B. Pharm (Phar 115, Pharm 115) (Sem.

1) Theory Examination 2011-12 Anatomy and physiology and pathophysiology 1 Paper ID. 5026, 0517 SOLVED BY SANDEEP SACHAN
1. (i) Write the composition of Plasma membrane. Composition Cell membranes contain a variety of biological molecules, notably lipids and proteins. Material is incorporated into the membrane, or deleted from it, by a variety of mechanisms:

Fusion of intracellular vesicles with the membrane (exocytosis) not only excretes the contents of the vesicle but also incorporates the vesicle membrane's components into the cell membrane. The membrane may form blebs around extracellular material that pinch off to become vesicles (endocytosis). If a membrane is continuous with a tubular structure made of membrane material, then material from the tube can be drawn into the membrane continuously. Although the concentration of membrane components in the aqueous phase is low (stable membrane components have low solubility in water), there is an exchange of molecules between the lipid and aqueous phases. Lipids

glycolipids: phosphatidylcholine (PtdCho),phosphatidylethanolamine (PtdEtn), phosphatidyli nositol(PtdIns), phosphatidylserine (PtdSer). The cell membrane consists of three classes of amphipathic lipids: phospholipids, glycolipids, and cholesterols. The amount of each depends upon the type of cell, but in the majority of cases phospholipids are the most abundant.In RBC studies, 30% of the plasma membrane is lipid. The fatty chains in phospholipids and glycolipids usually contain an even number of carbon atoms, typically between 16 and 20. The 16- and 18-carbon fatty acids are the most common. Fatty acids may be saturated or unsaturated, with the configuration of the double bonds nearly always cis. The length and the degree of unsaturation of fatty acid chains have a profound effect on membrane fluidity as unsaturated lipids create a kink, preventing the fatty acids from packing together as tightly, thus decreasing the melting temperature (increasing the fluidity) of the membrane. The ability of some organisms to regulate the fluidity of their cell membranes by altering lipid composition is called homeoviscous adaptation. The entire membrane is held together via non-covalent interaction of hydrophobic tails, however the structure is quite fluid and not fixed rigidly in place. Under physiological conditions phospholipid molecules in the cell membrane are in the liquid crystalline state. It means the lipid molecules are free to diffuse and exhibit rapid lateral diffusion along the layer in which they are present. However, the exchange of phospholipid molecules between intracellular and extracellular leaflets of the bilayer is a very slow process. Lipid rafts and caveolae are examples of cholesterol-enriched microdomains in the cell membrane.

In animal cells cholesterol is normally found dispersed in varying degrees throughout cell membranes, in the irregular spaces between the hydrophobic tails of the membrane lipids, where it confers a stiffening and strengthening effect on the membrane. Phospholipids forming lipid vesicles Lipid vesicles or lisosomes are circular pockets that are enclosed by a lipid bilayer. These structures are used in laboratories to study the effects of chemicals in cells by delivering these chemicals directly to the cell, as well as getting more insight into cell membrane permeability. Lipid vesicles and liposomes are formed by first suspending a lipid in an aqueous solution then agitating the mixture through sonication, resulting in a vesicle. By measuring the rate of efflux from that of the inside of the vesicle to the ambient solution, allows researcher to better understand membrane permeability. Vesicles can be formed with molecules and ions inside the vesicle by forming the vesicle with the desired molecule or ion present in the solution. Proteins can also be embedded into the membrane through solubilizing the desired proteins in the presence of detergents and attaching them to the phospholipids in which the liposome is formed. These provide researchers with a tool to examine various membrane protein functions. Carbohydrates Plasma membranes also contain carbohydrates, predominantly glycoproteins, but with some glycolipids (cerebrosides and gangliosides). For the most part, no glycosylation occurs on membranes within the cell; rather generally glycosylation occurs on the extracellular surface of the plasma membrane. The glycocalyx is an important feature in all cells, especially epithelia with microvilli. Recent data suggest the glycocalyx participates in cell adhesion, lymphocyte homing, and many others. The penultimate sugar is galactose and the terminal sugar is sialic acid, as the sugar backbone is modified in the golgi apparatus. Sialic acid carries a negative charge, providing an external barrier to charged particles. Proteins Proteins within the membrane are key to the functioning of the overall membrane. These proteins mainly transport chemicals and information across the membrane. Every membrane has a varying degree of protein content. Proteins can be in the form of peripheral or integral. Type Description Examples

Span the membrane and have a hydrophilic cytosolic domain, which interacts with internal molecules, a hydrophobic membrane-spanning Integral proteins domain that anchors it within the cell membrane, and a ortransmembrane hydrophilic extracellular domain that interacts with proteins external molecules. The hydrophobic domain consists of one, multiple, or a combination of -helices and sheet protein motifs.

Ion channels,proton pumps,G proteincoupled receptor

Covalently bound to single or multiple lipid molecules; Lipid anchored hydrophobically insert into the cell membrane and G proteins proteins anchor the protein. The protein itself is not in contact with the membrane.

Peripheral proteins

Attached to integral membrane proteins, or associated with peripheral regions of the lipid bilayer. These Some proteins tend to have only temporary interactions with enzymes,some biological membranes, and, once reacted the molecule, hormones dissociates to carry on its work in the cytoplasm.

The cell membrane plays host to a large amount of protein that is responsible for its various activities. The amount of protein differs between species and according to function, however the typical amount in a cell membrane is 50%. These proteins are undoubtedly important to a cell: Approximately a third of the genes in yeast code specifically for them, and this number is even higher in multicellular organisms. The cell membrane, being exposed to the outside environment, is an important site of cell-cell communication. As such, a large variety of protein receptors and identification proteins, such as antigens, are present on the surface of the membrane. Functions of membrane proteins can also include cell-cell contact, surface recognition, cytoskeleton contact, signaling, enzymatic activity, or transporting substances across the membrane. Most membrane proteins must be inserted in some way into the membrane. For this to occur, an N-terminus "signal sequence" of amino acids directs proteins to the endoplasmic reticulum, which inserts the proteins into a lipid bilayer. Once inserted, the proteins are then transported to their final destination in vesicles, where the vesicle fuses with the target membrane. 1 (ii) Write the functional unit in a Golgi complex. The Golgi apparatus (also known as the dictyosome or Golgi body) is an organelle in a cell. The Golgi apparatus, and Golgi body are the same thing. "The Golgi body and its vesicles function in the sorting, modifying, and packaging of macro-molecules that are secreted by the cell or used within the cell for various functions." 1(iii) Write the name of Clotting factor III. Tissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, andleukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin. Historically, thromboplastin was a lab reagent, usually derived from placental sources, used to assay prothrombin times (PT time). Thromboplastin, by itself, could activate the extrinsic coagulation pathway. Functions Coagulation TF is the cell surface receptor for the serine protease factor VIIa. The best known function of tissue factor is its role in blood coagulation. The complex of TF with factor VIIa catalyzes the conversion of the inactive protease factor X into the active protease factor Xa. Together with factor VIIa, tissue factor forms the tissue factor or extrinsic pathway of coagulation. This is opposed to the intrinsic (amplification) pathway which involves both activated factor IX and factor VIII. Both pathways lead to the activation of factor X (the common pathway) which combines with activated factor V in the presence of calcium and phospholipid to produce thrombin (thromboplastin activity).

Cytokine TF is related to a protein family known as the cytokine receptor class II family. The members of this receptor family are activated by cytokines. Cytokines are small proteins that can influence the behavior of white blood cells. Binding of VIIa to TF has also been found to start signaling processes inside the cell. The signaling function of TF/VIIa plays a role in angiogenesis and apoptosis. 1 (iv) Define the term Disease. Disease The term disease broadly refers to any condition that impairs normal function. Commonly, this term is used to refer specifically to infectious diseases, which are clinically evident diseases that result from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular organisms, and aberrant proteins known as prions. An infection that does not and will not produce clinically evident impairment of normal functioning, such as the presence of the normal bacteria and yeasts in the gut, is not considered a disease; by contrast, an infection that is asymptomatic during its incubation period, but expected to produce symptoms later, is usually considered a disease. Noninfectious diseases are all other diseases, including most forms of cancer,heart disease, and genetic disease. Death due to disease is called death by natural causes. There are four main types of disease: pathogenic disease, deficiency disease, hereditary disease, and physiological disease. Diseases can also be classified as communicable and non-communicable disease 1(v) Write another name of Folic acid.

Folic acid (also known as vitamin B9, vitamin Bc or folacin) and folate (the form naturally occurring in the body), as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9. Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions. The human body needs folate to synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in biological reactions involving folate. It is especially important in aiding rapid cell division and growth, such as in infancy and regnancy. Children and adults both require folic acid to produce healthy red blood cells and prevent anemia. 1(vi) Define Fibrous joint. Fibrous joints are connected by dense connective tissue, consisting mainly of collagen. Types These joints are also called "fixed" or "immoveable" joints, because they do not move. These joints have no joint cavity and are connected via fibrous connective tissue. The skull bones are connected by fibrous joints. Sutures are found between bones of the skull. In fetal skulls the sutures are wide to allow slight movement during birth. They later become rigid (synarthrodial). Syndesmoses are found between long bones of the body, such as the radius and ulna in forearm and the fibula and tibia in leg. Unlike other fibrous joints, syndesmoses are moveable (amphiarthrodial), albeit not to such degree as synovial joints. Gomphosis is a joint between the root of a tooth and the sockets in the maxilla or mandible. 1(vii) Write any two names of Protein deficiency disorders. MARASMUS Marasmus is a disease caused by a severe deficiency of protein and calories that affect infants and very young children, often resulting in weight loss and dehydration. Marasmus can develop into starvation and cause fatality caused by a lack of essential nutrients. People with marasmus appear bony with little muscle tissue, according to Food4Africa. KWASHIORKOR Kwashiorkor is a disease caused by a severe deficiency of protein in diets that contain calories mostly from carbohydrates such as yams, rice and bananas. It usually affects older children. People with kwashiorkor appear puffy in the abdomen area from retention of fluid, according to the University of Maryland Medical Center. Common symptoms of both marasmus and kwashiorkor include fatigue, irritability, diarrhea, stunted growth and impairment of cognition and mental health. DEFICIENCIES OF PROTEIN C AND PROTEIN S Deficiencies of protein C and protein S are inherited conditions that cause abnormal blood clotting, according to Medline Plus. Deficiency of protein C occurs in about 1 out of 300 people. Deficiency of protein S affects 1 in 20,000 people. Symptoms for these deficiencies include redness, pain, tenderness or swelling in the affected area. People with these protein deficiencies need to be careful about activities that increase risk of blood clots, such as prolonged sitting, bed rest, and long-time travel in cars and airplanes. Research by A. Hooda published in the "Annals of Indian Academy of Neurology" in 2009 discovered that protein S deficiency causes ischemic stroke. CACHEXIA

Cachexia is a condition that involves protein deficiency, depletion of skeletal muscle and an increased rate of protein degradation, Cachexia causes weight loss and mortality and is associated with cancer, AIDS, chronic kidney failure, heat disease, chronic obstructive pulmonary disease and rheumatoid arthritis, Patients with malignant cancer of the stomach, colon, liver, billiary tract and pancreas experience under nutrition from reduced intake of protein, calories and micronutrients, and have fatigue and a negative nitrogen balance as a result of loss of muscle mass from cachexia 1(viii) Define the term Anatomy, Physiology and Cell biology. Anatomy (from the Greek anatomia, from ana: separate, apart from, and temnein, to cut up, cut open) is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy (zootomy), and plant anatomy (phytotomy). In some of its facets anatomy is closely related to embryology, comparative anatomy and comparative embryology, through common roots in evolution. Anatomy is subdivided into gross anatomy (or macroscopic anatomy) and microscopic anatomy. Gross anatomy is the study of anatomical structures that can, when suitably presented or dissected, be seen by unaided vision with the naked eye. Microscopic anatomy is the study of minute anatomical structures on a microscopic scale. It includes histology (the study of tissues), and cytology (the study of cells). The terms microanatomy and histology are also sometimes used synonymously (in which case the distinction between histology and cell biology isn't strictly made as described here). Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or Medicine, awarded since 1901 by the Royal Swedish Academy of Sciences. Many U.S. universities offer physiology as a major. Human physiology is the science of the mechanical, physical, and biochemical functions of humans in good health, their organs, and the cells of which they are composed. The principal level of focus of physiology is at the level of organs and systems within systems. Much of the foundation of knowledge in human physiology was provided by animal experimentation. Physiology is closely related to anatomy; anatomy is the study of form, and physiology is the study of function. Due to the frequent connection between form and function, physiology and anatomy are intrinsically linked and are studied in tandem as part of a medical curriculum. Cell biology (formerly cytology, from the Greek kytos, "contain") is a scientific discipline that studies cells their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level. Cellbiology research encompasses both the great diversity of single-celled organisms like bacteria and protozoa, as well as the many specialized cells in multicellular organisms such as humans. Knowing the components of cells and how cells work is fundamental to all biological sciences. Appreciating the similarities and differences between cell types is particularly important to the fields of cell and molecular biology as well as to biomedical fields such as cancer research and developmental biology. These fundamental similarities and differences provide a unifying theme, sometimes allowing the principles learned from studying one cell type to be extrapolated and generalized to other cell types. Therefore, research in cell biology is closely related to genetics, biochemistry, molecular biology, immunology, and developmental biology.

