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

1) Theory Examination 2011-12 Anatomy and physiology and pathophysiology 1 Paper ID. 5026, 0517 1. (i) Write the composition of Plasma membrane. Composition Cell membranes contain a variety of biological molecules, notably lipids and pro teins. Material is incorporated into the membrane, or deleted from it, by a vari ety of mechanisms: Fusion of intracellular vesicles with the membrane (exocytosis) not only excrete s the contents of the vesicle but also incorporates the vesicle membrane's compo nents into the cell membrane. The membrane may form blebs around extracellular m aterial 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 (s table 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), pho sphatidylinositol(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 cel l, but in the majority of cases phospholipids are the most abundant.In RBC studi es, 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 conf iguration of the double bonds nearly always cis. The length and the degree of un saturation of fatty acid chains have a profound effect on membrane fluidity as u nsaturated lipids create a kink, preventing the fatty acids from packing togethe r 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. Und er physiological conditions phospholipid molecules in the cell membrane are in t he liquid crystalline state. It means the lipid molecules are free to diffuse an d exhibit rapid lateral diffusion along the layer in which they are present. How ever, the exchange of phospholipid molecules between intracellular and extracell ular leaflets of the bilayer is a very slow process. Lipid rafts and caveolae ar e examples of cholesterol-enriched microdomains in the cell membrane. In animal cells cholesterol is normally found dispersed in varying degrees throu ghout cell membranes, in the irregular spaces between the hydrophobic tails of t he membrane lipids, where it confers a stiffening and strengthening effect on th e membrane. Phospholipids forming lipid vesicles Lipid vesicles or lisosomes are circular pockets that are enclosed by a lipid bi layer. These structures are used in laboratories to study the effects of chemica ls in cells by delivering these chemicals directly to the cell, as well as getti ng more insight into cell membrane permeability. Lipid vesicles and liposomes ar e formed by first suspending a lipid in an aqueous solution then agitating the m ixture through sonication, resulting in a vesicle. By measuring the rate of effl ux from that of the inside of the vesicle to the ambient solution, allows resear cher to better understand membrane permeability. Vesicles can be formed with mol ecules and ions inside the vesicle by forming the vesicle with the desired molec ule or ion present in the solution. Proteins can also be embedded into the membr

ane through solubilizing the desired proteins in the presence of detergents and attaching them to the phospholipids in which the liposome is formed. These provi de researchers with a tool to examine various membrane protein functions. Carbohydrates Plasma membranes also contain carbohydrates, predominantly glycoproteins, but wi th some glycolipids (cerebrosides and gangliosides). For the most part, no glyco sylation occurs on membranes within the cell; rather generally glycosylation occ urs on the extracellular surface of the plasma membrane. The glycocalyx is an important feature in all cells, especially epithelia with m icrovilli. Recent data suggest the glycocalyx participates in cell adhesion, lym phocyte 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 negati ve 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 f orm of peripheral or integral. Type Description Examples Integral proteins ortransmembrane proteins Span the membrane and have a hydrophilic cytosol ic domain, which interacts with internal molecules, a hydrophobic membrane-spann ing domain that anchors it within the cell membrane, and a hydrophilic extracell ular domain that interacts with external molecules. The hydrophobic domain consi sts of one, multiple, or a combination of -helices nd sheet protein motifs. Ion ch nnels,proton pumps,G protein-coupled receptor Lipid nchored proteins Cov lently ound to single or multiple lipid molecules; hydropho ic lly insert i nto the cell mem r ne nd nchor the protein. The protein itself is not in cont ct with the mem r ne. G proteins

Peripher l proteins Att ched to integr l mem r ne proteins, or ssoci ted with peripher l regions of the lipid il yer. These proteins tend to h ve only tempor ry inter ctions with iologic l mem r nes, nd, once re cted the molecule, dissoci tes to c rry on i ts work in the cytopl sm. Some enzymes,some hormones The cell mem r ne pl ys host to l rge mount of protein th t is responsi le fo r its v rious ctivities. The mount of protein differs etween species nd cco rding to function, however the typic l mount in cell mem r ne is 50%. These p roteins re undou tedly import nt to cell: Approxim tely third of the genes in ye st code specific lly for them, nd this num er is even higher in multicell ul r org nisms. The cell mem r ne, eing exposed to the outside environment, is n import nt site of cell-cell communic tion. As such, l rge v riety of protei n receptors nd identific tion proteins, such s ntigens, re present on the su rf ce of the mem r ne. Functions of mem r ne proteins c n lso include cell-cell cont ct, surf ce recognition, cytoskeleton cont ct, sign ling, enzym tic ctivi ty, or tr nsporting su st nces cross the mem r ne. Most mem r ne proteins must e inserted in some w y into the mem r ne. For this to occur, n N-terminus "sign l sequence" of mino cids directs proteins to the endopl smic reticulum, which inserts the proteins into lipid il yer. Once in serted, the proteins re then tr nsported to their fin l destin tion in vesicles , where the vesicle fuses with the t rget mem r ne.

1 (ii) Write the function l unit The Golgi pp r tus ( lso known in cell. The Golgi pp r tus, ody nd its vesicles function in

in Golgi complex. s the dictyosome or Golgi ody) is n org nelle nd Golgi ody re the s me thing. "The Golgi the sorting, modifying, nd p ck ging of m cro-

1(v) Write nother n me of Folic cid. Folic cid ( lso known s vit min B9, vit min Bc or fol cin) nd fol te (the for m n tur lly occurring in the ody), s well s pteroyl-L-glut mic cid, pteroylL-glut m te, nd pteroylmonoglut mic cid re forms of the w ter-solu le vit min B9. Folic cid is itself not iologic lly ctive, ut its iologic l import nce is due to tetr hydrofol te nd other deriv tives fter its conversion to dihyd rofolic cid in the liver.Vit min B9 (folic cid nd fol te inclusive) is essent i l to numerous odily functions. The hum n ody needs fol te to synthesize DNA , rep ir DNA, nd methyl te DNA s well s to ct s cof ctor in iologic l re ctions involving fol te. It is especi lly import nt in iding r pid cell divisi on nd growth, such s in inf ncy nd regn ncy. Children nd dults oth requir e folic cid to produce he lthy red lood cells nd prevent nemi . 1(vi) Define Fi rous joint.

Cytokine TF is rel ted to protein f mily known s the cytokine receptor cl ss II f mily . The mem ers of this receptor f mily re ctiv ted y cytokines. Cytokines re sm ll proteins th t c n influence the eh vior of white lood cells. Binding of VII to TF h s lso een found to st rt sign ling processes inside the cell. The sign ling function of TF/VII pl ys role in ngiogenesis nd poptosis. 1 (iv) Define the term Dise se. Dise se The term dise se ro dly refers to ny condition th t imp irs norm l function. C ommonly, this term is used to refer specific lly to infectious dise ses, which re clinic lly evident dise ses th t result from the presence of p thogenic micro i l gents, including viruses, cteri , fungi, protozo , multicellul r org nis ms, nd err nt proteins known s prions. An infection th t does not nd will n ot produce clinic lly evident imp irment of norm l functioning, such s the pres ence of the norm l cteri nd ye sts in the gut, is not considered dise se; y contr st, n infection th t is symptom tic during its incu tion period, ut expected to produce symptoms l ter, is usu lly considered dise se. Non-infect ious dise ses re ll other dise ses, including most forms of c ncer,he rt dise se, nd genetic dise se. De th due to dise se is c lled de th y n tur l c uses. There re four m in type s of dise se: p thogenic dise se, deficiency dise se, heredit ry dise se, nd ph ysiologic l dise se. Dise ses c n lso e cl ssified s communic le nd non-communic le dise se

molecules th t re secreted y the cell or used within the cell for v rious func tions." 1(iii) Write the n me of Clotting f ctor III. Tissue f ctor, lso c lled pl telet tissue f ctor, f ctor III, throm okin se, or CD142 is protein present in su endotheli l tissue, pl telets, ndleukocytes n ecess ry for the initi tion of throm in form tion from the zymogen prothrom in. An incorrect synonym is throm opl stin. Historic lly, throm opl stin w s l r e gent, usu lly derived from pl cent l sources, used to ss y prothrom in times (PT time). Throm opl stin, y itself, could ctiv te the extrinsic co gul tion p thw y. Functions Co gul tion TF is the cell surf ce receptor for the serine prote se f ctor VII . The est known function of tissue f ctor is its role in lood co gul tion. The c omplex of TF with f ctor VII c t lyzes the conversion of the in ctive prote se f ctor X into the ctive prote se f ctor X . Together with f ctor VII , tissue f ctor forms the tissue f ctor or extrinsic p thw y of co gul tion. This is opposed to the intrinsic ( mplific tion) p thw y w hich involves oth ctiv ted f ctor IX nd f ctor VIII. Both p thw ys le d to th e ctiv tion of f ctor X (the common p thw y) which com ines with ctiv ted f ct or V in the presence of c lcium nd phospholipid to produce throm in (throm opl stin ctivity).

Fi rous joints re connected y dense connective tissue, consisting m inly of co ll gen. Types These joints re lso c lled "fixed" or "immove le" joints, ec use they do not move. These joints h ve no joint c vity nd re connected vi fi rous connectiv e tissue. The skull ones re connected y fi rous joints. Sutures re found etween ones of the skull. In fet l skulls the sutures re wi de to llow slight movement during irth. They l ter ecome rigid (syn rthrodi l ). Syndesmoses re found etween long ones of the ody, such s the r dius nd uln in fore rm nd the fi ul nd ti i in leg. Unlike other fi rous joints, synde smoses re move le ( mphi rthrodi l), l eit not to such degree s synovi l joi nts. Gomphosis is joint etween the root of tooth nd the sockets in the m xill or m ndi le. 1(vii) Write ny two n mes of Protein deficiency disorders. MARASMUS M r smus is dise se c used y severe deficiency of protein nd c lories th t ffect inf nts nd very young children, often resulting in weight loss nd dehy dr tion. M r smus c n develop into st rv tion nd c use f t lity c used y l c k of essenti l nutrients. People with m r smus ppe r ony with little muscle ti ssue, ccording to Food4Afric . KWASHIORKOR Kw shiorkor is dise se c used y severe deficiency of protein in diets th t cont in c lories mostly from c r ohydr tes such s y ms, rice nd n n s. It us u lly ffects older children. People with kw shiorkor ppe r puffy in the dome n re from retention of fluid, ccording to the University of M ryl nd Medic l Center. Common symptoms of oth m r smus nd kw shiorkor include f tigue, irrit ility, di rrhe , stunted growth nd imp irment of cognition nd ment l he lth. DEFICIENCIES OF PROTEIN C AND PROTEIN S Deficiencies of protein C nd protein S re inherited conditions th t c use no rm l lood clotting, ccording to Medline Plus. Deficiency of protein C occurs i n out 1 out of 300 people. Deficiency of protein S ffects 1 in 20,000 people. Symptoms for these deficiencies include redness, p in, tenderness or swelling i n the ffected re . People with these protein deficiencies need to e c reful out ctivities th t incre se risk of lood clots, such s prolonged sitting, e d rest, nd long-time tr vel in c rs nd irpl nes. Rese rch y A. Hood pu lish ed in the "Ann ls of Indi n Ac demy of Neurology" in 2009 discovered th t protei n S deficiency c uses ischemic stroke. CACHEXIA C chexi is condition th t involves protein deficiency, depletion of skelet l muscle nd n incre sed r te of protein degr d tion, C chexi c uses weight loss nd mort lity nd is ssoci ted with c ncer, AIDS, chronic kidney f ilure, he t dise se, chronic o structive pulmon ry dise se nd rheum toid rthritis, P tie nts with m lign nt c ncer of the stom ch, colon, liver, illi ry tr ct nd p ncr e s experience under nutrition from reduced int ke of protein, c lories nd micr onutrients, nd h ve f tigue nd neg tive nitrogen l nce s result of loss of muscle m ss from c chexi

1(viii) Define the term An tomy, Physiology nd Cell iology. An tomy (from the Greek n tomi , from n : sep r te, p rt from, nd temnein, to cut up, cut open) is r nch of iology nd medicine th t is the consider t ion of the structure of living things. It is gener l term th t includes hum n n tomy, nim l n tomy (zootomy), nd pl nt n tomy (phytotomy). In some of it s f cets n tomy is closely rel ted to em ryology, comp r tive n tomy nd comp r tive em ryology, through common roots in evolution. An tomy is su divided into gross n tomy (or m croscopic n tomy) nd microscopi c n tomy. Gross n tomy is the study of n tomic l structures th t c n, when su it ly presented or dissected, e seen y un ided vision with the n ked eye. Mic

roscopic n tomy is the study of minute n tomic l structures on microscopic s c le. It includes histology (the study of tissues), nd cytology (the study of c ells). The terms micro n tomy nd histology re lso sometimes used synonymously (in which c se the distinction etween histology nd cell iology isn't strictl y m de s descri ed here). Physiology is the science of the function of living systems. This includes how o rg nisms, org n systems, org ns, cells, nd io-molecules c rry out the chemic l or physic l functions th t exist in living system. The highest honor w rded in physiology is the No el Prize in Physiology or Medicine, w rded since 1901 y the Roy l Swedish Ac demy of Sciences. M ny U.S. universities offer physiology s m jor. Hum n physiology is the science of the mech nic l, physic l, nd iochemic l fun ctions of hum ns in good he lth, their org ns, nd the cells of which they re c omposed. The princip l level of focus of physiology is t the level of org ns n d systems within systems. Much of the found tion of knowledge in hum n physiolog y w s provided y nim l experiment tion. Physiology is closely rel ted to n to my; n tomy is the study of form, nd physiology is the study of function. Due t o the frequent connection etween form nd function, physiology nd n tomy re intrinsic lly linked nd re studied in t ndem s p rt of medic l curriculum. Cell iology (formerly cytology, from the Greek kytos, "cont in") is scientif ic discipline th t studies cells their physiologic l properties, their structure , the org nelles they cont in, inter ctions with their environment, their life c ycle, division nd de th. This is done oth on microscopic nd molecul r level . Cell iology rese rch encomp sses oth the gre t diversity of single-celled org nisms like cteri nd protozo , s well s the m ny speci lized cells in mult icellul r org nisms such s hum ns. Knowing the components of cells nd how cells work is fund ment l to ll iologi c l sciences. Appreci ting the simil rities nd differences etween cell types i s p rticul rly import nt to the fields of cell nd molecul r iology s well s to iomedic l fields such s c ncer rese rch nd development l iology. These fu nd ment l simil rities nd differences provide unifying theme, sometimes llow ing the principles le rned from studying one cell type to e extr pol ted nd ge ner lized to other cell types. Therefore, rese rch in cell iology is closely re l ted to genetics, iochemistry, molecul r iology, immunology, nd development l iology. 1(ix) Define Homeost sis. Homeost sis (from Greek: hmoios, "simil r" nd stsis, "st nding still") is the pr operty of system th t regul tes its intern l environment nd tends to m int in st le, const nt condition of properties like temper ture or pH. It c n e ei ther n open or closed system. Typic lly used to refer to living org nism, the concept c me from th t of mili eu interieur th t w s cre ted y Cl ude Bern rd nd pu lished in 1865. Multiple dyn mic equili rium djustment nd regul tion mech nisms m ke homeost sis possi le. 1(x) Write the composition of milk. The Milk Composition section descri es the chemic l nd physic l properties nd effects of p steuriz tion on the compounds in milk. A rief overview of the v ri tion in milk composition is provided elow s n introduction to this section. Topics covered re: C r ohydr te (L ctose) Milk C r ohydr te (L ctose) Milk cont ins pproxim tely 4.9% c r ohydr te th t is predomin tely l ctose with tr ce mounts of monos cch rides nd oligos cch rides. L ctose is dis cch rid e of glucose nd g l ctose. The structure of l ctose is: F t

