Physiology (1) PDF

Functional organization of the Human body and control of the Internal Environment: Introduction: - Vast fields of physiology can be divided into viral physiology, bacterial physiology, cellular physiology, plant physiology and many more subdivisions Human physiology: - Complex system...

Functional organization of the Human body and control of the Internal Environment: Introduction: - Vast fields of physiology can be divided into viral physiology, bacterial physiology, cellular physiology, plant physiology and many more subdivisions Human physiology: - Complex system help with survival - Cells tissue organs help into functions of human being - There is about 25 trillion red blood cells and 35-40 trillions cells total in a human body - Cells have different look but characteristics are the same Extracellular Fluid: - Extracellular fluid contains Oxygen, glucose, Amino Acids and fatty substances - Extracellular fluid is specialized at transportation of CO2 to lungs and waste products to the kidney - Extracellular fluid takes ⅓ outside the space of cell to protect it and is constantly circulating blood with a mix of between blood and intercellular cell between the tissues. - Intracellular fluid contains Potassium, Magnesium, Phosphate ions and is specialized into transporting ions throughout the body - 2 stages of transportation of extracellular fluid is through blood vessels and through capillaries or intercellular between the tissue All the blood in the circulation traverses the entire circuit an average of once each minute when body is at rest and as many as six times each minute when a person is extremely active. - As blood passes through blood capillaries, continual exchange of extracellular fluid occurs between the plasma portion of the blood and the interstitial fluid that fills the intercellular spaces. - - The nervous system is composed of three major parts—the sensory input portion, the central nervous system (or integrative portion), and the motor out- put portion. Sensory receptors detect the state of the body and its surroundings - PROTECTION OF THE BODY - - Immune System. The immune system includes white blood cells, tissue cells derived from white blood cells, the thymus, lymph nodes, and lymph vessels that protect the body from pathogens such as bacteria, viruses, parasites, and fungi. The immune system provides a mechanism for the body to carry out the following: (1) distinguish its own cells from harmful foreign cells and substances; and (2) destroy the invader by phagocytosis or by producing sensi- tized lymphocytes or specialized proteins (e.g., antibodies) that destroy or neutralize the invader. - Integumentary System. The skin and its various ap- pendages (including the hair, nails, glands, and other structures) cover, cushion, and protect the deeper tissues and organs of the body and generally provide a bound- ary between the body’s internal environment and the out- side world. The integumentary system is also important for temperature regulation and excretion of wastes, and it provides a sensory interface between the body and the external environment. The skin generally comprises about 12% to 15% of body weight. - A large portion of the blood pumped by the heart also passes through the walls of the gastrointes- tinal tract. Here different dissolved nutrients, including car- bohydrates, fatty acids, and amino acids, are absorbed from ingested food into the extracellular fluid of the blood. - - - In addition to human cells, trillions of microbes inhabit the body, living on the skin and in the mouth, gut, and nose. The gastrointestinal tract, for example, normally contains a complex and dynamic population of 400 to 1000 species of microorganisms that outnumber our human cells. Communities of microorganisms that inhabit the body, often called microbiota, can cause diseases, but most of the time they live in harmony with their human hosts and provide vital functions that are essential for survival of their hosts. Although the importance of gut microbiota in the digestion of foodstuffs is widely recognized, additional roles for the body’s microbes in nutrition, immunity, and other functions are just beginning to be appreciated and represent an intensive area of biomedical research. - - Homeostatic Compensations in Diseases. Disease is often considered to be a state of disrupted homeostasis. However, even in the presence of disease, homeostatic mechanisms continue to operate and maintain vital func- tions through multiple compensations. In some cases, these compensations may lead to major deviations of the body’s functions from the normal range, making it diffi- cult to distinguish the primary cause of the disease from the compensatory responses. For example, diseases that impair the kidneys’ ability to excrete salt and water may lead to high blood pressure, which initially helps return excretion to normal so that a balance between intake and renal excretion can be maintained. This balance is needed to maintain life, but, over long periods of time, the high blood pressure can damage various organs, including the kidneys, causing even greater increases in blood pressure and more renal damage. Thus, homeostatic compensa- tions that ensue after injury, disease, or major environ- mental challenges to the body may represent trade-offs that are necessary to maintain vital body functions but, in the long term, contribute to additional abnormalities of body function. The discipline of pathophysiology seeks to explain how the various physiological processes are al- tered in diseases or injury. - - This chapter outlines the different functional systems of the body and their contributions to homeostasis. We then briefly discuss the basic theory of the body’s control systems that allow the functional systems to operate in support of one another. Were it not for the muscles, the body could not move to obtain the foods required for nutrition. The musculoskeletal system also provides motility for protec- tion against adverse surroundings, without which the en- tire body, along with its homeostatic mechanisms, could be destroyed carbon di- oxide is released from the blood into lung alveoli; the res- piratory movement of air into and out of the lungs carries carbon dioxide to the atmosphere. Carbon dioxide is the most abundant of all the metabolism products. Kidneys. Passage of blood through the kidneys removes most of the other substances from the plasma besides car- bon dioxide that are not needed by cells. These substanc- es include different end products of cellular metabolism, such as urea and uric acid; they also include excesses of ions and water from the food that accumulate in the ex- tracellular fluid. The kidneys perform their function first by filtering large quantities of plasma through the glomerular capil- laries into the tubules and then reabsorbing into the blood substances needed by the body, such as glucose, amino acids, appropriate amounts of water, and many of the ions. Most of the other substances that are not needed by the body, especially metabolic waste products such as urea and creatinine, are reabsorbed poorly and pass through the renal tubules into the urine. Gastrointestinal Tract. Undigested material that enters the gastrointestinal tract and some waste products of me- tabolism are eliminated in the feces. positive feedback is useful, the positive feedback is part of an overall negative feedback process. For example, in the case of blood clotting, the positive feedback clotting process is a negative feedback process for the maintenance of normal blood volume. Also, the positive feedback that causes nerve signals allows the nerves to participate in thousands of negative feedback nervous control systems. some movements of the body occur so rap- idly that there is not enough time for nerve signals to travel from the peripheral parts of the body all the way to the brain and then back to the periphery again to control the movement. Therefore, the brain uses a mechanism called