Your SlideShare is downloading. ×
Pathophysiology of carbohydrates and proteins metabolism
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Introducing the official SlideShare app

Stunning, full-screen experience for iPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Pathophysiology of carbohydrates and proteins metabolism

6,434
views

Published on

By M.D., PhD, Marta R. Gerasymchuk …

By M.D., PhD, Marta R. Gerasymchuk
Pathophysiology department, Ivano-Frankivsk National Medical University

Published in: Health & Medicine, Technology

0 Comments
29 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
6,434
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
1,630
Comments
0
Likes
29
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide
  • Dietary proteins provide the body with amino acids for endogenous protein synthesis and are also a metabolic fuel for energy (1 g of protein provides 4 Kcal).
    Nine essential amino acids (histidine, isoleucine, leucine, lysine, methionine/cystine, henylalanine/tyrosine, theonine, tryptophan and valine) must be supplied by dietary intake as these cannot be synthesised in the body. The recommended average requirement of proteins for an adult is 0.6 g/kg of the desired weight per day. For a healthy person, 10-14% of caloric requirement should come from proteins.
  • The following metabolic changes take place in starvation:
    Glucose. Glucose stores of the body are sufficient for one day’s metabolic needs only. During fasting state, insulinindependent tissues such as the brain, blood cells and renal medulla continue to utilise glucose while insulin-dependent tissues like muscle stop taking up glucose. This results in release of glycogen stores of the liver to maintain normal blood glucose level. Subsequently, hepatic gluconeogenesis from other sources such as breakdown of proteins takes place.
    Protein stores and the triglycerides of adipose tissue have enough energy for about 3 months in an individual. Proteins breakdown to release amino acids which are used as fuel for hepatic gluconeogenesis so as to maintain glucose needs of the brain. This results in nitrogen imbalance due to excretion of nitrogen compounds as urea.
    3. Fats. After about one week of starvation, protein breakdown is decreased while triglycerides of adipose tissue breakdown to form glycerol and fatty acids. The fatty acids are converted into ketone bodies in the liver which are used by most organs including brain in place of glucose. Starvation can then continue till all the body fat stores are exhausted following which death occurs.
  • http://health.feedfury.com/content/40365945-thinnest-man-ex-male-model-weighes-only-40-kg-male-anorexia-pictures-anorexic-man-photo-male-model-anorexia.html
  • The major characteristic of long-term starvation is a decreased dependence on gluconeogenesis and an increased use of ketone bodies (products of lipid and pyruvate metabolism) as a cellular energy source. During long-term starvation, depressed insulin levels and increased glucagon, cortisone, epinephrine, and growth hormones promote lipolysis in adipose tissue. Lipolysis liberates fatty acids, which supply energy to cardiac and skeletal muscle cells, and ketone bodies, which sustain brain tissue. Fatty acid, or ketone body, oxidation meets most of the energy needs of the cells. (Some glucose is still needed as fuel for brain tissue.) Once the supply of adipose tissue is depleted, proteolysis begins. The breakdown of muscle and visceral protein is the last process the body engages to supply energy for life. Death results from severe alterations in electrolyte balance and loss of renal, pulmonary, and cardiac function.
    Adequate ingestion of appropriate nutrients is the obvious treatment for starvation. In medically induced starvation the body is maintained in a ketotic state until the desired amount of adipose tissue has been lysed. Starvation imposed by chronic disease, long-term illness, or malabsorption is treated with enteral or parenteral nutrition. Perioperative management of nutrition is necessary to prevent unnecessary starvation.
  • In severe malnutrition, notably kwashiorkor, a combination of low plasma protein, a poorly understood increased vascular permeability and deficiencies in vitamins and other essential dietary components is responsible.
    Proteins have a huge array of vital functions within the human body. Inadequate dietary protein can lead to a number of diseases, particularly in children. The child in the picture above is suffering from kwashiorkor, a disease rare in developed countries but more common in those that experience famine. Its symptoms include oedema (fluid accumulation beneath the skin), decreased muscle mass, failure to grow and a large belly that sticks out. This condition is fatal if untreated.
  • Kwashiorkor is a condition characterized most notably by protruding bellies among other symptoms. Think of the starving children in Africa which big bellies, except with even bigger bellies. Those who suffer from it typically aren’t straight up starving like you might think. Instead they are able to get a substantial amount of calories from starches (like yams), and yet they are much worse off than those who survive on only a fraction of the food. The reason for this discrepancy is that individuals with Kwashiokor are unable to receive the necessary proteins essential for life. If you’re wondering well people with Marasmus can’t get any protein either since their eating even less you would be absolutely right in a certain sense. However one thing that the body keeps in supply for emergency situations is protein in the form of muscle mostly. When we starve our bodies know were starving and consequently know that we need certain things essential for life. Instead of trying to preserve our beautiful biceps and six packs, it eats away at it so we can use the breakdown products for processes essential for life.
  • The sneaky part about Kwashiorkor is that even though the body get almost no protein from yams or any other starch in this particular case, the body is tricked into being satisfied (if you know where I’m going with this now don’t ruin it for someone else). So as all these sugars from the yams are flooding into our body, more than even what we need at the moment, our body starts telling itself store the energy were saved! And so it stores and stores the sugar, usually as fat, and consequently forgets about those “insignificant proteins.” Because during our starvation our hunger is the main problem, not the other stuff. So what happens is that without essential amino acids, we can’t make proteins that are very useful for living. Things like immune function go down as well as the oncotic pressure in our blood vessels which basically means all our blood leaks out and we have swelling all over the place (Hence the big bellies). Ultimately, Kwashiorkor victims die much more quickly than Marasmus victims. The scary thing is that in a sense, those dying from Kwashiorkor are actually eating to their death.
  • Marasmus is what you get when you basically don’t eat anything. Occasionally you might have a meal, but overall you’re starving. Think of it as a state anorexics are in. They are emaciated and probably have a lot of health problems on top of the psychological issues, but they survive for quite some time. When you really don’t have much to eat though and are starving you eventually die prematurely.
  • Carbohydrates. Dietary carbohydrates, are the major source of dietary calories, especially for the brain, RBCs and muscles (1 g of carbohydrate provides 4 Kcal). At least 55% of total caloric requirement should be derived from carbohydrates.