Milk F t Chemistry Milk cont ins pproxim tely 3.4% tot l f t. Milk f t h s the most complex f tty cid composition of the edi le f ts. Over 400 individu l f tty cids h ve een i dentified in milk f t. However, pproxim tely 15 to 20 f tty cids m ke up 90% o f the milk f t. The m jor f tty cids in milk f t re str ight ch in f tty cids th t re s tur ted nd h ve 4 to 18 c r ons (4:0, 6:0, 8:0, 10:0, 12:0, 14:0, 1 6:0, 18:0), monouns tur ted f tty cids (16:1, 18:1), nd polyuns tur ted f tty cids (18:2, 18:3). Some of the f tty cids re found in very sm ll mounts ut contri ute to the unique nd desir le fl vor of milk f t nd utter. For ex mpl e, the C14:0 nd C16:0 -hydroxy f tty cids spont neously form l ctones upon he t ing which enh nce the fl vor of utter. The f tty cid composition of milk f t is not const nt throughout the cow's l ct tion cycle. The f tty cids th t re 4 to 14 c r ons in length re m de in the m mm ry gl nd of the nim l. Some of the 16 c r on f tty cids re m de y the nim l nd some come from the nim l's diet. All of the 18 c r on f tty cids com e from the nim l's diet. There re system tic ch nges in milk f t composition t h t re due to the st ge of l ct tion nd the energy needs of the nim l. In e r ly l ct tion, the nim l's energy comes l rgely from ody stores nd there re l imited f tty cids v il le for f t synthesis, so the f tty cids used for milk f t production re o t ined from the diet nd tend to e the longer ch in 16:0, 18:0, 16:1 nd 18:2 f tty cids. L ter in l ct tion more of the f tty cids in milk re formed in the m mm ry gl nd so th t the concentr tion of the short ch i n f tty cids such s 4:0 nd 6:0 re higher th n they re in e rly l ct tion. T hese ch nges in f tty cid composition do not h ve gre t imp ct on milk's nutr ition l properties, ut m y h ve some effect on processing ch r cteristics for p roducts such s utter. Milk f t cont ins pproxim tely 65% s tur ted, 30% monouns tur ted, nd 5% polyu ns tur ted f tty cids. From nutrition l perspective, not ll f tty cids re cre ted equ l. S tur ted f tty cids re ssoci ted with high lood cholesterol nd he rt dise se. However, short ch in f tty cids (4 to 8 c r ons) re met ol ized differently th n long ch in f tty cids (16 to 18 c r ons) nd re not cons idered to e f ctor in he rt dise se.Conjug ted linoleic cid is tr ns f tty cid in milkf t th t is enefici l to hum ns in m ny w ys. These issues re dis cussed in the Milk nd Hum n He lth section. The f tty cids re rr nged on the triglyceride molecule (Figure 1) in specif ic m nner. Most of the short ch in f tty cids re t the ottom c r on position of the triglyceride molecule, nd the longer f tty cids tend to e in the midd le nd top positions. The distri ution of the f tty cids on the triglyceride ck one ffects the fl vor, physic l, nd nutrition l properties of milk f t. Protein Milk Protein Chemistry Milk cont ins 3.3% tot l protein. Milk proteins cont in ll 9 essenti l mino c ids required y hum ns. Milk proteins re synthesized in the m mm ry gl nd, ut 60% of the mino cids used to uild the proteins re o t ined from the cow's di et. Tot l milk protein content nd mino cid composition v ries with cow reed nd individu l nim l genetics. There re 2 m jor c tegories of milk protein th t re ro dly defined y their c hemic l composition nd physic l properties. The c sein f mily cont ins phosphor us nd will co gul te or precipit te t pH 4.6. The serum (whey) proteins do not cont in phosphorus, nd these proteins rem in in solution in milk t pH 4.6. Th e principle of co gul tion, or curd form tion, t reduced pH is the sis for ch eese curd form tion. In cow's milk, pproxim tely 82% of milk protein is c sein nd the rem ining 18% is serum, or whey protein. The c sein f mily of protein consists of sever l types of c seins (-s1, -s2 , , 6) nd e ch h s its own mino cid composition, genetic v ri tions, nd functio n l properties. The c seins re suspended in milk in complex c lled micelle th t is discussed elow in the physic l properties section. The c seins h ve r

nd

el tively r ndom, open structure due to the mino cid composition (high proline content). The high phosph te content of the c sein f mily llows it to ssoci t e with c lcium nd form c lcium phosph te s lts. The und nce of phosph te llo ws milk to cont in much more c lcium th n would e possi le if ll the c lcium w ere dissolved in solution, thus c sein proteins provide good source of c lcium for milk consumers. The 6-c sein is m de of c r ohydr te portion tt ched to the protein ch in nd is loc ted ne r the outside surf ce of the c sein micelle (see Figure 2 elow). In cheese m nuf cture, the 6-c sein is cle ved etween cer t in mino cids, nd this results in protein fr gment th t does not cont in t he mino cid phenyl l nine. This fr gment is c lled milk glycom cropeptide nd is unique source of protein for people with phenylketonuri . The serum (whey) protein f mily consists of pproxim tely 50% -l ctoglo ulin, 20% -l ct l umin, lood serum l umin, immunoglo ulins, l ctoferrin, tr nsferrin, n d m ny minor proteins nd enzymes. Like the other m jor milk components, e ch wh ey protein h s its own ch r cteristic composition nd v ri tions. Whey proteins do not cont in phosphorus, y definition, ut do cont in l rge mount of sulfu r-cont ining mino cids. These form disulfide onds within the protein c using the ch in to form comp ct spheric l sh pe. The disulfide onds c n e roken, le ding to loss of comp ct structure, process c lled den turing. Den tur tion is n dv nt ge in yogurt production ec use it incre ses the mount of w ter th t the proteins c n ind, which improves the texture of yogurt. This principle i s lso used to cre te speci lized whey protein ingredients with unique function l properties for use in foods. One ex mple is the use of whey proteins to ind w ter in me t nd s us ge products. The functions of m ny whey proteins re not cle rly defined, nd they m y not h ve specific function in milk ut m y e n rtif ct of milk synthesis. The fun ction of -l ctoglo ulin is thought to e c rrier of vit min A. It is interestin g to note th t -l ctoglo ulin is not present in hum n milk. -L ct l umin pl ys c ritic l role in the synthesis of l ctose in the m mm ry gl nd. Immunoglo ulins p l y role in the nim l's immune system, ut it is unknown if these functions re tr nsferred to hum ns. L ctoferrin nd tr nsferrin pl y n import nt role in iron sorption nd there is interest in using ovine milk s commerci l sourc e of l ctoferrin.

Vit mins in Milk Vit mins h ve m ny roles in the ody, including met olism co-f ctors, oxygen tr nsport nd ntioxid nts. They help the ody use c r ohydr tes, protein, nd f t . The specific content of vit mins in milk is listed in theNutrient Content T l es in the Nutrition F cts section. Milk cont ins the w ter solu le vit mins thi min (vit min B1), ri ofl vin (vit m in B2), ni cin (vit min B3), p ntothenic cid (vit min B5), vit min B6 (pyridoxi ne), vit min B12 (co l min), vit min C, nd fol te. Milk is good source of th i min, ri ofl vin nd vit min B12 . Milk cont ins sm ll mounts of ni cin, p nto thenic cid, vit min B6, vit min C, nd fol te nd is not considered m jor sou rce of these vit mins in the diet.

Deterior tion of Milk Protein Proteins c n e degr ded y enzyme ction or y exposure to light. The predomin nt c use of protein degr d tion is through enzymes c lled prote ses. Milk prote ses come from sever l sources: the n tive milk, ir orne cteri l cont min tion , cteri th t re dded intention lly for ferment tion, or som tic cells prese nt in milk. The ction of prote ses c n e desir le, s in the c se of yogurt nd cheese m nuf cture, so, for these processes, cteri with desir le proteoly tic properties re dded to the milk. Undesir le degr d tion (proteolysis) resu lts in milk with off-fl vors nd poor qu lity. The most import nt prote se in mi lk for cheese m nuf cturing is pl smin ec use it c uses proteolysis during ripe ning which le ds to desir le fl vors nd texture in cheese. Two mino cids in milk, methionine nd cystine re sensitive to light nd m y e degr ded with exposure to light. This results in n off-fl vor in the milk nd loss of nutrition l qu lity for these 2 mino cids.

Milk cont ins the f t solu le vit mins A, D, E, nd K. The content level of f t solu le vit mins in d iry products depends on the f t content of the product. Re duced f t (2% f t), lowf t (1% f t), nd skim milk must e fortified with vit mi n A to e nutrition lly equiv lent to whole milk. Fortific tion of ll milk with vit min D is volunt ry. Milk cont ins sm ll mounts of vit mins E nd K nd is not considered m jor source of these vit mins in the diet. Miner ls in Milk Miner ls h ve m ny roles in the ody including enzyme functions, one form tion, w ter l nce m inten nce, nd oxygen tr nsport. The specific content of miner ls in milk is listed in the Nutrient Content T les in the Nutrition F cts secti on. Milk is good source of c lcium, m gnesium, phosphorus, pot ssium, selenium, n d zinc. M ny miner ls in milk re ssoci ted together in the form of s lts, such s c lcium phosph te. In milk pproxim tely 67% of the c lcium, 35% of the m gn esium, nd 44% of the phosph te re s lts ound within the c sein micelle nd th e rem inder re solu le in the serum ph se. The f ct th t c lcium nd phosph te re ssoci ted s s lts ound with the protein does not ffect the nutrition l v il ility of either c lcium or phosph te. Milk cont ins sm ll mounts of copper, iron, m ng nese, nd sodium nd is not co nsidered m jor source of these miner ls in the diet. Effects of He t Tre tments & Light Exposure on the Vit min & Miner l Content in Milk The mild he t tre tment used in the typic l high temper ture short time (HTST) p steuriz tion of fluid milk does not ppreci ly ffect the vit min content. How ever, the higher he t tre tment used in ultr high temper ture (UHT) p steuriz t ion for extended shelf com ined with the incre sed stor ge life of these product s does c use losses of some w ter-solu le vit mins. Thi min is reduced from 0.45 to 0.42 mg/L, vit min B 12 is reduced from 3.0 to 2.7 g/L, nd vit min C is redu ced from 2.0 to 1.8 mg/L (Potter et l., 1984). Ri ofl vin is he t st le vit min nd is not ffected y severe he t tre tments. C lcium phosph te will migr te in nd out of the c sein micelle with ch nges in temper ture. This process is reversi le t moder te temper tures. This does not ffect the nutrition l properties of milk miner ls. At very high temper tures th e c lcium phosph te m y precipit te out of solution which c uses irreversi le ch nges in the c sein micelle structure. Exposure to light will decre se the ri ofl vin nd vit min A content in milk. Mi lk should e stored in cont iners th t provide rriers to light (op que pl stic or p per o rd) to m ximize vit min retention. Enzymes E ch enzyme h s specific site of ction on its t rget molecule, nd optim l co nditions (pH nd temper ture). There re l rge num er of enzymes in milk nd t he functions of m ny re not well-defined. It should e noted th t the enzymes i n milk do not m ke m jor contri ution to the digestion of milk in hum ns, whic h is ccomplished y enzymes in the hum n stom ch nd sm ll intestine. Lip ses re enzymes th t degr de f ts. The m jor lip se in milk is lipoprotein l ip se. It is ssoci ted with the c sein micelle. Agit tion during processing m y ring the lip se into cont ct with the milk f t resulting in f t degr d tion n d off-fl vors. P steuriz tion will in ctiv te the lip se in milk nd incre se sh elf life. Prote ses re enzymes th t degr de proteins. The m jor prote se in milk is pl sm in. Some prote ses re in ctiv ted y he t nd some re not. Protein degr d tion c n e undesir le nd result in itter off-fl vors, or it m y provide desir le texture to cheese during ripening. Prote ses re import nt in cheese m nuf c ture, nd consider le mount of inform tion is v il le in the cheese liter ture. Alk line phosph t se is he t sensitive enzyme in milk th t is used s indic to r of p steuriz tion. If milk is properly p steurized, lk line phosph t se is in ctiv ted. L ctoperoxid se is one of the most he t-st le enzymes found in milk. L ctoperox id se, when com ined with hydrogen peroxide nd thiocy n te, h s nti cteri l p

roperties. It is suggested th t the presence of l ctoperoxid se in r w milk inhi its the dise se c using microorg nisms (p thogens) present in milk. However, si nce there is no hydrogen peroxide or thiocy n te present in fresh milk, these co mpounds would h ve to e dded to milk in order to chieve the nti cteri l en efits. Lysozyme is nother enzyme th t h s some nti cteri l ctivities, lthou gh the mount of lysozyme present in milk is very sm ll. Unless otherwise st ted, the inform tion presented in this we site refers to cow 's milk. In gener l, the gross composition of cow's milk in the U.S. is 87.7% w ter, 4.9% l ctose (c r ohydr te), 3.4% f t, 3.3% protein, nd 0.7% miner ls (referred to s sh). Milk composition v ries depending on the species (cow, go t, sheep), r eed (Holstein, Jersey), the nim l's feed, nd the st ge of l ct tion. 1(xi) Write the chief function of the serum l umin in the Blood. M int ins osmotic pressure. Tr nsports thyroid hormones. Tr nsports other hormones, in p rticul r, ones th t re f t-solu le. Tr nsports f tty cids ("free" f tty cids) to the liver. Tr nsports unconjug ted iliru in. Tr nsports m ny drugs; serum l umin levels c n ffect the h lf-life of drugs. Competitively inds c lcium ions (C 2+). Buffers pH. Serum l umin, s neg tive cute-ph se protein, is down-regul ted in infl mm t ory st tes. As such, it is not v lid m rker of nutrition l st tus; r ther, it is m rker in infl mm tory st tes. Prevents photo-degr d tion of folic cid. molecules (such s proteins) y e ody ec use most su st nces impor nnot p ss through the hydropho ic the opposite to endocytosis is exo

1(xiii) Write the component of Nucleus. the nucleus (pl. nuclei;from L tin nucleus or nuculeus, me ning kernel) is mem r ne-enclosed org nelle found ineuk ryotic cells. It cont ins most of the cell' s genetic m teri l, org nized s multiple long line r DNA molecules in complex w ith l rge v riety of proteins, such s histones, to form chromosomes.