feed-forward control to cause required muscle contrac- tions. Sensory nerve signals from the moving parts apprise the brain about whether the movement is performed cor- rectly. If not, the brain corrects the feed-forward signals that it sends to the muscles the next time the movement is required. Then, if still further correction is necessary, this process will be performed again for subsequent move- ments. This process is called adaptive control. Adaptive control, in a sense, is delayed negative feedback. the body is actually a social order of about 35 to 40 trillion cells organized into different func- tional structures, some of which are called organs. Each functional structure contributes its share to the mainte- nance of homeostasis in the extracellular fluid, which is called the internal environment. As long as normal con- ditions are maintained in this internal environment, the cells of the body continue to live and function properly. Each cell benefits from homeostasis and, in turn, each cell contributes its share toward the maintenance of homeostasis. This reciprocal interplay provides continu- ous automaticity of the body until one or more functional systems lose their ability to contribute their share of func- tion. When this happens, all the cells of the body suffer. Extreme dysfunction leads to death; moderate dysfunc- tion leads to sickness. Endocrinology - Neurotransmitter is released by axon terminals of neurons into synaptic junctions - Endocrine hormones: are secretion of glands into circulating blood - Neuroendocrine hormones are secretion of neurons into circulating blood - Paracrines secretion of cells into extracellular fluid affect the neighboring cells of different types. - Autocines secretion of cells into extracellular fluid effect the function of the cells that produces them. - Cytokines: secretion of cells into extracellular fluid can work as paracrine autocrine and endocrine. Work as autocrine, paracrine and endocrine. Three general classes of hormones exist: - Proteins and polypeptides: hormones secreted by posterior and anterior pituitary gland, the pancreas (insulin and glucagon) parathyroid gland (parathyroid hormone, and many others. - Steroids: secreted by adrenal cortex (cortisol and aldosterone) ovaries and placenta (estrogen and progesterone) - Derivatives of the amino acid tyrosine, secreted by thyroid (thyroxine and triiodothyronine). Polypeptide and Protein Hormones Are Stored in Secretory Vesicles Until Needed - Polypeptides with >100 more amino acids are proteins - Polypeptides with 65% Similar Ionic Composition of Plasma and Interstitial Fluid - Permeable capillary membranes separating plasma and interstitial but their ionic composition is similar. - Only difference is higher protein in plasma, only small amount can be leaked into interstitial spaces in tissues - Donnan effect: cations in plasma is 2% slightly greater then in interstitial fluid - Plasma proteins has net negative charge and bind cations to hold extra amounts of them in plasma - Interstitials have higher concentration in interstitial fluid because negative charges of plasma proteins repel the negatively charged anions. INTRACELLULAR FLUID CONSTITUENTS - Cell membrane between intra and extra is permeable to water but not permeable to most electrolytes in body/ - Intracellular fluid contains only a small amount of sodium and chloride but instead it contains a large amount of potassium and phosphate ions plus magnesium and sulfate all of which have low concentration in the extra - Also it contains large protein almost 4 times as plasma. MEASUREMENT OF BODY FLUID COMPARTMENT VOLUMES— INDICATOR-DILUTION PRINCIPLE - By placing an indicator substance in the compartment dispersing it evenly throughout compartments fluid - VolumeB= (VolumeA) x (ConcentrationA) / (ConcentrationB) - Total amount of solution A - Concentration of fluid in chamber after substance has been dispersed B DETERMINATION OF VOLUMES OF SPECIFIC BODY FLUID COMPARTMENTS - Measurement of Total Body Water - Radioactive water (tritium) and heavy water (deuterium) can be used to measure total body water. - After a few hours of injected into the body dilution principle can be used to calculate tbw. - Antipyrine can also use, is very lipid soluble, penetrates cell membranes and extracellular compartments. - Measurement of Extracellular Fluid Volume.  - By The use of any substances disperse in plasma and interstitial fluid but isn't ready to permeate the cell membrane. - Radioactive sodium radioactive chloride and radioactive iothalamate, thiosulfate ion and inulin. - Takes 30 - 60 mins and happens in the extracellular. However radioactive sodium may diffuse a bit into the cells. Calculation of Intracellular Volume - Intracellular volume = Total body water −Extracellular volume Measurement of Plasma Volume - serum albumin labeled with radioactive iodine (125I- albumin) or with a dye that avidly binds to the plasma proteins, such as Evans blue dye (also called T-1824). Calculation of Interstitial Fluid Volume - Interstitial fluid volume = Extracellular fluid volume - Plasma volume Measurement of Blood Volume - Total Blood volume = Plasma volume / 1 - Hematocrit - For example, if the plasma volume is 3 liters and hematocrit is 0.40, the total blood volume would be calculated as follows: 3liters / 1 - 0.4 = 5 liters. Causes of Hyponatremia: Excess Water or Loss of Sodium - diarrhea and vomiting. Overuse of diuretics = loss of sodium plasma concentration = hyponatremia Hyponatremia Causes Cell Edema - Effects the brain especially other than tissue and organs - plasma sodium concentration rapidly falls below 115 to 120 mmol/L = brain swelling - Causes of Hypernatremia: Water Loss or Excess Sodium - Increased plasma sodium concentration - Loss of water = hypernatremia and dehydration Hypernatremia Causes Cell Shrinkage - Stimulates secretion of ADH protecting plasma and extra - Treatment can be achieved by administering a hypoosmotic sodium chloride or dextrose solution EDEMA: EXCESS FLUID IN THE TISSUES - 1) hyponatremia, as discussed earlier; (2) depression of the metabolic systems of the tissues; and (3) lack of adequate nutrition to the cells - Blood flow to tissue is decrease = no oxygen = low nutrients EXTRACELLULAR EDEMA - : (1) abnormal leakage of fluid from the plasma to the interstitial spaces across the capillaries; and (2) failure of the lymphatics to return fluid from the interstitium back into the blood, often called lymphedema. Factors That Can Increase Capillary Filtration - A large number of conditions can cause fluid accumu- lation in the interstitial spaces by abnormal leaking of fluid from the capillaries or by preventing the lymphat- ics from returning fluid from the interstitium back to the circulation. The following is a partial list of conditions that can cause extracellular edema by these two types of abnormalities: - I. Increased capillary pressure - A. Excessive kidney retention of salt and water - 1. Acute or chronic kidney failure 2. Mineralocorticoidexcess - B. High venous pressure and venous constriction 1. Heart failure - 2. Venous obstruction - 3. Failure of venous pumps - a) Paralysis of muscles - b) Immobilization of parts of the body c) Failure of venous valves - C. Decreased arteriolar resistance - 1. Excessive body heat - 2. Insufficiency of sympathetic nervous system 3. Vasodilatordrugs - II. Decreased plasma proteins - A. Loss of proteins in urine (nephrotic syndrome) - B. Loss of protein from denuded skin areas 1. Burns - 2. Wounds - C. Failure to produce proteins - 1. Liver disease (e.g., cirrhosis) - 2. Serious protein or caloric malnutrition - III. Increased capillary permeability - A. Immune reactions that cause release of hista- mine and other immune products - B. Toxins - C. Bacterial infections - D. Vitamin deficiency, especially vitamin C - E. Prolonged ischemia - F. Burns - IV. Blockage of lymph return A. Cancer - B. Infections (e.g., filarial nematodes) - C. Surgery - D. Congenital absence or abnormality of lymphatic - vessels - SUMMARY OF SAFETY FACTORS THAT PREVENT EDEMA - Putting together all the safety factors against edema, we find the following: - 1. The safety factor caused by low tissue compliance in the negative pressure range is about 3 mm Hg. - 2. The safety factor caused by increased lymph flow is about 7 mm Hg. - 3. The safety factor caused by washdown of proteins from the interstitial spaces is about 7 mm Hg. - Therefore, the total safety factor against edema is about 17 mm Hg. This means that the capillary pressure in a peripheral tissue could theoretically rise by 17 mm Hg, or approximately double the normal value, before marked edema would occur.  - Some examples of potential spaces are the pleural, peri- cardial, peritoneal, and synovial cavities, including both the joint cavities and the bursae. Virtually all these poten- tial spaces have surfaces that almost touch each other, with only a thin layer of fluid in between, and the surfaces slide over each other. To facilitate the sliding, a viscous proteinaceous fluid lubricates the surfaces. - Fluid Is Exchanged Between Capillaries and Potential Spaces. The surface membrane of a potential space usu- ally does not offer significant resistance to the passage of fluids, electrolytes, or even proteins, which all move back and forth between the space and interstitial fluid in the surrounding tissue with relative ease. Therefore, each po- tential space is in reality a large tissue space. Consequent- ly, fluid in the capillaries adjacent to the potential space diffuses not only into the interstitial fluid but also into the potential space. Lymphatic Vessels Drain Protein From the Potential Spaces. Proteins collect in the potential spaces because of leakage out of the capillaries, similar to the collection of protein in the interstitial spaces throughout the body. The protein must be removed through lymphatics or other channels and returned to the circulation. Each potential space is directly or indirectly connected with lymph ves- sels. In some cases, such as the pleural cavity and peri- toneal cavity, large lymph vessels arise directly from the cavity itself. - Edema Fluid in the Potential Spaces Is Called Effusion. - When edema occurs in the subcutaneous tissues adja- cent to the potential space, edema fluid usually collects in the potential space as well; this fluid is called effusion. Thus, lymph blockage or any of the multiple abnormali- ties that can cause excessive capillary filtration can cause effusion in the same way that interstitial edema is caused. The abdominal cavity is especially prone to collect effu- sion fluid, and in this case, the effusion is called ascites. In serious cases, 20 liters or more of ascitic fluid can ac- cumulate. - The other potential spaces, such as the pleural cavity, pericardial cavity, and joint spaces, can become seriously swollen when generalized edema is present. Also, injury or local infection in any one of the cavities often blocks the lymph drainage, causing isolated swelling in the cavity. - The dynamics of fluid exchange in the pleural cavity are discussed in detail in Chapter 39. These dynamics are mainly representative of all the other potential spaces as well. The normal fluid pressure in most or all of the potential spaces in the nonedematous state is negative in the same way that this pressure is negative (subatmo- spheric) in loose subcutaneous tissue. For example, the interstitial fluid hydrostatic pressure is normally about −7 to −8 mm Hg in the pleural cavity, −3 to −5 mm Hg in the joint spaces, and −5 to −6 - Body Fluid: - Solid 40% male - Water 60% male - Greater adipose tissue in female and muscle mass in male affect these numbers Total body fluid - ECF = ⅓ fluid = 15L - ICF = ⅔ = 25L Plasma - 20% Fluid in circulation - Interstitial fluid is 80% - Intracellular fluid Mainly get fluid from drinking and food Basically in GI tract We need 2500ml per day to cover for water loss Water enters firstly extracellular fluid from GI tract and move through different body components Then moves to interstitial fluid and intracellular fluid Intra contains ⅔ Extra contains ⅓ No energy require to use for moving water pass these components Osmosis Semi permeable separating jar into two parts Osmosis is when solids from less area move to higher concentration area Fluid output = kidney Gi tract lungs and skin 2500 ml each day roughly Excess fluid = lymphatic vessel that drains into the venous circulation Electrolytes we can find are Na K Ca Cl which can move between plasma and interstitial the sermipermeable membrane The concentration of both areas are about the same When get to interstitial fluid through lipid membrane, these electrolytes relies on the transport channel, channeling mean trading like for potassium to enter the lipid layer sodium has to move out and all this require ATP. Proteins are found in plasma and theyre albumin, albumin helps maintaining osmotic gradient, helps keep water in blood vessels. Main cation in interstitial fluid is potassium Main ation in extracellular is cl Main anion in intracellular fluid are the negatively charged protein but main electrolyte is phosphate Phospho rate ion in the phosphate form is the main anion in the intracellular fluid Bicarbonate is important for acid base balance Sodium is main extracellular fluid cation Chloride is main extra fluid anion Potassium is main intracellular fluid cation Phoshor ate is main intracellular fluid anion HCO3 important in acid base balance Thermoregulation Homeostatic process to keep body in check, 37 C and 98F\ Core temperature remains constant even tho when exposed to 55F or 130F Skin temperature is when referring skins ability to lose heat to surroundings Normal core temp Always be a range of normal from less than 36C to greater than 37.5 Average normal is between 98F and 98.6F orally and 1F higher when rectally Increases during exercise and varies surrounding. Can rise to 101 to 104 when extremely active When cold can drop to 96F When heat builds up in body is greater than heat is being lost it builds up in the body and temp rises and conversely Heat production Heat is a by-product of metabolism Metabolic rate of the body 1. Basal rate 2. Muscle activity (shivering) 3. Effect of thyroxine 4. Effect of epinephrine norepinephrine and sympathetic stimulation 5. Chemical activity 6. Digestion absorption Heat loss These typa heat then transfer from organs and tissues to skin when it loses to air. 1. How fast it gets to skin 2. How fast it transfers to air Insulator system of the body - Subcutaneous tissues act as heat insulator, conducts heat ⅓ as readily other tissues and in male is 3 quarters the usual suits of cloths. - Is an effective means of maintaining normal internal core temp allowing heat from organs to get to the surroundings. Blood flow to skin from body core provide heat transfer - the skin is an effective controlled “heat radiator” system, and the flow of blood to the skin is a most effective mechanism for heat transfer from the body core to the skin Control of Heat Conduction to the Skin by the Sympathetic Nervous System - Controlled by arterioles and arteriovenous anastomoses supply blood to the venous plexus of the skin. (vasoconstriction) Basic Physics of Heat Loss From the Skin Surface - radiation, conduction, and evaporation -radiation is if when our body temp is higher than surrounding objects we tend to radiate heat toward surrounding rather than conversed. Conductive Heat Loss Occurs by Direct Contact With an Object. - About 3% is lost from body by direct conduction (conduction to air) - Molecules of skin constantly undergoes vibratory motion. - Air convection when theres an equally amount of heat in air and body. Convective Heat Loss Results From Air Movement - 15% if person sitting when there no gross air movement Cooling Effect of Wind - Air constantly replaced and heat loss increases. Low velocity of air is about the squareroot of wind velocity so the faster wind current the better cooling. Conduction and Convection of Heat From a