  • Where does the sugar in our body go?
    It's well and good that sugar from fruit and grain gets into our bodies, but what happens to it thereafter?  Let's look at a model of our "Sugar Central" or, more correctly, blood sugar.  The barrel represents the storeroom of sugar in the body.  Food provides input in good times (read "after a meal").  There are three major routes out of that storeroom:
  • Major index which describes metabolism of carbohydrates, is a sugar level in blood. In healthy peoples it is 4,4-6,6 mmol/l.
     This value is summary result of complicated interaction of many exogenous and endogenous influences.
    The first it reflects a balance between amount of glucose which entrance in blood and by amount of glucose which is utilized by cells. 
    The second, glucose level in blood reflects an effect of simultaneous regulatory influence on carbohydrates metabolism of the nervous system and endocrine glands:
    front pituitary gland (somatotropic, thyreotropic, adrenocorticotropic hormones),
    adrenal cortex (adrenalin ,noradrenalin) layer,
    pancreas (insulin, glucagone, somatostatin),
    thyroid (thyroxin, triiodthyronine).
    Among enumerated hormones only insulin lowers glucose concentration in blood the rest of hormones increase it.
    Counter-insulin hormones
    ACTH, growth hormone, cortisol, thyroid hormone, glucagon, adrenaline
    1.Stimulate absorption of carbohydrates (cortisol, thyroid hormone)
    2. Increase glycogenolysis in liver and muscles, inhibit glycogenesis (adrenaline, cortisol, thyroid)
    3. Inhibit hexokinase activity and therefore its utilization (cortisol, growth hormone)
    4. Stimulate gluconeogenesis (cortisol, thyroid, glucagon)
    5. Activate insulinase (growth hormone, thyroid)
  • http://ajpendo.physiology.org/content/298/4/E807
    Neither MIP-GFP nor Glucagon-Cre-YFP islets show a difference in the direction of islet blood flow during hyperglycemia and hypoglycemia. However, total islet blood flow intensity increased in the hyperglycemic state (Fig. 3A). After a bolus injection of fluorescent dextran, the amount of fluorescence measured in the islet vasculature was greater during hyperglycemia than during hypoglycemia (Fig. 3, A and 3B). To assess whether this change in flow intensity could be attributed to the duration of insulin administration, the order of the hypoglycemic and hyperglycemic clamp experiments was varied (i.e., in some studies we performed the hyperglycemic clamp before the hypoglycemic clamp and in others we clamped hypoglycemia before hyperglycemia). Islet blood flow intensity was decreased during hypoglycemia regardless of whether hypoglycemia or hyperglycemia was clamped first (Fig. 3, C and D), indicating that blood flow intensity changes were likely due to changes in blood glucose rather than to the order of hyperglycemia/hypoglycemia or duration of insulin administration.
  • Hyperglycemia is connected, foremost with lowering of glucose utilization by muscular and fatty tissues. Lowering of glucose utilization has membranogenic nature. In case of insulinopenia and in case of insulin-resistance interaction of insulin and receptor is damaged.
    Therefore protein-transporters of glucose are not included in membranes of cells-targets. This limits glucose penetration in cells. It is use on power needs (in myocytes) diminishes.
    Lypogenesis is slowed-glucose deposit in fats form (in lypocytes).
    Glycogenesis slows- synthesis of glycogene (in hepatocytes and myocytes). On other hand, attached to diabetes a supplementary amount of glucose is secreted in blood. In liver and muscles of diabetics glycogenolysis is a  very active. Definite endowment in hyperglycemia belongs to gluconeogenesis. Here with glucose will is derivated in liver from amino acids (mainly from alanine).
  • ORAL GLUCOSE TOLERANCE TEST. Oral GTT is performed principally for patients with borderline fasting plasma glucose value (i.e. between 100-140 mg/dl). The patient who is scheduled for oral GTT is instructed to eat a high carbohydrate diet for at least 3 days prior to the test and come after an overnight fast on the day of the test (for at least 8 hours). A fasting blood sugar sample is first draw.
    Then 75 gm of glucose dissolved in 300 ml of water is given. Blood and urine specimen are collected at half-hourly intervals for at least 2 hours. Blood or plasma glucose content is measured and urine is tested for glucosuria to determine the approximate renal threshold for glucose. Venous whole blood concentrations are 15% lower than plasma glucose values.
  • Pathogenesis of insulin-dependent diabetes mellitus
    Insulin-dependent diabetes mellitus has genetic base.
    Inclination to diabetes of this type is conditioned by some genes of major histocompatibility complex (MHC).
    The system of HLA genes is situated on small extent of short shoulder of 6 chromosome. Here are identified several locuses – A, B, C and area D which includes three locuses – DP,  DQ and DR.
    High probability of insulin-depending diabetes mellitus is to area D and nominally  with locuses DR.
    Genes DR3 and DR4 are diabetogenic.
    The very high risk of illness is created in those person who have both gene – DR3 and DR4.
    Inclination to insulin-depending diabetes is associated also with locus DQ (genes DQ2 and DQ8).
    Diabetes arises only in part of person with diabetogenic genes. For example, alleles DR3 and DR4 occur in 50-60 % healthy person of european race, and illness develops only in 0,25 %. Inheritance of insulin-depending diabetes is conditioned, presumably, by not one gene, but by group of kindred genes.
    Where in essence of genetic defect in peoples with genes DR3, DR4, DQ2, DQ8?
    Exact answer on these questions while is not found. Think, that the enumerated genes in lone or in combinations form a low resistibility of β-cells of pancreas to external actions. β-Cells of such persons lightly collapse and very difficult restore. High readiness to destruction combines in them by limited capacity for regeneration. The system of HLA genes are inherited from generation to generation, therefore inclination of β-cells to destruction also is inherited from generation to generation. However general amount of β-cells is attached to birth identically in patients and healthy.
    Typical affection of Langergans islets attached to insulin-depending diabetes is infiltration of them by lymphocytes and selective destruction of β-cells. Clinical illness picture develops when 80-95% of β-cells are already destroyed.