1(xiv) Give the function of golgi odies. The Golgi pp r tus (Golgi complex) is n org nelle found in most euk ryotic cel ls. It w s identified in 1898 y the It li n physici nC millo Golgi, fter whom the Golgi pp r tus is n med. It processes nd p ck ges proteins inside of the cell nd efore they m ke their w y to their destin tion; it is p rticul rly import nt in the processing of pro teins for secretion. The Golgi pp r tus forms p rt of the cellul r endomem r ne system. Function Cells synthesise l rge num er of different m cromolecules. The Golgi pp r tus is integr l in modifying, sorting, nd p ck ging these m cromolecules for cell secretion (exocytosis) or use within the cell. It prim rily modifies proteins d elivered from the rough endopl smic reticulum ut is lso involved in the tr nsp ort of lipids round the cell, nd the cre tion of lysosomes. In this respect i t c n e thought of s simil r to post office; it p ck ges nd l els items wh ich it then sends to different p rts of the cell. Enzymes within the cistern e re le to modify the proteins y ddition of c r ohydr tes (glycosyl tion) nd phosph tes (phosphoryl tion). In order to do so, the Golgi imports su st nces such s nucleotide sug rs from the cytosol. These m odific tions m y lso form sign l sequence which determines the fin l destin t ion of the protein. For ex mple, the Golgi pp r tus dds m nnose-6-phosph te

1(xii) Define Endocytosis. Endocytosis is process y which cells sor ngulfing them. It is used y ll cells of the t nt to them re l rge pol r molecules th t c pl sm or cell mem r ne. The process which is cytosis.

l el to proteins destined for lysosomes. The Golgi pl ys n import nt role in the synthesis of proteoglyc ns, which re m olecules present in the extr cellul r m trix of nim ls. It is lso m jor site of c r ohydr te synthesis. This includes the production of glycos minoglyc ns ( GAGs), long un r nched polys cch rides which the Golgi then tt ches to protei n synthesised in the endopl smic reticulum to form proteoglyc ns. Enzymes in th e Golgi polymerize sever l of these GAGs vi xylose link onto the core protein . Another t sk of the Golgi involves the sulf tion of cert in molecules p ssing through its lumen vi sulfotr nfer ses th t g in their sulfur molecule from do nor c lled PAPs. This process occurs on the GAGs of proteoglyc ns s well s on the core protein. The level of sulf tion is very import nt to the proteoglyc ns' sign lling ilities s well s giving the proteoglyc n its over ll neg tive ch rge. The phosphoryl tion of molecules requires th t ATP is imported into the lumen of the Golgi nd then utilised y resident kin ses such s c sein kin se 1 nd c s ein kin se 2. One molecule th t is phosphoryl ted in the Golgi is Apolipoprotein , which forms molecule known s VLDL th t is constituent of lood serum. It is thought th t the phosphoryl tion of these molecules is import nt to help id in their sorting for secretion into the lood serum. The Golgi h s put tive role in poptosis, with sever l Bcl-2 f mily mem ers lo c lised there, s well s to the mitochondri . A newly ch r cterized protein, GA AP (Golgi nti- poptotic protein), lmost exclusively resides in the Golgi nd p rotects cells from poptosis y n s-yet undefined mech nism. 1(xv) Define sickle cell nemi . Sickle cell nemi Anemi - sickle cell; Hemoglo in SS dise se (H SS); Sickle cell dise se Sickle cell nemi is dise se p ssed down through f milies in which red lood cells form n norm l crescent sh pe. (Red lood cells re norm lly sh ped like disc. C uses, incidence, nd risk f ctors Sickle cell nemi is c used y n norm l type of hemoglo in c lled hemoglo in S. Hemoglo in is protein inside red lood cells th t c rries oxygen. Hemoglo in S ch nges the sh pe of red lood cells, especi lly when the cells re exposed to low oxygen levels. The red lood cells ecome sh ped like crescents or sickl es. The fr gile, sickle-sh ped cells deliver less oxygen to the ody's tissues. They c n lso get stuck more e sily in sm ll lood vessels, nd re k into pieces th t interupt he lthy lood flow. Sickle cell nemi is inherited from oth p rents. If you inherit the hemoglo in S gene from one p rent nd norm l hemoglo in (A) from your other p rent, you wi ll h ve sickle cell tr it. People with sickle cell tr it do not h ve the symptom s of sickle cell nemi . Sickle cell dise se is much more common in people of Afric n nd Mediterr ne n d escent. It is lso seen in people from South nd Centr l Americ , the C ri e n, nd the Middle E st. Symptoms Symptoms usu lly don't occur until fter ge 4 months. Almost ll p tients with sickle cell nemi h ve p inful episodes (c lled crises ), which c n l st from hours to d ys. These crises c n ffect the ones of the ck, the long ones, nd the chest. Some p tients h ve one episode every few ye rs. Others h ve m ny episodes per ye r. The crises c n e severe enough to require hospit l st y. Common symptoms include: Att cks of domin l p in, Bone p in, Bre thlessness, Del yed growth nd pu er ty, F tigue, Fever, P leness, R pid he rt r te, Ulcers on the lower legs (in do lescents nd dults), Yellowing of the eyes nd skin (j undice) Other symptoms include: Chest p in, Excessive thirst, Frequent urin tion, P inful nd prolonged erection (pri pism - occurs in 10 - 40% of men with the dise se), Poor eyesight/ lindnes s, Strokes, Skin ulcers

Signs nd tests Tests commonly performed to di gnose nd monitor p tients with sickle cell nemi include: Complete lood count (CBC), Hemoglo in electrophoresis, Sickle cell test Other tests m y include: Biliru in, Blood oxygen, CT sc n or MRI, Peripher l sme r, Serum cre tinine, Ser um hemoglo in Serum pot ssium, Urin ry c sts or lood in the urine, White lood cell count Tre tment The go l of tre tment is to m n ge nd control symptoms, nd to limit the num er of crises. P tients with sickle cell dise se need ongoing tre tment, even when they re not h ving p inful crisis. Folic cid supplements should e t ken. Folic cid is needed to m ke red lood c ells. Tre tment for sickle cell crisis includes: Blood tr nsfusions (m y lso e given regul rly to prevent stroke) P in medicines Plenty of fluids Other tre tments for sickle cell nemi m y include: Hydroxyure (Hydre ), medicine th t m y help reduce the num er of p in episode s (including chest p in nd difficulty re thing) in some people Anti iotics to prevent cteri l infections, which re common in children with s ickle cell dise se Tre tments for complic tions of sickle cell nemi m y include: Kidney di lysis or kidney tr nspl nt for kidney dise se Drug reh ilit tion nd counseling for psychologic l complic tions G ll l dder remov l in those with g llstone dise se Hip repl cement for v scul r necrosis of the hip Tre tments, including surgery, for persistent, p inful erections (pri pism) Surgery for eye pro lems Wound c re, zinc oxide, or surgery for leg ulcers Bone m rrow or stem cell tr nspl nts c n cure sickle cell nemi . However, they re current not n option for most p tients. Sickle cell nemi p tients re oft en un le to find well-m tched donors. 1(xvi) Define the Coron l Pl ne nd S git l Pl ine. S gitt l pl ne is vertic l pl ne which p sses from front to re r dividing the ody into right nd left sections. The terms medi n pl ne or mid-s gitt l pl ne re sometimes used to descri e the s gitt l pl ne running through the midline. This pl ne cuts the ody into h lves ( ssuming il ter l symmetry), p ssing through midline structures such s the n vel nd spine. It is one of the lines defining the right upper qu dr nt of the hum n domen. It is lso worth mentioning th t terms such s p r s gitt l re sometimes used t o descri e pl ne p r llel to the midline; however, this term is unnecess ry, s ince ny pl ne p r llel to nd on either side of the medi l pl ne is s gitt l y definition. In gener l, pl nes th t re p r llel to the s gitt l pl ne, ut do not p ss thro ugh the midline, re known s p r s gitt l. The midcl vicul r line crosses through the cl vicle. Other s gitt l lines/pl nes include the l ter l stern l nd p r stern l. A coron l pl ne ( lso known s the front l pl ne) is ny vertic l pl ne th t div ides the ody into ventr l nd dors l ( elly nd ck) sections. It is one of the pl nes of the ody used to descri e the loc tion of ody p rts in rel tion to e ch other. Section B

A mi ch ndri n c n ains u er and inner membranes c mp sed f ph sph lipid bila yers and pr eins. The w membranes, h wever, have differen pr per ies. Beca use f his d uble- embraned rganiza i n, here are five dis inc c mpar men s wi hin he mi ch ndri n. There is he u er mi ch ndrial membrane, he in erme mbrane space ( he space be ween he u er and inner membranes), he inner mi c h ndrial membrane, he cris ae space (f rmed by inf ldings f he inner membrane ), and he ma rix (space wi hin he inner membrane). Ou er membrane The u er mi ch ndrial membrane, which encl ses he en ire rganelle, has a pr ein- -ph sph lipid ra i similar ha f he eukary ic plasma membrane (ab u 1:1 by weigh ). I c n ains large numbers f in egral pr eins called p rins . These p rins f rm channels ha all w m lecules 5000 Dal ns r less in m lecu lar weigh freely diffuse fr m ne side f he membrane he her. Larger pr eins can en er he mi ch ndri n if a signaling sequence a heir N- erminu s binds a large mul isubuni pr ein called ransl case f he u er membrane , which hen ac ively m ves hem acr ss he membrane. Disrup i n f he u er me mbrane permi s pr eins in he in ermembrane space leak in he cy s l, lea ding cer ain cell dea h. The mi ch ndrial u er membrane can ass cia e wi h he end plasmic re iculum (ER) membrane, in a s ruc ure called MAM (mi ch ndri a-ass cia ed ER-membrane). This is imp r an in ER-mi ch ndria calcium signalin g and inv lved in he ransfer f lipids be ween he ER and mi ch ndria. In er membrane space The in ermembrane space is he space be ween he u er membrane and he inner me mbrane. Because he u er membrane is freely permeable small m lecules, he c ncen ra i ns f small m lecules such as i ns and sugars in he in ermembrane sp ace is he same as he cy s l. H wever, large pr eins mus have a specific si gnaling sequence be ransp r ed acr ss he u er membrane, s he pr ein c m p si i n f his space is differen fr m he pr ein c mp si i n f he cy s l. One pr ein ha is l calized he in ermembrane space in his way is cy chr me c Inner membrane The inner mi ch ndrial membrane c n ains pr eins wi h five ypes f func i ns:

2. Attempt ny six question: (i) Descri e the Structure nd function of the mitochondri . Mitochondrion In cell iology, mitochondrion (plur l mitochondri ) is mem r ne-enclosed or g nelle found in most euk ryotic cells. These org nelles r nge from 0.5 to 1.0 m icrometers (m) in di meter. Mitochondri re sometimes descri ed s "cellul r pow er pl nts" ec use they gener te most of the cell's supply of denosine triphosp h te (ATP), used s source of chemic l energy. In ddition to supplying cellu l r energy, mitochondri re involved in r nge of other processes, such s sig n ling, cellul r differenti tion, cell de th, s well s the control of the cell cycle nd cell growth. Mitochondri h ve een implic ted in sever l hum n dise ses, including mitochondri l disorders nd c rdi c dysfunction, nd m y pl y role in the ging process. The word mitochondrion comes from the Greek r mi s, read ch ndri n, granule. Several charac eris ics make mi ch ndria unique. The number f mi ch ndria in a cell varies widely by rganism and issue ype. Many cells have nly a single mi ch ndri n, whereas hers can c n ain several h usand mi ch ndria. The rg anelle is c mp sed f c mpar men s ha carry u specialized func i ns. These c mpar men s r regi ns include he u er membrane, he in ermembrane space, he inner membrane, and he cris ae andma rix. Mi ch ndrial pr eins vary depending n he issue and he species. In humans, 615 dis inc ypes f pr eins have b een iden ified fr m cardiacmi ch ndria, whereas in Murinae (ra s), 940 pr eins enc ded by dis inc genes have been rep r ed. The mi ch ndrial pr e me is h ugh be dynamically regula ed. Al h ugh m s f a cell's DNA is c n ained in he cell nucleus, he mi ch ndri n has i s wn independen gen me. Fur her, i s DNA sh ws subs an ial similari y bac erial gen mes. S ruc ure

Th se ha perf rm he red x reac i ns f xida ive ph sph ryla i n ATP syn hase, which genera es ATP in he ma rix Specific ransp r pr eins ha regula e me ab li e passage in and u f he ma rix 4. Pr ein imp r machinery. 5. Mi ch ndria fusi n and fissi n pr ein I c n ains m re han 151 differen p lypep ides, and has a very high pr ein-ph sph lipid ra i (m re han 3:1 by weigh , which is ab u 1 pr ein f r 15 ph sph lipids). The inner membrane is h me ar und 1/5 f he al pr ein in a mi ch ndri n. In addi i n, he inner membrane is rich in an unusual ph sph lip id, cardi lipin. This ph sph lipid was riginally disc vered in c w hear s in 19 42, and is usually charac eris ic f mi ch ndrial and bac erial plasma membrane s. Cardi lipin c n ains f ur fa y acids ra her han w , and may help make he inner membrane impermeable. Unlike he u er membrane, he inner membrane d e sn' c n ain p rins, and is highly impermeable all m lecules. Alm s all i ns and m lecules require special membrane ransp r ers en er r exi he ma rix . Pr eins are ferried in he ma rix via he ransl case f he inner membrane (TIM) c mplex r via Oxa1. In addi i n, here is a membrane p en ial acr ss he inner membrane, f rmed by he ac i n f he enzymes f he elec r n ransp r chain. Cris ae Cr ss-sec i nal image f cris ae in ra liver mi ch ndri n dem ns ra e he l ikely 3D s ruc ure and rela i nship he inner membrane. The inner mi ch ndrial membrane is c mpar men alized in numer us cris ae, whi ch expand he surface area f he inner mi ch ndrial membrane, enhancing i s ab ili y pr duce ATP. F r ypical liver mi ch ndria, he area f he inner memb rane is ab u five imes grea er han he u er membrane. This ra i is variable and mi ch ndria fr m cells ha have a grea er demand f r ATP, such as muscle cells, c n ain even m re cris ae. These f lds are s udded wi h small r und b die s kn wn as F1 par icles r xys mes. These are n simple rand m f lds bu ra he r invagina i ns f he inner membrane, which can affec verall chemi sm ic fun c i n. One recen ma hema ical m deling s udy has sugges ed ha he p ical pr per ies f he cris ae in filamen us mi ch ndria may affec he genera i n and pr pag a i n f ligh wi hin he issue. Ma rix The ma rix is he space encl sed by he inner membrane. I c n ains ab u 2/3 f he al pr ein in a mi ch ndri n. The ma rix is imp r an in he pr duc i n f ATP wi h he aid f he ATP syn hase c n ained in he inner membrane. The ma rix c n ains a highly-c ncen ra ed mix ure f hundreds f enzymes, special mi ch ndrial rib s mes, RNA, and several c pies f he mi ch ndrial DNA gen me. Of he enzymes, he maj r func i ns include xida i n f pyruva e and fa y acids, and he ci ric acid cycle. Mi ch ndria have heir wn gene ic ma erial, and he machinery manufac ure heir wn RNAs and pr eins (see: pr ein bi syn hesis). A published human mi ch ndrial DNA sequence revealed 16,569 base pairs enc ding 37 al genes: 22 RNA , 2 rRNA, and 13 pep ide genes. The 13 mi ch ndrial pep ides in humans are in e gra ed in he inner mi ch ndrial membrane, al ng wi hpr eins enc ded by gene s ha reside in he h s cell's nucleus. Mi ch ndria-ass cia ed ER membrane (MAM) The mi ch ndria-ass cia ed ER membrane (MAM) is an her s ruc ural elemen ha is increasingly rec gnized f r i s cri ical r le in cellular physi l gy and h m e s asis. Once c nsidered a echnical snag in cell frac i na i n echniques, he alleged ER vesicle c n aminan s ha invariably appeared in he mi ch ndrial f rac i n have been re-iden ified as membran us s ruc ures derived fr m he MAM he in erface be ween mi ch ndria and he ER. Physical c upling be ween hese w rganelles had previ usly been bserved in elec r n micr graphs and has m re rece n ly been pr bed wi h flu rescence micr sc py. Such s udies es ima e ha a he MAM, which may c mprise up 20% f he mi ch ndrial u er membrane, he ER a nd mi ch ndria are separa ed by a mere 10-25 nm and held ge her by pr ein e

1. 2. 3.