1(ix) Define Homeostasis. Homeostasis (from Greek: hmoios, "similar" and stsis, "standing still") is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH. It can be either an open or closed system. Typically used to refer to a living organism, the concept came from that of milieu interieur that was created by Claude Bernard and published in 1865. Multiple dynamic equilibrium adjustment and regulation mechanisms make homeostasis possible.

1(x) Write the composition of milk. The Milk Composition section describes the chemical and physical properties and effects of pasteurization on the compounds in milk. A brief overview of the variation in milk composition is provided below as an introduction to this section. Topics covered are: Carbohydrate (Lactose) Milk Carbohydrate (Lactose) Milk contains approximately 4.9% carbohydrate that is predominately lactose with trace amounts of monosaccharides and oligosaccharides. Lactose is a disaccharide of glucose and galactose. The structure of lactose is:

Fat

Milk Fat Chemistry Milk contains approximately 3.4% total fat. Milk fat has the most complex fatty acid composition of the edible fats. Over 400 individual fatty acids have been identified in milk fat. However, approximately 15 to 20 fatty acids make up 90% of the milk fat. The major fatty acids in milk fat are straight chain fatty acids that are saturated and have 4 to 18 carbons (4:0, 6:0, 8:0, 10:0, 12:0, 14:0, 16:0, 18:0), monounsaturated fatty acids (16:1, 18:1), and polyunsaturated fatty acids (18:2, 18:3). Some of the fatty acids are found in very small amounts but contribute to the unique and desirable flavor of milk fat and butter. For example, the C14:0 and C16:0 -hydroxy fatty acids spontaneously form lactones upon heating which enhance the flavor of butter. The fatty acid composition of milk fat is not constant throughout the cow's lactation cycle. The fatty acids that are 4 to 14 carbons in length are made in the mammary gland of the animal. Some of the 16 carbon fatty acids are made by the animal and some come from the animal's diet. All of the 18 carbon fatty acids come from the animal's diet. There are systematic changes in milk fat composition that are due to the stage of lactation and the energy needs of the animal. In early lactation, the animal's energy comes largely from body stores and there are limited fatty acids available for fat synthesis, so the fatty acids used for

milk fat production are obtained from the diet and tend to be the longer chain 16:0, 18:0, 16:1 and 18:2 fatty acids. Later in lactation more of the fatty acids in milk are formed in the mammary gland so that the concentration of the short chain fatty acids such as 4:0 and 6:0 are higher than they are in early lactation. These changes in fatty acid composition do not have a great impact on milk's nutritional properties, but may have some effect on processing characteristics for products such as butter. Milk fat contains approximately 65% saturated, 30% monounsaturated, and 5% polyunsaturated fatty acids. From a nutritional perspective, not all fatty acids are created equal. Saturated fatty acids are associated with high blood cholesterol and heart disease. However, short chain fatty acids (4 to 8 carbons) are metabolized differently than long chain fatty acids (16 to 18 carbons) and are not considered to be a factor in heart disease.Conjugated linoleic acid is a trans fatty acid in milkfat that is beneficial to humans in many ways. These issues are discussed in the Milk and Human Health section. The fatty acids are arranged on the triglyceride molecule (Figure 1) in a specific manner. Most of the short chain fatty acids are at the bottom carbon position of the triglyceride molecule, and the longer fatty acids tend to be in the middle and top positions. The distribution of the fatty acids on the triglyceride backbone affects the flavor, physical, and nutritional properties of milk fat.

Protein

Milk Protein Chemistry Milk contains 3.3% total protein. Milk proteins contain all 9 essential amino acids required by humans. Milk proteins are synthesized in the mammary gland, but 60% of the amino acids used to build the proteins are obtained from the cow's diet. Total milk protein content and amino acid composition varies with cow breed and individual animal genetics. There are 2 major categories of milk protein that are broadly defined by their chemical composition and physical properties. The casein family contains phosphorus and will coagulate or precipitate at pH 4.6. The serum (whey) proteins do not contain phosphorus, and these proteins remain in solution in milk at pH 4.6. The principle of coagulation, or curd formation, at reduced pH is the basis for cheese curd formation. In cow's milk, approximately 82% of milk protein is casein and the remaining 18% is serum, or whey protein.

The casein family of protein consists of several types of caseins (-s1, -s2 , , and 6) and each has its own amino acid composition, genetic variations, and functional properties. The caseins are suspended in milk in a complex called a micelle that is discussed below in the physical properties section. The caseins have a relatively random, open structure due to the amino acid composition (high proline content). The high phosphate content of the casein family allows it to associate with calcium and form calcium phosphate salts. The abundance of phosphate allows milk to contain much more calcium than would be possible if all the calcium were dissolved in solution, thus casein proteins provide a good source of calcium for milk consumers. The 6-casein is made of a carbohydrate portion attached to the protein chain and is located near the outside surface of the casein micelle (see Figure 2 below). In cheese manufacture, the 6-casein is cleaved between certain amino acids, and this results in a protein fragment that does not contain the amino acid phenylalanine. This fragment is called milk glycomacropeptide and is a unique source of protein for people with phenylketonuria. The serum (whey) protein family consists of approximately 50% -lactoglobulin, 20% lactalbumin, blood serum albumin, immunoglobulins, lactoferrin, transferrin, and many minor proteins and enzymes. Like the other major milk components, each whey protein has its own characteristic composition and variations. Whey proteins do not contain phosphorus, by definition, but do contain a large amount of sulfur-containing amino acids. These form disulfide bonds within the protein causing the chain to form a compact spherical shape. The disulfide bonds can be broken, leading to loss of compact structure, a process called denaturing. Denaturation is an advantage in yogurt production because it increases the amount of water that the proteins can bind, which improves the texture of yogurt. This principle is also used to create specialized whey protein ingredients with unique functional properties for use in foods. One example is the use of whey proteins to bind water in meat and sausage products. The functions of many whey proteins are not clearly defined, and they may not have a specific function in milk but may be an artifact of milk synthesis. The function of lactoglobulin is thought to be a carrier of vitamin A. It is interesting to note that lactoglobulin is not present in human milk. -Lactalbumin plays a critical role in the synthesis of lactose in the mammary gland. Immunoglobulins play a role in the animal's immune system, but it is unknown if these functions are transferred to humans. Lactoferrin and transferrin play an important role in iron absorption and there is interest in using bovine milk as a commercial source of lactoferrin.

Deterioration of Milk Protein Proteins can be degraded by enzyme action or by exposure to light. The predominant cause of protein degradation is through enzymes called proteases. Milk proteases come from several sources: the native milk, airborne bacterial contamination, bacteria that are added intentionally for fermentation, or somatic cells present in milk. The action of proteases can be desirable, as in the case of yogurt and cheese manufacture, so, for these processes, bacteria with desirable proteolytic properties are added to the milk. Undesirable degradation (proteolysis) results in milk with off-flavors and poor quality. The most important protease in milk for cheese manufacturing is plasmin because it causes proteolysis during ripening which leads to desirable flavors and texture in cheese. Two amino acids in milk, methionine and cystine are sensitive to light and may be degraded with exposure to light. This results in an off-flavor in the milk and loss of nutritional quality for these 2 amino acids.

Vitamins in Milk Vitamins have many roles in the body, including metabolism co-factors, oxygen transport and antioxidants. They help the body use carbohydrates, protein, and fat. The specific content of vitamins in milk is listed in theNutrient Content Tables in the Nutrition Facts section. Milk contains the water soluble vitamins thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), vitamin B6 (pyridoxine), vitamin B12 (cobalamin), vitamin C, and folate. Milk is a good source of thiamin, riboflavin and vitamin B12 . Milk contains small amounts of niacin, pantothenic acid, vitamin B6, vitamin C, and folate and is not considered a major source of these vitamins in the diet. Milk contains the fat soluble vitamins A, D, E, and K. The content level of fat soluble vitamins in dairy products depends on the fat content of the product. Reduced fat (2% fat), lowfat (1% fat), and skim milk must be fortified with vitamin A to be nutritionally equivalent to whole milk. Fortification of all milk with vitamin D is voluntary. Milk contains small

amounts of vitamins E and K and is not considered a major source of these vitamins in the diet. Minerals in Milk Minerals have many roles in the body including enzyme functions, bone formation, water balance maintenance, and oxygen transport. The specific content of minerals in milk is listed in the Nutrient Content Tables in the Nutrition Facts section. Milk is a good source of calcium, magnesium, phosphorus, potassium, selenium, and zinc. Many minerals in milk are associated together in the form of salts, such as calcium phosphate. In milk approximately 67% of the calcium, 35% of the magnesium, and 44% of the phosphate are salts bound within the casein micelle and the remainder are soluble in the serum phase. The fact that calcium and phosphate are associated as salts bound with the protein does not affect the nutritional availability of either calcium or phosphate. Milk contains small amounts of copper, iron, manganese, and sodium and is not considered a major source of these minerals in the diet. Effects of Heat Treatments & Light Exposure on the Vitamin & Mineral Content in Milk The mild heat treatment used in the typical high temperature short time (HTST) pasteurization of fluid milk does not appreciably affect the vitamin content. However, the higher heat treatment used in ultra high temperature (UHT) pasteurization for extended shelf combined with the increased storage life of these products does cause losses of some water-soluble vitamins. Thiamin is reduced from 0.45 to 0.42 mg/L, vitamin B 12 is reduced from 3.0 to 2.7 g/L, and vitamin C is reduced from 2.0 to 1.8 mg/L (Potter et al., 1984). Riboflavin is a heat stable vitamin and is not affected by severe heat treatments. Calcium phosphate will migrate in and out of the casein micelle with changes in temperature. This process is reversible at moderate temperatures. This does not affect the nutritional properties of milk minerals. At very high temperatures the calcium phosphate may precipitate out of solution which causes irreversible changes in the casein micelle structure. Exposure to light will decrease the riboflavin and vitamin A content in milk. Milk should be stored in containers that provide barriers to light (opaque plastic or paperboard) to maximize vitamin retention. Enzymes Each enzyme has a specific site of action on its target molecule, and optimal conditions (pH and temperature). There are a large number of enzymes in milk and the functions of many are not well-defined. It should be noted that the enzymes in milk do not make a major contribution to the digestion of milk in humans, which is accomplished by enzymes in the human stomach and small intestine. Lipases are enzymes that degrade fats. The major lipase in milk is lipoprotein lipase. It is associated with the casein micelle. Agitation during processing may bring the lipase into

contact with the milk fat resulting in fat degradation and off-flavors. Pasteurization will inactivate the lipase in milk and increase shelf life. Proteases are enzymes that degrade proteins. The major protease in milk is plasmin. Some proteases are inactivated by heat and some are not. Protein degradation can be undesirable and result in bitter off-flavors, or it may provide a desirable texture to cheese during ripening. Proteases are important in cheese manufacture, and a considerable amount of information is available in the cheese literature. Alkaline phosphatase is a heat sensitive enzyme in milk that is used as indicator of pasteurization. If milk is properly pasteurized, alkaline phosphatase is inactivated. Lactoperoxidase is one of the most heat-stable enzymes found in milk. Lactoperoxidase, when combined with hydrogen peroxide and thiocyanate, has antibacterial properties. It is suggested that the presence of lactoperoxidase in raw milk inhibits the disease causing microorganisms (pathogens) present in milk. However, since there is no hydrogen peroxide or thiocyanate present in fresh milk, these compounds would have to be added to milk in order to achieve the antibacterial benefits. Lysozyme is another enzyme that has some antibacterial activities, although the amount of lysozyme present in milk is very small. Unless otherwise stated, the information presented in this website refers to cow's milk. In general, the gross composition of cow's milk in the U.S. is 87.7% water, 4.9% lactose (carbohydrate), 3.4% fat, 3.3% protein, and 0.7% minerals (referred to as ash). Milk composition varies depending on the species (cow, goat, sheep), breed (Holstein, Jersey), the animal's feed, and the stage of lactation. 1(xi) Write the chief function of the serum albumin in the Blood.

Maintains osmotic pressure. Transports thyroid hormones. Transports other hormones, in particular, ones that are fat-soluble. Transports fatty acids ("free" fatty acids) to the liver. Transports unconjugated bilirubin. Transports many drugs; serum albumin levels can affect the half-life of drugs. Competitively binds calcium ions (Ca2+). Buffers pH. Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is not a valid marker of nutritional status; rather, it is a marker in inflammatory states. Prevents photo-degradation of folic acid.

