body cells depends on precise regulation of the composition of the interstitial fluid surrounding them. Because of this, interstitial fluid is often called the body’s internal environment. The composition of interstitial fluid changes as substances move back and forth between it and blood plasma. Such exchange of materials occurs across the thin walls of the smallest blood vessels in the body, the blood capillaries. This movement in both directions across capillary walls provides needed materials, such as glucose, oxygen, ions, and so on, to tissue cells. It also removes wastes, such as carbon dioxide, from interstitial fluid  INTERNAL ENVIRONMENT Unicellular organisms – e.g; Amoeba – totally dependent on the external aquatic medium Muliticellular organisms , by and large, are independent of the external environment Reason - ‘ millieu interieur’ or the internal environment – Claude Bernard (1887)  millieu interieur “ The living body though it has need of the surrounding environment, is nevertheless relatively independent of it. This independence, which the organism has of its external environment, derives from the fact that the in the tissues living being, are in fact withdrawn from direct external influences and are protected by a veritable internal environment which is constituted in particular by the fluids circulating in the body” – Claude Bernard.  INTERNAL ENVIRONMENT An important aspect of homeostasis is maintaining the volume and composition of body fluids, dilute, watery solutions containing dissolved chemicals that are found inside cells as well as surrounding them. Internal environment is the watery medium that bathes all the cells of the body This is termed the EXTRACELLULAR FLUID (ECF) ECF comprises the PLASMA of blood and the INTERCELLULAR FLUID (interstitial fluid) surrounding the cells of the body The fluid contained within the cells is termed the INTRACELLULAR FLUID (ICF) ECF contains large amounts of NaCl, HCO3 ions and nutrients plus waste products – e.g; carbon dioxide ICF differs significantly from ECF – contains large amounts of Potassium, Phosphate and Magnesium ions The fluid within cells is intracellular fluid (intra- inside), abbreviated ICF. The fluid outside body cells is extracellular fluid (extra- outside), abbreviated ECF. The ECF that fills the narrow spaces between cells of tissues is known as interstitial fluid (inter-STISH- al; inter- between). Dynamic exchange exists between ECF and ICF Cells derive their nutrients from their immediate ECF, even though the constituents of the ECF are ultimately derived from the external environment This confers , in higher organisms, certain level of independence from their external environment Summary:The fluid within cells is intracellular fluid (intra- inside), abbreviated ICF. The fluid outside body cells is extracellular fluid (extra- outside), abbreviated ECF. The ECF that fills the narrow spaces between cells of tissues is known as interstitial fluid (in-ter-STISH-al; inter- between). interstitial fluid is often called the body’s internal environment.  Cell-cell communication The human body is composed of trillions of cells. Those cells need to communicate with one another in a rapid and effective manner to convey physiological information.  What do celsneedto communicate effectively? Language (that they can mutually understand) Electrical and chemical signals There are FOUR basic methods of cell-to-cell communication in our bodies: (1)gap junctions which allow direct cytoplasmic transfer of electricaland chemical signals between adjacent cells. (2)contact-dependent signals, in which surface molecules on one cell membrane bind to surface molecules on another cellmembrane. (3)local communication is accomplished by paracrine and autocrine signaling that is mediated by chemicals that diffuse through the extracellular fluid. (4)long-distance communication through a combination of electrical signals carried by nerve cells and chemical signals transported in the blood.  Identify the type of communication? C D B A Gap junctions form direct cytoplasmic connections between adjacent cells. Contact-dependent signals require interaction membrane between molecules on two cells. Autocrine signals act on the same cell that secreted them. Paracrine signals are secreted by one cell and diffuse to adjacent cells.  Important characteristics of each type of cell-cell communication Gap junctions -Theyare not all alike(Different in different tissues) -20 different connexin isoforms. -Theonly waythat allow direct transfer of electric signalsin-between the cells. Contact-dependentsignals - It ismediatedby Celladhesion molecules (CAMS) - Such contact-dependent signalling occurs in the immune systemand during growth and development. - CAMshavenow been shown to act asreceptors in cell- to-cell signaling. - CAMs are linked to the cytoskeleton and to intracellular enzymes. Through these linkages, CAMs transfer signals in both directions across cell membranes.  