hering c mplexes. Purified MAM fr m subcellular frac i na i n has sh wn be enriched in enzymes inv lved in ph sph lipid exchange, in addi i n channels ass cia ed wi h Ca2+ signaling. These hin s f a pr minen r le f r he MAM in he regula i n f cel lular lipid s res and signal ransduc i n have been b rne u , wi h significan implica i ns f r mi ch ndrial-ass cia ed cellular phen mena, as discussed bel w. N nly has he MAM pr vided insigh in he mechanis ic basis underlying s uch physi l gical pr cesses as in rinsic ap p sis and he pr paga i n f calciu m signaling, bu i als fav rs a m re refined view f he mi ch ndria. Th ugh f en seen as s a ic, is la ed p werh uses hijacked for cellular metabolism throug h an ancient endosymbiotic event, the evolution of the MAM underscores the exten t to which mitochondria have been integrated into overall cellular physiology, w ith intimate physical and functional coupling to the endomembrane system. Phospholipid transfer The MAM is enrichad in enzymes involved in lipid biosynthesis, such as phosphati dylserine synthase on the ER face and phosphatidylserine decarboxylase on the mi tochondrial face. Because mitochondria are dynamic organelles constantly underg oing fission and fusion events, they require a constant and well-regulated suppl y of phospholipids for membrane integrity. But mitochondria are not only a dest ination for the phospholipids they finish synthesis of; rather, this organelle a lso plays a role in inter-organelle trafficking of the intermediates and product s of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, an d 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 standar d vesicular mechanism of lipid transfer, evidence indicates that the physical pr oximity of the ER and mitochondrial membranes at the MAM allows for lipid flippi ng between apposed bilayers. Despite this unusual and seemingly energetically un favorable mechanism, such transport does not require ATP. Instead, it has been s hown to be dependent on a multiprotein tethering structure termed the ER-mitocho ndria encounter structure, or ERMES, although it remains unclear whether this st ructure 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 in tracellular lipid trafficking. In particular, the MAM appears to be an intermedi ate 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 ser ves 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 r ole for the mitochondria was widely accepted, in part because the low affinity o f Ca2+ channels localized to the outer mitochondrial membrane seemed to fly in t he face of this organelles purported responsiveness to changes in intracellular C a2+ flux. But the presence of the MAM resolves this apparent contradiction: the close physical association between the two organelles results in Ca2+ microdoma ins at contact points that facilitate efficient Ca2+ transmission from the ER to the mitochondria. Transmission occurs in response to so-called Ca2+ puffs generat ed 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 deter mined in large part by MAM dynamics. Although reuptake of Ca2+ by the ER (concom itant with its release) modulates the intensity of the puffs, thus insulating mi tochondria 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 fr ee ions released into the cytosol can be funneled. This Ca2+ tunneling occurs t hrough 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 elec trochemical gradient generated during oxidative phosphorylation, which makes tun

neling 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 mem brane facilitate feedback regulation coordinated by MAM function. In particular, clearance of Ca2+ by the MAM allows for spatio-temporal patterning of Ca2+ sign aling because Ca2+ alters IP3R activity in a biphasic manner. SERCA is likewise affected by mitochondrial feedback: uptake of Ca2+ by the MAM stimulates ATP pro duction, 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 c ertain window of Ca2+ uptake sustains the mitochondria, and consequently the cel l, at homeostasis. Sufficient intraorganelle Ca2+ signaling is required to stimu late metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle. However, once Ca2+ signaling in the mitochondria passes a ce rtain threshold, it stimulates the intrinsic pathway of apoptosis in part by col lapsing the mitochondrial membrane potential required for metabolism. Studies ex amining the role of pro- and anti-apoptotic factors support this model; for exam ple, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to re duce 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 neurodegener ative 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 element s involved is secondary to other, non-structural functions. ERMES, a multiprotei n complex of interacting ER- and mitochondrial-resident membrane proteins, is re quired 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 f or insertion of transmembrane beta-barrel proteins into the lipid bilayer. Other proteins implicated in scaffolding likewise have functions independent of struc tural tethering at the MAM; for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle cont act sites, although mitofusins were first identified for their role in fission a nd fusion events between individual mitochondria. Glucose-related protein 75 (g rp75) 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-reside nt IP3R has been proposed to preserve communication at the MAM during the metabo lic 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 f or overall cellular physiology and homeostasis. The MAM thus offers a perspectiv e on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. Inst ead, this mitochondrial-ER interface emphasizes the integration of the mitochond ria, 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 locatio n according to cell type. A single mitochondrion is often found in unicellular o rganisms. Conversely, numerous mitochondria are found in human liver cells, with about 10002000 mitochondria per cell, making up 1/5 of the cell volume. The mit

ochondria can be found nestled between myofibrils of muscle or wrapped around th e sperm flagellum. Often they form a complex 3D branching network inside the ce ll with the cytoskeleton. The association with the cytoskeleton determines mitoc hondrial shape, which can affect the function as well. Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is critical to the as sociation with the cytoskeleton. Function The most prominent roles of mitochondria are to produce ATP (i.e., phosphorylati on of ADP) through respiration, and to regulate cellular metabolism. The central set of reactions involved in ATP production are collectively known as the citri c acid cycle, or the Krebs Cycle. However, the mitochondrion has many other func tions in addition to the production of ATP. Energy conversion A dominant role for the mitochondria is the production of ATP, as reflected by t he 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 resp iration, is dependent on the presence of oxygen. When oxygen is limited, the gly colytic products will be metabolized by anaerobic respiration, a process that is independent of the mitochondria. The production of ATP from glucose has an appr oximately 13-fold higher yield during aerobic respiration compared to anaerobic respiration. Recently it has been shown that plant mitochondria can produce a li mited 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 comb ined with coenzyme A to form CO2, acetyl-CoA, and NADH. The acetyl-CoA is the primary substrate to enter the citric acid cycle, also kno wn as the tricarboxylic acid (TCA) cycle or Krebs cycle. The enzymes of the citr ic acid cycle are located in the mitochondrial matrix, with the exception of suc cinate 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 on e molecule of FADH2) that are a source of electrons for the electron transport c hain, 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 st eps via the electron transport chain. These energy-rich molecules are produced w ithin the matrix via the citric acid cycle but are also produced in the cytoplas m by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electro n transport chain using a glycerol phosphate shuttle. Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, and cytochrome c oxi dase) 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 sma ll percentage of electrons may prematurely reduce oxygen, forming reactive oxyge n species such as superoxide. This can cause oxidative stress in the mitochondri a and may contribute to the decline in mitochondrial function associated with th e aging process. As the proton concentration increases in the intermembrane space, a strong elect rochemical gradient is established across the inner membrane. The protons can re turn 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 i s called chemiosmosis, and was first described by Peter Mitchell who was awarde d 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 cla rification 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 mitochond

rial uncoupling and is due to thefacilitated diffusion of protons into the matri x. The process results in the unharnessed potential energy of the proton electro chemical gradient being released as heat. The process is mediated by a proton ch annel called thermogenin, or UCP1. Thermogenin is a 33kDa protein first discover ed in 1973. Thermogenin is primarily found in brown adipose tissue, or brown fat , and is responsible for non-shivering thermogenesis. Brown adipose tissue is fo und in mammals, and is at its highest levels in early life and in hibernating an imals. In humans, brown adipose tissue is present at birth and decreases with ag e. Storage of calcium ions The concentrations of free calcium in the cell can regulate an array of reaction s and is important for signal transduction in the cell. Mitochondria can transie ntly 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 the m very good "cytosolic buffers" for calcium. The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there is a significant interpl ay between the mitochondrion and ER with regard to calcium. The calcium is take n 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 p rotein or via "calcium-induced-calcium-release" pathways. This can initiate calc ium spikes or calcium waves with large changes in the membrane potential. These can activate a series ofsecond messenger system proteins that can coordinate pro cesses such as neurotransmitter release in nerve cells and release of hormones i n 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 regulat ing any of these functions can result in mitochondrial diseases. Origin Mitochondria have many features in common with prokaryotes. As a result, they ar e 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 prot eins such as those of the respiratory chain. The CoRR hypothesis proposes that t his co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the twenty-two tRNAsnecessary for the translati on of messenger RNAs into protein. The circular structure is also found in proka ryotes, and the similarity is extended by the fact that mitochondrial DNA is org anized with a variant genetic code similar to that of Proteobacteria. This sugge sts that their ancestor, the so-called proto-mitochondrion, was a member of the Proteobacteria. In particular, the proto-mitochondrion was probably closely rela ted to the rickettsia. However, the exact relationship of the ancestor of mitoch ondria to the alpha-proteobacteria and whether the mitochondria was formed at th e same time or after the nucleus, remains controversial. A recent study by researchers of the University of Hawaii at Mnoa and the Oregon S tate University, seems to indicate that SAR11 could be the ancestor of mitochond rion existing in most eukaryotic cells. The ribosomes coded for by the mitochondrial DNA are similar to those from bacte ria 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 popular ized by Lynn Margulis. The endosymbiotic hypothesis suggests that mitochondria d escended from bacteria that somehow survived endocytosis by another cell, and be came incorporated into the cytoplasm. The ability of these bacteria to conduct r espiration in host cells that had relied on glycolysis andfermentation would hav e provided a considerable evolutionary advantage. In a similar manner, host cell s 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, m etamonads, and archamoebae. These groups appear as the most primitive eukaryotes on phylogenetic treesconstructed using rRNA information, which once suggested t hat 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 gen es 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 necessar y for mitochondrial function are encoded by the mitochondrial genome; most are c oded by genes in the cell nucleus and the corresponding proteins are imported in to the mitochondrion. The exact number of genes encoded by the nucleus and the m itochondrial genome differs between species. In general, mitochondrial genomes a re circular, although exceptions have been reported. In general, mitochondrial D NA lacks introns, as is the case in the human mitochondrial genome; however, int rons have been observed in some eukaryotic mitochondrial DNA, such as that of y east and protists, including Dictyostelium discoideum. In animals the mitochondrial genome is typically a single circular chromosome th at is approximately 16-kb long and has 37 genes. The genes, while highly conserv ed, 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. Reco mbination has been shown to occur between the minichromosomes. The reason for th is difference is not known. While slight variations on the standard code had been predicted earlier, none wa s discovered until 1979, when researchers studying human mitochondrial genes det ermined that they used an alternative code. Many slight variants have been disco vered since, including various alternative mitochondrial codes. Further, the AU A, 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 produc ed. It is stimulated by decreased O2 in circulation, which is detected by the ki dneys, which then secrete the hormone erythropoietin. This hormone stimulates pr oliferation and differentiation of red cell precursors, which activates increase d erythropoiesis in the hemopoietic tissues, ultimately producing red blood cell s. In postnatal birds and mammals (including humans), this usually occurs withi n the red bone marrow. In the early fetus, erythropoiesis takes place in the me sodermal cells of the yolk sac. By the third or fourth month, erythropoiesis mov es to the spleen and liver. After seven months, erythropoiesis occurs in the bo ne marrow. Decreased level of physical activity can cause an increase in erythro poiesis. However, in humans with certain diseases and in some animals, erythrop oiesis 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 aro und five years old. The tibia and femur cease to be important sites of hematopoi esis 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). T he 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 t he absence of disease or infirmity." Although this definition has been subject t o controversy, in particular as having a lack of operational value and the probl em created by use of the word "complete", it remains the most enduring. Classif ication systems such as the WHO Family of International Classifications, includi ng the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Diseases (ICD), are commonly used to def ine and measure the components of health. The maintenance and promotion of health is achieved through different combinatio n of physical, mental, and social well-being, together sometimes referred to as thehealth triangle. The WHO s 1986 Ottawa Charter for Health Promotion furthered t hat 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 persona l 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 a nimal 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 i mpacts for the benefit of humans, such as in the sense of healthy communities, h ealthy cities or healthy environments. In addition to health care interventions and a person s surroundings, a number of other factors are known to influence th e health status of individuals, including their background, lifestyle, and econo mic and social conditions; these are referred to as "determinants of health". Generally, the context in which an individual lives is of great importance on he alth status and quality of life. It is increasingly recognized that health is ma intained 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 det erminants of health include the social and economic environment, the physical en vironment, 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, Emplo yment/working conditions, Social environments, Physical environments, Personal h ealth practices and coping skills, Healthy child development, Biology and geneti cs, 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 co llagen. 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 connectiv e tissue. The skull bones are connected by fibrous joints. Sutures are found between bones of the skull. In fetal skulls the sutures are wi de 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 uln a in forearm and the fibula and tibia in leg. Unlike other fibrous joints, synde smoses are moveable (amphiarthrodial), albeit not to such degree as synovial joi nts. 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 Conc entration No energy needed Is diffusion Active transport requires energy and can move substabces against their concentra tion gradient: And passive transport does not require energy and can move substa nces 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 to nus) is the continuous and passive partial contraction of the muscles, or the mu scles resistance to passive stretch during resting state. It helps maintain postu re, 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 use d. 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 ro les in the human body. Vitamins are divided into two groups: water-soluble (B-co mplex 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 li ver and fatty tissues, and are eliminated much more slowly than water-soluble vi tamins. 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. E ating a normal, well-balanced diet will not lead to toxicity in otherwise health y individuals. However, taking vitamin supplements that contain mega doses of vi tamins A, D, E and K may lead to toxicity. Remember, the body only needs small a mounts of any vitamin. While diseases caused by a lack of fat-soluble vitamins are rare in the United S tates, symptoms of mild deficiency can develop without adequate amounts of vitam ins 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 h elping the eyes adjust to light changes, vitamin A plays an important role in bo ne growth, tooth development, reproduction, cell division and gene expression. A lso, the skin, eyes and mucous membranes of the mouth, nose, throat and lungs de pend on vitamin A to remain moist. The best way to ensure your body gets enough vitamin A is to eat a variety of fo ods. Vitamin A is supplied primarily by certain foods of animal origin like dair y 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 beta-carotene. The recommendation for vitamin A intake is expressed as micrograms (mcg) of reti nol activity equivalents (RAE). Retinol activity equivalents account for the fac t that the body converts only a portion of beta-carotene to retinol. One RAE equ als 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 vitam in A deficiency include decreased resistance to infections, faulty tooth develop ment, and slower bone growth. In the United States, toxic or excess levels of vitamin A are of more concern th an deficiencies. The tolerable upper intake level for adults is 3,000 mcg RAE. I t would be difficult to reach this level consuming food alone. But some multivit amin supplements contain high doses of vitamin A. If you take a multivitamin, ch eck the label to be sure the majority of vitamin A provided is in the form of be ta-carotene, which appears to be safe. Symptoms of vitamin A toxicity include dr y, itchy skin, headache, nausea, and loss of appetite. Signs of severe overuse o ver 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 b y 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 pediatricia n or Registered Dietitian. Table 1: Vitamin facts. Vitamin Source Physiological Functions Deficiency Overconsumption A (retinol) (provitamin A, such as beta carotene) Vitamin A: liver, vitami n 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. Helps to form skin and mucous membranes and keep them healthy, thus increasing resistance to infections; essential for night vis ion; promotes bones and tooth development. Beta carotene is an antioxidant and m ay protect against cancer. Mild: night blindness, diarrhea, intestinal infe ctions, impaired vision. Severe: inflammation of eyes, keratinization of skin and eyes. Blindness in chil dren. Mild: nausea, irritability, blurred vision. Severe: growth retardation, enlargement of liver and spleen, loss of hair, bone pain, increased pressure in skull, skin changes. D Vitamin D-fortified dairy products, fortified margarine, fish oils, egg yolk. Synthesized by sunlight action on skin. Promotes hardening of bones and teeth, increases the absorption of calcium. Severe: rickets in children; ost eomalacia in adults. Mild: nausea, weight loss, irritability. Severe: mental and physical growth retardation, kidney damage, movement of calci um from bones into soft tissues. E Vegetable oil, margarine, butter, shortening, green and leafy vegetables , wheat germ, whole grain products, nuts, egg yolk, liver. Protects vitamin s A and C and fatty acids; prevents damage to cell membranes. Antioxidant.