    In such patients mass of pancreas is less, than in healthy people. Amount and volume of Langergans islets also is less. Thus insulin-depending diabetes is result of equilibrium violation between destruction of β-cells and their regeneration. Both process – increase of destruction and limitation of regeneration – are genetically conditioned.
    Depending upon affection mechanism of β-cells there are two forms of insulin-dependent diabetes mellitus – autoimmune and virus-inductive.
  • Diabetogenic action has diet is result of diet, which contains a surplus of high-calorie products. They are fats and purified simple carbohydrates. Such action is result of diet, which contains a small amount of complex carbohydrates (food fibres).
    Inhibiting influence of obesity on insulin receptors very clearly displays in conditions of low physical activity. Regular physical exercises on the contrary raise receptor affinity to insulin and raise tolerance to glucose.
  • http://bjo.bmj.com/content/89/6/730.full
  • Transcript

    • 1. 1. Regulation of protein metabolism. 2. Starvation. 3. Kwashiorkor. 4. Marasmus. 5. Regulation of glucose metabolism. 6. Diabetus mellitus. 7. Types of diabetus mellitus. 8. Complications of diabetus mellitus.
    • 2. • Disorders related to mmaallnnuuttrriittiioonn, while potentially preventable, produce moderate to severe disabilities. • Nearly 800 million people in the world do not have enough to eat, most of them living in developing countries. In these regions, inadequate amounts of food (causing conditions such as child malnutrition and retarded growth) and inadequate diversity of food (causing micronutrient deficiencies) continue to be priority health problems. • MMaallnnuuttrriittiioonn increases the risk of disease and early death and affects all age groups, but it is especially common among poor people and those with inadequate access to health education, clean water, and sanitation. • DD ii aabbeetteess mmeelllliittuuss is a disease resulting from absolute or relative insulin insufficiency and accompanying by disturbance of metabolism mainly, carbohydrate one. • The main manifestation of diabetes mellitus is hyperglycemia, sometimes reaching 25 mmol/l, glucosuria with glucose in urine up to 555-666 mmol/l (100-200 g/day), polyuria (to 10-12 L of urine per day), polyphagia and polydipsia.
    • 3.  PPrrootteeiinnss ffrroomm tthhee ddiieett mmuusstt bbee bbrrookkeenn iinnttoo aammiinnoo aacciiddss ttoo bbee aabbssoorrbbeedd.. PPrrootteeiinn ddiiggeessttiioonn bbeeggiinnss iinn tthhee ssttoommaacchh wwiitthh tthhee aaccttiioonn ooff ppeeppssiinn.. PPeeppssiinnooggeenn,, tthhee eennzzyymmee pprreeccuurrssoorr ooff ppeeppssiinn,, iiss sseeccrreetteedd bbyy tthhee cchhiieeff cceellllss iinn rreessppoonnssee ttoo aa mmeeaall aanndd aacciidd ppHH..  AAcciidd iinn tthhee ssttoommaacchh iiss rreeqquuiirreedd ffoorr tthhee ccoonnvveerrssiioonn ooff ppeeppssiinnooggeenn ttoo ppeeppssiinn.. PPeeppssiinn iiss iinnaaccttiivvaatteedd wwhheenn iitt eenntteerrss tthhee iinntteessttiinnee bbyy tthhee aallkkaalliinnee ppHH..  PPrrootteeiinnss aarree bbrrookkeenn ddoowwnn ffuurrtthheerr bbyy ppaannccrreeaattiicc eennzzyymmeess,, ssuucchh aass ttrryyppssiinn,, cchhyymmoottrryyppssiinn,, ccaarrbbooxxyyppeeppttiiddaassee,, aanndd eellaassttaassee..  AAss wwiitthh ppeeppssiinn,, tthhee ppaannccrreeaattiicc eennzzyymmeess aarree sseeccrreetteedd aass pprreeccuurrssoorr mmoolleeccuulleess.. TTrryyppssiinnooggeenn,, wwhhiicchh llaacckkss eennzzyymmaattiicc aaccttiivviittyy,, iiss aaccttiivvaatteedd bbyy aann eennzzyymmee llooccaatteedd oonn tthhee bbrruusshh bboorrddeerr cceellllss ooff tthhee dduuooddeennaall eenntteerrooccyytteess.. AAccttiivvaatteedd ttrryyppssiinn aaccttiivvaatteess aaddddiittiioonnaall ttrryyppssiinnooggeenn mmoolleeccuulleess aanndd ootthheerr ppaannccrreeaattiicc pprreeccuurrssoorr pprrootteeoollyyttiicc eennzzyymmeess..  TThhee aammiinnoo aacciiddss aarree lliibbeerraatteedd iinnttrraammuurraallllyy oorr oonn tthhee ssuurrffaaccee ooff tthhee vviillllii bbyy bbrruusshh bboorrddeerr eennzzyymmeess tthhaatt ddeeggrraaddee pprrootteeiinnss iinnttoo ppeeppttiiddeess tthhaatt aarree oonnee,, ttwwoo,, oorr tthhrreeee aammiinnoo aacciiddss lloonngg.. SSiimmiillaarr ttoo gglluuccoossee,, mmaannyy aammiinnoo aacciiddss aarree ttrraannssppoorrtteedd aaccrroossss tthhee mmuuccoossaall mmeemmbbrraannee iinn aa ssooddiiuumm--lliinnkkeedd pprroocceessss tthhaatt uusseess tthhee NNaa++//KK++-- AATTPPaassee ppuummpp aass aann eenneerrggyy ssoouurrccee..
    • 4.  SSttaarrvvaattiioonn iiss aa ssttaattee ooff oovveerraallll ddeepprriivvaattiioonn ooff nnuuttrriieennttss.. IIttss ccaauusseess mmaayy bbee tthhee ffoolllloowwiinngg::  II)) ddeelliibbeerraattee ffaassttiinngg——rreelliiggiioouuss oorr ppoolliittiiccaall;;  IIII)) ffaammiinnee ccoonnddiittiioonnss iinn aa ccoouunnttrryy oorr ccoommmmuunniittyy;;  IIIIII)) sseeccoonnddaarryy uunnddeerrnnuuttrriittiioonn ssuucchh aass dduuee ttoo cchhrroonniicc wwaassttiinngg ddiisseeaasseess ((iinnffeeccttiioonnss,, iinnffllaammmmaattoorryy ccoonnddiittiioonnss,, lliivveerr ddiisseeaassee)),, ccaanncceerr eettcc..  CCaanncceerr rreessuullttss iinn mmaalliiggnnaanntt ccaacchheexxiiaa aass aa rreessuulltt ooff wwhhiicchh ccyyttookkiinneess aarree eellaabboorraatteedd ee..gg.. ttuummoouurr nneeccrroossiiss ffaaccttoorr--αα,, eellaassttaasseess,, pprrootteeaasseess eettcc..  AA ssttaarrvveedd iinnddiivviidduuaall hhaass llaaxx,, ddrryy sskkiinn,, wwaasstteedd mmuusscclleess aanndd aattrroopphhyy ooff iinntteerrnnaall oorrggaannss..