Local communications are carried out by ParacrineandAutocrine Signals -In somecases amolecule mayact as both an autocrine signal and a paracrine signal. -All cels in the body canrelease paracrine signals. -The signal molecules reach their target cells by diffusing through the interstitial fluid. Because distance is a limiting factor for diffusion, the effective range of paracrine signals is restricted to adjacent cells. -An example of a paracrine molecule is histamine, a chemical released from damaged cells. When you scratch yourself with a pin, the red, raised wheal that results is due in part to the local release of histamine from the injured tissue.  Communications: Electrical or Chemical Long-distance communication between cells is the responsibilityof the nervousand endocrinesystems. The endocrine system communicates by using hormones; chemical signals that are secreted into the blood and distributed all over the body by the circulation. Hormones come in contact with most cells of the body, but only those cells with receptors for the hormone are targetcells  Thenervoussystem usesa combination of chemical signals andelectrical signals. - An electrical signal travels along a nerve cell (neuron) until it reaches the terminal end of the cell, where it is translated into a chemical signal secreted by the neuron. Such a chemical signal is called aneurocrine. If aneurocrine molecule diffuses from the neuron acrossa narrow extracellularspace to atargetcell and has a rapid effect, it is called a neurotransmitter  If aneurocrine actsmore slowly asanautocrine or paracrine signal,it iscalled a neuromodulator. If aneurocrine releasedby aneuron diffuses into the blood for distribution, it iscalled a neurohormone  Cellular signaling is primarily chemical Cells can detect both chemical and physical signals. Physical signals are generally converted to chemical signals at the level of the receptor. Receptors sense diverse stimuli but initiate a limited repertoire of cellular signals Receptors contain: a ligand-binding domain and an effector domain Cells may express different receptors for the same ligand. The same ligand may have different effects on the cell depending on the effector domain of its receptor. Ligand binding drives the receptor toward the active conformation Signals are sorted and integrated in signaling pathways (usually multisteps and comprise activation of secondary messengers) Second messengers provide readily diffusible pathways for information Overview of cellsignalling  Intro-Homeostasis Homeostasis (ho¯me¯-o¯-STA ¯ -sis; homeo- sameness; -stasis standing still) is the condition of equilibrium (balance) in the body’s internal environment due to the constant interaction of the body’s many regulatory processes. Homeostasis is a dynamic condition. In response to changing conditions, the body’s equilibrium can shift among points in a narrow range that is compatible with maintaining life. For example, the level of glucose in blood normally stays between 70 and 110 milligrams of glucose per 100 milliliters of blood. Each structure, from the cellular level to the systemic level, contributes in some way to keeping the internal environment of the body within normal limits.  HOMEOSTASIS -CONTROL SYSTEMS Homeostasis in the human body is continually being disturbed. Some disruptions come from the external environment in the form of physical insults such as the intense heat or a lack of enough oxygen. Other disruptions originate in the internal environment, such as a blood glucose level that falls too low when you skip breakfast. Homeostatic imbalances may also occur due to psychological stresses in our social environment—the demands of work and school, for example. In most cases the disruption of homeostasis is mild and temporary, and the responses of body cells quickly restore balance in the internal environment However, in some cases the disruption of homeostasis may be intense and prolonged, as in poisoning, overexposure to temperature extreme’s, severe infection, or major surgery.  CONTROL SYSTEMS - TYPES The body can regulate its internal environment through many feedback systems. A feedback system or feedback loop is a cycle of events in which the status of a body condition is monitored, evaluated, changed, re-monitored, re-evaluated Each monitored variable, such as body temperature, blood pressure, or blood glucose level, is termed a controlled condition. Any disruption that changes a controlled condition is called a stimulus. Components: A feedback system includes three basic components—a receptor, a control center, and an effector Homeostatic control mechanisms have at least 3 interdependent components: Receptor - sensor that responds to stimuli Control centre - determines set point, analyses input and determines appropriate response(output) Effector - provides means for control centres response.  