Almost impossible to produce without starvation; possible anemia in low birth-we ight infants. Nontoxic under normal conditions. Severe: nausea, digestive tract disorders. K Dark green leafy vegetables, liver; also made by bacteria in the intesti ne. Helps blood to clot. Excessive bleeding. None reported. Vitamin D Vitamin D plays a critical role in the bodys use of calcium and phosphorous. It i ncreases the amount of calcium absorbed from the small intestine and helps form and maintain bones. Children especially need adequate amounts of vitamin D to de velop strong bones and healthy teeth. The primary food sources of vitamin D are milk and other dairy products fortifie d with vitamin D. Vitamin D is also found in oily fish (e.g., herring, salmon an d sardines) as well as in cod liver oil. In addition to the vitamin D provided b y food, we obtain vitamin D through our skin which makes vitamin D in response t o sunlight. An Adequate Intake (AI) for has been established for vitamin D (see Table 2). Th e AIs for vitamin D appear as micrograms (mcg) of cholecalciferol. Ten mcg of ch olecalciferol 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 ad ults 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 yea r of age and older (see Table 3). High doses of vitamin D supplements coupled wi th large amounts of fortified foods may cause accumulations in the liver and pro duce signs of poisoning. Signs of vitamin D toxicity include excess calcium in t he blood, slowed mental and physical growth, decreased appetite, nausea and vomi ting. 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 cloth es that cover most of their skin or live in northern climates where little sun i s seen in the winter, then vitamin D deficiency may occur. Rather than give chil dren a supplement, add fortified foods to their diet, such as vitamin D fortifie d 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 ade quate sun exposure, at least 800 to 1,000 IU of Vitamin D3 may be needed to reac h the circulating level required to maximize Vitamin Ds beneficial health effects . Table 2: Dietary Reference Intakes (DRI) for fat soluble vitamins. Life Stage Group Vitamin A (mcg1) Vitamin A (IU) Vitamin D (mcg2) Vitamin D (IU) Vitamin E (mg a-TE3) Vitamin E (IU) Infants 0.0-0.5 400* 1333 5* 200 4* 6 0.5-1.0 500* 1666 5* 200 5* 7.5 Children 1-3 300 1000 5* 200 6 9 4-8 400 1333 5* 200 7 10.5 Males 9-13 14-18 19-30 31-50 51-70 71+ Females 9-13 14-18 19-30 31-50 51-70 71+ 600 900 900 900 900 900 600 700 700 700 700 700 2000 3000 3000 3000 3000 3000 2000 2333 2333 2333 2333 2333 5* 5* 5* 5* 10* 15* 5* 5* 5* 5* 10* 15* 200 200 200 200 400 600 200 200 200 200 400 600 11 15 15 15 15 15 11 15 15 15 15 15 16.5 22.5 22.5 22.5 22.5 22.5 16.5 22.5 22.5 22.5 22.5 22.5

Pregnant <18 750 2500 5* 200 15 22.5 19-30 770 2566 5* 200 15 22.5 31-50 770 5* 200 15 22.5 Lactating <18 1,300 4000 5* 200 19 28.8 19-30 1,300 4333 5* 200 19 28.8 31-50 1,300 4333 5* 200 19 28.8 *Indicates an Adequate Intake (AI). All other values are Recommended Dietary All owance (RDA). 1As retinol activity equivalents (RAEs). 1 RAE = 1mcg retinol or 12 mcg beta-car otene. 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 a nd 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 canc er than non-supplement users. On the other hand, there are many studies that sho w a link between regularly eating antioxidant-rich fruits and vegetables and a l ower 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-t ocopherol (see Table 2). One milligram of alpha-tocopherol equals to 1.5 Interna tional 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 vitam in E include vegetable oils and margarines. Vitamin E is also found in fruits an d vegetables, grains, nuts, seeds and fortified cereals. Vitamin E deficiency is rare. Cases of vitamin E deficiency only occur in premat ure infants and people unable to absorb fats. The tolerable upper intake levels for vitamin E are shown in Table 3. Large dose s of vitamin E pose a hazard to people who take blood-thinning medications. Peop le taking statin drugs are also not advised to take supplemental vitamin E becau se it may interfere with how the medication works. Vitamin K Naturally produced by the bacteria in the intestines, vitamin K plays an essenti al role in normal blood clotting and helps promote bone health. Good food sources of vitamin K are green vegetables such as turnip greens, spina ch, cauliflower, cabbage and broccoli, and certain vegetables oils including soy bean oil, cottonseed oil, canola oil and olive oil. Animal foods, in general, co ntain limited amounts of vitamin K. To help ensure people receive sufficient amounts of vitamin K, an Adequate Intak e (AI) has been established for each age group (see Table 2). Without sufficient amounts of vitamin K, hemorrhaging can occur. Deficiencies ma y appear in infants, or in people who take anticoagulants or antibiotic drugs. N ewborn babies lack the intestinal bacteria to produce vitamin K and need a suppl ement for the first week. People on anticoagulant drugs (blood thinners) may bec ome 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. P eople taking antibiotics may lack vitamin K temporarily because intestinal bacte ria are sometimes killed as a result of long-term use of antibiotics. Also, peop le with chronic diarrhea may have problems absorbing sufficient amounts of vitam in K through the intestine and should consult their physician to determine if su pplementation 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. L arge doses are not advised. Table 3. Tolerable upper intake levels (UL)*. Life Stage Group Vitamin A (mcg) Vitamin D (mcg) Vitamin E (mg aTE)

Infants 0.0-0.5 0.5-1.0 Children 4-8 Males/Females 14-18 19-70 >71

600 600 1-3 900 9-13 2,800 3,000 3,000

25 25 600 50 1,700 50 50 50

ND1 ND 50 300 50 800 1,000 1,000

200 600

Pregnant & Lactating 19-50 3,000

<18 50

2,800 1,000

50

800

*A UL for vitamin K was not established. 1ND = 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). Ma ke 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 mee t 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 r ecommended 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 o f connective tissue. "Connective tissue" is a fibrous tissue. It is one of the four traditional class es of tissues (the others being epithelial, muscle, and nervous tissue). Connect ive 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 m ain components; cells, fibers, and extracellular matrix, all embedded in the bod y fluids. Fibroblasts are the cells responsible for the production of connective tissue. The interaction of the fibers, the extracellular matrix and the water t ogether, form the pliable connective tissue as a whole. Connective tissue makes up a variety of physical structures including, tendons and the connective framew ork of fibers in muscles, capsules and ligaments around joints, cartilage, bone, adipose tissue, blood and lymphatic tissue. CT is classified into three subtype s; 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 ca rtilage, bone, adipose tissue, blood, hematopoietic tissue (tissue that makes bl ood cells) and lymphatic tissue. and the most abundant protein in mammals, makin g 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 i s paramount to continued survival. The process of blood clotting and then the su bsequent dissolution of the clot, following repair of the injured tissue, is ter med 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 fl ow of blood to the area of injury. 2. Next, platelets become activated by thrombin and aggregate at the site of inj ury, forming a temporary, loose platelet plug. The protein fibrinogen is primari ly responsible for stimulating platelet clumping. Platelets clump by binding to collagen that becomes exposed following rupture of the endothelial lining of ves sels. Upon activation, platelets release the nucleotide, ADP and the eicosanoid, TXA2 (both of which activate additional platelets), serotonin, phospholipids, l ipoproteins, and other proteins important for the coagulation cascade. In additi on to induced secretion, activated platelets change their shape to accommodate t he 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 platelet s it is termed a white thrombus; if red blood cells are present it is called are d 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 o f 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 o n a common pathway that leads to clot formation. Both pathways are complex and i nvolve numerous different proteins termed clotting factors. Fibrin clot formatio n in response to tissue injury is the most clinically relevant event of hemostas is under normal physiological conditions. This process is the result of the acti vation of the extrinsic pathway. The formation of a red thrombus or a clot in re sponse 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 norma l physiological conditions. Most significant clinically is the activation of the intrinsic pathway by contact of the vessel wall with lipoprotein particles, VLD Ls and chylomicrons. This process clearly demonstrates the role of hyperlipidemi a in the generation of atherosclerosis. The intrinsic pathway can also be activa ted 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, rel ease 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 di sease, (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 (G PIb-GPIX-GPV) and collagen fibrils. The GPIb part of the complex is composed of two proteins, GPIb nd GPI encoded y sep r te genes. The import nce of this inte r ction etween vWF nd the GPI -GPIX-GPV complex of pl telets is demonstr ted y the inherit nce of leeding disorders c used y defects in three of the four p roteins of the complex, the most common of which is Bern rd-Soulier syndrome ( l so c lled gi nt pl telet syndrome). In ddition to its role s ridge etween pl telets nd exposed coll gen on en dotheli l surf ces, vWF inds to nd st ilizes co gul tion f ctor VIII. Binding of f ctor VIII y vWF is required for norm l surviv l of f ctor VIII in the cir cul tion. von Wille r nd f ctor is complex multimeric glycoprotein th t is produced y

nd stored in the -gr nules of pl telets. It is lso synthesized y meg k ryocytes nd found ssoci ted with su endotheli l connective tissue. The initi l ctiv tion of pl telets is induced y throm in inding to specific r eceptors on the surf ce of pl telets, there y initi ting sign l tr nsduction c sc de. The throm in receptor is coupled to G-protein th t, in turn, ctiv tes phospholip se C- (PLC-). PLC- hydrolyzes phosphatidylinositol-4,5-bisphosphate (PI P2) leadin to the formation of inositol trisphosphate (IP3) and diacyl lycerol (DAG). IP3 induces the release of intracellular Ca2+ stores, and DAG activates p rotein kinase C (PKC). The colla en to which platelets adhere as well as the release of intracellular C a2+ leads to the activation of phospholipase A2 (PLA2), which then hydrolyzes me mbrane phospholipids, leadin to liberation of arachidonic acid. The arachidonic acid release leads to an increase in the production and subsequent release of t hromboxane A2(TXA2). TXA2 is a potent vasoconstrictor and inducer of platelet a re ation that functions by bindin to receptors that function throu h the PLC- p athway. Another enzyme activated by the released intracellular Ca2+ stores is myosin li ht chain kinase (MLCK). Activated MLCK phosphorylates the li ht chain of myosin which then interacts with actin, resultin in altered platelet morpholo y and mo tility. One of the many effects of PKC is the phosphorylation and activation of a specif ic 47,000-Dalton platelet protein. This activated protein induces the release of platelet ranule contents; one of which is ADP. ADP further stimulates platelet s increasin the overall activation cascade. The important role of ADP in platel et activation can be appreciated from the use of the ADP receptor anta onist, Pl avix (clopido rel), in the control of thrombosis (see below). ADP also modifies t he platelet membranes leadin to exposure platelet lycoprotein receptor complex : GPIIb-GPIIIa. GPIIb-GPIIIa constitutes a receptor for vWF and fibrino en, resu ltin in fibrino en-induced platelet a re ation. The GPIIb-GPIIIa complex is a member of the inte rin family of cell-surface receptors that interact with the e xtracellular matrix. The GPIIb-GPIIIa complex is also called inte rin II -3. The i mport nce of the GPII -GPIII in pl telet ctiv tion nd co gul tion is demonstr ted y the f ct th t leeding disorders result from inherited defects in this g lycoprotein complex. The most commonly inherited pl telet dysfunction is Gl nzm nn throm stheni which results from defects in the GPII protein of this comple x. In ddition, the import nce of this complex in over ll hemost sis is demonstr ted y the use of nti odies th t lock this receptor s nti-co gul nts (e.g. ReoPro, cixim : see elow). Activ tion of pl telets is required for their consequent ggreg tion to pl tel et plug. However, equ lly signific nt is the role of ctiv ted pl telet surf ce phospholipids in the ctiv tion of the co gul tion c sc de.

Prim ry F ctors F ctor Trivi l N me(s) P thw y Ch r cteristic Prek llikrein (PK) Fletcher f ctor Intrinsic Functions with HMWK nd f ctor XII High molecul r weight kininogen (HMWK) cont ct ctiv tion cof ctor; Fitzger ld, Fl uje c Willi ms f ctor Intrinsic Co-f ctor in k llikrein nd f ct or XII ctiv tion, necess ry in f ctor XII ctiv tion of XI, precursor for r d ykinin ( potent v sodil tor nd inducer of smooth muscle contr ction I Fi rinogen Both II Prothrom in Both Cont ins N-term. gl segment III Tissue F ctor Extrinsic IV C lcium Both V Pro ccelerin, l ile f ctor, cceler tor (Ac-) glo ulin Both Protein cof ctor VI (s me s V ) Accelerin Both This is V , redund nt to F ctor V

VII Proconvertin, serum prothrom in conversion cceler tor (SPCA), cothrom o pl stin Extrinsic Endopeptid se with gl residues VIII Antihemophili c f ctor A, ntihemophilic glo ulin (AHG) Intrinsic Protein cof ctor IX Christm s F ctor, ntihemophilic f ctor B,pl sm throm opl stin componen t (PTC) Intrinsic Endopeptid se with gl residues X Stu rt-Prower F ctor Both Endopeptid se with gl residues XI Pl sm throm opl stin ntecedent (PTA) Intrinsic Endopeptid se XII H gem n F ctor Intrinsic Endopeptid se XIII Protr nsglut min se, fi rin st ilizing f ctor (FSF), fi rinolig se Both Tr nspeptid se Function l Cl ssific tion of Clotting F ctors Zymogens of Serine Prote ses Activities F ctor XII inds to exposed coll gen t site of vessel w ll injury, ctiv t ed y high-MW kininogen nd k llikrein F ctor XI ctiv ted y f ctor XII F ctor IX ctiv ted y f ctor XI in presence of C 2+ F ctor VII ctiv ted y throm in in presence of C 2+ F ctor X ctiv ted on surf ce of ctiv ted pl telets y ten se complex n d y f ctor VII in presence of tissue f ctor nd C 2+ F ctor II ctiv ted on surf ce of ctiv ted pl telets y prothrom in se co mplex Cof ctors Activities F ctor VIII ctiv ted y throm in; f ctor VIII is cof ctor in the ctiv t ion of f ctor X y f ctor IX F ctor V ctiv ted y throm in; f ctor V is cof ctor in the ctiv tion of prothrom in y f ctor X F ctor III (tissue f ctor) su endotheli l cell-surf ce glycoprotein th t cts s cof ctor for f ctor VII Fi rinogen Activity F ctor I cle ved y throm in to form fi rin clot Tr nsglut min se Activity F ctor XIII ctiv ted y throm in in presence of C 2+; st ilizes fi rin clo t y cov lent cross-linking Regul tory/Other Proteins Activities von Wille r nd f ctor ssoci ted with su endotheli l connective tissue; serves s ridge etween pl telet glycoprotein GPI /IX nd coll gen Protein C ctiv ted to protein C y throm in ound to throm omodulin; the n degr des f ctors VIII nd V Protein S cts s cof ctor of protein C; oth proteins cont in gl resid ues Throm omodulin protein on the surf ce of endotheli l cells; inds throm in, whi ch then ctiv tes protein C Antithrom in III most import nt co gul tion inhi itor, controls ctivitie s of throm in, nd f ctors IX , X , XI nd XII The Clotting C sc des The clotting c sc des: The intrinsic c sc de (which h s less in vivo signific nc e in norm l physiologic l circumst nces th n the extrinsic c sc de) is initi ted when cont ct is m de etween lood nd exposed neg tively ch rged surf ces. The extrinsic p thw y is initi ted upon v scul r injury which le ds to exposure of tissue f ctor, TF ( lso identified s f ctor III), su endotheli l cell-surf ce glycoprotein th t inds phospholipid. The green dotted rrow represents point of cross-over etween the extrinsic nd intrinsic p thw ys. The two p thw ys co nverge t the ctiv tion of f ctor X to X . F ctor X h s role in the further ctiv tion of f ctor VII to VII s depicted y the green rrow. Active f ctor X hydrolyzes nd ctiv tes prothrom in to throm in. Throm in c n then ctiv te f ctors XI, VIII nd V furthering the c sc de. Ultim tely the role of throm in is to convert fri rinogen to fi rin nd to ctiv te f ctor XIII to XIII . F ctor X III ( lso termed tr nsglut min se) cross-links fi rin polymers solidifying the