1(xii) Define Endocytosis. Endocytosis is a process by which cells absorb molecules (such as proteins) by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane. The process which is the opposite to endocytosis is exocytosis. 1(xiii) Write the component of Nucleus.

the nucleus (pl. nuclei;from Latin nucleus or nuculeus, meaning kernel) is a membraneenclosed organelle found ineukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. 1(xiv) Give the function of golgi bodies. The Golgi apparatus (Golgi complex) is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physicianCamillo Golgi, after whom the Golgi apparatus is named. It processes and packages proteins inside of the cell and before they make their way to their destination; it is particularly important in the processing of proteins for secretion. The Golgi apparatus forms a part of the cellular endomembrane system. Function Cells synthesise a large number of different macromolecules. The Golgi apparatus is integral in modifying, sorting, and packaging these macromolecules for cell secretion (exocytosis) or use within the cell. It primarily modifies proteins delivered from the rough endoplasmic reticulum but is also involved in the transport of lipids around the cell, and the creation of lysosomes. In this respect it can be thought of as similar to a post office; it packages and labels items which it then sends to different parts of the cell. Enzymes within the cisternae are able to modify the proteins by addition of carbohydrates (glycosylation) and phosphates (phosphorylation). In order to do so, the Golgi imports substances such as nucleotide sugars from the cytosol. These modifications may also form a signal sequence which determines the final destination of the protein. For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes. The Golgi plays an important role in the synthesis of proteoglycans, which are molecules present in the extracellular matrix of animals. It is also a major site of carbohydrate synthesis. This includes the production of glycosaminoglycans (GAGs), long unbranched polysaccharides which the Golgi then attaches to a protein synthesised in the endoplasmic reticulum to form proteoglycans. Enzymes in the Golgi polymerize several of these GAGs via a xylose link onto the core protein. Another task of the Golgi involves the sulfation of certain molecules passing through its lumen via sulfotranferases that gain their sulfur molecule from a donor called PAPs. This process occurs on the GAGs of proteoglycans as well as on the core protein. The level of sulfation is very important to the proteoglycans' signalling abilities as well as giving the proteoglycan its overall negative charge. The phosphorylation of molecules requires that ATP is imported into the lumen of the Golgi and then utilised by resident kinases such as casein kinase 1 and casein kinase 2. One molecule that is phosphorylated in the Golgi is Apolipoprotein, which forms a molecule known as VLDL that is a constituent of blood serum. It is thought that the phosphorylation of these molecules is important to help aid in their sorting for secretion into the blood serum. The Golgi has a putative role in apoptosis, with several Bcl-2 family members localised there, as well as to the mitochondria. A newly characterized protein, GAAP (Golgi anti-apoptotic protein), almost exclusively resides in the Golgi and protects cells from apoptosis by an asyet undefined mechanism. 1(xv) Define sickle cell anemia. Sickle cell anemia Anemia - sickle cell; Hemoglobin SS disease (Hb SS); Sickle cell disease

Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal crescent shape. (Red blood cells are normally shaped like a disc. Causes, incidence, and risk factors Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells that carries oxygen. Hemoglobin S changes the shape of red blood cells, especially when the cells are exposed to low oxygen levels. The red blood cells become shaped like crescents or sickles. The fragile, sickle-shaped cells deliver less oxygen to the body's tissues. They can also get stuck more easily in small blood vessels, and break into pieces that interupt healthy blood flow. Sickle cell anemia is inherited from both parents. If you inherit the hemoglobin S gene from one parent and normal hemoglobin (A) from your other parent, you will have sickle cell trait. People with sickle cell trait do not have the symptoms of sickle cell anemia. Sickle cell disease is much more common in people of African and Mediterranean descent. It is also seen in people from South and Central America, the Caribbean, and the Middle East. Symptoms Symptoms usually don't occur until after age 4 months. Almost all patients with sickle cell anemia have painful episodes (called crises), which can last from hours to days. These crises can affect the bones of the back, the long bones, and the chest. Some patients have one episode every few years. Others have many episodes per year. The crises can be severe enough to require a hospital stay. Common symptoms include:

Attacks of abdominal pain, Bone pain, Breathlessness, Delayed growth and puberty, Fatigue, Fever, Paleness, Rapid heart rate, Ulcers on the lower legs (in adolescents and adults), Yellowing of the eyes and skin (jaundice)

Other symptoms include:

Chest pain, Excessive thirst, Frequent urination, Painful and prolonged erection (priapism - occurs in 10 - 40% of men with the disease), Poor eyesight/blindness, Strokes, Skin ulcers

Signs and tests Tests commonly performed to diagnose and monitor patients with sickle cell anemia include:

Complete blood count (CBC), Hemoglobin electrophoresis, Sickle cell test

Other tests may include: Bilirubin, Blood oxygen, CT scan or MRI, Peripheral smear, Serum creatinine, Serum hemoglobin Serum potassium, Urinary casts or blood in the urine, White blood cell count Treatment The goal of treatment is to manage and control symptoms, and to limit the number of crises.

Patients with sickle cell disease need ongoing treatment, even when they are not having a painful crisis. Folic acid supplements should be taken. Folic acid is needed to make red blood cells. Treatment for a sickle cell crisis includes:

Blood transfusions (may also be given regularly to prevent stroke) Pain medicines Plenty of fluids

Other treatments for sickle cell anemia may include:

Hydroxyurea (Hydrea), a medicine that may help reduce the number of pain episodes (including chest pain and difficulty breathing) in some people Antibiotics to prevent bacterial infections, which are common in children with sickle cell disease

Treatments for complications of sickle cell anemia may include:

Kidney dialysis or kidney transplant for kidney disease Drug rehabilitation and counseling for psychological complications Gallbladder removal in those with gallstone disease Hip replacement for avascular necrosis of the hip Treatments, including surgery, for persistent, painful erections (priapism) Surgery for eye problems Wound care, zinc oxide, or surgery for leg ulcers

Bone marrow or stem cell transplants can cure sickle cell anemia. However, they are current not an option for most patients. Sickle cell anemia patients are often unable to find wellmatched donors.

1(xvi) Define the Coronal Plane and Sagital Plaine. Sagittal plane is a vertical plane which passes from front to rear dividing the body into right and left sections. The terms median plane or mid-sagittal plane are sometimes used to describe the sagittal plane running through the midline. This plane cuts the body into halves (assuming bilateral symmetry), passing through midline structures such as the navel and spine. It is one of the lines defining the right upper quadrant of the human abdomen. It is also worth mentioning that terms such as parasagittal are sometimes used to describe a plane parallel to the midline; however, this term is unnecessary, since any plane parallel to and on either side of the medial plane is sagittal by definition.

In general, planes that are parallel to the sagittal plane, but do not pass through the midline, are known as parasagittal. The midclavicular line crosses through the clavicle. Other sagittal lines/planes include the lateral sternal and parasternal. A coronal plane (also known as the frontal plane) is any vertical plane that divides the body into ventral and dorsal (belly and back) sections. It is one of the planes of the body used to describe the location of body parts in relation to each other.

Section B
2. Attempt any six question: (i) Describe the Structure and function of the mitochondria. Mitochondrion In cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers (m) in diameter. Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. Mitochondria have been implicated in several human diseases, including mitochondrial disorders and cardiac dysfunction, and may play a role in the aging process. The word mitochondrion comes from the Greek or mitos, thread chondrion, granule. Several characteristics make mitochondria unique. The number of mitochondria in a cell varies widely by organism and tissue type. Many cells have only a single mitochondrion, whereas others can contain several thousand mitochondria. The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae andmatrix. Mitochondrial proteins vary depending on the tissue and the species. In humans, 615 distinct types of proteins have been identified from cardiacmitochondria, whereas in Murinae (rats), 940 proteins encoded by distinct genes have been reported. The mitochondrial proteome is thought to be dynamically regulated. Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. Further, its DNA shows substantial similarity to bacterial genomes. Structure

A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. The two membranes, however, have different properties. Because of this double- embraned organization, there are five distinct compartments within the mitochondrion. There is the outer mitochondrial membrane, the intermembrane space (the space between the outer and inner membranes), the inner mitochondrial membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane). Outer membrane The outer mitochondrial membrane, which encloses the entire organelle, has a protein-tophospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). It contains large numbers of integral proteins called porins. These porins form channels that allow molecules 5000 Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other. Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death. The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ERmembrane). This is important in ER-mitochondria calcium signaling and involved in the transfer of lipids between the ER and mitochondria. Inter membrane space The intermembrane space is the space between the outer membrane and the inner membrane. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol. However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c Inner membrane The inner mitochondrial membrane contains proteins with five types of functions: 1. Those that perform the redox reactions of oxidative phosphorylation 2. ATP synthase, which generates ATP in the matrix

3. Specific transport proteins that regulate metabolite passage into and out of the matrix 4. Protein import machinery. 5. Mitochondria fusion and fission protein It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable. Unlike the outer membrane, the inner membrane doesn't contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1. In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain. Cristae Cross-sectional image of cristae in rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane. The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times greater than the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. These folds are studded with small round bodies known as F1 particles or oxysomes. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function. One recent mathematical modeling study has suggested that the optical properties of the cristae in filamentous mitochondria may affect the generation and propagation of light within the tissue. Matrix The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total protein in a mitochondrion. The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highlyconcentrated mixture of hundreds of enzymes, special mitochondrial ribosomes,tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle. Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes: 22 tRNA, 2 rRNA, and 13 peptide genes. The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along withproteins encoded by genes that reside in the host cell's nucleus. Mitochondria-associated ER membrane (MAM) The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once

considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAMthe interface between mitochondria and the ER. Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy. Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10-25 nm and held together by protein tethering complexes. Purified MAM from subcellular fractionation has shown to be enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca2+ signaling. These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has the MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated powerhouses hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to the endomembrane system. Phospholipid transfer The MAM is enrichad in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face. Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity. But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism. Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles. In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between apposed bilayers. Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP. Instead, it has been shown to be dependent on a multiprotein tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the energy barrier for lipid flipping. The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to very-low-density lipoprotein, or VLDL, assembly and secretion. The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism. Calcium signaling A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, in part because the low affinity of Ca2+ channels localized to the outer mitochondrial membrane seemed to fly in the face of this organelles purported responsiveness to changes in intracellular Ca2+ flux. But the presence of the MAM resolves

this apparent contradiction: the close physical association between the two organelles results in Ca2+ microdomains at contact points that facilitate efficient Ca2+ transmission from the ER to the mitochondria. Transmission occurs in response to so-called Ca2+ puffs generated by spontaneous clustering and activation of IP3R, a canonical ER membrane Ca2+ channel. The fate of these puffsin particular, whether they remain restricted to isolated locales or integrated into Ca2+ waves for propagation throughout the cellis determined in large part by MAM dynamics. Although reuptake of Ca2+ by the ER (concomitant with its release) modulates the intensity of the puffs, thus insulating mitochondria to a certain degree from high Ca2+ exposure, the MAM often serves as a firewall that essentially buffers Ca2+ puffs by acting as a sink into which free ions released into the cytosol can be funneled. This Ca2+ tunneling occurs through the low-affinity Ca2+receptor VDAC1, which recently has been shown to be physically tethered to the IP3R clusters on the ER membrane and enriched at the MAM. The ability of mitochondria to serve as a Ca2+sink is a result of the electrochemical gradient generated during oxidative phosphorylation, which makes tunneling of the cation an exergonic process. But transmission of Ca2+ is not unidirectional; rather, it is a two-way street. The properties of the Ca2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ signaling because Ca2+ alters IP3R activity in a biphasic manner. SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca2+ for continued Ca2+ efflux at the MAM. Thus, the MAM is not a passive buffer for Ca2+ puffs; rather it helps modulate further Ca2+ signaling through feedback loops that affect ER dynamics. Regulating ER release of Ca2+ at the MAM is especially critical because only a certain window of Ca2+ uptake sustains the mitochondria, and consequently the cell, at homeostasis. Sufficient intraorganelle Ca2+ signaling is required to stimulate metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle. However, once Ca2+ signaling in the mitochondria passes a certain threshold, it stimulates the intrinsic pathway of apoptosis in part by collapsing the mitochondrial membrane potential required for metabolism. Studies examining the role of pro- and anti-apoptotic factors support this model; for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli. Given the need for such fine regulation of Ca2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM. Molecular basis for tethering Recently advances in the identification of the tethers between the mitochondrial and ER membranes suggest that the scaffolding function of the molecular elements involved is secondary to other, non-structural functions. ERMES, a multiprotein complex of interacting ER- and mitochondrial-resident membrane proteins, is required for lipid transfer at the MAM and exemplifies this principle. One of its components, for example, is also a constituent of the protein complex required for insertion of transmembrane beta-barrel proteins into the lipid bilayer. Other proteins implicated in scaffolding likewise have functions independent of structural tethering at the MAM; for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle contact sites, although mitofusins were first identified for their role in fission and fusion events between

individual mitochondria. Glucose-related protein 75 (grp75) is another dual-function protein. In addition to the matrix pool of grp75, a portion serves as a chaperone that physically links the mitochondrial and ER Ca2+ channels VDAC and IP3R for efficient Ca2+ transmission at the MAM. Another prominent tether is Sigma-1R, another chaperone whose stabilization of ER-resident IP3R has been proposed to preserve communication at the MAM during the metabolic stress response. Perspective The MAM is a critical signaling, metabolic, and trafficking hub in the cell that allows for the integration of ER and mitochondrial physiology. Coupling between these organelles is not simply structural but functional as well and critical for overall cellular physiology and homeostasis. The MAM thus offers a perspective on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. Instead, this mitochondrial-ER interface emphasizes the integration of the mitochondria, the product of an endosymbiotic event, into diverse cellular processes. Organization and distribution Mitochondria are found in nearly all eukaryotes. They vary in number and location according to cell type. A single mitochondrion is often found in unicellular organisms. Conversely, numerous mitochondria are found in human liver cells, with about 10002000 mitochondria per cell, making up 1/5 of the cell volume. The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum. Often they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well. Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is critical to the association with the cytoskeleton. Function The most prominent roles of mitochondria are to produce ATP (i.e., phosphorylation of ADP) through respiration, and to regulate cellular metabolism. The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs Cycle. However, the mitochondrion has many other functions in addition to the production of ATP. Energy conversion A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose,pyruvate, and NADH, which are produced in the cytosol. This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited, the glycolytic products will be metabolized by anaerobic respiration, a process that is independent of the mitochondria. The production of ATP from glucose has an approximately 13-fold higher yield during aerobic respiration compared to anaerobic respiration. Recently it has been shown that plant mitochondria can produce a limited amount of ATP without oxygen by using the alternate substrate nitrite. Pyruvate and the citric acid cycle Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH.