    • 5.  AAnnoorreexxiiaa nneerrvvoossaa  11.. PPaatthhooggeenneessiiss  a. Self-induced starvation leading to PEM  b. Distorted body image  22.. CClliinniiccaall ffiinnddiinnggss::  a. Secondary amenorrhea  1) Decreased gonadotropin-releasing hormone  • Caused by excessive loss of body fat and weight  2) Decreased serum gonadotropins produces hypoestrinism.  b. Osteoporosis  1) Caused by hypoestrinism  • Estrogen normally enhances osteoblastic activity and inhibits osteoclastic activity,  2) Lack of estrogen leads to decreased osteoblastic activity and increased osteoclastic activity.  c. Increased lanugo (fine, downy hair)  d. Increased hormones associated with stress (e.g., cortisol, growth hormone)  e. Most common cause of death is ventricular arrhythmia FFrreenncchh mmooddeell aanndd aaccttrreessss IIssaabbeellllee CCaarroo IIssaabbeellllee CCaarroo
    • 6.  Ex-model FFrraaiill JJeerreemmyy GGiilllliittzzeerr has suffered from anorexia for 25 years.  He now weighes only 41.275 kg
    • 7. BBuulliimmiiaa nneerrvvoossaa 1. Pathogenesis • Bingeing with self-induced vomiting 22.. CClliinniiccaall ffiinnddiinnggss:: a. Complications of vomiting 1) Acid injury to tooth enamel 2) Hypokalemia and metabolic alkalosis b. Ventricular arrhythmia is the must common cause of death.
    • 8. PPRROOTTEEIINN--EENNEERRGGYY MMAALLNNUUTTRRIITTIIOONN  TThhee iinnaaddeeqquuaattee ccoonnssuummppttiioonn ooff pprrootteeiinn aanndd eenneerrggyy aass aa rreessuulltt ooff pprriimmaarryy ddiieettaarryy ddeeffiicciieennccyy oorr ccoonnddiittiioonneedd ddeeffiicciieennccyy mmaayy ccaauussee lloossss ooff bbooddyy mmaassss aanndd aaddiippoossee ttiissssuuee,, rreessuullttiinngg iinn pprrootteeiinn eenneerrggyy oorr pprrootteeiinn ccaalloorriiee mmaallnnuuttrriittiioonn ((PPEEMM oorr PPCCMM))..  TThhee pprriimmaarryy ddeeffiicciieennccyy iiss mmoorree ffrreeqquueenntt dduuee ttoo ssoocciiooeeccoonnoommiicc ffaaccttoorrss lliimmiittiinngg tthhee qquuaannttiittyy aanndd qquuaalliittyy ooff ddiieettaarryy iinnttaakkee,, ppaarrttiiccuullaarrllyy pprreevvaalleenntt iinn tthhee ddeevveellooppiinngg ccoouunnttrriieess ooff AAffrriiccaa,, AAssiiaa aanndd SSoouutthh AAmmeerriiccaa.. TThhee iimmppaacctt ooff ddeeffiicciieennccyy iiss mmaarrkkeedd iinn iinnffaannttss aanndd cchhiillddrreenn..
    • 9.  TThhee ssppeeccttrruumm ooff cclliinniiccaall ssyynnddrroommeess pprroodduucceedd aass aa rreessuulltt ooff PPEEMM iinncclluuddeess tthhee ffoolllloowwiinngg::  11.. KKwwaasshhiioorrkkoorr wwhhiicchh iiss rreellaatteedd ttoo pprrootteeiinn ddeeffiicciieennccyy tthhoouugghh ccaalloorriiee iinnttaakkee mmaayy bbee ssuuffffiicciieenntt..  22.. MMaarraassmmuuss iiss ssttaarrvvaattiioonn iinn iinnffaannttss ooccccuurrrriinngg dduuee ttoo oovveerraallll llaacckk ooff ccaalloorriieess..  HHoowweevveerr,, iitt mmuusstt bbee rreemmeemmbbeerreedd tthhaatt mmiixxeedd ffoorrmmss ooff kkwwaasshhiioorrkkoorr--mmaarraassmmuuss ssyynnddrroommee mmaayy aallssoo ooccccuurr.. MMaarraassmmiicc kkwwaasshhiioorrkkoorr ((eeddeemmaattoouuss,, sseevveerree cchhiillddhhoooodd mmaallnnuuttrriittiioonn)) iiss aa ccoommbbiinnaattiioonn ooff cchhrroonniicc eenneerrggyy ddeeffiicciieennccyy aanndd cchhrroonniicc oorr aaccuuttee pprrootteeiinn ddeeffiicciieennccyy..