clot. HMWK = high molecul r weight kininogen. PK = prek llikrein. PL = phospholi pid. Activ tion of Prothrom in to Throm in The common point in oth p thw ys is the ctiv tion of f ctor X to f ctor X . F ctor X ctiv tes prothrom in (f ctor II) to throm in (f ctor II ). Throm in, in turn, converts fi rinogen to fi rin. The ctiv tion of throm in occurs on the s urf ce of ctiv ted pl telets nd requires form tion of prothrom in se complex . This complex is composed of the pl telet phospholipids, phosph tidylinositol nd phosph tidylserine, C 2+, f ctors V nd X , nd prothrom in. F ctor V is c of ctor in the form tion of the prothrom in se complex, simil r to the role of f ctor VIII in ten se complex form tion. Like f ctor VIII ctiv tion, f ctor V is ctiv ted to f ctor V y me ns of minute mounts nd is in ctiv ted y incre s ed levels of throm in. F ctor V inds to specific receptors on the surf ces of ctiv ted pl telets nd forms complex with prothrom in nd f ctor X . Prothrom in is 72,000-D lton, single-ch in protein cont ining ten gl residues in its N-termin l region. Within the prothrom in se complex, prothrom in is cle ved t 2 sites y f ctor X . This cle v ge gener tes 2-ch in ctive throm in molecule cont ining n A nd B ch in which re held together y single disul fide ond. In ddition to its role in ctiv tion of fi rin clot form tion, throm in pl ys n import nt regul tory role in co gul tion. Throm in com ines with throm omoduli n present on endotheli l cell surf ces forming complex th t converts protein C to protein C . The cof ctor protein S nd protein C degr de f ctors V nd VII I , there y limiting the ctivity of these 2 f ctors in the co gul tion c sc de (see det ils elow). Throm in lso inds to cl ss of G-protein-coupled receptors c lled prote se c tiv ted receptors (PARs), specific lly PAR-1, -3 nd -4. PARs utilize unique m ech nism to convert the result of extr cellul r proteolytic cle v ge into n int r cellul r sign ling event. PARs c rry their own lig nd which rem ins in ctive u ntil prote se cle v ge, such s y throm in, "unm sks" the lig nd. Following thr om in cle v ge the unm sked lig nd is still p rt of the int ct PAR ut is now c p le of inter cting with the lig nd- inding dom in of the PAR resulting in th e ctiv tion of numerous sign ling c sc des. Bec use the ctiv tion of PARs requ ires proteolytic cle v ge the ctiv tion process is irreversi le. The sign ling c sc des ctiv ted y throm in- ctiv ted PARs include rele se of the interleukin s, (ILs), IL-1 nd IL-6, incre sed secretion of intercellul r dhesion molecule1 (ICAM-1) nd v scul r cell dhesion molecule-1 (VCAM-1). The throm in-induced sign ling lso le ds to incre sed pl telet ctiv tion nd leukocyte dhesion. Throm in lso ctiv tes throm in- ctiv t le fi rinolysis inhi itor (TAFI) thus modul ting fi rinolysis (degr d tion of fi rin clots). TAFI is lso known s c r oxypeptid se U (CPU) whose ctivity le ds to remov l of C-termin l lysines from p rti lly degr ded fi rin. This le ds to n imp irment of pl sminogen ctiv tio n, there y reducing the r te of fi rin clot dissolution (i.e. fi rinolysis). Control of Throm in Levels The in ility of the ody to control the circul ting level of ctive throm in wo uld le d to dire consequences. There re 2 princip l mech nisms y which throm i n ctivity is regul ted. The predomin nt form of throm in in the circul tion is the in ctive prothrom in, whose ctiv tion requires the p thw ys of proenzyme c tiv tion descri ed ove for the co gul tion c sc de. At e ch step in the c sc d e, feed ck mech nisms regul te the l nce etween ctive nd in ctive enzymes. The ctiv tion of throm in is lso regul ted y 4 specific throm in inhi itors A ntithrom in III is the most import nt since it c n lso inhi it the ctivities o f f ctors IX , X , XI nd XII , pl smin, nd k llikrein. The ctivity of ntith rom in III is potenti ted in the presence of hep rin y the following me ns: hep rin inds to specific site on ntithrom in III, producing n ltered conform tion of the protein, nd the new conform tion h s higher ffinity for throm in s well s its other su str tes. This effect of hep rin is the sis for its cl inic l use s n ntico gul nt. The n tur lly occurring hep rin ctiv tor of nt ithrom in III is present s hep r n nd hep r n sulf te on the surf ce of vessel endotheli l cells. It is this fe ture th t controls the ctiv tion of the intri

nsic co gul tion c sc de. However, throm in ctivity is lso inhi ited y 2-m croglo ulin, hep rin cof ctor II nd 1- ntitrypsin. Although minor pl yer in throm in regul tion 1- ntitrypsi n is the prim ry serine prote se inhi itor of hum n pl sm . Its physiologic l si gnific nce is demonstr ted y the f ct th t l ck of this protein pl ys c us ti ve role in the development of emphysem . Activ tion of Fi rinogen to Fi rin Fi rinogen (f ctor I) consists of 3 p irs of polypeptides ([A][B][])2. The 6 chains are covalently linked near their N-terminals throu h disulfide bonds. The A and B portions of the A nd B ch ins comprise the fi rinopeptides, A nd B, respectiv ely. The fi rinopeptide regions of fi rinogen cont in sever l glut m te nd sp rt te residues imp rting high neg tive ch rge to this region nd id in the so lu ility of fi rinogen in pl sm . Active throm in is serine prote se th t hydr olyses fi rinogen t four rg-gly (R-G) onds etween the fi rinopeptide nd the nd portions of the protein. Throm in-medi ted rele se of the fi rinopeptides gener tes fi rin monomers with su unit structure ()2. These monomers spontaneously a re ate in a re ular array, formin a somewhat weak fibrin clot. In addition to fibrin activation, thrombin converts factor XIII to factor XIIIa, a hi hly specific trans lutaminase that i ntroduces cross-links composed of covalent bonds between the amide nitro en of lutamines and -amino group of lysin s in th fibrin monom rs. Dissolution of Fibrin Clots D gradation of fibrin clots is th function of plasmin, a s rin prot as that c irculat s as th inactiv pro nzym , plasminog n. Any fr circulating plasmin i s rapidly inhibit d by 2- ntipl smin. Pl sminogen inds to oth fi rinogen nd fi rin, there y eing incorpor ted into clot s it is formed. Tissue pl sminogen ctiv tor (tPA) nd, to lesser degree, urokin se re serine prote ses which c onvert pl sminogen to pl smin. In ctive tPA is rele sed from v scul r endotheli l cells following injury; it inds to fi rin nd is consequently ctiv ted. Urok in se is produced s the precursor, prourokin se y epitheli l cells lining excr etory ducts. The role of urokin se is to ctiv te the dissolution of fi rin clot s th t m y e deposited in these ducts. Active tPA cle ves pl sminogen to pl smin which then digests the fi rin; the res ult is solu le degr d tion product to which neither pl smin nor pl sminogen c n ind. Following the rele se of pl sminogen nd pl smin they re r pidly in ctiv ted y their respective inhi itors. The inhi ition of tPA ctivity results from inding to specific inhi itory proteins. At le st 4 distinct inhi itors h ve ee n identified, of which 2: pl sminogen ctiv tor-inhi itors type 1 (PAI-1) nd ty pe 2 (PAI-2) re of gre test physiologic l signific nce. Blood Co gul tion Tests nd Interpret tions Bleeding time ss ys re used to ev lu te the v scul r nd pl telet responses th t re ssoci ted with hemost sis. The leeding time is frequent ss y perform ed on preoper tive p tients to ensure there is n dequ te response to vessel in jury prior to surgery. As indic ted ove, the r pid responses to v scul r injur y (occurring within seconds) re vessel constriction nd pl telet dhesion to th e vessel w ll. The Ivy method for determining the leeding time involves the use of lood pressure cuff (sphygmom nometer) which is pl ced on the fore rm nd infl ted to 40mmHg. A superfici l incision is then m de on the fore rm nd the t ime it t kes for leeding to stop is recorded. With the Ivy method leeding shou ld stop within 19 minutes. Any leeding time gre ter th n 15 minutes would e ind ic tive of defect in the initi l responses of vessels nd pl telets to v scul r injury. A less inv sive leeding time ss y involves the use of l ncet or sp eci l needle nd 34mm deep prick is m de on the fingertip or e rlo e. This lee ding time ss y is referred to s the Duke method nd in this ss y leeding sho uld ce se within 13 minutes. The leeding time is ffected (prolonged) y ny def ect in pl telet function, y v scul r disorders, nd in von Wille r nd dise se ut is not ffected y other co gul tion f ctors. Disorders th t re commonly ss oci ted with n incre sed leeding time include throm ocytopeni , dissemin ted i ntr v scul r co gul tion (DIC), Bern rd-Soulier syndrome nd Gl nzm nn throm st heni . A norm l leeding times re lso found in p tients with Cushing syndrome,

severe liver dise se, leukemi , nd one m rrow f ilure. Defects ssoci ted with f ctors of the p thw ys of lood co gul tion c n lso e ssessed with specific ss ys. The prothrom in time (PT) is n ss y designed t o screen for defects in fi rinogen, prothrom in, nd f ctors V, VII, nd X nd t hus me sures ctivities of the extrinsic p thw y of co gul tion. When ny of the se f ctors is deficient then the PT is prolonged. A norm l PT is 11.012.5 seconds . A PT gre ter th n 20 seconds is indic tive of co gul tion deficit. The PT is m e sured using pl sm fter the lood cells re removed. A lood s mple is collec ted in tu e cont ining citr te or EDTA to chel te ny c lcium nd thus inhi it co gul tion nd then the cells re removed y centrifug tion. After the cells re removed excess c lcium is dded to the pl sm to initi te co gul tion. The mo st common me sure of PT is to divide the time of co gul tion of p tients lood y th t of known st nd rd nd this v lue is referred to s the intern tion l norm lized r tio (INR). Norm l INR v lues r nge from 0.81.2. PT is used to determ ine the correct dos ge of the w rf rin cl ss of nti-co gul tion drugs (e.g. Cou m din), for the presence of liver dise se or d m ge, nd to ev lu te vit min K s t tus. The p rti l throm opl stin time (PTT) is used to ss y for defects in the intrin sic p thw y of co gul tion. The PTT ss y h s een modified y the ddition of ctiv tors th t shorten the norm l clotting time nd this form of the ss y is re ferred to s the ctiv ted p rti l throm opl stin time ( PTT). The PTT is norm l ly prescri ed in p tients with unexpl ined leeding or clotting. The ss y will ev lu te the function of fi rinogen, prothrom in, nd f ctors V, VIII, IX, X, XI , nd XII. A defect in ny of these f ctors will result in prolonged PTT (or PTT). A norm l PTT is 6070 seconds, where s for the PTT the norm l r nge is 3040 seconds. The PTT is st nd rd ss y used to ssess the effic cy of hep rin nti co gul nt ther py. Prolonged PTTs re ssoci ted with cquired or congenit l le eding disorders ssoci ted with co gul tion f ctor deficiency, vit min K deficie ncy, liver dise se, DIC, von Wille r nd dise se, leukemi , hemophili , nd durin g hep rin dministr tion. (ii) Define dise se. Descri e in det il Dise se c using gents. A dise se is n norm l condition ffecting the ody of n org nism. It is ofte n construed to e medic l condition ssoci ted with specific symptoms nd sign s.[1] It m y e c used y extern l f ctors, such s infectious dise se, or it m y e c used y intern l dysfunctions, such s utoimmune dise ses. In hum ns, "d ise se" is often used more ro dly to refer to ny condition th t c usesp in, dy sfunction, distress, soci l pro lems, nd/or de th to the person fflicted, or s imil r pro lems for those in cont ct with the person. In this ro der sense, it sometimes includes injuries, dis ilities, disorders, syndromes, infections, is ol ted symptoms, devi nt eh viors, nd typic l v ri tions of structure nd fun ction, while in other contexts nd for other purposes these m y e considered di stinguish le c tegories. Dise ses usu lly ffect people not only physic lly, u t lso emotion lly, s contr cting nd living with m ny dise ses c n lter one's perspective on life, nd their person lity. De th due to dise se is c lled de th y n tur l c uses. There re four m in type s of dise se: p thogenic dise se, deficiency dise se, heredit ry dise se, nd ph ysiologic l dise se. Dise ses c n lso e cl ssified s communic le nd non-communic le dise se. Dise se The term dise se ro dly refers to ny condition th t imp irs norm l function. C ommonly, this term is used to refer specific lly to infectious dise ses, which re clinic lly evident dise ses th t result from the presence of p thogenic micro i l gents, including viruses, cteri , fungi, protozo , multicellul r org nis ms, nd err nt proteins known s prions. An infection th t does not nd will n ot produce clinic lly evident imp irment of norm l functioning, such s the pres ence of the norm l cteri nd ye sts in the gut, is not considered dise se; y contr st, n infection th t is symptom tic during its incu tion period, ut expected to produce symptoms l ter, is usu lly considered dise se. Non-infect ious dise ses re ll other dise ses, including most forms of c ncer,he rt dise