Person Suspended in Water - Is thousand times better than air - When in water is better then when in air for cooling Evaporation  - 0.58 calories of heat is lost for each gram of water evaporates - When no sweats evap still happen in breath in skin about 600-700ml a day = 16-19 calories per hour - Cant be controlled due to diffusion of water inside the skin Evaporation is a Necessary Cooling Mechanism at Very High Air Temperatures. - Body heat temp increases when surroundings is hot and body start to evaporized, people without sweat glands die due to heat stroke cuz body fail to heat up Clothing Reduces Conductive and Convective Heat Loss. - Clothing in and private areas reduces flow of convection air currents and the rate of heat loss from body conduction and convection is greatly depressed get it down to 1/6th - Cloths wet = hard to radiate heat out Temperature-Decreasing Mechanisms When the Body Is Too Hot - Vasodilation of skin blood vessels: sympathetic centers increase rate ò heat transfer to skin b y blood vessels become dilated - Sweating: body core temp rises, addition 1C increase causes sweat to remove 10 times the basal rate of body heat production - Decrease in heat production: Shivering, chemical thermogenesis are strongly inhibited. Temperature-Increasing Mechanisms When the Body Is Too Cold - Skin vasoconstriction throughout the body: stimulation of posterior hypothalamic sympathetic centers - Piloerection means hair standing upright “goose bumps”. Important in animal to make a thick layer to protect skin from the cold surroudnings - Increase in thermogenesis (heat production): metabolic systems is increased by promoting shivering, sympathetic excitation of heat production, and thyroxine secretion 1. primary motor center for shivering located in posterior hypothalamus for shivering 2. Increasing in rate of cellular metabolism by sympathetic circulation or norepinephrine and epinephrine. This effect is called chemical thermogenesis, or nonshivering thermogenesis 3. Cooling the anterior hypothalamic- preoptic area also increases production of the neurosecretory hormone thyrotropin-releasing hormone by the hypothalamus. This hormone is carried by way of the hypothalamic portal veins to the anterior pituitary gland, where it stimulates secretion of thyroid- stimulating hormone. “SET POINT” FOR TEMPERATURE CONTROL 37.1C all the temperature control mechanisms continually attempt to bring the body temperature back to this set point level. Feedback Gain for Body Temperature Control - The feedback gain of the temperature control system is equal to the ratio of the change in environmental temperature to the change in body core temperature minus 1.0 - temperature of humans changes about 1°C for each 25°- to 30°C- change in environmental temperature. Skin Temperature Can Slightly Alter the Set Point for Core Temperature Control BEHAVIORAL CONTROL OF BODY TEMPERATURE - Temperature controlling area in the brain give psychic sensation of being overheated - When cold it gets signals from skin and deep body receptors of feeling cold - Most effective in cold environments Fever - temperature- regulating centers affected by toxic substances or abnormalities in the brain causing high body temp. Fever is an elevation of body temperature due to a “resetting of the thermostat” > 99 degree F Bacterial / Viral Infections, trauma,lesions of CNS, exposure to high temperatures & drug induced. Increased heat production by shivering (rigor) & increased metabolism Diminished heat loss by vasoconstriction Skin is warm & flushed Subsides by sweating Thermoreceptors detect changes in the balance between heat loss & production due to metabolic rate (exercise). Two types Peripheral on Skin Central in hypothalamus (integrating center), spinal cord, abdominal organs. Output from hypothalamus is sent to effectors via sympathetic nerves to sweat glands, skin arterioles & adrenal medulla. Motor neuron to skeletal muscles. Core temp is maintained relatively constantly. Peripheral thermoreceptors help identify heat & cold. Sweating and Its Regulation by the Autonomic Nervous System Stimulation of the anterior hypothalamus-preoptic area in the brain either electrically or by excess heat causes sweat- ing. The nerve impulses from this area that cause sweating are transmitted in the autonomic pathways to the spinal cord and then through sympathetic outflow to the skin. It should be recalled from the discussion of the autonomic nervous system in Chapter 61 that the sweat glands are innervated by cholinergic nerve fibers (fibers that secrete acetylcholine but that run in the sympathetic nerves along with the adrenergic fibers). These glands can also be stimulated to some extent by epinephrine or norepinephrine circulating in the blood, even though the glands themselves do not have adrenergic innervation. This mechanism is important during exercise, when these hormones are secreted by the adrenal medullae and the body needs to lose excessive amounts of heat produced by the active muscles. Mechanism of Sweat Secretion. In Figure 74-5, the sweat gland is shown to be a tubular structure consist- ing of two parts: (1) a deep subdermal coiled portion that secretes the sweat, and (2) a duct portion that passes out- ward through the dermis and epidermis of the skin. As is true of so many other glands, the secretory portion of the sweat gland secretes a fluid called the primary secretion or precursor secretion; the concentrations of constituents in the fluid are then modified as the fluid flows through the duct. The precursor secretion is an active secretory product of the epithelial cells lining the coiled portion of the sweat gland. Cholinergic sympathetic nerve fibers ending on or near the glandular cells elicit the secretion. The composition of the precursor secretion is simi- lar to that of plasma, except that it does not contain plasma proteins. The concentration of sodium is about 142 mEq/L, and that of chloride is about 104 mEq/L, with much smaller concentrations of the other solutes of plasma. As this precursor solution flows through the duct portion of the gland, it is modified by reab- sorption of most of the sodium and chloride ions. The degree of this reabsorption depends on the rate of sweating. When the sweat glands are stimulated only slightly, the precursor fluid passes through the duct slowly. In this case, essentially all the sodium and chloride ions are reab- sorbed, and the concentration of each falls to as low as 5 mEq/L. This process reduces the osmotic pressure of the sweat fluid to such a low level that most of the water is also reabsorbed, which concentrates most of the other constituents. Therefore, at low rates of sweating, such constituents as urea, lactic acid, and potassium ions are usually very concentrated. Conversely, when the sweat glands are strongly stimulated by the sympathetic nervous system, large amounts of precur- sor secretion are formed, and the duct may reabsorb only slightly more than half the sodium chloride; the concentra- tions of sodium and chloride ions are then (in an unacclima- tized person) a maximum of about 50 to 60 mEq/L, slightly less than half the concentrations in plasma. Furthermore, the sweat flows through the glandular tubules so rapidly that lit- tle of the water is reabsorbed. Therefore, the other dissolved constituents of sweat are only moderately increased in con- centration; urea is about twice that in the plasma, lactic acid about 4 times, and potassium about 1.2 times. A significant loss of sodium chloride occurs in the sweat when a person is unacclimatized to heat. Much less electrolyte loss occurs, despite increased sweating capac- ity, once a person has become acclimatized. REGULATION OF BODY TEMPERATURE—ROLE OF THE HYPOTHALAMUS The precise dimensions of this curve depend on the wind movement of the air, the amount of moisture in the air, and even the nature of the surroundings. In general, a nude person in dry air between 55°F and 130°F is capable of maintaining a normal body core temperature somewhere between 97°F and 100°F. The temperature of the body is regulated almost entirely by nervous feedback mechanisms, and almost all these mechanisms operate through temperature- regulating centers located in the hypothalamus. For these feedback mechanisms to operate, there must also be temperature detectors to determine when body temperature becomes either too high or too low. NEURONAL EFFECTOR MECHANISMS THAT DECREASE OR INCREASE BODY TEMPERATURE When the hypothalamic temperature centers detect that the body temperature is either too high or too low, they institute appropriate temperature-decreasing or temperature-increasing procedures. The reader is probably familiar with most of these procedures from personal experience, but special features are described in the fol- lowing sections.  - - Interstitial fluid is outside of the cell Cytosol is inner part of the cell Both are being separated by plasma membrane or cell membrane Membrane transport - Passive transport do not require energy - Active transport require energy Passive transport - Simple diffusion: small non polar solutes, move between lipid bilayer - Facilitated diffusion: small charged or polar solutes, pass through plasma membrane - Channel mediated uses ions move through a water filled channel leak channels and gated channels, continuously open and stimulus channel. - Carrier meditated: movement of small polar molecules across the membrane - Glucose bind to carrier protein and change shape and move glucose molecule to the other side - Osmosis: passive movement of water through selectively permeable membrane - Occurs when different concentration of water - It can happens when water slip between phospholipid molecules that make up the plasma membrane - Or through integral protein water channels called aquaporins - Molecules from high concentration to low concentration to achieve equilibrium Diffusion - Movement of substances move from high concentration area to low concentration area Active processes - Active transport: movement of solute against concentration gradient (low to high) - 2 types - Primary transport: cellular protein pump called ion move ions across the membrane against their concentration gradient, atp binds sodium ions atp break down to adp and p, p binds to pump releasing energy causing pump to change shape and get the ions to the other side. Potassium charge back and revert the shape of the pump - Secondary active transport: substance is moved against its concentration gradient by the movement of a second substance down its concentration gradient - Substance moving from high to low provide energy to move second substance to move low to high - Symport - 2 substances moved in same direction - antiport - 2 substances moved in opposite directions - Vestibular transport: transport by vesicle. Which is a membrane bound sac filled with mats Vesticle transport: exocytosis and endocytosis require the use of energy - Transport of larger substances by membranous sac - Exocytosis: mats secreted from cell to interstitial fluid outside of cell  - Vesicle fuses with membrane fuse and content is released outside the cell - Endocytosis: cell intakes contents from outside of cell - Plasma membrane traps the substance by folding inward lipid them forms vesicle - Phagocytosis: vesicles fuses with a lysosome (contains digestive enzyme breaks down particle into component molecules) is also called cell eating. - Pinocytosis: cell drinking, when plasma membrane folds inward and engulf (trap) interstitial fluids contain solutes can be used for cells - receptor mediated endocytosis: involves using receptor bind with molecules in interstitial fluids and folds enclosing to form new vesicle. Transport of Substances through cell membranes: - Extracellular contains large sodium and less potassium (intracellular is the opposite) - Extracellular contains chloride ions where as intra is very little - THE CELL MEMBRANE IS A LIPID BILAYER WITH CELL MEMBRANE TRANSPORT PROTEINS - Penetrating proteins interrupt lipid bilayer function as transport proteins - Proteins allows free movement of water are called channel proteins - Carrier proteins bind with molecules or ions then move then interstices “Diffusion” Versus “Active Transport.” - Diffusion = random molecular movement of substances molecule by molecule through intermolecular space or bind with a carrier protein (kinetic motion of matter) - Active transport = movement of ions or other substances across the membrane with a carrier protein. From low concentration to high concentration (kinetic energy) DIFFUSION - Molecules and ions are constantly moving is called HEAT - GREATER MOTION = HIGHER TEMPERATURE - Motion ceases at absolute 0 temperature - A moving molecule hit a stationary molecule transferring over some kinetic energy and go on, this continuity movement is called diffusion - Ions concept is the same but less rapidly due to its large size DIFFUSION THROUGH THE CELL MEMBRANE - simple diffusion and facilitated diffusion - simple diffusion = kinetic movement of molecules or ions through a membrane without carrier proteins. Rate depends on amount velocity and number sizes - 2 ways for simple diffusion, 1 is through interstices of lipid bilayer and 2 is water channels penetrating through membrane. - Facilitated diffusion = interaction with a carrier protein  Diffusion of Lipid- Soluble Substances Through the Lipid Bilayer. - Lipid solubility = how rapidly it diffuses (O2, N2 and CO2) Diffusion of Water and Other Lipid- Insoluble Mole cules Through Protein Channels. - body’s cell membranes contain protein “pores” called aquaporins and it permits water through the membrane - Urea penetration falls behind water because its size is 20% bigger making it 1000 times less than that of water. DIFFUSION THROUGH PROTEIN PORES AND CHANNELS—SELECTIVE PERMEABILITY AND “GATING” OF CHANNELS - Metabolism: - Foods bring energy to various physiology systems of the cell Coupled reactions - Carb fats and proteins can be oxidized in the cells -> energy releases - Energy is released in all form of heat, can be burned with pure oxygen by fire - Energy is needed movement for muscle function - Concentrate solutes in the case of glandular secretion and other cell function - Chemical reactions must be coupled with the physiologic function systems. Free Energy: - Energy is liberated from oxidation of food is called Free energy of food oxidation (ΔG) - Calories / mol of substance - Energy liberated by complete oxidation of 1 mole (180g) is 686k calories Adenosine Triphosphate is the “Energy Currency” of the body: Or ATP - ATP is linked to energy-utilizing (using) and energy-producing (producing) functions of the body - ATP is Energy currency - Can be gained and spent repeatedly  - Carbs, Proteins and fat use to convert adenosine diphosphate ADP into ATP - It is labile chemical compound - ATP is a combination of adenine, ribose and three phosphate radicals - Last 2 phosphate radicals are connected with remainder of molecule by high energy bond. - High energy bonds per mole atp is 7300 calories standard condition. - Usual condition under concentration and temperature is 12000 calories. - ATP - 1200 cals ADP (PO3) - 1200 cals AMP (2PO3) - Present in cytoplasm and nucleoplasm - All these happen during coupled reactions Central Role of Glucose in Carbohydrate Metabolism - Glucose, fructose and galactose, - After the absorption of intestinal tract, much of fructose and galactose rapidly converted into glucose in the liver - Glucose helps transporting carbs to tissue cells - Fructose and galactose present in circulating blood - Monosaccharides after released from liver, final product is almost entirely Glucose because liver contain glucose phosphatase and glucose6phosphate be degraded to glucose and phosphate. - 95% of monosaccharides circulate in the blood are normally the final conversion of glucose. Glucose Transport Through Cell Membranes - Glucose then transported through cell membrane into Cellular Cytoplasm. - Molecule of glucose is too heavy to