Components: A receptor is a body structure that monitors changes in a controlled condition and sends input to a control center. Typically, the input is in the form of nerve impulses or chemical signals. A control center in the body, for example, the brain, sets the range of values within which a controlled condition should be maintained, evaluates the input it receives from receptors, and generates output commands when they are needed. Output from the control center typically occurs as nerve impulses, or hormones or other chemical signals. An effector is a body structure that receives output from the control center and produces a response or effect that changes the controlled condition. Nearly every organ or tissue in the body can behave as an effector  FEEDBACK SYSTEM A group of receptors and effectors communicating with their control center forms a feedback system that can regulate a controlled condition in the body’s internal environment. In a feedback system, the response of the system “feeds back” information to change the controlled condition in some way, either negating it (negative feedback) or enhancing it (positive feedback). 1.NEGATIVE FEEDBACK 2.POSITIVE FEEDBACK 3.FEEDFORWARD CONTROL  HOMEOSTATIC MECHANISMS MAY FAIL DUE TO.. Congenital metabolic disorders Ageing ( Homeostenosis) Chromosomal abnormalities Environment Factors -UV radiation -Chemical pollutants  Homeostatic Imbalance Disturbances of homeostasis or the body`s normal equilibrium. Overwhelming of negative feedback mechanism by destructive positive feedback mechanisms. Homeostatic Imbalances In The Body 1. Integumentary system – Burns, cutaneous lesions (cold sores, Psoriasis ), skin cancer. 2. Skeletal System – Rickets, Abnormal spinal curvatures (Scoliosis,kyphosis,lordosis), Osteoporosis. 3. Muscular System – Muscular Dystrophy, Myasthenia Gravis. 4.Nervous system – Multiple sclerosis, Huntington’s disease, Parkinson’s disease, Alzheimers disease. 5.Endocrine System – Goitre, Grave’s disease, Pituitary dwarfism, Infertility. 6. CVS – Pericarditis. Valvular stenosis, Varicose veins, Atherosclerosis. 7.Lymphatic System – Allergies, Immunodeficiencies (AIDS), Autoimmune disease ( Lupus, Rheumatoid Arthritis, etc ). 8.Respiratory System – Sinusitis, tonsillitis, Pleurisy, Emphysema, Bronchitis, Cystic fibrosis 9.Digestive System – Gall stones, Heartburn, Gastric ulcers. 10.Urinary System- Kidney stones, Addison’sdisease, Polycystic kidney disease. 11.Reproductive system – Pelvic inflammatory disease, Cervical cancer, Testicular cancer. HomeostasismodelversusAllostasis model Homeostasis Allostasis  Homeostasis-SETPOINT - Homeostasis means stability through constancy. - There is a set point for the variable as body temperature. Any tendency to deviate it from the set point, there are mechanisms to bring it back to the set point. - Some parameters are regulated quite closely to their set point as oxygen, pH, temperature, glucose and osmotic pressure. - Failure of homeostasis results in diseases. Failure of the pancreas to release insulin results in diabetes.  Allostasis In Allostasis there is prediction of the needs of the body that results in re-setting of the set point. The body organs try to achieve thenew set point. If that is happening for short periods of time it is physiological but if it happens for sustained time it mayturn to a pathology. Theprediction is the function ofour brain (howwe perceiveand plan to act). Examplesare exerciseand exposureto stress. Reponsesof a normal cellto stress & cellularinjuries  Examplesof cell injuries and type ofcellular response Injuries Cellularresponse 1) Altered physiological stimuli as: - Increased stimulation (increasedGH -Hypertrophy release) &Hyperplasia Adaptation - Decreasedstimulation -Atrophy -Chronicirritation - Metaplasia 2)Chemicalinjuriesand reducedoxygen supply : - Acutetransient - Acutereversibleinjury - Progressive andsevere - Irreversible cellinjury Celldeath  Adaptation Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to severe physiologic or pathologic changesin their environment. Forms of adaptations: Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ. The increased size of the cells is due to the synthesis of more structural components of the cells. The main stimulus for hypertrophy is 1.increased workload ascardiachypertrophy due to hypertension 2.excessivestimulation asuterus hypertrophy during pregnancy (oestrogenstimulation). 