The acetyl-CoA is the primary substrate to enter the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II. The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH2) that are a source of electrons for the electron transport chain, and a molecule ofGTP (that is readily converted to an ATP). NADH and FADH2: the electron transport chain The redox energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle. Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H+) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process. As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis, and was first described by Peter Mitchell who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase. Heat production Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to thefacilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. The process is mediated by a proton channel called thermogenin, or UCP1. Thermogenin is a 33kDa protein first discovered in 1973. Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age. Storage of calcium ions The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium. In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium. The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there is a significant interplay between the mitochondrion and ER with regard to calcium. The calcium is taken up into the matrix by a calcium uniporter on the inner mitochondrial membrane. It is primarily driven by the mitochondrial membrane potential. Release of this calcium back into

the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-inducedcalcium-release" pathways. This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series ofsecond messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. Additional functions Mitochondria play a central role in many other metabolic tasks, such as:

Regulation of the membrane potentia. Apoptosis-programmed cell death. Calcium signaling (including calcium-evoked apoptosis). Cellular proliferation regulation. Regulation of cellular metabolism. Certain heme synthesis reactions. Steroid synthesis.

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases. Origin Mitochondria have many features in common with prokaryotes. As a result, they are believed to be originally derived from endosymbiotic prokaryotes. A mitochondrion contains DNA, which is organized as several copies of a single, circular chromosome. This mitochondrial chromosome contains genes for redox proteins such as those of the respiratory chain. The CoRR hypothesis proposes that this co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the twenty-two tRNAsnecessary for the translation of messenger RNAs into protein. The circular structure is also found in prokaryotes, and the similarity is extended by the fact that mitochondrial DNA is organized with a variant genetic code similar to that of Proteobacteria. This suggests that their ancestor, the so-called proto-mitochondrion, was a member of the Proteobacteria. In particular, the proto-mitochondrion was probably closely related to the rickettsia. However, the exact relationship of the ancestor of mitochondria to the alpha-proteobacteria and whether the mitochondria was formed at the same time or after the nucleus, remains controversial. A recent study by researchers of the University of Hawaii at Mnoa and the Oregon State University, seems to indicate that SAR11 could be the ancestor of mitochondrion existing in most eukaryotic cells. The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure. They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes, which are coded for by nuclear DNA. The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis. The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis andfermentation would have provided a considerable evolutionary advantage. In a similar manner, host cells with symbiotic bacteria capable of photosynthesis would have

had an advantage. The incorporation of symbiotes would have increased the number of environments in which the cells could survive. This symbiotic relationship probably developed 1.7-2 billion years ago. A few groups of unicellular eukaryotes lack mitochondria: the microsporidians, metamonads, and archamoebae. These groups appear as the most primitive eukaryotes on phylogenetic treesconstructed using rRNA information, which once suggested that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attractionthey are derived groups and retain genes or organelles derived from mitochondria (e.g., mitosomes and hydrogenosomes). Genome

The human mitochondrial genome is a circular DNA molecule of about 16 kilobases. It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 for rRNA.[65] One mitochondrion can contain two to ten copies of its DNA. As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion. The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. In general, mitochondrial genomes are circular, although exceptions have been reported. In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome; however, introns have been observed in some eukaryotic mitochondrial DNA, such as that of yeast and protists, including Dictyostelium discoideum. In animals the mitochondrial genome is typically a single circular chromosome that is approximately 16-kb long and has 37 genes. The genes, while highly conserved, may vary in location. Curiously, this pattern is not found in the human body louse (Pediculus humanus). Instead this mitochondrial genome is arranged in 18 minicircular chromosomes, each of which is 34 kb long and has one to three genes. This pattern is also found in other sucking lice, but not in chewing lice. Recombination has been shown to occur between the minichromosomes. The reason for this difference is not known. While slight variations on the standard code had been predicted earlier, none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code. Many slight variants have been discovered since, including various alternative mitochondrial codes. Further, the AUA, AUC, and AUU codons are all allowable start codons.

(ii) Write a brief note on Erythropoiesis. Erythropoiesis is the process by which red blood cells (erythrocytes) are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells. In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the spleen and liver. After seven months, erythropoiesis occurs in the bone marrow. Decreased level of physical activity can cause an increase in erythropoiesis. However, in humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is termed extramedullary erythropoiesis. The bone marrow of essentially all the bones produces RBCs until a person is around five years old. The tibia and femur cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.

(iii) Define health. Write a short note on factor affecting Health. Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain (as in good health or healthy). The World Health Organization (WHO) defined health in its broader sense in 1946 as "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity." Although this definition has been subject to controversy, in particular as having a lack of operational value and the problem created by use of the word "complete", it remains the most enduring. Classification systems such as the WHO Family of International Classifications, including the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Diseases (ICD), are commonly used to define and measure the components of health.

The maintenance and promotion of health is achieved through different combination of physical, mental, and social well-being, together sometimes referred to as thehealth triangle. The WHO's 1986 Ottawa Charter for Health Promotion furthered that health is not just a state, but also "a resource for everyday life, not the objective of living. Health is a positive concept emphasizing social and personal resources, as well as physical capacities." Systematic activities to prevent or cure health problems and promote good health in humans are delivered by health care providers. Applications with regard to animal health are covered by the veterinary sciences. The term "healthy" is also widely used in the context of many types of non-living organizations and their impacts for the benefit of humans, such as in the sense of healthy communities, healthy cities or healthy environments. In addition to health care interventions and a person's surroundings, a number of other factors are known to influence the health status of individuals, including their background, lifestyle, and economic and social conditions; these are referred to as "determinants of health". Generally, the context in which an individual lives is of great importance on health status and quality of life. It is increasingly recognized that health is maintained and improved not only through the advancement and application of health science, but also through the efforts and intelligent lifestyle choices of the individual and society. According to the World Health Organization, the main determinants of health include the social and economic environment, the physical environment, and the person's individual characteristics and behaviors.[9] More specifically, key factors that have been found to influence whether people are healthy or unhealthy include:[9][10][11] Income and social status, Social support networks, Education and literacy, Employment/working conditions, Social environments, Physical environments, Personal health practices and coping skills, Healthy child development, Biology and genetics, Health care services, Gender, Culture. (iv) Describe the fibrous joint in brief. Fibrous joint Fibrous joints are connected by dense connective tissue, consisting mainly of collagen. Types These joints are also called "fixed" or "immoveable" joints, because they do not move. These joints have no joint cavity and are connected via fibrous connective tissue. The skull bones are connected by fibrous joints. Sutures are found between bones of the skull. In fetal skulls the sutures are wide to allow slight movement during birth. They later become rigid (synarthrodial).

Fibrous joints (sultures in the skull).

Syndesmoses are found between long bones of the body, such as the radius and ulna in forearm and the fibula and tibia in leg. Unlike other fibrous joints, syndesmoses are moveable (amphiarthrodial), albeit not to such degree as synovial joints. Gomphosis is a joint between the root of a tooth and the sockets in the maxilla or mandible.

(v) Write the difference between Active and Passive transport. Active transport requires energy; passive transport does not. Energy consumption Diffusion is simply the movement of solute from an area of greater concentration to lower concentration. Passive transport is the transport of molecules that do not require energy. Active Transport Movement from Low Concentration to High Concentration ATP used Opposite diffusionPassive transport Movement from High Concentration to Low Concentration No energy needed Is diffusion Active transport requires energy and can move substabces against their concentration gradient: And passive transport does not require energy and can move substances only down their concentration. (vi) Write a short note on Muscle tone. Muscle tone In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial contraction of the muscles, or the muscles resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.

(vii)

Describe in brief fat soluble vitamin.

Fat-Soluble Vitamins Small amounts of vitamins A, D, E and K are needed to maintain good health. Foods that contain these vitamins will not lose them when cooked. The body does not need these every day and stores them in the liver when not used. Most people do not need vitamin supplements. Megadoses of vitamins A, D, E or K can be toxic and lead to health problems. Vitamins are essential nutrients your body needs in small amounts for various roles in the human body. Vitamins are divided into two groups: water-soluble (B-complex and C) and fat-soluble (A, D, E and K). Unlike water-soluble vitamins that need regular replacement in the body, fat-soluble vitamins are stored in the liver and fatty tissues, and are eliminated much more slowly than water-soluble vitamins. Because fat-soluble vitamins are stored for long periods, they generally pose a greater risk for toxicity than water-soluble vitamins when consumed in excess. Eating a normal, wellbalanced diet will not lead to toxicity in otherwise healthy individuals. However, taking vitamin supplements that contain mega doses of vitamins A, D, E and K may lead to toxicity. Remember, the body only needs small amounts of any vitamin. While diseases caused by a lack of fat-soluble vitamins are rare in the United States, symptoms of mild deficiency can develop without adequate amounts of vitamins in the diet. Additionally, some health problems may decrease the absorption of fat, and in turn, decrease the absorption of vitamins A, D, E and K. Consult your doctor about this. Table 1 lists sources of fat-soluble vitamins, their basic functions in the body, major deficiency symptoms caused by a lack of these vitamins, and symptoms of over-consumption. Vitamin A Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division and gene expression. Also, the skin, eyes and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. The best way to ensure your body gets enough vitamin A is to eat a variety of foods. Vitamin A is supplied primarily by certain foods of animal origin like dairy products, fish and liver. Some foods of plant origin contain beta-carotene, an antioxidant that the body converts to vitamin A. Beta-carotene, or provitamin A, comes from fruits and vegetables. Carrots, pumpkin, winter squash, dark green leafy vegetables and apricots are rich sources of betacarotene. The recommendation for vitamin A intake is expressed as micrograms (mcg) of retinol activity equivalents (RAE). Retinol activity equivalents account for the fact that the body converts only a portion of beta-carotene to retinol. One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene (see Table 2).

True vitamin A deficiency in the United States is rare. Night blindness and very dry, rough skin may indicate a lack of vitamin A. Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth. In the United States, toxic or excess levels of vitamin A are of more concern than deficiencies. The tolerable upper intake level for adults is 3,000 mcg RAE. It would be difficult to reach this level consuming food alone. But some multivitamin supplements contain high doses of vitamin A. If you take a multivitamin, check the label to be sure the majority of vitamin A provided is in the form of beta-carotene, which appears to be safe. Symptoms of vitamin A toxicity include dry, itchy skin, headache, nausea, and loss of appetite. Signs of severe overuse over a short period of time include dizziness, blurred vision and slowed growth. Vitamin A toxicity also can cause severe birth defects and may increase the risk for hip fractures. Physicians sometimes recommend that young infants take vitamin supplements that contain vitamin A. However, toddlers and children need protection from too much vitamin A due to their smaller body size. Typical foods eaten in large amounts by toddlers and children usually contain sufficient amounts of vitamin A. Provide a variety of foods for your children, and if in doubt, check with a pediatrician or Registered Dietitian. Table 1: Vitamin facts. Physiological Functions

Vitamin A (retinol) (provitamin A, such as beta carotene)

Source Vitamin A: liver, vitamin A fortified milk and dairy products, butter, whole milk, cheese, egg yolk. Provitamin A: carrots, leafy green vegetables, sweet potatoes, pumpkins, winter squash, apricots, cantaloupe. Vitamin Dfortified dairy products, fortified margarine, fish oils, egg yolk. Synthesized by

Deficiency

Overconsumption Mild: nausea, irritability, blurred vision. Severe: growth retardation, enlargement of liver and spleen, loss of hair, bone pain, increased pressure in skull, skin changes.

Helps to form skin Mild: night and mucous blindness, membranes and keep diarrhea, them healthy, thus intestinal increasing resistance infections, to infections; impaired essential for night vision. vision; promotes Severe: bones and tooth inflammation of development. Beta eyes, carotene is an keratinization of antioxidant and may skin and eyes. protect against Blindness in cancer. children.

Promotes hardening of bones and teeth, increases the absorption of calcium.

Severe: rickets in children; osteomalacia in adults.

Mild: nausea, weight loss, irritability. Severe: mental and physical growth retardation, kidney damage, movement of calcium from bones

sunlight action on skin. E Vegetable oil, margarine, butter, shortening, green and leafy vegetables, wheat germ, whole grain products, nuts, egg yolk, liver. Protects vitamins A and C and fatty acids; prevents damage to cell membranes. Antioxidant. Almost impossible to produce without starvation; possible anemia in low birthweight infants.

into soft tissues.

Nontoxic under normal conditions. Severe: nausea, digestive tract disorders.

Dark green Helps blood to clot. leafy vegetables, liver; also made by bacteria in the intestine.

Excessive bleeding.

None reported.