be transport through pores of cell membrane (180-100) - But thanks to Facilitated Diffusion it makes it happen. - Glucose bind with protein carrier molecules to penetrate through the cell membrane wall and if one side has more glucose than the other then glucose from high will go to low glucose area. - In Special cells Glucose use Active sodium glucose co-transport in which activate transport of sodium provides energy for absorbing glucose against a concentration difference. Insulin increases Facilitated Diffusion of Glucose - Insulin makes glucose transport 10 times better. - Without insulin glucose relies on liver and brain cells to transport Phosphorylation of Glucose - Phosphorylation happens due to glucokinase in oliver and by hexokinase - It is irreversible except in liver cells, glucose phosphatase in liver activates and reverse the reaction  - Serves to capture to glucose in the cell cuz of it instantaneous binding with phosphate - Glucose will not diffuse back out except from liver cells that have phosphatase. Glycogen is stored in the liver and muscle - Is a large polymer of glucose - Liver cells can store large amount of glycogen - 5%-8% in liver cells and 1-3% in muscle cells - Precipitate in Solid Granules Anaerobic release of energy: - When Oxygen becomes unavailable and oxidative phosphorylation cant take place - Glycolysis releases energy into the cells cuz it doesnt require oxygen - This process can be lifesaving for a few mins but is wasteful of glucose Citrid acid cycle: - Tricarboxylic acid cycle - Acetyl portion of acetyl-CoA degraded to CO2 and H2 atoms - Occurs in matrix of mitochondria - Releases energy to ATP and all be oxidized - Acetyl combines with oxaloacetic to form citric acid - Co2 and H2 are released - ATP only formed once during ketoglutaric and succinic acid Glycogenesis-formation of glycogen The chemical reactions for glycogenesis are illustrated in Figure 68-4 which shows that glucose-6-phosphate can be- come glucose-1-phosphate; this substance is converted to uridine diphosphate glucose, which is finally converted into glycogen. Several specific enzymes are required to cause these conversions, and any monosaccharide that can be converted into glucose can enter into the reactions. Certain smaller compounds, including lactic acid, glycerol, pyruvic acid, and some deaminated amino acids, can also be con- verted into glucose or closely allied compounds and then converted into glycogen. Glycogenolysis—Breakdown of Stored Glycogen Glycogenolysis means the breakdown of the cell’s stored glycogen to re-form glucose in the cells. The glucose can then be used to provide energy. Glycogenolysis does not occur by reversal of the same chemical reactions that form glycogen; instead, each succeeding glucose molecule on each branch of the glycogen polymer is split away by phosphorylation, catalyzed by the enzyme phos- phorylase. Under resting conditions, the phosphorylase is in an inactive form, and thus glycogen remains stored. When it is necessary to re-form glucose from glycogen, the phosphorylase must first be activated. This activation can be accomplished in several ways, including activa- tion by epinephrine or by glucagon, as described in the next section. Blood Glucose The normal blood glucose concentration in a person who has not eaten a meal within the past 3 to 4 hours is about 90 mg/dl. After a meal containing large amounts of car- bohydrates, this level seldom rises above 140 mg/dl un- less the person has diabetes mellitus. The regulation of blood glucose concentration is in- timately related to the pancreatic hormones insulin and glucagon; this subject is discussed in detail in relation to the functions of these hormones. Lipid metabolism: - Neutral fat known as triglycerides phospholipids cholesterol. - Fatty acids (long chai hydrocarbon organic acids) - Triglycerides mainly provide energy for the different metabolic process. Structure: - Stearic acid 18 carbon chain and fully saturated - Oleic acid 18 carbon chain but one double bond - Palmitic acid has 16 carbon atoms and fully saturated Triglycerides transportation from gastro intestinal by lymph the chylomicrons - Triglycerides split into monoglycerides and fatty acids - Pas thru intestinal epithelal cells they resyntesized called droplets chylomycrons - Chylomicrons: 9% phospholipids 3% cholesterol and 1% apolipoproteins Removal of chylomicrons from blood - After large meal chylomicron in plasma rise 1% - 2% total plasma and appears turbud and sometimes yellow and become clear less than an hour Chylomicron Triglycerides Are Hydrolyzed by Lipoprotein Lipase, and Fat Is Stored in Adipose Tissue. - Capillaries of various tissues remove chylomicron from blood (lipoprotein lipase) “Free Fatty Acids” Are Transported in the Blood in Combination With Albumin - When fat that has been stored in the adipose tissue is to be used elsewhere in the body to provide energy, it must first be transported from the adipose tissue to the other tissue. It is transported mainly in the form of free fatty acids. This transport is achieved by hydrolysis of the triglycerides back into fatty acids and glycerol. Fat Deposits Large quantities of fat are stored in two major tissues of the body, the adipose tissue and the liver. The adipose tissue is usually called fat deposits, or simply tissue fat. Adipose Tissue A major function of adipose tissue is storage of triglycer- ides until they are needed to provide energy elsewhere in the body. Additional functions are to provide heat insula- tion for the body, as discussed in Chapter 74, and secretion of hormones, such as leptin and adiponectin, which affect multiple body functions, including appetite and energy ex- penditure, as discussed in Chapter 72. Fat Cells (Adipocytes) Store Triglycerides. The fat cells (adipocytes) of adipose tissue are modified fibroblasts that store almost pure triglycerides in quantities as great as 80% to 95% of the entire cell volume. Triglycerides inside the fat cells are generally in a liquid form. When the tissues are exposed to prolonged cold, the fatty acid chains of the cell triglycerides, over a period of weeks, become either shorter or more unsaturated to decrease their melting point, there- by always allowing the fat to remain in a liquid state. This characteristic is particularly important because only liquid fat can be hydrolyzed and transported from the cells. Fat cells can synthesize very small amounts of fatty acids and triglycerides from carbohydrates; this function supple- ments the synthesis of fat in the liver, as discussed later in the chapter. Tissue Lipases Permit Exchange of Fat Between Adipose Tissue and the Blood. As discussed earlier, large quantities of lipases are present in adipose tissue. Some of these enzymes catalyze the deposition of cell triglycerides from the chylomicrons and lipoproteins. Others, when ac- tivated by hormones, cause splitting of the triglycerides of the fat cells to release free fatty acids. Because of the rapid exchange of fatty acids, the triglycerides in fat cells are re- newed about once every 2 to 3 weeks, which means that the fat stored in the tissues today is not the same fat that was stored last month, thus emphasizing the dynamic state of storage fat. Liver Lipids The principal functions of the liver in lipid metabolism are to (1) degrade fatty acids into small compounds that can be used for energy; (2) synthesize triglycerides, mainly from carbohydrates, but to a lesser extent from proteins as well; and (3) synthesize other lipids from fatty acids, especially cholesterol and phospholipids. Large quantities of triglycerides appear in the liver dur- ing (1) the early stages of starvation, (2) in diabetes mel- litus, and (3) in any other condition in which fat instead of carbohydrates is being used for energy. In these condi- tions, large quantities of triglycerides are mobilized from the adipose tissue, transported as free fatty acids in the blood, and redeposited as triglycerides in the liver, where the initial stages of much of