    • 10.  11.. PPaatthhooggeenneessiiss aa.. IInnaaddeeqquuaattee pprrootteeiinn iinnttaakkee bb.. AAddeeqquuaattee ccaalloorriicc iinnttaakkee ccoonnssiissttiinngg mmaaiinnllyy ooff ccaarrbboohhyyddrraatteess cc.. PPrrootteeiinn iinn lliivveerr aanndd ootthheerr oorrggaannss ((ii..ee..,, vviisscceerraall pprrootteeiinn)) iiss ddeeccrreeaasseedd.. dd.. MMuussccllee pprrootteeiinn ((ii..ee..,, ssoommaattiicc pprrootteeiinn)) iiss rreellaattiivveellyy uunncchhaannggeedd..  22.. CClliinniiccaall ffiinnddiinnggss:: aa.. PPiittttiinngg eeddeemmaa aanndd aasscciitteess  •• CCaauusseedd bbyy hhyyppooaallbbuummiinneemmiiaa aanndd lloossss ooff ppllaassmmaa oonnccoottiicc pprreessssuurree.. bb.. FFaattttyy lliivveerr 11)) CCaauusseedd bbyy ddeeccrreeaasseedd ssyynntthheessiiss ooff aappoolliippoopprrootteeiinnss.. 22)) AAppoolliippoopprrootteeiinn BB--110000 iiss rreeqquuiirreedd ffoorr aasssseemmbbllyy aanndd sseeccrreettiioonn ooff vveerryy llooww ddeennssiittyy lliippoopprrootteeiinnss ((VVLLDDLLss)) iinn tthhee lliivveerr.. cc.. DDiiaarrrrhheeaa -- ccaauusseedd bbyy lloossss ooff tthhee bbrruusshh bboorrddeerr eennzzyymmeess aanndd ppaarraassiittiicc iinnffeeccttiioonnss dd.. AAnneemmiiaa aanndd ddeeffeeccttss iinn cceellll--mmeeddiiaatteedd iimmmmuunniittyy ((CCMMII))
    • 11. EErroossiioonnss aanndd ssccaalliinngg iinn kkwwaasshhiioorrkkoorr..
    • 12. 11.. PPaatthhooggeenneessiiss aa.. DDiieettaarryy ddeeffiicciieennccyy ooff bbootthh pprrootteeiinn aanndd ccaalloorriieess bb.. DDeeccrreeaassee iinn ssoommaattiicc pprrootteeiinn ((mmuussccllee pprrootteeiinn)) 22.. CClliinniiccaall ffiinnddiinnggss:: aa.. EExxttrreemmee mmuussccllee wwaassttiinngg ((""bbrroooommssttiicckk eexxttrreemmiittiieess"")) 11)) BBrreeaakkddoowwnn ooff mmuussccllee pprrootteeiinn ffoorr eenneerrggyy;; 22)) LLoossss ooff ssuubbccuuttaanneeoouuss ffaatt;; bb.. GGrroowwtthh rreettaarrddaattiioonn;; aanneemmiiaa;; ddeeffeeccttss iinn cceellll--mmeeddiiaatteedd iimmmmuunniittyy ((CCMMII)) cc.. TTyyppiiccaallllyy ooccccuurrss iinn cchhiillddrreenn yyoouunnggeerr tthhaann 11 yy..oo..,, wwhhoo aarree ddeepprriivveedd ooff bbrreeaasstt--ffeeeeddiinngg aanndd ddoo nnoott hhaavvee aann aaddeeqquuaattee iinnttaakkee ooff ssuubbssttiittuuttee nnuuttrriieennttss..
    • 13. FFeeaattuurree KKwwaasshhiioorrkkoorr MMaarraassmmuuss DDeeffiinniittiioonn PPrrootteeiinn ddeeffiicciieennccyy wwiitthh ssuuffffiicciieenntt ccaalloorriiee iinnttaakkee SSttaarrvvaattiioonn iinn iinnffaannttss wwiitthh oovveerraallll llaacckk ooff ccaalloorriieess CClliinniiccaall ffeeaattuurreess OOccccuurrss iinn cchhiillddrreenn bbeettwweeeenn 66 mmoonntthhss aanndd 33 yyeeaarrss ooff aaggee CCoommmmoonn iinn iinnffaannttss uunnddeerr 11 yyeeaarr ooff aaggee GGrroowwtthh ffaaiilluurree GGrroowwtthh ffaaiilluurree WWaassttiinngg ooff mmuusscclleess bbuutt pprreesseerrvveedd aaddiippoossee ttiissssuueess WWaassttiinngg ooff aallll ttiissssuueess iinncclluuddiinngg mmuusscclleess aanndd aaddiippoossee ttiissssuueess OOeeddeemmaa,, llooccaalliisseedd oorr ggeenneerraalliisseedd,, pprreesseenntt OOeeddeemmaa aabbsseenntt EEnnllaarrggeedd ffaattttyy lliivveerr NNoo hheeppaattiicc eennllaarrggeemmeenntt SSeerruumm pprrootteeiinnss llooww SSeerruumm pprrootteeiinnss llooww AAnnaaeemmiiaa pprreesseenntt AAnnaaeemmiiaa pprreesseenntt ‘‘FFllaagg ssiiggnn’’——aalltteerrnnaattee bbaannddss ooff lliigghhtt ((ddeeppiiggmmeenntteedd)) aanndd ddaarrkk ((ppiiggmmeenntteedd)) hhaaiirr MMoonnkkeeyy--lliikkee ffaaccee,, pprroottuubbeerraanntt aabbddoommeenn,, tthhiinn lliimmbbss MMoorrpphhoollooggyy EEnnllaarrggeedd ffaattttyy lliivveerr NNoo ffaattttyy lliivveerr AAttrroopphhyy ooff ddiiffffeerreenntt ttiissssuueess aanndd oorrggaannss bbuutt ssuubbccuuttaanneeoouuss ffaatt pprreesseerrvveedd AAttrroopphhyy ooff ddiiffffeerreenntt ttiissssuueess aanndd oorrggaannss iinncclluuddiinngg ssuubbccuuttaanneeoouuss ffaatt
    • 14. HHoollooddoommoorr
    • 15. Gout is a syndrome caused by an inflammatory response to uric acid production or excretion resulting in high levels of uric acid in the blood (hyperuricemia ) and in other body fluids, including synovial fluid. MMaanniiffeesstteedd bbyy tthhee ffoolllloowwiinngg ffeeaattuurreess,, ooccccuurrrriinngg ssiinnggllyy oorr iinn ccoommbbiinnaattiioonn:: 1. Increased serum uric acid concentration (hhyyppeerruurriiccaaeemmiiaa). 2. Recurrent attacks of characteristic type of acute arthritis in which ccrryyssttaallss ooff mmoonnoossooddiiuumm uurraattee mmoonnoohhyyddrraattee may be demonstrable in the leucocytes present in the synovial fluid. 3. Aggregated deposits of monosodium urate monohydrate (ttoopphhii) in and around the joints of the extremities. 4. Renal disease involving interstitial tissue and blood vessels. 5. Uric acid nneepphhrroolliitthhiiaassiiss. 6. Other factors include age (rare before 30 years), genetic predisposition (XX--lliinnkkeedd aalltteerraattiioonn ooff eennzzyymmee hhyyppooxxaanntthhiinnee--gguuaanniinnee pphhoosspphhoorriibboossyyllttrraannssffeerraassee [[HHGGPPRRTT]]), excessive alcohol consumption, obesity, certain drugs (especially tthhiiaazziiddeess), and lead toxicity.