Vitamin D Vitamin D plays a critical role in the bodys use of calcium and phosphorous. It increases the amount of calcium absorbed from the small intestine and helps form and maintain bones. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth. The primary food sources of vitamin D are milk and other dairy products fortified with vitamin D. Vitamin D is also found in oily fish (e.g., herring, salmon and sardines) as well as in cod liver oil. In addition to the vitamin D provided by food, we obtain vitamin D through our skin which makes vitamin D in response to sunlight. An Adequate Intake (AI) for has been established for vitamin D (see Table 2). The AIs for vitamin D appear as micrograms (mcg) of cholecalciferol. Ten mcg of cholecalciferol equals 400 International Units (IU). Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults is called osteomalacia, which results in muscular weakness and weak bones. These conditions are rare in the United States. The tolerable upper intake level for vitamin D is set at 50 mcg for people 1 year of age and older (see Table 3). High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning. Signs of vitamin D toxicity include excess calcium in the blood, slowed mental and physical growth, decreased appetite, nausea and vomiting. It is important that infants and young children do not consume excess amounts of vitamin D regularly. Children exposed to the sun for 5 to 10 minutes daily will produce enough vitamin

D. However, if children live in inner cities, wear clothes that cover most of their skin or live in northern climates where little sun is seen in the winter, then vitamin D deficiency may occur. Rather than give children a supplement, add fortified foods to their diet, such as vitamin D fortified milk and other dairy products. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension and infectiouse disease. In the absence of adequate sun exposure, at least 800 to 1,000 IU of Vitamin D3 may be needed to reach the circulating level required to maximize Vitamin Ds beneficial health effects. Table 2: Dietary Reference Intakes (DRI) for fat soluble vitamins. Life Vitamin Vitamin Vitamin Vitamin Vitamin Vitamin E (IU) Stage A A (IU) D D (IU) E (mg aGroup (mcg1) (mcg2) TE3) Infants 0.0-0.5 400* 0.5-1.0 500* Children 1-3 4-8 Males 9-13 300 400 600 1333 1666 1000 1333 2000 3000 3000 3000 3000 3000 2000 2333 2333 2333 2333 2333 2500 5* 5* 5* 5* 5* 5* 5* 5* 10* 15* 5* 5* 5* 5* 10* 15* 5* 200 200 200 200 200 200 200 200 400 600 200 200 200 200 400 600 200 4* 5* 6 7 11 15 15 15 15 15 11 15 15 15 15 15 15 6 7.5 9 10.5 16.5 22.5 22.5 22.5 22.5 22.5 16.5 22.5 22.5 22.5 22.5 22.5 22.5

14-18 900 19-30 900 31-50 900 51-70 900 71+ Females 9-13 900 600

14-18 700 19-30 700 31-50 700 51-70 700 71+ Pregnant <18 700 750

19-30 770 31-50 770 Lactating <18 1,300

2566

5* 5*

200 200 200 200 200

15 15 19 19 19

22.5 22.5 28.8 28.8 28.8

4000 4333 4333

5* 5* 5*

19-30 1,300 31-50 1,300

*Indicates an Adequate Intake (AI). All other values are Recommended Dietary Allowance (RDA). 1 As retinol activity equivalents (RAEs). 1 RAE = 1mcg retinol or 12 mcg beta-carotene. 2 As cholecalciferol. 10 mcg cholecalciferol = 400 IU of vitamin D. 3 As alpha-tocopherol equivalents. 1 mg of alpha-tocopherol = 1.5 IU of vitamin E. Vitamin E Vitamin E acts as an antioxidant, protecting vitamins A and C, red blood cells and essential fatty acids from destruction. Research from a decade ago suggested that taking antioxidant supplements, vitamin E in particular, might help prevent heart disease and cancer. However, newer findings indicate that people who take antioxidant supplements are not better protected against heart disease and cancer than non-supplement users. On the other hand, there are many studies that show a link between regularly eating antioxidant-rich fruits and vegetables and a lower risk for heart disease, cancer and several other diseases. The RDA for vitamin E is based on the most active and usable form called alpha-tocopherol (see Table 2). One milligram of alpha-tocopherol equals to 1.5 International Units (IU).About 60 percent of vitamin E in the diet comes from vegetable oil or products made with vegetable oils. Therefore, good food sources of vitamin E include vegetable oils and margarines. Vitamin E is also found in fruits and vegetables, grains, nuts, seeds and fortified cereals. Vitamin E deficiency is rare. Cases of vitamin E deficiency only occur in premature infants and people unable to absorb fats. The tolerable upper intake levels for vitamin E are shown in Table 3. Large doses of vitamin E pose a hazard to people who take blood-thinning medications. People taking statin drugs are also not advised to take supplemental vitamin E because it may interfere with how the medication works. Vitamin K Naturally produced by the bacteria in the intestines, vitamin K plays an essential role in normal blood clotting and helps promote bone health. Good food sources of vitamin K are green vegetables such as turnip greens, spinach, cauliflower, cabbage and broccoli, and certain vegetables oils including soybean oil, cottonseed oil, canola oil and olive oil. Animal foods, in general, contain limited amounts of vitamin K.

To help ensure people receive sufficient amounts of vitamin K, an Adequate Intake (AI) has been established for each age group (see Table 2). Without sufficient amounts of vitamin K, hemorrhaging can occur. Deficiencies may appear in infants, or in people who take anticoagulants or antibiotic drugs. Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week. People on anticoagulant drugs (blood thinners) may become deficient in vitamin K, but should not change their vitamin K intake without consulting a physician because the effectiveness of the drug may be affected. People taking antibiotics may lack vitamin K temporarily because intestinal bacteria are sometimes killed as a result of long-term use of antibiotics. Also, people with chronic diarrhea may have problems absorbing sufficient amounts of vitamin K through the intestine and should consult their physician to determine if supplementation is necessary. Although a tolerable upper intake level has not been established for vitamin K, excessive amounts can cause the breakdown of red blood cells and liver damage. Large doses are not advised. Table 3. Tolerable upper intake levels (UL)*. Life Stage Vitamin A Vitamin D Vitamin Group (mcg) (mcg) (mg a-TE) Infants 0.0-0.5 0.5-1.0 Children 1-3 4-8 Males/Females 9-13 14-18 19-70 >71 Pregnant Lactating & <18 19-50 600 600 600 900 1,700 2,800 3,000 3,000 2,800 3,000 25 25 50 50 50 50 50 50 50 50 ND1 ND 200 300 600 800 1,000 1,000 800 1,000 not established. E

*A UL for vitamin K was 1 ND = not determinable due to insufficient data. Standards for Measuring Intake

Vitamin requirements are expressed in small units. Most are given in milligrams (mg) or micrograms (mcg). When comparing vitamin amounts on labels, note whether values are in micrograms (mcg), milligrams (mg) or International Units (IU). Make sure you compare the same units. Dietary Reference Intakes (DRI) are dietary standards for desirable and/or safe vitamin intake levels published by the Food and Nutrition Board of the National Academy of Sciences National Research Council. DRIs include three sets of values: recommended dietary allowances (referred to as RDAs) which are intended to meet the nutrient needs of healthy individuals; tolerable upper intake levels (UL) which are designed to help people avoid harmful effects caused by consuming too much of a nutrient; and adequate intakes (AI), which are established when there is not enough scientific evidence to set an RDA and are based on diets known to be nutritionally adequate for U.S. and Canadian populations. Table 2 lists the recommended amounts of fat-soluble vitamins that individuals in the United States need daily for good health. Table 3 provides the tolerable upper intake levels.

(viii) Classify the connective tissue. Describe the functional characteristic of connective tissue. "Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues (the others being epithelial, muscle, and nervous tissue). Connective Tissue (CT) is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of the body and act as an entity. CT has 3 main components; cells, fibers, and extracellular matrix, all embedded in the body fluids. Fibroblasts are the cells responsible for the production of connective tissue. The interaction of the fibers, the extracellular matrix and the water together, form the pliable connective tissue as a whole. Connective tissue makes up a variety of physical structures including, tendons and the connective framework of fibers in muscles, capsules and ligaments around joints, cartilage, bone, adipose tissue, blood and lymphatic tissue. CT is classified into three subtypes; Embryonic CT, Proper CT, and Special CT. The Proper CT subtype include dense regular CT, dense irregular CT, and loose CT. The Special CT subtype includes cartilage, bone, adipose tissue, blood, hematopoietic tissue (tissue that makes blood cells) and lymphatic tissue. and the most abundant protein in mammals, making up about 25% of the total protein content.

Functions of connective tissue

Storage of energy Protection of organs Providing structural framework for the body Connection of body tissues

Section C
3. Attempt Any Four Questions: (i) Write a detail description on Blood coagulation.

Blood Coagulation The ability of the body to control the flow of blood following vascular injury is paramount to continued survival. The process of blood clotting and then the subsequent dissolution of the clot, following repair of the injured tissue, is termed hemostasis. Hemostasis, composed of 4 major events that occur in a set order following the loss of vascular integrity: 1. The initial phase of the process is vascular constriction. This limits the flow of blood to the area of injury. 2. Next, platelets become activated by thrombin and aggregate at the site of injury, forming a temporary, loose platelet plug. The protein fibrinogen is primarily responsible for stimulating platelet clumping. Platelets clump by binding to collagen that becomes exposed following rupture of the endothelial lining of vessels. Upon activation, platelets release the nucleotide, ADP and the eicosanoid, TXA2 (both of which activate additional platelets), serotonin, phospholipids, lipoproteins, and other proteins important for the coagulation cascade. In addition to induced secretion, activated platelets change their shape to accommodate the formation of the plug. 3. To insure stability of the initially loose platelet plug, a fibrin mesh (also called the clot) forms and entraps the plug. If the plug contains only platelets it is termed a white thrombus; if red blood cells are present it is called ared thrombus 4. Finally, the clot must be dissolved in order for normal blood flow to resume following tissue repair. The dissolution of the clot occurs through the action of plasmin Two pathways lead to the formation of a fibrin clot: the intrinsic and extrinsic pathway. Although they are initiated by distinct mechanisms, the two converge on a common pathway that leads to clot formation. Both pathways are complex and involve numerous different proteins termed clotting factors. Fibrin clot formation in response to tissue injury is the most clinically relevant event of hemostasis under normal physiological conditions. This process is the result of the activation of the extrinsic pathway. The formation of a red thrombus or a clot in response to an abnormal vessel wall in the absence of tissue injury is the result of the intrinsic pathway. The intrinsic pathway has low significance under normal physiological conditions. Most significant clinically is the activation of the intrinsic pathway by contact of the vessel wall with lipoprotein particles, VLDLs and chylomicrons. This process clearly demonstrates the role of hyperlipidemia in the generation of atherosclerosis. The intrinsic pathway can also be activated by vessel wall contact with bacteria. Platelet Activation and von Willebrand Factor (vWF) In order for hemostasis to occur, platelets must adhere to exposed collagen, release the contents of their granules, and aggregate. The adhesion of platelets to the collagen exposed on endothelial cell surfaces is mediated by von Willebrand factor (vWF). Inherited deficiencies of vWF are the causes of von Willebrand disease, (vWD) (also see below for more details). The function of vWF is to act as a bridge between a specific glycoprotein complex on the surface of platelets (GPIb-GPIX-GPV) and collagen fibrils. The GPIb part of the complex is composed of two proteins, GPIb and GPIb encoded by separate genes. The importance of this interaction between vWF and the GPIb-GPIX-GPV complex of platelets is demonstrated by the inheritance of bleeding disorders caused by defects in three of the four proteins of the complex, the most common of which is Bernard-Soulier syndrome (also called giant platelet syndrome).

In addition to its role as a bridge between platelets and exposed collagen on endothelial surfaces, vWF binds to and stabilizes coagulation factor VIII. Binding of factor VIII by vWF is required for normal survival of factor VIII in the circulation. von Willebrand factor is a complex multimeric glycoprotein that is produced by and stored in the -granules of platelets. It is also synthesized by megakaryocytes and found associated with subendothelial connective tissue. The initial activation of platelets is induced by thrombin binding to specific receptors on the surface of platelets, thereby initiating a signal transduction cascade. The thrombin receptor is coupled to a G-protein that, in turn, activates phospholipase C- (PLC-). PLC hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) leading to the formation of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces the release of intracellular Ca2+ stores, and DAG activates protein kinase C (PKC). The collagen to which platelets adhere as well as the release of intracellular Ca2+ leads to the activation of phospholipase A2 (PLA2), which then hydrolyzes membrane phospholipids, leading to liberation of arachidonic acid. The arachidonic acid release leads to an increase in the production and subsequent release of thromboxane A2(TXA2). TXA2 is a potent vasoconstrictor and inducer of platelet aggregation that functions by binding to receptors that function through the PLC- pathway. Another enzyme activated by the released intracellular Ca2+ stores is myosin light chain kinase (MLCK). Activated MLCK phosphorylates the light chain of myosin which then interacts with actin, resulting in altered platelet morphology and motility. One of the many effects of PKC is the phosphorylation and activation of a specific 47,000Dalton platelet protein. This activated protein induces the release of platelet granule contents; one of which is ADP. ADP further stimulates platelets increasing the overall activation cascade. The important role of ADP in platelet activation can be appreciated from the use of the ADP receptor antagonist, Plavix (clopidogrel), in the control of thrombosis (see below). ADP also modifies the platelet membranes leading to exposure platelet glycoprotein receptor complex: GPIIb-GPIIIa. GPIIb-GPIIIa constitutes a receptor for vWF and fibrinogen, resulting in fibrinogen-induced platelet aggregation. The GPIIbGPIIIa complex is a member of the integrin family of cell-surface receptors that interact with the extracellular matrix. The GPIIb-GPIIIa complex is also called integrin IIb-3. The importance of the GPIIb-GPIIIa in platelet activation and coagulation is demonstrated by the fact that bleeding disorders result from inherited defects in this glycoprotein complex. The most commonly inherited platelet dysfunction is Glanzmann thrombasthenia which results from defects in the GPIIb protein of this complex. In addition, the importance of this complex in overall hemostasis is demonstrated by the use of antibodies that block this receptor as anti-coagulants (e.g. ReoPro, abciximab: see below). Activation of platelets is required for their consequent aggregation to a platelet plug. However, equally significant is the role of activated platelet surface phospholipids in the activation of the coagulation cascade.