3.druginduced. Whatever the exact cause and mechanism of cardiac hypertrophy, it eventually reaches a limit beyond which enlargement of muscle mass is no longer able to compensate for the increased burden. In extreme cases myocyte death can occur by either apoptosis or necrosis. The net result of thesechangesis cardiac failure. Mechanisms of hypertrophy increased production of cellular proteins triggered by growth factors (including TGF- β, insulin-like growth factor-1 [IGF-1], fibroblast growth factor), and vasoactive agents (such as α-adrenergic agonists,endothelin-1, and angiotensin II). Hyperplasia is an increase in the number of ce ls in an organ or tissue, usually resulting in increased mass of the organ or tissue. Hyperplasia takes place if the cell population is capable of dividing. Hyperplasia can be physiologicor pathologicand occurtogether withhypertrophy. Causes/types ofhyperplasia Physiologic Hyperplasia as hormonal hyperplasia as proliferation of the glandular epithelium of the female breast at puberty and during pregnancy by hormones. It is usually accompanied by enlargement (hypertrophy) of the glandular epithelial cells. Compensatory hyperplasia that is seen after damage or partial resection of a tissue as in individuals who donate one lobe of the liver for transplantation, the remainingcellsproliferate sothat the organsoongrows backto its originalsize. Pathologic Hyperplasia which are mostly caused by excesses of hormones or growth factors acting on target cells. Endometrial hyperplasia is an example of abnormal hormone-inducedhyperplasia and that is induced by viral infections.  Atrophy is reduced size of an organ or tissue resulting from a decrease in cell sizeand number.It canbe physiologic or pathologic. Physiologic atrophyis commonduring normal development. Onemore exampleis decreased uterus sizeshortly after parturition, and this is aform of physiologic atrophy. Causes of atrophy Decreased workload (disuse atrophy). - Exampleis immobilization when a bone is fractured.Theinitial decreasein cell sizeisreversibleonceactivity is resumed. Loss of innervation (denervation atrophy).Damageto the nerves leadsto atrophyof the musclefiberssupplied by thosenerves. Diminishedblood supply.Adecreasein blood supply (ischemia) to atissue as a result of slowly developing arterial occlusive diseaseresults in atrophy of the tissue. Inadequatenutrition. Loss of endocrinestimulation. Pressure,tissue compression forany lengthof timecancauseatrophy. Mechanisms ofAtrophy - Decreasedprotein synthesis and increasedprotein degradation in cels. Metaplasia is a reversible change in which one differentiated cell type is replaced by another celltype. The most common epithelial metaplasia is columnar to squamous , as occurs in the respiratory tract in response to chronicirritation. The normal ciliated columnar epithelial cel s of the trachea and bronchi are often replaced by stratified squamousepithelial cels. The influences that predispose to metaplasia, if persistent, may initiate malignant transformation  Acclimatization Acclimatization describes adaptive physiological or behavioural changes within an organism in responseto their natural climateor environment. Usual y completely reversible once stress is removed, body reverts back to pre- acclimatization condition. Humansgo and stay a high altitude (where oxygen is low) naturally acclimatize to their new environment by developing an increase in the number of red blood cells to increase the oxygen carrying capacity of the blood, in order to compensatefor lower levels of oxygen in the air. This acclimatization is a slow process that may takes days to few  Apoptosis: Programmed Cell Death The total number of cells is regulated in our body is regulated by controlling the rate of cell division andthe rate of celldeath. When cells are no longerneededor become a threat to the organism,they undergoa suicidalprogrammed cell death, orapoptosis. Studies suggestthat abnormalities of apoptosis mayplayakeyrole in neurodegenerative diseasessuch as Alzheimer’s disease. Somedrugsthat havebeen usedsuccessfully for chemotherapy appearto induce apoptosisin cancercells.  Mechanism of apoptosis This process involves a specific proteolytic cascade that causes the cell to shrink and condense, to disassemble its cytoskeleton, and to alter its cell surface so that a neighboring phagocytic cell, such as a macrophage, can attach to the cell membraneand digest the cell.  BIOLOGICALCLOCK Biological clock is an inherent timing mechanism in a living system (as a cell) that is inferred to exist in order to explain various cyclical behaviors and physiological processes. Thecyclical changescanbedaily, monthly, or seasonal Diurnal variations in our body temperature, arterial blood pressure,bronchialtone, cortisollevel andothers. It explainthe reasonof patientswith getting their attacks late night or early morning. It canalsoexplainthe better timing for  SuprachiasmaticNucleus(SCN) is the centrefor control of the biologicalclock APPLIED HOMEOSTASIS A dehydrated patient with sunken eyes, loss of skin elasticity, & drowsiness  Tutorial 1. Define ‘Homeostasis’,and control system 2. Explain the mechanism of homeostasis with a common example. 3. State basic methods of cell-to-cell communication in the human body. 4. Differentiate homeostasis from a lostasis citing one example for each. 5. State the significance of cellularapoptosis. 6. Explain applied physiology of Homeostasis with examples Thank you