fat degradation begin. Thus, under normal physiological conditions, the total amount of triglycerides in the liver is determined to a great extent by the overall rate at which lipids are being used for energy. The liver may also store large amounts of lipids in peo- ple who are obese or have lipodystrophy, a condition char- acterized by atrophy or genetic deficiency of adipocytes. In both of these conditions, excess fat that cannot be stored in adipose tissue accumulates in the liver and, to a lesser ex- tent, in other tissues that normally store minimal amounts of lipids. The liver cells, in addition to containing triglycerides, contain large quantities of phospholipids and cholesterol, which are continually synthesized by the liver. Also, the liver cells are much more capable of desaturating fatty ac- ids than are other tissues, and thus liver triglycerides nor- mally are much more unsaturated than the triglycerides of adipose tissue. This capability of the liver to desaturate fatty acids is functionally important to all tissues of the body because many structural elements of all cells contain rea- sonable quantities of unsaturated fats, and their principal source is the liver. This desaturation is accomplished by a dehydrogenase in the liver cells Use of Triglycerides for Energy: Formation of Adenosine Triphosphate The dietary intake of fat varies considerably in persons of different cultures, averaging as little as 10% to 15% of ca- loric intake in some Asian populations to as much as 35% to 50% of the calories in many Western populations. For many persons the use of fats for energy is therefore as im- portant as the use of carbohydrates. In addition, many of the carbohydrates ingested with each meal are converted into triglycerides, stored, and used later in the form of fatty acids released from the triglycerides for energy. Hydrolysis of Triglycerides Into Fatty Acids and Glyc- erol. The first stage in using triglycerides for energy is their hydrolysis into fatty acids and glycerol. Then, both the fatty acids and the glycerol are transported in the blood to the active tissues, where they will be oxidized to give energy. Almost all cells—with some exceptions, such as brain tis- sue and red blood cells—can use fatty acids for energy. Glycerol, upon entering the active tissue, is immedi- ately changed by intracellular enzymes into glycerol-3- phosphate, which enters the glycolytic pathway for glucose breakdown and is thus used for energy. Before the fatty ac- ids can be used for energy, they must be processed further in the mitochondria. Entry of Fatty Acids Into Mitochondria. Degradation and oxidation of fatty acids occur only in the mitochondria. Therefore, the first step for the use of fatty acids is their transport into the mitochondria using carnitine as a carrier. Once inside the mitochondria, fatty acids split away from carnitine and are degraded and oxidized. Degradation of Fatty Acids to Acetyl Coenzyme A by Beta-Oxidation. Fatty acids are degraded in the mitochon- dria by progressive release of two-carbon segments in the form of acetyl coenzyme A (acetyl-CoA). This degradation process, which is shown in Figure 69-3, is called beta- oxidation of fatty acids. To understand the essential steps in the beta-oxidation process, note that in Equation 1 in Obesity—Excess Deposition of Fat Obesity is discussed in Chapter 72 in relation to dietary bal- ances, but briefly, it is caused by the ingestion of greater amounts of food than can be used by the body for energy. The excess food, whether fats, carbohydrates, or proteins, is or more fatty acid molecules and one phosphoric acid radi- cal, and they usually contain a nitrogenous base. Although the chemical structures of phospholipids are somewhat variant, their physical properties are similar because they are all lipid soluble, transported in lipoproteins, and used throughout the body for various structural purposes, such as in cell membranes and intracellular membranes. Formation of Phospholipids. Phospholipids are syn- thesized in essentially all cells of the body, although cer- tain cells have a special ability to form great quantities of them. Probably 90% of phospholipids are formed in liver cells; substantial quantities are also formed by the intestinal epithelial cells during lipid absorption from the gut. The rate of phospholipid formation is governed to some extent by the usual factors that control the overall rate of fat metabolism because, when triglycerides are deposited in the liver, the rate of phospholipid formation increases. Also, specific chemical substances are needed for the for- mation of some phospholipids. For instance, choline, either obtained in the diet or synthesized in the body, is neces- sary for formation of lecithin, because choline is the nitrog- enous base of the lecithin molecule. In addition, inositol is necessary for formation of some cephalins. Specific Uses of Phospholipids. Phospholipids have sev- eral functions, including the following: 1. Phospholipids are an important constituent of lipopro- teins in the blood and are essential for formation and function of most of these lipoproteins; in the absence of phospholipids, serious abnormalities of transport of cholesterol and other lipids can occur. 2. Thromboplastin, which is necessary to initiate the clotting process, is composed mainly of one of the cephalins. 3. Large quantities of sphingomyelin are present in the nervous system; this substance acts as an electrical in- sulator in the myelin sheath around nerve fibers. 4. Phospholipids are donors of phosphate radicals when these radicals are necessary for different chemical reac- tions in the tissues. 5. One of the most important functions of phospholipids is participation in formation of structural elements— mainly membranes—in cells throughout the body, as discussed in the next section of this chapter in connec- tion with a similar function for cholesterol. Cholesterol Cholesterol, is present in the normal diet, and it can be absorbed slowly from the gastrointestinal tract into the intestinal lymph. It is highly fat soluble but only slightly soluble in water. It is specifically capable of forming esters with fatty acids. Indeed, about 70% of the cholesterol in the lipoproteins of the plasma is in the form of cholesterol esters. Formation of Cholesterol. Besides the cholesterol ab- sorbed each day from the gastrointestinal tract, which is called exogenous cholesterol, an even greater quantity is formed in the cells of the body, called endogenous cholester- ol. Essentially all the endogenous cholesterol that circulates in the lipoproteins of the plasma is formed by the liver, but all other cells of the body form at least some cholesterol, which is consistent with the fact that many of the membra- nous structures of all cells are partially composed of this substance. The basic structure of cholesterol is a sterol nucleus, which is synthesized entirely from multiple molecules of acetyl-CoA. In turn, the sterol nucleus can be modified by various side chains to form (1) cholesterol; (2) cholic acid, which is the basis of the bile acids formed in the liver; and (3) many important steroid hormones secreted by the adre- nal cortex, the ovaries, and the testes. Blood: Includes functions; Transport protection and regulation Transport: delivering Oxygen and nutrients to body cells, transport metabolic wastes to lungs and kidneys for elimination, transporting hormones from endocrine organs to target organs Protection: Preventing blood loss and Infection. Regulation: Maintaining body temperature, Maintaining normal pH buffers Maintaining adequate fluid volume in the circulatory system. Composition of blood: - Blood is the only fluid tissue in body - Type of connective tissues are plasma and formed elements - Cells are suspended in plasma - Formed elements includes: erythrocytes, leukocytes and platelets Blood yields 3 layers, Erythrocytes on bottom take about 45% of whole blood, 47% in male and 42% in female Plasma on top takes about 55% White