Primary Factors Factor Prekallikrein (PK) Trivial Name(s) Fletcher factor Pathway Characteristic Intrinsic Functions with HMWK and factor XII

Co-factor in kallikrein and factor XII High molecular contact activation cofactor; activation, necessary in factor XIIa weight Fitzgerald, Flaujeac Intrinsic activation of XI, precursor for kininogen bradykinin (a potent vasodilator and Williams factor (HMWK) inducer of smooth muscle contraction I II III IV V Fibrinogen Prothrombin Tissue Factor Calcium Both Both Extrinsic Both Protein cofactor This is Va, redundant to Factor V Contains N-term. gla segment

Proaccelerin, labile factor, Both accelerator (Ac-) globulin Both

VI (same as Va) Accelerin

VII

Proconvertin, serum prothrombin conversion Extrinsic Endopeptidase with gla residues accelerator (SPCA), cothromboplastin Antihemophiliac factor A, antihemophilic globulin Intrinsic Protein cofactor (AHG) Christmas Factor, antihemophilic factor Intrinsic Endopeptidase with gla residues B,plasma thromboplastin component (PTC) Stuart-Prower Factor Both Endopeptidase with gla residues

VIII

IX

X XI XII XIII

Plasma thromboplastin Intrinsic Endopeptidase antecedent (PTA) Hageman Factor Intrinsic Endopeptidase Transpeptidase

Protransglutaminase, fibrin stabilizing factor (FSF), Both fibrinoligase

Functional Classification of Clotting Factors Zymogens Proteases Factor XII Factor XI Factor IX Factor VII Factor X Factor II Cofactors Factor VIII Factor V Factor III (tissue factor) Fibrinogen Factor I Transglutaminase Factor XIII Regulatory/Other Proteins von Willebrand factor Protein C Protein S Thrombomodulin of Serine Activities binds to exposed collagen at site of vessel wall injury, activated by high-MW kininogen and kallikrein activated by factor XIIa activated by factor XIa in presence of Ca2+ activated by thrombin in presence of Ca2+ activated on surface of activated platelets by tenase complex and by factor VIIa in presence of tissue factor and Ca2+ activated on surface of activated platelets by prothrombinase complex Activities activated by thrombin; factor VIIIa is a cofactor in the activation of factor X by factor IXa activated by thrombin; factor Va is a cofactor in the activation of prothrombin by factor Xa a subendothelial cell-surface glycoprotein that acts as a cofactor for factor VII Activity cleaved by thrombin to form fibrin clot Activity activated by thrombin in presence of Ca2+; stabilizes fibrin clot by covalent cross-linking Activities associated with subendothelial connective tissue; serves as a bridge between platelet glycoprotein GPIb/IX and collagen activated to protein Ca by thrombin bound to thrombomodulin; then degrades factors VIIIa and Va acts as a cofactor of protein C; both proteins contain gla residues protein on the surface of endothelial cells; binds thrombin, which

then activates protein C Antithrombin III most important coagulation inhibitor, controls activities of thrombin, and factors IXa, Xa, XIa and XIIa

The Clotting Cascades

The clotting cascades: The intrinsic cascade (which has less in vivo significance in normal physiological circumstances than the extrinsic cascade) is initiated when contact is made between blood and exposed negatively charged surfaces. The extrinsic pathway is initiated upon vascular injury which leads to exposure of tissue factor, TF (also identified as factor III), a subendothelial cell-surface glycoprotein that binds phospholipid. The green dotted arrow represents a point of cross-over between the extrinsic and intrinsic pathways. The two pathways converge at the activation of factor X to Xa. Factor Xa has a role in the further activation of factor VII to VIIa as depicted by the green arrow. Active factor Xa hydrolyzes and activates prothrombin to thrombin. Thrombin can then activate factors XI, VIII and V furthering the cascade. Ultimately the role of thrombin is to convert fribrinogen to fibrin and to activate factor XIII to XIIIa. Factor XIIIa (also termed transglutaminase) cross-links fibrin polymers solidifying the clot. HMWK = high molecular weight kininogen. PK = prekallikrein. PL = phospholipid. Activation of Prothrombin to Thrombin The common point in both pathways is the activation of factor X to factor Xa. Factor Xa activates prothrombin (factor II) to thrombin (factor IIa). Thrombin, in turn, converts

fibrinogen to fibrin. The activation of thrombin occurs on the surface of activated platelets and requires formation of a prothrombinase complex. This complex is composed of the platelet phospholipids, phosphatidylinositol and phosphatidylserine, Ca2+, factors Va and Xa, and prothrombin. Factor V is a cofactor in the formation of the prothrombinase complex, similar to the role of factor VIII in tenase complex formation. Like factor VIII activation, factor V is activated to factor Va by means of minute amounts and is inactivated by increased levels of thrombin. Factor Va binds to specific receptors on the surfaces of activated platelets and forms a complex with prothrombin and factor Xa. Prothrombin is a 72,000-Dalton, single-chain protein containing ten gla residues in its N-terminal region. Within the prothrombinase complex, prothrombin is cleaved at 2 sites by factor Xa. This cleavage generates a 2-chain active thrombin molecule containing an A and a B chain which are held together by a single disulfide bond. In addition to its role in activation of fibrin clot formation, thrombin plays an important regulatory role in coagulation. Thrombin combines with thrombomodulin present on endothelial cell surfaces forming a complex that converts protein C to protein Ca. The cofactor protein S and protein Ca degrade factors Va and VIIIa, thereby limiting the activity of these 2 factors in the coagulation cascade (see details below). Thrombin also binds to a class of G-protein-coupled receptors called protease activated receptors (PARs), specifically PAR-1, -3 and -4. PARs utilize a unique mechanism to convert the result of extracellular proteolytic cleavage into an intracellular signaling event. PARs carry their own ligand which remains inactive until protease cleavage, such as by thrombin, "unmasks" the ligand. Following thrombin cleavage the unmasked ligand is still a part of the intact PAR but is now capable of interacting with the ligand-binding domain of the PAR resulting in the activation of numerous signaling cascades. Because the activation of PARs requires proteolytic cleavage the activation process is irreversible. The signaling cascades activated by thrombin-activated PARs include release of the interleukins, (ILs), IL-1 and IL-6, increased secretion of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The thrombin-induced signaling also leads to increased platelet activation and leukocyte adhesion. Thrombin also activates thrombin-activatable fibrinolysis inhibitor (TAFI) thus modulating fibrinolysis (degradation of fibrin clots). TAFI is also known as carboxypeptidase U (CPU) whose activity leads to removal of C-terminal lysines from partially degraded fibrin. This leads to an impairment of plasminogen activation, thereby reducing the rate of fibrin clot dissolution (i.e. fibrinolysis). Control of Thrombin Levels The inability of the body to control the circulating level of active thrombin would lead to dire consequences. There are 2 principal mechanisms by which thrombin activity is regulated. The predominant form of thrombin in the circulation is the inactive prothrombin, whose activation requires the pathways of proenzyme activation described above for the coagulation cascade. At each step in the cascade, feedback mechanisms regulate the balance between active and inactive enzymes. The activation of thrombin is also regulated by 4 specific thrombin inhibitors Antithrombin III is the most important since it can also inhibit the activities of factors IXa, Xa, XIa and XIIa, plasmin, and kallikrein. The activity of antithrombin III is potentiated in the presence of heparin by the following means: heparin binds to a specific site on antithrombin III, producing an altered conformation of the protein, and the new

conformation has a higher affinity for thrombin as well as its other substrates. This effect of heparin is the basis for its clinical use as an anticoagulant. The naturally occurring heparin activator of antithrombin III is present as heparan and heparan sulfate on the surface of vessel endothelial cells. It is this feature that controls the activation of the intrinsic coagulation cascade. However, thrombin activity is also inhibited by 2-macroglobulin, heparin cofactor II and 1-antitrypsin. Although a minor player in thrombin regulation 1-antitrypsin is the primary serine protease inhibitor of human plasma. Its physiological significance is demonstrated by the fact that lack of this protein plays a causative role in the development of emphysema. Activation of Fibrinogen to Fibrin Fibrinogen (factor I) consists of 3 pairs of polypeptides ([A][B][])2. The 6 chains are covalently linked near their N-terminals through disulfide bonds. The A and B portions of the A and B chains comprise the fibrinopeptides, A and B, respectively. The fibrinopeptide regions of fibrinogen contain several glutamate and aspartate residues imparting a high negative charge to this region and aid in the solubility of fibrinogen in plasma. Active thrombin is a serine protease that hydrolyses fibrinogen at four arg-gly (RG) bonds between the fibrinopeptide and the a and bportions of the protein. Thrombin-mediated release of the fibrinopeptides generates fibrin monomers with a subunit structure ()2. These monomers spontaneously aggregate in a regular array, forming a somewhat weak fibrin clot. In addition to fibrin activation, thrombin converts factor XIII to factor XIIIa, a highly specific transglutaminase that introduces cross-links composed of covalent bonds between the amide nitrogen of glutamines and -amino group of lysines in the fibrin monomers. Dissolution of Fibrin Clots Degradation of fibrin clots is the function of plasmin, a serine protease that circulates as the inactive proenzyme, plasminogen. Any free circulating plasmin is rapidly inhibited by 2-antiplasmin. Plasminogen binds to both fibrinogen and fibrin, thereby being incorporated into a clot as it is formed. Tissue plasminogen activator (tPA) and, to a lesser degree, urokinase are serine proteases which convert plasminogen to plasmin. Inactive tPA is released from vascular endothelial cells following injury; it binds to fibrin and is consequently activated. Urokinase is produced as the precursor, prourokinase by epithelial cells lining excretory ducts. The role of urokinase is to activate the dissolution of fibrin clots that may be deposited in these ducts. Active tPA cleaves plasminogen to plasmin which then digests the fibrin; the result is soluble degradation product to which neither plasmin nor plasminogen can bind. Following the release of plasminogen and plasmin they are rapidly inactivated by their respective inhibitors. The inhibition of tPA activity results from binding to specific inhibitory proteins. At least 4 distinct inhibitors have been identified, of which 2: plasminogen activator-inhibitors type 1 (PAI-1) and type 2 (PAI-2) are of greatest physiological significance. Blood Coagulation Tests and Interpretations Bleeding time assays are used to evaluate the vascular and platelet responses that are associated with hemostasis. The bleeding time is a frequent assay performed on preoperative patients to ensure there is an adequate response to vessel injury prior to

surgery. As indicated above, the rapid responses to vascular injury (occurring within seconds) are vessel constriction and platelet adhesion to the vessel wall. The Ivy method for determining the bleeding time involves the use of a blood pressure cuff (sphygmomanometer) which is placed on the forearm and inflated to 40mmHg. A superficial incision is then made on the forearm and the time it takes for bleeding to stop is recorded. With the Ivy method bleeding should stop within 19 minutes. Any bleeding time greater than 15 minutes would be indicative of a defect in the initial responses of vessels and platelets to vascular injury. A less invasive bleeding time assay involves the use of a lancet or special needle and a 34mm deep prick is made on the fingertip or earlobe. This bleeding time assay is referred to as the Duke method and in this assay bleeding should cease within 13 minutes. The bleeding time is affected (prolonged) by any defect in platelet function, by vascular disorders, and in von Willebrand disease but is not affected by other coagulation factors. Disorders that are commonly associated with an increased bleeding time include thrombocytopenia, disseminated intravascular coagulation (DIC), Bernard-Soulier syndrome and Glanzmann thrombasthenia. Abnormal bleeding times are also found in patients with Cushing syndrome, severe liver disease, leukemia, and bone marrow failure. Defects associated with factors of the pathways of blood coagulation can also be assessed with specific assays. The prothrombin time (PT) is an assay designed to screen for defects in fibrinogen, prothrombin, and factors V, VII, and X and thus measures activities of the extrinsic pathway of coagulation. When any of these factors is deficient then the PT is prolonged. A normal PT is 11.012.5 seconds. A PT greater than 20 seconds is indicative of coagulation deficit. The PT is measured using plasma after the blood cells are removed. A blood sample is collected in a tube containing citrate or EDTA to chelate any calcium and thus inhibit coagulation and then the cells are removed by centrifugation. After the cells are removed excess calcium is added to the plasma to initiate coagulation. The most common measure of PT is to divide the time of coagulation of a patients blood by that of a known standard and this value is referred to as the international normalized ratio (INR). Normal INR values range from 0.81.2. PT is used to determine the correct dosage of the warfarin class of anti-coagulation drugs (e.g. Coumadin), for the presence of liver disease or damage, and to evaluate vitamin K status. The partial thromboplastin time (PTT) is used to assay for defects in the intrinsic pathway of coagulation. The PTT assay has been modified by the addition of activators that shorten the normal clotting time and this form of the assay is referred to as the activated partial thromboplastin time (aPTT). The PTT is normally prescribed in patients with unexplained bleeding or clotting. The assay will evaluate the function of fibrinogen, prothrombin, and factors V, VIII, IX, X, XI, and XII. A defect in any of these factors will result in a prolonged PTT (or aPTT). A normal PTT is 6070 seconds, whereas for the aPTT the normal range is 3040 seconds. The PTT is a standard assay used to assess the efficacy of heparin anticoagulant therapy. Prolonged PTTs are associated with acquired or congenital bleeding disorders associated with coagulation factor deficiency, vitamin K deficiency, liver disease, DIC, von Willebrand disease, leukemia, hemophilia, and during heparin administration. (ii) Define disease. Describe in detail Disease causing agents. A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs.[1] It may be caused by external factors, such as infectious disease, or it may be caused by