se, nd genetic dise se. P thogens re org nisms, frequently microorg nisms, or components of these org n isms, th t c use dise se. Micro i l p thogens include v rious species of cteri , viruses, nd protozo . M ny dise ses c used y micro i lp thogens, nd the fr equency of these dise ses, re n tion l security issue. P thogens nd dise se. A dise se is ny condition c used y the presence of n i nv ding org nism or toxic component th t d m ges the host. In hum ns, dise ses c n e c used y the growth of microorg nisms such s cteri , viruses, nd pr otozo . B cteri l growth, however, is not m nd tory to c use dise se. For ex mpl e, some cteri l p thogens c use dise se y virtue of toxic component of the cteri l cell such s lipopolys cch ride. Fin lly, the d m ging symptoms of d ise se c n e the result of the ttempts y the host's immune system to rid the ody of the inv der. One ex mple is the immune-rel ted d m ge c used to the lung s of those fflicted withcystic fi rosis, s the ody unsuccessfully ttempts to er dic te the chronic infections c used y Pseudomon s eruginos . Not ll p thogens c use dise ses th t h ve the s me severity of symptoms. For ex mple, n infection with theinfluenz virus c n c use the short term ches nd f ever th t re h llm rks of the flu, or it c n c use more dire symptoms, dependin g on the type of virus th t c uses the infection. B cteri lso v ry in the d m ge c used. For ex mple, the ingestion of food cont min ted with S lmonell enter itic c uses intestin l upset. But, consumption of Escherichi coli O157:H7 c us es severe dise se, which c n perm nently d m ge the kidneys nd which c n even e f t l. Types of cteri l p thogens. There re three c tegories of cteri l p thogens. O lig t p thogens re those cteri th t must c use dise se in order to e tr nsmitted from one host to nother. These cteri must lso infect host in or der to survive, in contr st to other cteri th t re c p le of surviv l outsi de of host. Ex mples of o lig te cteri l p thogens include Myco cterium tu erculosis nd Treponem p llidum. Opportunistic p thogens c n e tr nsmitted from one host to nother without h vi ng to c use dise se. However, in host whose immune system is not functioning p roperly, the cteri c n c use n infection th t le ds to dise se. In those c ses, the dise se c n help the cteri spre d to nother host. Ex mples of oppo rtunistic cteri l p thogens include Vi rio choler e nd Pseudomon s eruginos . Fin lly, some cteri l p thogens c use dise se only ccident lly. Indeed, the d ise se ctu lly limits the spre d of the cteri to nother host. Ex mples of t hese " ccident l' p thogens include Neisseri meningitides ndB cteroides fr gil is. Spre d of p thogens. P thogens c n e spre d from person to person in num er o f w ys. Not ll p thogens use ll the v il le routes. For ex mple, the influen z virus is tr nsmitted from person to person through the ir, typic lly vi sne ezing or coughing. But the virus is not tr nsmitted vi w ter. In contr st, Esch erichi coli is re dily tr nsmitted vi w ter, food, nd lood, ut is not re di ly tr nsmitted vi ir or the ite of n insect. While routes of tr nsmission v ry for different p thogens, given p thogen will use given route of tr nsmission. This h s een used in the we poniz tion of p thogens. The est-known ex mple is nthr x. The cterium th t c uses nthr xB c illus nthr cisc n form n environment lly h rdy form c lled spore. The spore i s very sm ll nd light. It c n flo t on currents of ir nd c n e re thed into the lungs, where the cteri resume growth nd swiftly c use serious nd oft en f t l form of nthr x. As demonstr ted in the United St tes in the l st few m onths of 2001, nthr x spores re e sily sent through the m il to t rgets. As we ll, the powdery spores c n e rele sed from n ircr ft. Over m jor ur n cent er, modeling studies h ve indic ted th t the resulting c su lties could num er i n the hundreds of thous nds. Cont min tion of w ter y p thogens is nother insidious route of dise se spre d . W ter c n look cryst l cle r despite the presence of millions of cteri in e ch milliliter. Viruses, which re much sm ller, c n e present in even higher n um ers without ffecting the ppe r nce of the liquid. Thus, w ter c n e e sily l ced with enough p thogens to c use illness.

(iii) Dr w ne t l eled di gr m of skelet l muscle. Give the n tomy nd phy siology of skelet l muscle. Skelet l muscle is form of stri ted muscle tissue existing under control of th e som tic nervous system- i.e. it is volunt rily controlled. It is one of three m jor muscle types, the others eing c rdi c nd smooth muscle. As their n me su ggests, most skelet l muscles re tt ched to ones y undles of coll gen fi er s known s tendons. Skelet l muscle is m de up of individu l components known s muscle fi ers. Thes e fi ers re formed from the fusion of development l myo l sts ( type of em ryo nic progenitor cell th t gives rise to muscle cell). The muscle fi ers re lon

Food- orne p thogens c use millions of c ses of dise se nd hundreds of de ths e ch ye r in the United St tes lone. Frequently the responsi le micro es re c teri , viruses, or protozo th t usu lly reside in the intestin l tr ct of hum n s or other cre tures. Ex mples of such microorg nisms include Escherichi coli O 157:H7, C mpylo cter jejuni, nd rot virus. P thogens c n e tr nsmitted to hum ns through cont ct with nim ls, irds, nd other living cre tures th t n tur lly h r or the microorg nism. The gent of nt hr xB cillus nthr cisn tur lly dwells in sheep. Other ex mples include Brucell ortic (Brucellosis), Coxiell urnetti (Q fever), nd viruses th t c use hemorr h gic feverssuch s E ol nd M r urg. P thogenic mech nisms. Microorg nisms h ve v rious str tegies to est lish n in fection in host. Some micro-org nisms recognize molecules on the surf ce of th e host cell, nd use these s receptors. The inding of cteri or viruses to r eceptors rings the microorg nism in close cont ct with the host surf ce. The n ture of the inter ction etween the host receptor molecule nd the tt chm ent molecule on the surf ce of the cteri , virus, or protozo n h s in some c s es een defined, even to the genetic level. The use of recom in nt DNA technolog ywhere t rget section of genetic m teri l is removed from one org nism nd inse rted into cert in region of the genetic m teri l of nother org nism, in w y th t does not ffect the expression of the gene llows the genetic m nipul tion o f microorg nism so s to enh nce its ility to c use n infection. Altern tiv ely, inserting gene th t codes for toxin into cterium th t is norm l i nh it nt of n environment like the intestin l tr ct could produce formid le p thogen. This ltered cteri would re dily ssoci te with host cells, ut wo uld lso c rry the toxin. Viruses lmost lw ys d m ge the host cells. Bec use viruses c nnot reproduce on their own, they rely on thereplic tion mech nism of the host cell to m ke more copies of themselves (i.e., they re o lig te p thogens). Then, the new vir l p rticles will exit the cell nd se rch for nother cell to infect. This exit is o ften very physic lly d m ging to the host cell. Thus, vir l infections c n e de triment l ec use of the loss of function of host cells. Some vir l p thogens re c p le of c using dise se long fter they h ve infec ted host. This del yed response occurs ec use the vir l genetic m teri l eco mes incorpor ted into the genetic m teri l of the host. There fter, the vir l ge netic m teri l is replic ted long with th t of the host, using the replic tion enzymes nd other m chinery of the host. But, in response to num er of sign ls , the vir l m teri l c n e excised from the host m teri l nd form the templ te for the m nuf cture nd ssem ly of new virus p rticles. A prominent ex mple of such virus is theHum n Immunodeficiency Virus, which is cknowledged to e th e c use of Acquired Immunodeficiency Syndrome. Bec use viruses must infect other cells in order to replic te, they h ve develop ed me ns of esc ping ( t le st for time) the defensive responses of the host. This efficiency of tt ck h s not esc ped the ttention of molecul r iologists ent on the m licious use of viruses. By inserting gene coding for toxic compo und into vir l genome, p rticul rly into the genome of n infectious virus (i. e., influenz or cold viruses) the virus ecomes iowe pon. For ex mple, scien tists in the former Soviet Union ttempted to construct n influenz virus th t cont ined the gene coding for co r toxin.

g, cylindric l, multinucle ted cells composed of myofi rils. The myofi rils re composed of ctin nd myosin myofi rils repe ted s s rcomere, the sic funct ion l unit of the muscle fi er nd responsi le for skelet l muscle's stri ted p pe r nce nd forming the sic m chinery necess ry for muscle contr ction. The t erm muscle refers to multiple undles of muscle fi ers held together y connecti ve tissue. An tomy nd Physiology of Skelet l Muscle

The hum n ody h s three types of muscles: Skelet l, smooth, nd c rdi c. Bec us e Sports M ss ge Ther pists re m inly concerned with skelet l muscles, they wil l e the ones prim rily discussed throughout this text. Skelet l muscles re prim rily tt ched to the ones of the ody nd, unlike smo oth nd c rdi c muscles, re under volunt ry control. They comprise most of the flesh of the ody nd constitute out 40% to 50% of persons total body w ight. Sk l tal muscl s p rform th following functions: Produc mov m nt of joints by contracting. Pr v nt und sir d mov m nt of joints. Produc h at (through th splitting of Ad nosin Triphosphat (ATP) during contraction.) Sk l tal muscl is compris d of long cylindrical multinucl at c lls which li p arall l to ach oth r. Each c ll is surround d by a thin lastic m mbran call d th sarcol mmawhich nclos s its cont nts. Within th m mbran is th fluid pro toplasm, or th sarcoplasm, of th c ll which contains myofibrils (discuss d lat r in this t xt) and th sarcoplasmic r ticulum, compris d of a n twork of small c hann ls and fluid-fill d sacs. Sk l tal muscl c lls ar also call d fib rs. Ov rlaying th sarcol mma of ach fib r is a thin lay r of conn ctiv tissu call d th ndomysium. Th fib rs ar group d tog th r into many individual bundl s which ar cov r d with a lay r of conn ctiv tissu call d th p rimysium. Th s bundl s ar known as fascicl s an d tog th r th y form a muscl . Th ntir muscl is cov r d by y t anoth r thin lay r of conn ctiv tissu call d th pimysium, which its lf is cov r d by conn ctiv tissu call d fascia. Th s last two prot ctiv lay rs ar tap r d at th nds and form th t ndons which attach a muscl to bon , cartilag or conn ctiv tissu . Each individual muscl fib r contains v ry fin , long prot in strands call d myo fibrils, which ar align d sid -by-sid and xt nd th l ngth of th fib r. Th y ar th units which l ngth n and contract th muscl . Th myofibrils ar "actua lly chains of tiny contractil units, call d sarcom r s, which ar align d nd-t o- nd lik boxcars in a train along th l ngth of th myofibrils." Th Sarcom r s ar form d by v n fin r strands known asmyofilam nts. Th myofilam nts ar co mpris d of prot ins which form dark thick strandsA bandsand light thin strandsI ban dsand ar what giv sk l tal muscl its striat d app aranc . Th I bands ar also call d actin filam nts b caus th y ar primarily mad of a prot in call d actin, but th y also contain two oth r prot instroponin and tropo myosin. Th A bands ar also known as myosin filam nts b caus th y ar form d f rom a prot in call d myosin; th y contain ATPas nzym s which split ATP to prod uc th n rgy for muscl contraction. Th myosin filam nts contain "lollipop" p roj ctions, r f rr d to as cross-bridg s or myosin h ads, which spiral around it s l ngth. During muscl contraction, th s proj ctions attach to binding (activ ) sit s on actin filam nts to produc mov m nt. In r sting muscl , th troponin and tropomyosin cov r th activ sit s and inhibit th myosin h ads from bonding to th actin filam nts, th r by pr v nting muscl contraction. Sk l tal muscl is stimulat d to contract by impuls s transmitt d by sp cializ d n rv c lls call d motor n urons. Th c ll body of a motor n uron r sid s in th c ntral n rvous syst m and its axon xt nds to th muscl . In th muscl , th axon is divid d into num rous axonal t rminals, ach of which conn cts with indi

vidual muscl fib rs. Th int rs ction wh r th axonal t rminals and muscl fib rs conn ct is call d th n uromuscular junction. A motor n uron and th muscl f ib rs to which it conn cts ar tog th r known as a motor unit. Wh n an action pot ntial trav ls down th muscl fib r m mbran and r ach s th axonal t rminals, th n urotransmitt r known as ac tylcholin stimulat s th r l as of calcium ions into th sarcoplasm from th sarcoplasmic r ticulum. Calciu m ions quickly attach to troponin in th actin filam nts, which caus s troponin to pull on th tropomyosin (to which troponin is attach d) th r by xposing th activ sit s of th actin filam nt and allowing it to int ract with th myosin h ads. As a r sult, th ATPaz nzym s on th myosin h ads b com activat d and s plit ATP, which n rgiz s th link b tw n th actin and myosin filam nts and ca us s muscl contraction. Onc a muscl has contract d, calcium is r absorb d bac k into th sarcoplasmic r ticulum, which allows troponin and tropomyosin to onc again inhibit th link b tw n actin and mysoin. As a r sult, th muscl onc a gain r turns to a r lax d stat . Although it is not known pr cis ly how actin and myosin produc muscl contracti ons, th "sliding filam nt th ory" propos d by H. E. Huxl y in th 1950s is a pos sibl xplanation: (Th th ory) sugg sts that stimulation of th (muscl ) fib r prompts th tiny cro ssbridg s that xt nd from th myosin filam nt (to) attach to activ sit s on th actin filam nt. Th r l as of calcium ions within th muscl fib r xpos s th s activ sit s, facilitating th attachm nt of th two (filam nts) to on anot h r. Each crossbridg x rts a pull on th actin filam nt, causing th actin and myosin filam nts to slid past on anoth r. Und r th influ nc of (ATP) r l as d in th binding proc ss, ach crossbridg is th n disconn ct d from its bindin g sit on th actin filam nt and mov s to a n ighboring sit . Sinc th proc ss happ ns simultan ously in all of th c lls of a muscl , th ntir muscl contra cts. As h althcar prof ssionals, Th rap utic & Sports Massag th rapists n d to b as ducat d and knowl dg abl about th workings of th human n uromuscular and sk l tal syst ms as possibl . Not only do s knowl dg h lp us facilitat our cli nts r cov ry proc ss from myofascial pain and dysfunction, it also nabl s us to b tt r ducat thos cli nts as to th injury and r cov ry proc ss. Additionall y, th massag th rapy prof ssions imag has b n marr d by thos in th "adult nt rtainm nt" fi ld. In our struggl to r gain soci tys r cognition of massag th rapists as h althcar prof ssionals, it is imp rativ that w continuously stri v to incr as our knowl dg bas of th workings of th human body.