blood cells and platelets in buffy coat is less than 1% Physical characteristics and volume - Blood is sticky opaque fluid with metallic taste - Color varies with O2 content - High Oxygen in blood shows a scarlet red color and low oxygen in blood shows a dark red color - pH is from 7.35 to 7.45 - Average volumes of blood in male is 5 to 6 Liters and in female is 4 to 5 Lites Blood plasma: - Blood plasma is straw-colored sticky fluid - About 90% of it is water - Over 100 dissolved solutes including nutrients, gases, hormone, wastes, proteins and inorganic ions - It remains in blood and not taken up by cells - Proteins produced mostly by liver which is Albumin and it makes up 60% of plasma proteins, it works as a carrier of other molecules as blood buffer and contributes to plasma osmotic pressure - Formed elements: - Formed elements include red, white blood cells and platelets - The only complete cells are white blood cells - red blood cells have no nuclei or organelles - Platelets are cell fragments - Most formed elements can only survive in blood streams for a few days - Most blood cells originate from bone marrow and do not divide Erythrocytes: - Erythrocyte has a diameter of 7.5 micrometer and contribute to gas transport - It contains plasma membrane, spectrin (flexibility to change shape) - Characteristics are that it is biconcave shape, contains 97% hemoglobin and doesnt have mitochondria - Functions are gastransport, hemoglobin binds with oxygen  - Red hue gives blood the color red - Globin composed of 4 poly peptides, 2 alpha and 2 beta - Red blood cell range in 4-6 million cells per microliter of blood - Oxygen loading in lungs is called Oxyhemoglobin - Oxygen unloading in tissues is called Deoxyhemoglobin - Carbondioxide loading in tissues is about 20% of CO2 in blood binds to Hemoglobin and is called carbaminohemoglobin Hematopoiesis is formation of all blood cells Hematopoietic stem cell is hemocytoblasts gives rise to all formed cells committed cells cant change - New blood cell enter sinusoids Production of Erythrocytes: - Stages: Erythropoiesis is formation of red blood cells (lives for 15 days) - Hematopoietic stem cell transform into Myeloid Stem cell - Myeloid stem cell transform into proerythroblast - Proerythroblast divides into basophilic erythroblast - Basophilic erythroblast synthesize ribosome into stain blue - Polychromatic erythroblast synthesize with red hue turn into pink and blue areas - Orthochromatic erythroblast contains hemoglobin and turns into pink color Regulation and Requirement of erythropoiesis - Too few red blood cell leads to Hypoxia - Too much red blood cell lead to increase blood viscosity - There is about 2 million red blood cells made every second - Red blood cell destruction and balance depends on Hormonal controls, dietary requirements: - Erythropoietin is blood hormone and it is released by kidney Hypoxia-induced factor can be accumulated through cause of hypoxia and hormonal control - Cause of Hypoxia are hemorrhage, Pneumonia, Iron deffiencency - Cause of Hormonal control is that Erythrocytes and high oxygen inhibit erythropoietin - Erythropoietin causes Red blood cell maturing faster - Testosterone enhances erythropoietin production Dietary requirement for erythropoiesis: - Amino acids, Lipids and carbohydrates - There needs to be a constant 65% of Iron in blood - Iron by itself is toxic so it needs to bind with protein - Iron stored in cells called ferritin and hemosiderin - Transported in blood is called transferin - Vitamin B12 and folic acid helps rapidly dividing cells Anemia - Causes by Hemorrhage, Iron deficiency, chronic hemorrhagic anemia, Pernicious Anemia which is auto immune destroys intrinsic factor which helps absorbing B12 lead to large blood cells called macrophages. - Renal Anemia is Kidney fails to produce erythropoietin - Aplastic Anemia happens when there is destruction or inhibition of red bone marrow can be caused by drugs chemicals radiations or viruses. - Premature lysis of red blood cells referred as hemolytic anemias and can be caused by incompatible transfusion or infections or hemoglobin abnormalities and usually is genetic disorder resulting in abnormal globins like thalassemias and sickle-cell anemia. - Thalassemias is typically found in people of mediterranean ancestry, usually happen when theres an absent of one globin chain, red blood cells are thin and deficient in hemoglobin  - Sickle cell anemia is Hemoglobin S or mutated hemoglobin, only 1 amino acid is wrong in a globin beta chain out of 146 amino acids Red blood cells become crescent-shaped when oxygen levels are low Misshapen Red blood cells rupture easily and block small vessels. Prevalent in black people and people with sickle cell do not contract malari and often individual with 2 copies of Hb-s develop sickle-cell anemia whereas individual with 1 copy have milder disease and better chance of surviving malaria. - Treatment of sickle cell anemia is transfusion or inhaled nitric oxide - To prevent sickle cell we use stem cell transplants, gene therapy, nitric oxie for vasodilation and hyfroxyurea induces formation of fetal hemoglobin (which does not sickle) Erythrocytes disorders is polycemia cause by excess of red blood cells and increase in blood viscosity causing slugish blood flow. Polycythemia vera is bone marrow cancer leading to excess red blood cells, hematocrit may go as high as 80% and treatment is therapeutic phlebotomy. Second polycemia caused by low oxygen levels or increased EPO production. Leukocytes are complete cells but has shorter life then red blood cells - There are 3 components in leukocytes: Basophil, eosinophil and neutrophil - Agranulocytes has lymphocyte and Monocyte - Lymphocyte is 25%, T lymph is cell mediated from thyroid and B lymph is from bone marrow and is for antibodies - Monocyte is rare and from 3-8 % has a kidney shape and later turn into macrophages. - Leukopoiesis is production of white blood cells from bone marrow, contani interleukins and colony stimulating factor - Leukocytes originate from hemocytoblast, lymphoid stem cells produces lymphocytes and myeloid stem ells produces from other elements - Granulocytes productions: Myelobast produces Myeloline - Promyelocytes produces lysosomes - Myelocytes produces Granules - Band cells produces nuclei form carved arc - Mature granulocyte is nuclei become segmented before being released in blood, 10 times are stored in bone marrow than blood, 3 times more whiteblood cells are formed than red blood cells because white blood cells have a shorter life, cut short by fighting microbes. Agranulocyte productions is monoblast to promonocyte and then to monocyte, is share common precursor with neutrophils and can live up to several months. Homeostatic imbalance: - Hematopoietic hormones of EPO and CSF are used clinically and can stimulate bone marrow of cancer patients receiving chemotherapy or stem cell transplants, also used to increase protective immune responses of AIDS patients. Leukocytes disorders: include overproduction of abnormal white blood cells like leukemia and infectious mononucleosis, abnormally low white blood cell is called leukopenia, can be drug induced. White blood cells clone involved myeloid leukemia involves myeloblast descendants and lymphocytic leukemia involves lymphocytes Leukemias acute derives from stem cells and primarily affect children, chronic leukemia involves proliferation of later cell stages and prevalent in older people. Without treatment all leukemia are fatal, death is from internal hemorrhage or overhwhelming infections, cancerous cells fill red bone marrow. Treatments are irradiation, antileukemia drugs or stem cell transplants Infectious mononucleosis is highly contagious viral disease, usually seen in young adults, caused by epstein barr virus and results in high numbers of typical agranulocytes, involves lymphocytes that become enlarged, originally thought cells were monocytes so disease name mononucleosis. Symptoms are sore throat low fever tired and achy -