internal dysfunctions, such as autoimmune diseases. In humans, "disease" is often used more broadly to refer to any condition that causespain, dysfunction, distress, social problems, and/or death to the person afflicted, or similar problems for those in contact with the person. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories. Diseases usually affect people not only physically, but also emotionally, as contracting and living with many diseases can alter one's perspective on life, and their personality. Death due to disease is called death by natural causes. There are four main types of disease: pathogenic disease, deficiency disease, hereditary disease, and physiological disease. Diseases can also be classified as communicable and non-communicable disease. Disease The term disease broadly refers to any condition that impairs normal function. Commonly, this term is used to refer specifically to infectious diseases, which are clinically evident diseases that result from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular organisms, and aberrant proteins known as prions. An infection that does not and will not produce clinically evident impairment of normal functioning, such as the presence of the normal bacteria and yeasts in the gut, is not considered a disease; by contrast, an infection that is asymptomatic during its incubation period, but expected to produce symptoms later, is usually considered a disease. Non-infectious diseases are all other diseases, including most forms of cancer,heart disease, and genetic disease. Pathogens are organisms, frequently microorganisms, or components of these organisms, that cause disease. Microbial pathogens include various species of bacteria, viruses, and protozoa. Many diseases caused by microbialpathogens, and the frequency of these diseases, are a national security issue. Pathogens and disease. A disease is any condition caused by the presence of an invading organism or a toxic component that damages the host. In humans, diseases can be caused by the growth of microorganisms such as bacteria, viruses, and protozoa. Bacterial growth, however, is not mandatory to cause disease. For example, some bacterial pathogens cause disease by virtue of a toxic component of the bacterial cell such as lipopolysaccharide. Finally, the damaging symptoms of a disease can be the result of the attempts by the host's immune system to rid the body of the invader. One example is the immune-related damage caused to the lungs of those afflicted withcystic fibrosis, as the body unsuccessfully attempts to eradicate the chronic infections caused by Pseudomonas aeruginosa. Not all pathogens cause diseases that have the same severity of symptoms. For example, an infection with theinfluenza virus can cause the short term aches and fever that are hallmarks of the flu, or it can cause more dire symptoms, depending on the type of virus that causes the infection. Bacteria also vary in the damage caused. For example, the ingestion of food contaminated with Salmonella enteritica causes intestinal upset. But, consumption of Escherichia coli O157:H7 causes a severe disease, which can permanently damage the kidneys and which can even be fatal. Types of bacterial pathogens. There are three categories of bacterial pathogens. Obligat pathogens are those bacteria that must cause disease in order to be transmitted from one

host to another. These bacteria must also infect a host in order to survive, in contrast to other bacteria that are capable of survival outside of a host. Examples of obligate bacterial pathogens include Mycobacterium tuberculosis and Treponema pallidum. Opportunistic pathogens can be transmitted from one host to another without having to cause disease. However, in a host whose immune system is not functioning properly, the bacteria can cause an infection that leads to a disease. In those cases, the disease can help the bacteria spread to another host. Examples of opportunisticbacterial pathogens include Vibrio cholerae and Pseudomonas aeruginosa. Finally, some bacterial pathogens cause disease only accidentally. Indeed, the disease actually limits the spread of the bacteria to another host. Examples of these "accidental' pathogens include Neisseria meningitides andBacteroides fragilis. Spread of pathogens. Pathogens can be spread from person to person in a number of ways. Not all pathogens use all the available routes. For example, the influenza virus is transmitted from person to person through the air, typically via sneezing or coughing. But the virus is not transmitted via water. In contrast, Escherichia coli is readily transmitted via water, food, and blood, but is not readily transmitted via air or the bite of an insect. While routes of transmission vary for different pathogens, a given pathogen will use a given route of transmission. This has been used in the weaponization of pathogens. The best-known example is anthrax. The bacterium that causes anthraxBacillus anthracis can form an environmentally hardy form called a spore. The spore is very small and light. It can float on currents of air and can be breathed into the lungs, where the bacteria resume growth and swiftly cause a serious and often fatal form of anthrax. As demonstrated in the United States in the last few months of 2001, anthrax spores are easily sent through the mail to targets. As well, the powdery spores can be released from an aircraft. Over a major urban center, modeling studies have indicated that the resulting casualties could number in the hundreds of thousands. Contamination of water by pathogens is another insidious route of disease spread. Water can look crystal clear despite the presence of millions of bacteria in each milliliter. Viruses, which are much smaller, can be present in even higher numbers without affecting the appearance of the liquid. Thus, water can be easily laced with enough pathogens to cause illness. Food-borne pathogens cause millions of cases of disease and hundreds of deaths each year in the United States alone. Frequently the responsible microbes are bacteria, viruses, or protozoa that usually reside in the intestinal tract of humans or other creatures. Examples of such microorganisms include Escherichia coli O157:H7, Campylobacter jejuni, and rotavirus. Pathogens can be transmitted to humans through contact with animals, birds, and other living creatures that naturally harbor the microorganism. The agent of anthraxBacillus anthracisnaturally dwells in sheep. Other examples include Brucella abortic (Brucellosis), Coxiella burnetti (Q fever), and viruses that cause hemorrhagic feverssuch as Ebola and Marburg. Pathogenic mechanisms. Microorganisms have various strategies to establish an infection in a host. Some micro-organisms recognize molecules on the surface of the host cell, and use these as receptors. The binding of bacteria or viruses to receptors brings the microorganism in close contact with the host surface.

The nature of the interaction between the host receptor molecule and the attachment molecule on the surface of the bacteria, virus, or protozoan has in some cases been defined, even to the genetic level. The use of recombinant DNA technologywhere a target section of genetic material is removed from one organism and inserted into a certain region of the genetic material of another organism, in a way that does not affect the expression of the geneallows the genetic manipulation of a microorganism so as to enhance its ability to cause an infection. Alternatively, inserting a gene that codes for a toxin into a bacterium that is a normal inhabitant of an environment like the intestinal tract could produce a formidable pathogen. This altered bacteria would readily associate with host cells, but would also carry the toxin. Viruses almost always damage the host cells. Because viruses cannot reproduce on their own, they rely on thereplication mechanism of the host cell to make more copies of themselves (i.e., they are obligate pathogens). Then, the new viral particles will exit the cell and search for another cell to infect. This exit is often very physically damaging to the host cell. Thus, viral infections can be detrimental because of the loss of function of host cells. Some viral pathogens are capable of causing a disease long after they have infected a host. This delayed response occurs because the viral genetic material becomes incorporated into the genetic material of the host. Thereafter, the viral genetic material is replicated along with that of the host, using the replication enzymes and other machinery of the host. But, in response to a number of signals, the viral material can be excised from the host material and form the template for the manufacture and assembly of new virus particles. A prominent example of such a virus is theHuman Immunodeficiency Virus, which is acknowledged to be the cause of Acquired Immunodeficiency Syndrome. Because viruses must infect other cells in order to replicate, they have developed means of escaping (at least for a time) the defensive responses of the host. This efficiency of attack has not escaped the attention of molecular biologists bent on the malicious use of viruses. By inserting gene coding for a toxic compound into a viral genome, particularly into the genome of an infectious virus (i.e., influenza or cold viruses) the virus becomes a bioweapon. For example, scientists in the former Soviet Union attempted to construct an influenza virus that contained the gene coding for cobra toxin. (iii)Draw a neat labeled diagram of skeletal muscle. Give the anatomy and physiology of skeletal muscle. Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle. As their name suggests, most skeletal muscles are attached to bones by bundles of collagen fibers known as tendons. Skeletal muscle is made up of individual components known as muscle fibers. These fibers are formed from the fusion of developmental myoblasts (a type of embryonic progenitor cell that gives rise to a muscle cell). The muscle fibers are long, cylindrical, multinucleated cells composed of myofibrils. The myofibrils are composed of actin and myosin myofibrils repeated as a sarcomere, the basic functional unit of the muscle fiber and responsible for skeletal muscle's striated appearance and forming the basic machinery necessary for muscle contraction. The term muscle refers to multiple bundles of muscle fibers held together by connective tissue.

Anatomy and Physiology of Skeletal Muscle

The human body has three types of muscles: Skeletal, smooth, and cardiac. Because Sports Massage Therapists are mainly concerned with skeletal muscles, they will be the ones primarily discussed throughout this text. Skeletal muscles are primarily attached to the bones of the body and, unlike smooth and cardiac muscles, are under voluntary control. They comprise most of the flesh of the body and constitute about 40% to 50% of a persons total body weight. Skeletal muscles perform the following functions: Produce movement of joints by contracting. Prevent undesired movement of joints. Produce heat (through during contraction.) the splitting of Adenosine Triphosphate (ATP)

Skeletal muscle is comprised of long cylindrical multinucleate cells which lie parallel to each other. Each cell is surrounded by a thin elastic membrane called the sarcolemmawhich encloses its contents. Within the membrane is the fluid protoplasm, or thesarcoplasm, of the cell which contains myofibrils (discussed later in this text) and thesarcoplasmic reticulum, comprised of a network of small channels and fluid-filled sacs. Skeletal muscle cells are also called fibers. Overlaying the sarcolemma of each fiber is a thin layer of connective tissue called the endomysium. The fibers are grouped together into many individual bundles which are covered with a layer of connective tissue called theperimysium. These bundles are known as fascicles and together they form a muscle. The entire muscle is covered by yet another thin layer of connective tissue called theepimysium, which itself is covered by connective tissue called fascia. These last two protective layers are tapered at the ends and form the tendons which attach a muscle to bone, cartilage or connective tissue. Each individual muscle fiber contains very fine, long protein strands called myofibrils, which are aligned side-by-side and extend the length of the fiber. They are the units which lengthen and contract the muscle. The myofibrils are "actually chains of tiny contractile units, called sarcomeres, which are aligned end-to-end like boxcars in a train along the length of the myofibrils." The Sarcomeres are formed by even finer strands known asmyofilaments. The myofilaments are comprised of proteins which form dark thick

strandsA bandsand light thin strandsI bandsand are what give skeletal muscle its striated appearance. The I bands are also called actin filaments because they are primarily made of a protein called actin, but they also contain two other proteinstroponin and tropomyosin. The A bands are also known as myosin filaments because they are formed from a protein called myosin; they contain ATPase enzymes which split ATP to produce the energy for muscle contraction. The myosin filaments contain "lollipop" projections, referred to as crossbridges or myosin heads, which spiral around its length. During muscle contraction, these projections attach to binding (active) sites on actin filaments to produce movement. In resting muscle, the troponin and tropomyosin cover the active sites and inhibit the myosin heads from bonding to the actin filaments, thereby preventing muscle contraction. Skeletal muscle is stimulated to contract by impulses transmitted by specialized nerve cells called motor neurons. The cell body of a motor neuron resides in the central nervous system and its axon extends to the muscle. In the muscle, the axon is divided into numerous axonal terminals, each of which connects with individual muscle fibers. The intersection where the axonal terminals and muscle fibers connect is called theneuromuscular junction. A motor neuron and the muscle fibers to which it connects are together known as a motor unit. When an action potential travels down the muscle fiber membrane and reaches the axonal terminals, the neurotransmitter known as acetylcholine stimulates the release of calcium ions into the sarcoplasm from the sarcoplasmic reticulum. Calcium ions quickly attach to troponin in the actin filaments, which causes troponin to pull on the tropomyosin (to which troponin is attached) thereby exposing the active sites of the actin filament and allowing it to interact with the myosin heads. As a result, the ATPaze enzymes on the myosin heads become activated and split ATP, which energizes the link between the actin and myosin filaments and causes muscle contraction. Once a muscle has contracted, calcium is reabsorbed back into the sarcoplasmic reticulum, which allows troponin and tropomyosin to once again inhibit the link between actin and mysoin. As a result, the muscle once again returns to a relaxed state. Although it is not known precisely how actin and myosin produce muscle contractions, the "sliding filament theory" proposed by H. E. Huxley in the 1950s is a possible explanation: (The theory) suggests that stimulation of the (muscle) fiber prompts the tiny crossbridges that extend from the myosin filament (to) attach to active sites on the actin filament. The release of calcium ions within the muscle fiber exposes these active sites, facilitating the attachment of the two (filaments) to one another. Each crossbridge exerts a pull on the actin filament, causing the actin and myosin filaments to slide past one another. Under the influence of (ATP) released in the binding process, each crossbridge is then disconnected from its binding site on the actin filament and moves to a neighboring site. Since the process happens simultaneously in all of the cells of a muscle, the entire muscle contracts. As healthcare professionals, Therapeutic & Sports Massage therapists need to be as educated and knowledgeable about the workings of the human neuromuscular and skeletal systems as possible. Not only does knowledge help us facilitate our clients recovery process from myofascial pain and dysfunction, it also enables us to better educate those clients as to the injury and recovery process. Additionally, the massage therapy professions image has been marred by those in the "adult entertainment" field. In our struggle to regain societys recognition of massage therapists as healthcare professionals, it is imperative that we continuously strive to increase our knowledge base of the

workings of the human body. (iv) Comment on Neuromuscular Junction in detail. A neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract. In vertebrates, the signal passes through the neuromuscular junction via the neurotransmitter acetylcholine. Mechanism of action The neuromuscular junction is the location where the neuron activates muscle to contract. This is a step in the excitation-contraction coupling of skeletal muscle. 1. Upon the arrival of an action potential at the presynaptic neuron terminal, voltagedependent calcium channels open and Ca2+ ions flow from theextracellular fluid into the presynaptic neuron's cytosol. 2. This influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron's cell membrane through SNAREproteins. 3. Fusion of the vesicular membrane with the presynaptic cell membrane results in the emptying of the vesicle's contents (acetylcholine) into thesynaptic cleft, a process known as exocytosis. 4. Acetylcholine diffuses into the synaptic cleft and binds to the nicotinic acetylcholine receptors bound to the motor end plate. 5. These receptors are ligand-gated ion channels, and when they bind acetylcholine, they open, allowing sodium ions to flow in and potassium ions to flow out of the muscle's cytosol. 6. Because of the differences in electrochemical gradients across the plasma membrane, more sodium moves in than potassium out, producing a local depolarization of the motor end plate known as an end-plate potential (EPP). 7. This depolarization spreads across the surface of the muscle fiber and continues the excitation-contraction coupling to contract the muscle. 8. The action of acetylcholine is terminated when the enzyme acetylcholinesterase degrades part of the neurotransmitter (producing choline and anacetate group) and the rest of it diffuses away. 9. The choline produced by the action of acetylcholinesterase is recycled it is transported, through reuptake, back into the presynaptic terminal, where it is used to synthesize new acetylcholine molecules. Acetylcholine is a neurotransmitter synthesized in the human body from dietary choline and acetyl-CoA (ACoA). One of the first neurotransmitters discovered, the substance was originally referred to as "vagusstoff" because it was found to be released by the stimulation of the vagus nerve. Later, it was established that acetylcholine is, in fact, important in the stimulation of all muscle tissue and that its action may be either excitatory or inhibitory, depending on a number of factors. Within the body, the synaptic action of acetylcholine usually quickly comes to a halt, the neurotransmitter naturally breaking down soon after its release. However, some nerve gases are designed to thwart this breakdown, causing prolonged stimulation of the receptor cells and resulting in severe muscle spasms. Development of the neuromuscular junction