(iv) Comm nt on N uromuscular Junction in d tail. A n uromuscular junction (NMJ) is th synaps or junction of th axon t rminal o f a motor n uron with th motor nd plat , th highly- xcitabl r gion of muscl fib r plasma m mbran r sponsibl for initiation of action pot ntials across th muscl s surfac , ultimat ly causing th muscl to contract. In v rt brat s, t h signal pass s through th n uromuscular junction via th n urotransmitt r ac tylcholin . M chanism of action Th n uromuscular junction is th location wh r th n uron activat s muscl to contract. This is a st p in th xcitation-contraction coupling of sk l tal musc l . 1. Upon th arrival of an action pot ntial at th pr synaptic n uron t rmin al, voltag -d p nd nt calcium chann ls op n and Ca2+ ions flow from th xtrac ll ular fluid into th pr synaptic n uron s cytosol. 2. This influx of Ca2+ caus s n urotransmitt r-containing v sicl s to dock and fus to th pr synaptic n uron s c ll m mbran through SNAREprot ins. 3. Fusion of th v sicular m mbran with th pr synaptic c ll m mbran r su lts in th mptying of th v sicl s cont nts (ac tylcholin ) into th synaptic c l ft, a proc ss known as xocytosis. 4. Ac tylcholin diffus s into th synaptic cl ft and binds to th nicotini c ac tylcholin r c ptors bound to th motor nd plat . 5. Th s r c ptors ar ligand-gat d ion chann ls, and wh n th y bind ac tyl

cholin , th y op n, allowing sodium ions to flow in and potassium ions to flow o ut of th muscl s cytosol. 6. B caus of th diff r nc s in l ctroch mical gradi nts across th plasm a m mbran , mor sodium mov s in than potassium out, producing a local d polariz ation of th motor nd plat known as an nd-plat pot ntial (EPP). 7. This d polarization spr ads across th surfac of th muscl fib r and c ontinu s th xcitation-contraction coupling to contract th muscl . 8. Th action of ac tylcholin is t rminat d wh n th nzym ac tylcholin st ras d grad s part of th n urotransmitt r (producing cholin and anac tat g roup) and th r st of it diffus s away. 9. Th cholin produc d by th action of ac tylcholin st ras is r cycl d it is transport d, through r uptak , back into th pr synaptic t rminal, wh r it is us d to synth siz n w ac tylcholin mol cul s. Ac tylcholin is a n urotransmitt r synth siz d in th human body from di tary c holin and ac tyl-CoA (ACoA). On of th first n urotransmitt rs discov r d, th substanc was originally r f rr d to as "vagusstoff" b caus it was found to b r l as d by th stimulation of th vagus n rv . Lat r, it was stablish d that ac tylcholin is, in fact, important in th stimulation of all muscl tissu and that its action may b ith r xcitatory or inhibitory, d p nding on a numb r o f factors. Within th body, th synaptic action of ac tylcholin usually quickly com s to a halt, th n urotransmitt r naturally br aking down soon aft r its r l as . How v r, som n rv gas s ar d sign d to thwart this br akdown, causing prolong d stimulation of th r c ptor c lls and r sulting in s v r muscl spasm s. D v lopm nt of th n uromuscular junction Th compl x s ri s of st ps l ading to th formation of th n uromuscular juncti on during mbryonic d v lopm nt ar only partially und rstood. During d v lopm nt, th growing nd of motor n uron axons s cr t a prot in know n as agrin This prot in binds to s v ral r c ptors on th surfac of sk l tal muscl . Th r c ptor which s ms to b r quir d for formation of th n uromuscular junct ion is th MuSK prot in (Muscl sp cific kinas ). MuSK is a r c ptor tyrosin kinas - m aning that it induc s c llular signaling by causing th r l as of phosphat mol cul s to particular tyrosin s on its lf, and on prot ins which bind th cytoplasmic domain of th r c ptor. Upon activation by its ligand agrin, MuSK signals via two prot ins call d "Dok-7 " and "rapsyn", to induc "clust ring" of ac tylcholin r c ptors (AChR). In addition to th AChR and MuSK, oth r prot ins ar th n gath r d, to form th ndplat to th n uromuscular junction. Th n rv t rminat s onto th ndplat , forming th NMJ. Knockout studi s Th s findings w r d monstrat d in part by mous "knockout" studi s. In mic wh ich ar d fici nt for ith r agrin or MuSK, th n uromuscular junction do s not form. Furth r, mic d fici nt in Dok-7did not form ith r ac tylcholin r c ptor clust rs or n uromuscular synaps s. Many oth r prot ins also compris th NMJ, and ar r quir d to maintain its int grity. N uromuscular block A block or d cr as in th transmission across th n uromuscular junction can ca us a compl t or r lativ loss of muscl function. It can r sult from n uromusc ular junction dis as s or b int ntionally induc d with n uromuscular blocking d rugs. It can also b a sid ff ct of oth r drugs that ar g n rally not classif i d as n uromuscular blocking drugs, such as som an sth tic drugs. Th d gr of n uromuscular block may b stimat d by Bromag scor , which origi nally had four grad s d signat with th Roman num rals I until IV, but lat r co mpl m nt d by Br n t al with an inv rs grading with Hindu-Arabic num rals: Bromag scor Grad Crit ria Approximat d gr of block IV 1 Compl t block, inability to mov f t or kn s 100% III 2 Almost compl t block, ability to mov f t only, with inability

to fl x kn s 66% II 3 Partial block, ability to fl x kn s 33% 4 D t ctabl w akn ss of hip fl xion whil supin , ability of full fl xion of kn s 5 No d t ctabl w akn ss of hip fl xion whil supin I 6 Fr mov m nt of l gs and f t, ability to p rform partial kn b nd 0% In unconscious pati nts, such as during an sth sia, n ural block can b ass ss d by a "train-of-four" by stimulating muscl sfrom surfac l ctrod s. (v) Giv th d tail d structur of bon s of skull. Th skull is a bony structur in th h ad of many animals that supports th stru ctur s of th fac and forms a cavity for th brain. Th skull is compos d of two parts: th cranium and th mandibl . A skull withou t a mandibl is only a cranium. Animals that hav skulls ar call dcraniat s. Th skull is a part of th sk l ton. Functions of th skull includ prot ction of th brain, fixing th distanc b tw n th y s to allow st r oscopic vision, and fixing th position of th ars t o h lp th brain us auditory cu s to judg dir ction and distanc of sounds. In som animals, th skull also has a d f nsiv function ( .g. horn dungulat s); t h frontal bon is wh r horns ar mount d. Th English word "skull" is probably d riv d from Old Nors "skalli" m aning bal d, whil th word cranium com s from th Gr k root ( i ). I hum s, s i the m mm ls, the f eme ti ed divisi f the s ull i t th e c ium d m dible is t usu lly f ll wed. I ste d, f the pu p ses f des c ibi g thei t my d e ume ti g thei b es, m mm li d hum s ulls e divided diffe e tly: They e deemed t c sist f tw c teg ic l p ts: The eu c ium d the visce c ium. The eu c ium ( b i c se) is p tec tive v ult su u di g the b i . The visce c ium ( ls spl ch c ium f ci l s elet ) is f med by the b es supp ti g the f ce. B th p ts h ve diffe e t emb y l gic l igi s. Except f the m dible, ll f the b es f the s ull e j i ed t gethe by su tu es, igid ticul ti s pe mitti g ve y little m veme t. f t l view

side view

Fe tu e L c ti Desc ipti gle f j w m dible b c f j w the c e f the j w whe e the m dible b dy tu s upw ds i t the mus ve l p cess m xill , t f teeth ug sities ss ci ted with t th devel p me t c dyle f m dible t p f mus f m dible b ll-li e e d t the mus f the m dible th t f ms hi ge with the temp l b e c l sutu e t p f he d betwee f t l d p iet l c i l b es e f t he m j j i ts sutu es betwee the pl tes f the f t l d p iet l c i l b es exte l c ustic me tus betwee mus f m dible d m st id p cess h le i the temp l c i l b e ll wi g the p ss ge f s u d t e te the i e e ethm id b e eye c vity c i l b e f mi g p t f the eye c vity f ehe d b ss f t l tube sity f ehe d fe tu e f the f t l b e th t f ms the "bumps" i the f ehe d b ve the eyeb ws f t l b e t p f f ce (f ehe d) d f t t p f he d e f the m j c i l b es th t f ms the f ehe d d f t t p f the he d; ughly c ve s the f t l l bes f the b i gl bell ce te f f ehe d e i the ce te f the f ehe d, b etwee the eyeb ws, th t ssumes v i us sh pes diffe e t i dividu ls

(vi) Defi e H me st sis. Expl i b ut feedb c system d thei b sic c mp e t. H me st sis (f m G ee : hm i s, "simil " d stsis, "st di g still") is the p pe ty f system th t egul tes its i te l e vi me t d te ds t m i t i st ble, c st t c diti f p pe ties li e tempe tu e pH. It c be eit he pe cl sed system. It w s defi ed by Cl ude Be d d l te by W lte B df d C i 1926, 19 29 d 1932. Typic lly used t efe t livi g g ism, the c cept c me f m th t f mili eu i te ieu th t w s c e ted by Cl ude Be d d published i 1865. Multiple

l c im l b e i e c e f eye s c et sm ll b e f mi g c vity f the te gl d l mbd id sutu e b c f he d sutu e j i t betwee the ccipit l d p iet l c i l b es m dible j w b e l we p t f j w the l we j w b e is the ly s ull b e th t m ves, i.e., du i g m stic ti , speech, d exp essi ; c ies the l we teeth m xill uppe p t f j w the tw m xill e f m the ce te f the f ce wit h m y tt chi g muscles; c y the uppe teeth; f m p t f the eye bit; ct li e eyst es i t which the the f ci l b es fit m st id p cess l we p t f temp l b e, behi d mus f j w built up e f the l we temp l b e whe e imp t t ec muscles tt ch me t l p tube ce chi b ss fe tu e f the m dible t the l we f t p t f the chi which u de lies p t f the chi b ss me t l tube sities chi b ss du l bulb us f m ti f the m dible th t u de lies p t f the chi b ss s l b e se f ms the uppe p t f the se d s l b idge; the l we p t f the b idge is f med f c til ge s l c ch s l c vity f m ti s c e ti g p t f the s l c vity s l spi e ce te f se fe tu e f m xill f ci l b e t ce te f se t which septum is tt ched ccipit l b e the l we e f the he d m j c i l b e t the l we b c f the he d; c ve s ccipit l l be f the b i p iet l b e t p d side f he d m j c i l b e th t f ms p t f the t p, b c , d side f the he d d ughly c ve s the p iet l l be f the b i mus f m dible b c p t f the m dible the m e ve tic l p t f the m dible sphe id b e temple d eye bit e c i l b e th t f ms p t f the eye c vity squ m s l sutu e side f he d betwee p iet l d temp l b es e f the m j j i ts sutu es betwee the p iet l d temp l c i l b es sup bi l f me uppe bit f eye h le i the f t l b e whe e e ves d bl d vessels p ss th ugh; f ms tch i the bit f the eye sup bit l p cess eyeb ws f m ti f the f t l b e b ve th e bit f the eye, u de d b ve the eyeb ws th t ffects the ppe ce f the eyeb ws temp l b e side f the he d, b ve the e c i l b e the side f th e he d th t ughly c ve s the temp l l be f the b i ; it exte ds d w behi d the e t w ds the j w temp l li es f t p t f temple d l we p t f f t l b es li es i the f t l b e u d the temple v lme s l c vity f ci l b e the ce te li e f the se th t f ms p t f the s l c vity zyg m tic b e chee the p i cip l chee b e; igi f zyg m tic d the f ci l muscles zyg m tic p cess b es b de i g zyg m tic b e the temp l d m xill b es h ve e s ext t the zyg m tic b e


P sitive feedb c is mech ism by which utput is e h ced, such s p tei levels. H weve , i de t v id y fluctu ti i the p tei level, the me ch ism is i hibited st ch stic lly (I), the ef e whe the c ce t ti f the ctiv ted p tei (A) is p st the th esh ld ([I]), the l p mech ism is ctiv ted d the c ce t ti f A i c e ses exp e ti lly if d[A]= [A] P sitive feedb c mech isms e desig ed t ccele te e h ce the utput c e ted by stimulus th t h s l e dy bee ctiv ted. U li e eg tive feedb c mech isms th t i iti te t m i t i egul te physi l gic l fu cti s withi set d w ge, the p sitive feedb c mech ism s e desig ed t push levels ut f m l ges. T chieve this pu p se, s e ies f eve ts i iti tes c sc di g p cess th t builds t i c e se the effect f the stimulus. This p cess c be be efici l but is ely used by the b dy due t is s f the ccele ti 's bec mi g u c t ll ble. O e p sitive feedb c ex mple eve t i the b dy is bl d pl telet ccumul ti , which, i tu , c uses bl d cl tti g i esp se t b e te i the li i g f bl d vessels. A the ex mple is the ele se f xyt ci t i te sify the c t cti s th t t e pl ce du i g childbi th. Neg tive feedb c Neg tive feedb c mech isms c sist f educi g the utput ctivity f y g system b c t its m l ge f fu cti i g. A g d ex mple f this i s egul ti g bl d p essu e. Bl d vessels c se se esist ce f bl d fl w g i st the w lls whe bl d p essu e i c e ses. The bl d vessels ct s the ece pt s d they el y this mess ge t the b i . The b i the se ds mess ge t the he t d bl d vessels, b th f which e the effect s. The he t te w uld dec e se s the bl d vessels i c e se i di mete ( w s v s dil ti ). This ch ge w uld c use the bl d p essu e t f ll b c t its m l ge. Th e pp site w uld h ppe whe bl d p essu e dec e ses, d w uld c use v s c st icti . A the imp t t ex mple is see whe the b dy is dep ived f f d. The b dy w uld the eset the met b lic set p i t t l we th m l v lue. This w uld ll w the b dy t c ti ue t fu cti , t sl we te, eve th ugh the b dy i s st vi g. The ef e, pe ple wh dep ive themselves f f d while t yi g t l s e weight w uld fi d it e sy t shed weight i iti lly d much h de t l se m e fte . This is due t the b dy e djusti g itself t l we met b lic set p i t t ll w the b dy t su vive with its l w supply f e e gy. Exe cise c ch ge this effect by i c e si g the met b lic dem d. A the g d ex mple f eg tive feedb c mech ism is tempe tu e c t l. The hyp th l mus, which m it s the b dy tempe tu e, is c p ble f dete mi i g eve the slightest v i ti f m l b dy tempe tu e (37 deg ees Celsius). Resp se t such v i ti c uld be stimul ti f gl ds th t p duce swe t t educ e the tempe tu e sig li g v i us muscles t shive t i c e se b dy tempe tu e. B th feedb c s e equ lly imp t t f the he lthy fu cti i g f e's b dy. C mplic ti s c ise if y f the tw feedb c s e ffected lte ed i

dy mic equilib ium djustme t d egul ti mech isms m e h me st sis p ssib le. C t l mech isms All h me st tic c t l mech isms h ve t le st th ee i te depe de t c mp e ts f the v i ble bei g egul ted: The ecept is the se si g c mp e t th t m it s d esp ds t ch ges i the e vi me t. Whe the ecept se ses st imulus, it se ds i f m ti t "c t l ce te ", the c mp e t th t sets the ge t which v i ble is m i t i ed. The c t l ce te dete mi es pp p i te esp se t the stimulus. I m st h me st tic mech isms, the c t l ce t e is the b i . The c t l ce te the se ds sig ls t effect , which c be muscles, g s the st uctu es th t eceive sig ls f m the c t l ce te . Afte eceivi g the sig l, ch ge ccu s t c ect the devi ti by ei the e h ci g it with p sitive feedb c dep essi g it with eg tive feedb c . P sitive feedb c


y w y. H me st tic imb l ce M y dise ses e esult f distu b ce f h me st sis, c diti w s h me st tic imb l ce. As it ges, eve y g ism will l se efficie cy i its c t l systems. The i efficie cies g du lly esult i u st ble i te l e vi me t th t i c e ses the is f ill ess. I dditi , h me st tic imb l ce is ls esp sible f the physic l ch ges ss ci ted with gi g. Eve m e se i us th ill ess d the ch cte istics f gi g is de th. He t f ilu e h s bee see whe e mi l eg tive feedb c mech isms bec me ve whelmed, d des t uctive p sitive feedb c mech isms the t e ve . Dise ses th t esult f m h me st tic imb l ce i clude di betes, dehyd ti , hyp glycemi , hype glycemi , g ut, d y dise se c used by t xi p ese t i the bl dst e m. All f these c diti s esult f m the p ese ce f i c e s ed m u t f p ticul subst ce. I ide l ci cumst ces, h me st tic c t l mech isms sh uld p eve t this imb l ce f m ccu i g, but, i s me pe ple, t he mech isms d t w efficie tly e ugh the qu tity f the subst ce ex ceeds the levels t which it c be m ged. I these c ses, medic l i te ve ti is ecess y t est e the b l ce, pe m e t d m ge t the g s m y es ult. Acc di g t the f ll wi g qu te, eve y ill ess h s spects t it th t e es ult f l st h me st sis: "Just s we live i c st tly ch gi g w ld, s d the cells d tissues su vive i c st tly ch gi g mic e vi me t. The ' m l' 'physi l gic' st te the is chieved by d ptive esp ses t the ebb d fl w f v i us stimul i pe mitti g the cells d tissues t d pt d t live i h m y withi thei mic e vi me t. Thus, h me st sis is p ese ved. It is ly whe the stimuli be c me m e seve e, the esp se f the g ism b e s d w , th t dise se esu lts - ge e liz ti s t ue f the wh le g ism s it is f the i dividu l cell."