    • 16. When the uric acid reaches a certain concentration in fluids, it crystallizes, forming insoluble precipitates that are deposited in connective tissues throughout the body. Crystallization in synovial fluid causes acute, painful inflammation of the joint, a condition known as gouty arthritis. With time, crystal deposition in subcutaneous tissues causes the formation of small, white nodules, or tophi, that are visible through the skin. Crystal aggregates deposited in the kidneys can form urate renal stones and lead to renal failure. In classic gouty arthritis, monosodium urate crystals form and cause joint inflammation. Pseudogout is caused by the formation of calcium pyrophosphate dihydrate (CPPD) crystals. The effect of either crystal is the same— the onset of a cytokinemediated acute inflammatory response.
    • 17.  Carbohydrates must be broken down into monosaccharides, or single sugars, before they can be absorbed from the small intestine.  The average daily intake of carbohydrate in the American diet is approximately 350 to 400 g. SSttaarrcchh makes up approximately 50% of this total, sucrose (i.e., table sugar) approximately 30%, lactose (i.e., milk sugar) approximately 6%, and maltose approximately 1.5%.  Digestion of starch begins in the mouth with the action of amylase. Pancreatic secretions also contain an amylase. Amylase breaks down starch into several disaccharides, including maltose, isomaltose, and α- dextrins. The brush border enzymes convert the disaccharides into monosaccharides that can be absorbed. DDiieettaarryy CCaarrbboohhyyddrraatteess EEnnzzyymmee MMoonnoossaacccchhaarriiddeess PPrroodduucceedd Lactose Lactase Glucose and galactose Sucrose Sucrase Fructose and glucose Starch Amylase Maltose, maltotriase, and α-dextrins Maltose and maltotriose Maltase Glucose and glucose α-Dextrins α-Dextrimase Glucose and glucose
    • 18.  SSuuccrroossee yyiieellddss gglluuccoossee aanndd ffrruuccttoossee,, llaaccttoossee iiss ccoonnvveerrtteedd ttoo gglluuccoossee aanndd ggaallaaccttoossee,, aanndd mmaallttoossee iiss ccoonnvveerrtteedd ttoo ttwwoo gglluuccoossee mmoolleeccuulleess.. WWhheenn tthhee ddiissaacccchhaarriiddeess aarree nnoott bbrrookkeenn ddoowwnn ttoo mmoonnoossaacccchhaarriiddeess,, tthheeyy ccaannnnoott bbee aabbssoorrbbeedd bbuutt rreemmaaiinn aass oossmmoottiiccaallllyy aaccttiivvee ppaarrttiicclleess iinn tthhee ccoonntteennttss ooff tthhee ddiiggeessttiivvee ssyysstteemm,, ccaauussiinngg ddiiaarrrrhheeaa..  PPeerrssoonnss wwhhoo aarree ddeeffiicciieenntt iinn llaaccttaassee,, tthhee eennzzyymmee tthhaatt bbrreeaakkss ddoowwnn llaaccttoossee,, eexxppeerriieennccee ddiiaarrrrhheeaa wwhheenn tthheeyy ddrriinnkk mmiillkk oorr eeaatt ddaaiirryy pprroodduuccttss..  FFrruuccttoossee iiss ttrraannssppoorrtteedd aaccrroossss tthhee iinntteessttiinnaall mmuuccoossaa bbyy ffaacciilliittaatteedd ddiiffffuussiioonn,, wwhhiicchh ddooeess nnoott rreeqquuiirree eenneerrggyy eexxppeennddiittuurree.. IInn tthhiiss ccaassee,, ffrruuccttoossee mmoovveess aalloonngg aa ccoonncceennttrraattiioonn ggrraaddiieenntt..
    • 19.  GGlluuccoossee aanndd ggaallaaccttoossee aarree ttrraannssppoorrtteedd bbyy wwaayy ooff aa ssooddiiuummddeeppeennddeenntt ccaarrrriieerr ssyysstteemm tthhaatt uusseess aaddeennoossiinnee ttrriipphhoosspphhaattee aanndd tthhee NNaa++//KK++--AATTPPaassee ppuummpp aass aann eenneerrggyy ssoouurrccee..  WWaatteerr aabbssoorrppttiioonn ffrroomm tthhee iinntteessttiinnee iiss lliinnkkeedd ttoo aabbssoorrppttiioonn ooff oossmmoottiiccaallllyy aaccttiivvee ppaarrttiicclleess,, ssuucchh aass gglluuccoossee aanndd ssooddiiuumm.. IItt ffoolllloowwss tthhaatt aann iimmppoorrttaanntt ccoonnssiiddeerraattiioonn iinn ffaacciilliittaattiinngg tthhee ttrraannssppoorrtt ooff wwaatteerr aaccrroossss tthhee iinntteessttiinnee ((aanndd ddeeccrreeaassiinngg ddiiaarrrrhheeaa)) aafftteerr tteemmppoorraarryy ddiissrruuppttiioonn iinn bboowweell ffuunnccttiioonn iiss ttoo iinncclluuddee ssooddiiuumm aanndd gglluuccoossee iinn tthhee fflluuiiddss tthhaatt aarree ttaakkeenn..
    • 20. • 1. TToo tthhee lliivveerr. Here excess sugar from meals is stored to cover sugar shortages between meals and to make fat from excess sugar. • Transport of sugar goes both to and from the liver. The liver fills the "Sugar Central" between meals. • 2. TToo tthhee bbrraaiinn. The brain is completely dependent upon sugar combustion for its supply of energy, in any case under normal conditions. It uses really huge amounts of sugar. • 33.. TToo mmuusscclleess aanndd ffaatt ttiissssuuee.. At least 40% of the body is comprised of skeletal muscles. These can use both fats and sugar to supply energy. •The rate of sugar uptake and burning follows physical activity; more work; more sugar burned. • MMuusscclleess do take up and store glucose to cover future activity but they cannot release sugar back to the blood stream or "Sugar Central". •FFaatt ttiissssuuee stores surplus sugar as fat. About half of this comes from the liver, the rest is made by fat itself.