The complex series of steps leading to the formation of the neuromuscular junction during embryonic development are only partially understood. During development, the growing end of motor neuron axons secrete a protein known as agrin This protein binds to several receptors on the surface of skeletal muscle. The receptor which seems to be required for formation of the neuromuscular junction is the MuSK protein (Muscle specific kinase). MuSK is a receptor tyrosine kinase - meaning that it induces cellular signaling by causing the release of phosphate molecules to particular tyrosines on itself, and on proteins which bind the cytoplasmic domain of the receptor. Upon activation by its ligand agrin, MuSK signals via two proteins called "Dok-7" and "rapsyn", to induce "clustering" of acetylcholine receptors (AChR). In addition to the AChR and MuSK, other proteins are then gathered, to form the endplate to the neuromuscular junction. The nerve terminates onto the endplate, forming the NMJ. Knockout studies These findings were demonstrated in part by mouse "knockout" studies. In mice which are deficient for either agrin or MuSK, the neuromuscular junction does not form. Further, mice deficient in Dok-7did not form either acetylcholine receptor clusters or neuromuscular synapses. Many other proteins also comprise the NMJ, and are required to maintain its integrity. Neuromuscular block A block or decrease in the transmission across the neuromuscular junction can cause a complete or relative loss of muscle function. It can result from neuromuscular junction diseases or be intentionally induced with neuromuscular blocking drugs. It can also be a side effect of other drugs that are generally not classified as neuromuscular blocking drugs, such as some anesthetic drugs. The degree of neuromuscular block may be estimated by Bromage score, which originally had four grades designate with the Roman numerals I until IV, but later complemented by Breen et al with an inverse grading with Hindu-Arabic numerals: Bromage score Grade IV III II 1 2 3 4 5 I 6 Criteria Complete block, inability to move feet or knees Approximate degree of block 100%

Almost complete block, ability to move feet only, with inability 66% to flex knees Partial block, ability to flex knees Detectable weakness of hip flexion while supine, ability of full flexion of knees No detectable weakness of hip flexion while supine Free movement of legs and feet, ability to perform partial knee 0% bend 33%

In unconscious patients, such as during anesthesia, neural block can be assessed by a "trainof-four" by stimulating musclesfrom surface electrodes. (v) Give the detailed structure of bones of skull. The skull is a bony structure in the head of many animals that supports the structures of the face and forms a cavity for the brain. The skull is composed of two parts: the cranium and the mandible. A skull without a mandible is only a cranium. Animals that have skulls are calledcraniates. The skull is a part of the skeleton. Functions of the skull include protection of the brain, fixing the distance between the eyes to allow stereoscopic vision, and fixing the position of the ears to help the brain use auditory cues to judge direction and distance of sounds. In some animals, the skull also has a defensive function (e.g. hornedungulates); the frontal bone is where horns are mounted. The English word "skull" is probably derived from Old Norse "skalli" meaning bald, while the word cranium comes from the Greek root (kranion). In humans, as in other mammals, the aforementioned division of the skull into the cranium and mandible is not usually followed. Instead, for the purposes of describing their anatomy and enumerating their bones, mammalian and human skulls are divided differently: They are deemed to consist of two categorical parts: The neurocranium and the viscerocranium. The neurocranium (or braincase) is a protective vault surrounding the brain. The viscerocranium (alsosplanchnocranium or facial skeleton) is formed by the bones supporting the face. Both parts have different embryological origins. Except for the mandible, all of the bones of the skull are joined together by sutures, rigid articulations permitting very little movement.

frontal view

side view Feature Location Description the corner of the jaw where the mandible body turns upwards into the ramus of a ball-like end to the ramus of the mandible that forms a hinge with the temporal bone

angle of jaw or back of jaw mandible aveolar process condyle mandible coronal suture of top of ramus mandible

maxilla, root of teeth rugosities associated with tooth development

top of head between one of the major joints or sutures between the plates frontal and parietal of the frontal and parietal cranial bones cranial bones

between ramus of external acoustic a hole in the temporal cranial bone allowing the mandible and meatus passage of sound to enter the inner ear mastoid process ethmoid bone eye cavity a cranial bone forming part of the eye cavity a feature of the frontal bone that forms the "bumps" in the forehead above the eyebrows forehead boss or forehead frontal tuberosity frontal bone

top of face one of the major cranial bones that forms the (forehead) and front forehead and front top of the head; roughly covers top of head the frontal lobes of the brain center of forehead an area in the center of the forehead, between the eyebrows, that assumes various shapes on different individuals

glabella lacrimal bone lambdoid suture

inner corner of eye a small bone forming a cavity for the tear gland socket back of head suture or joint between the occipital and parietal cranial bones the lower jaw bone is the only skull bone that moves, i.e., during mastication, speech, and expression; carries the lower teeth

mandible or jaw lower part of jaw bone

maxilla

upper part of jaw

the two maxillae form the center of the face with many attaching muscles; carry the upper teeth; form part of the eye orbit; act like keystones into which the other facial bones fit

mastoid process mental protuberance mental tuberosities nasal bone nasal concha nasal spine occipital bone parietal bone ramus mandible sphenoid bone

lower part of built up area of the lower temporal bone where temporal bone, important neck muscles attach behind ramus of jaw chin boss chin boss nose nasal cavity center of nose a feature of the mandible at the lower front part of the chin which underlies part of the chin boss a dual bulbous formation of the mandible that underlies part of the chin boss forms the upper part of the nose and nasal bridge; the lower part of the bridge is formed of cartilage formations creating part of the nasal cavity feature of maxilla facial bone at center of nose to which septum is attached

the lower rear of the a major cranial bone at the lower back of the head; head covers occipital lobe of the brain a major cranial bone that froms part of the top, back, top and side of head and side of the head and roughly covers the parietal lobe of the brain of back part of the the more vertical part of the mandible mandible temple and eye orbit a cranial bone that forms part of the eye cavity area

side of head one of the major joints or sutures between the squamosal suture between parietal and parietal and temporal cranial bones temporal bones supraorbial foramen supraorbital process temporal bone upper orbit of eye a hole in the frontal bone where nerves and blood vessels pass through; forms a notch in the orbit of the eye a formation of the frontal bone above the orbit of the eye, under and above the eyebrows that affects the appearance of the eyebrows

eyebrows

a cranial bone on the side of the head that roughly side of the head, covers the temporal lobe of the brain; it extends above the ear down behind the ear towards the jaw front part of temple and lower part of lines in the frontal bone around the temple frontal bones nasal cavity cheek a facial bone on the centerline of the nose that forms part of the nasal cavity the principal cheek bone; origin of zygomatic and other facial muscles

temporal lines volmer zygomatic bone

zygomatic process

bones bordering the temporal and maxilla bones have areas next to zygomatic bone the zygomatic bone

(vi) Define Homeostasis. Explain about feedback system and their basic component. Homeostasis (from Greek: hmoios, "similar" and stsis, "standing still") is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH. It can be either an open or closed system. It was defined by Claude Bernard and later by Walter Bradford Cannon in 1926, 1929 and 1932. Typically used to refer to a living organism, the concept came from that of milieu interieur that was created by Claude Bernard and published in 1865. Multiple dynamic equilibrium adjustment and regulation mechanisms make homeostasis possible. Control mechanisms All homeostatic control mechanisms have at least three interdependent components for the variable being regulated: The receptor is the sensing component that monitors and responds to changes in the environment. When the receptor senses a stimulus, it sends information to a "control center", the component that sets the range at which a variable is maintained. The control center determines an appropriate response to the stimulus. In most homeostatic mechanisms, the control center is the brain. The control center then sends signals to an effector, which can be muscles, organs or other structures that receive signals from the control center. After receiving the signal, a change occurs to correct the deviation by either enhancing it with positive feedback or depressing it with negative feedback. Positive feedback

Positive feedback is a mechanism by which an output is enhanced, such as protein levels. However, in order to avoid any fluctuation in the protein level, the mechanism is inhibited stochastically (I), therefore when the concentration of the activated protein (A) is past the threshold ([I]), the loop mechanism is activated and the concentration of A increases exponentially if d[A]=k [A] Positive feedback mechanisms are designed to accelerate or enhance the output created by a stimulus that has already been activated. Unlike negative feedback mechanisms that initiate to maintain or regulate physiological functions within a set and narrow range, the positive feedback mechanisms are designed to push levels out of normal ranges. To achieve this purpose, a series of events initiates a cascading process that builds to increase the effect of the stimulus. This process can be beneficial but is rarely used by the body due to risks of the acceleration's becoming uncontrollable. One positive feedback example event in the body is blood platelet accumulation, which, in turn, causes blood clotting in response to a break or tear in the lining of blood vessels.

Another example is the release of oxytocin to intensify the contractions that take place during childbirth. Negative feedback Negative feedback mechanisms consist of reducing the output or activity of any organ or system back to its normal range of functioning. A good example of this is regulating blood pressure. Blood vessels can sense resistance of blood flow against the walls when blood pressure increases. The blood vessels act as the receptors and they relay this message to the brain. The brain then sends a message to the heart and blood vessels, both of which are the effectors. The heart rate would decrease as the blood vessels increase in diameter (known as vasodilation). This change would cause the blood pressure to fall back to its normal range. The opposite would happen when blood pressure decreases, and would cause vasoconstriction. Another important example is seen when the body is deprived of food. The body would then reset the metabolic set point to a lower than normal value. This would allow the body to continue to function, at a slower rate, even though the body is starving. Therefore, people who deprive themselves of food while trying to lose weight would find it easy to shed weight initially and much harder to lose more after. This is due to the body readjusting itself to a lower metabolic set point to allow the body to survive with its low supply of energy. Exercise can change this effect by increasing the metabolic demand. Another good example of negative feedback mechanism is temperature control. The hypothalamus, which monitors the body temperature, is capable of determining even the slightest variation of normal body temperature (37 degrees Celsius). Response to such variation could be stimulation of glands that produce sweat to reduce the temperature or signaling various muscles to shiver to increase body temperature. Both feedbacks are equally important for the healthy functioning of one's body. Complications can arise if any of the two feedbacks are affected or altered in any way. Homeostatic imbalance Many diseases are a result of disturbance of homeostasis, a condition known as homeostatic imbalance. As it ages, every organism will lose efficiency in its control systems. The inefficiencies gradually result in an unstable internal environment that increases the risk for illness. In addition, homeostatic imbalance is also responsible for the physical changes associated with aging. Even more serious than illness and other characteristics of aging is death. Heart failure has been seen where nominal negative feedback mechanisms become overwhelmed, and destructive positive feedback mechanisms then take over. Diseases that result from a homeostatic imbalance include diabetes, dehydration, hypoglycemia, hyperglycemia, gout, and any disease caused by a toxin present in the bloodstream. All of these conditions result from the presence of an increased amount of a particular substance. In ideal circumstances, homeostatic control mechanisms should prevent this imbalance from occurring, but, in some people, the mechanisms do not work efficiently enough or the quantity of the substance exceeds the levels at which it can be managed. In these cases, medical intervention is necessary to restore the balance, or permanent damage to the organs may result. According to the following quote, every illness has aspects to it that are a result of lost homeostasis: "Just as we live in a constantly changing world, so do the cells and tissues survive in a constantly changing microenvironment. The 'normal' or 'physiologic' state then is achieved by

adaptive responses to the ebb and flow of various stimuli permitting the cells and tissues to adapt and to live in harmony within their microenvironment. Thus, homeostasis is preserved. It is only when the stimuli become more severe, or the response of the organism breaks down, that disease results - a generalization as true for the whole organism as it is for the individual cell."