    • 21. RReegguullaattiioonn ooff gglluuccoossee mmeettaabboolliissmm  TThhee gglluuccoossee ccoonncceennttrraattiioonn iinn bblloooodd ddeessccrriibbeess ccaarrbboohhyyddrraatteess mmeettaabboolliissmm bbootthh ooff hheeaalltthhyy mmaann aanndd ssiicckk.. IIllllnneesssseess bbaassee ooff wwhhiicchh iiss ddiissoorrddeerr ooff ccaarrbboohhyyddrraatteess mmeettaabboolliissmm ccaann ffllooww wwiitthh rriissee ooff gglluuccoossee ccoonncceennttrraattiioonn iinn bblloooodd aanndd wwiitthh lloowweerriinngg ooff iitt..  RRiissee ooff gglluuccoossee ccoonncceennttrraattiioonn iiss nnaammeedd hhyyppeerrgglliicceemmiiaa lloowweerriinngg hhyyppoogglliicceemmiiaa..  FFoorr eexxaammppllee,, hhyyppeerrgglliicceemmiiaa iiss vveerryy ttyyppiiccaall ffoorr ddiiaabbeetteess mmeelllliittuuss,, hhyyppooggllyycceemmiiaa –– ffoorr ggllyyccooggeennoossiiss..
    • 22. Impairments ooff gglluuccoossee bbaallaannccee Normal glucose level in the blood 65 -110 mg/% 3.85 - 6.05 mmol/L (5.5 mmol/L) • Hypoglycemia (less than 2.5 mmol/L results in coma) • Hyperglycemia 3.85 6.05 HHyyppooggllyycceemmiiaa NORM HHyyppeerrggllyycceemmiiaa GGLLUUCCOOSSEE
    • 23. BBlloooodd GGlluuccoossee && HHoorrmmoonneess HHoorrmmoonnee  IInnssuulliinn  GGlluuccoorrttooccooiiddss  GGlluuccaaggoonn  GGrroowwtthh HHoorrmmoonnee  EEppiinneepphhrriinnee AAccttiioonn  ¯ GGlluuccoossee  ­ GGlluuccoossee  ­ GGlluuccoossee  ­ GGlluuccoossee  ­ GGlluuccoossee
    • 24. Counter-iinnssuulliinn hhoorrmmoonneess AACCTTHH,, ggrroowwtthh hhoorrmmoonnee,, ccoorrttiissooll,, tthhyyrrooiidd hhoorrmmoonnee,, gglluuccaaggoonn,, aaddrreennaalliinnee 1. Stimulate absorption of carbohydrates ((ccoorrttiissooll,, tthhyyrrooiidd hhoorrmmoonnee)) 2.  glycogenolysis in liver and muscles,  glycogenesis ((aaddrreennaalliinnee,, ccoorrttiissooll,, tthhyyrrooiidd)) 3. Inhibit hexokinase activity and therefore its utilization ((ccoorrttiissooll,, ggrroowwtthh hhoorrmmoonnee)) 4. Stimulate gluconeogenesis ((ccoorrttiissooll,, tthhyyrrooiidd,, gglluuccaaggoonn)) 5. Activate insulinase ((ggrroowwtthh hhoorrmmoonnee,, tthhyyrrooiidd))
    • 25. HHyyppooggllyycceemmiiaa EExxooggeennoouuss EEnnddooggeennoouuss Functional
    • 26. EExxooggeennoouuss hhyyppooggllyycceemmiiaa • IInnssuulliinn iinnjjeeccttiioonn • AAllccoohhooll ((ddeevveellooppss 66--3366 hhoouurrss aafftteerr hheeaavvyy ccoonnssuummppttiioonn)) • SSoommee ddrruuggss ((ee..gg.. ssaalliiccyyllaatteess)) • LLoonngg tteerrmm pphhyyssiiccaall eexxeerrcciissee
    • 27. EEnnddooggeennoouuss hhyyppooggllyycceemmiiaa  iinnssuulliinnoommaa ((hhyyppeerrppllaassiiaa ooff b--cceellllss)  ggllyyccooggeennoossiiss  hheerreeddiittaarryy ffrruuccttoossee iinnttoolleerraannccee  iinnssuuffffiicciieennccyy iinn pphhoosspphhooeennoollppyyrruuvvaattee ccaarrbbooxxyykkiinnaassee  HHeeppaattoocceelllluullaarr iinnssuuffffiicciieennccyy  IImmppaaiirreedd aabbssoorrppttiioonn IIsslleett bblloooodd ffllooww dduurriinngg hhyyppeerrggllyycceemmiiaa aanndd hhyyppooggllyycceemmiiaa.. IImmaaggeess ttaakkeenn aatt ppeeaakk fflluuoorreesscceennccee iinntteennssiittyy iinn tthhee ssaammee iisslleett uunnddeerr eexxppeerriimmeennttaall ddeessiiggnn 11 dduurriinngg hhyyppeerrggllyycceemmiiaa ((AA)) aanndd hhyyppooggllyycceemmiiaa ((BB)) oorr uunnddeerr eexxppeerriimmeennttaall ddeessiiggnn 22 dduurriinngg hhyyppooggllyycceemmiiaa ((CC)) aanndd hhyyppeerrggllyycceemmiiaa ((DD)).. GGlluuccoossee-ddeeppeennddeenntt bblloooodd ffllooww ddyynnaammiiccss iinn mmuurriinnee ppaannccrreeaattiicc iisslleettss iinn vviivvoo LLaarraa RR.. NNyymmaann ,, EErriicc FFoorrdd ,, AAllvviinn CC.. PPoowweerrss ,, DDaavviidd WW.. PPiissttoonn // AAmmeerriiccaann JJoouurrnnaall ooff PPhhyyssiioollooggyy - EEnnddooccrriinnoollooggyy aanndd MMeettaabboolliissmmPPuubblliisshheedd 11 AApprriill 22001100VVooll.. 229988nnoo.. EE880077- EE881144DDOOII:: 1100..11115522//aajjppeennddoo..0000771155..22000099
    • 28. FFuunnccttiioonnaall HHyyppooggllyycceemmiiaa 11..AAlliimmeennttaarryy ((aafftteerr ggaassttrreeccttoommyy,, ddeemmppiinngg ssyynnddrroommee) 22..SSppoonnttaanneeoouuss rreeaaccttiivvee ((ccaauussee iiss nnoott kknnoowwnn ® ddiiaarrrrhheeaa,, ttaacchhyyccaarrddyy,, ttrreemmoorr,, hheeaaddaacchhee,, wweeaakknneessss) 33..AAllccoohhooll ((ccoonnssuummppttiioonn iinn hhuunnggrryy ssttaattee) 44..EEnnddooccrriinnee iinnssuuffffiicciieennccyy ((ddeeccrreeaassee iinn ccoouunntteerr--iinnssuulliinn hhoorrmmoonnee ¯) 55.. HHeeppaattiicc ffaaiilluurree 66.. MMaallnnuuttrriittiioonn 77.. HHeeaavvyy pphhyyssiiccaall llooaadd ((wwiitthhoouutt ccaarrbboohhyyddrraattee uuppttaakkee) 88.. TTrraannssiieenntt ffuunnccttiioonnaall hhyyppooggllyycceemmiiaa ooff cchhiillddrreenn • NNeeoonnaattaall ((1100%%) • MMaatteerrnnaall ddiiaabbeetteess • EErryytthhrroobbllaassttoossiiss • KKeettooggeenniicc
    • 29. Manifestations ooff hhyyppeerrggllyycceemmiiaa  GGlluuccoossuurriiaa  PPoollyyuurriiaa  PPoollyyddyyppssiiaa  HHyyppoohhyyddrraattiioonn ooff tthhee oorrggaanniissmm  AArrtteerriiaall hhyyppootteennssiioonn MMaanniiffeessttaattiioonnss ooff hhyyppooggllyycceemmiiaa  SSttaarrvvaattiioonn  TTrreemmoorr  EExxcceessssiivvee sswweeaattiinngg  TTaacchhyyccaarrddiiaa  HHeeaaddaacchhee,, ddiizzzziinneessss  IImmppaaiirreedd vviissiioonn  AAnnxxiieettyy,, ffeeaarr  IImmppaaiirreedd ccooggnniittiioonn
    • 30. • DDiiaabbeetteess mmeelllliittuuss iiss nnoott aa ssiinnggllee ddiisseeaassee bbuutt aa ggrroouupp ooff cclliinniiccaallllyy hheetteerrooggeenneeoouuss ddiissoorrddeerrss tthhaatt hhaavvee gglluuccoossee iinnttoolleerraannccee iinn ccoommmmoonn.. IItt eennccoommppaasssseess mmaannyy ccaauussaallllyy uunnrreellaatteedd ddiisseeaasseess aanndd iinncclluuddeess mmaannyy ddiiffffeerreenntt eettiioollooggiieess ooff ddiissttuurrbbeedd gglluuccoossee ttoolleerraannccee.. • TThhee tteerrmm ddiiaabbeetteess mmeelllliittuuss iiss uusseedd ttoo ddeessccrriibbee aa ssyynnddrroommee cchhaarraacctteerriizzeedd bbyy cchhrroonniicc hhyyppeerrggllyycceemmiiaa aanndd ootthheerr ddiissttuurrbbaanncceess ooff ccaarrbboohhyyddrraattee,, ffaatt,, aanndd pprrootteeiinn mmeettaabboolliissmm..
    • 31. CCllaassssiiffiiccaattiioonn  PPrriimmaarryy DDMM –– ((pprriimmaarryy -- nnoo ootthheerr ddiisseeaassee))  TTyyppee II –– IIDDDDMM // JJuuvveenniillee –– 1100%%.. (absolute insulin deficiency) Subtype 1A (immune-mediated) DM characterised by autoimmune destruction of β-cells which usually leads to insulin deficiency. Subtype 1B (idiopathic) DM characterised by insulin deficiency with tendency to develop ketosis but these patients are negative for autoimmune markers.  TTyyppee IIII –– NNIIDDDDMM //AAdduulltt oonnsseett –– 8800%%.. (insulin resistance with an insulin secretory deficit)  MMOODDYY ((Maturity-onset diabetes of the young)) –– 55%% mmaattuurriittyy oonnsseett -- GGeenneettiicc (other specific types)  GGeessttaattiioonnaall DDiiaabbeetteess  SSeeccoonnddaarryy DDMM –– ((sseeccoonnddaarryy ttoo ootthheerr ddiiss..))  PPaannccrreeaattiittiiss,, ttuummoorrss,, hheemmoocchhrroommaattoossiiss..  IInnffeeccttiioouuss –– ccoonnggeenniittaall rruubbeellllaa,, CCMMVV..  EEnnddooccrriinnooppaatthhyy..  DDrruuggss –– CCoorrttiiccoosstteerrooiiddss..
    • 32. The criteria for the diagnosis of diabetes include symptoms, elevated fasting plasma glucose (FPG) concentration, and/or abnormal oral glucose tolerance test (OGTT). Two conditions associated with a high risk for diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), are considered prediabetes.
    • 33. NNoorrmmaall PPaannccrreeaattiicc IIsslleett:: ßß αα ßß cceellllss (Insulin) αα cceellllss (Glucagon) δδ cceellllss (Somatostatin) pppp CCeellllss (pan prot)
    • 34. TTyyppee--II TTyyppee--IIII  Less common  Age < 25 Years  Insulin- Dependent  Onset: Weeks  Acute Metabolic complications  Autoantibody: Yes  Family History: No  Insulin levels: very low  Islets: Insulitis  50% in twins  More common  Adult >25 Years  Insulin Independent *  Months to years  Chronic Vascular complications  No  Yes  Normal or high *  Normal / Exhaustion  60-80% in twins
    • 35. Insulin-ddeeppeennddeenntt ddiiaabbeetteess mmeelllliittuuss  IInnssuulliinn-ddeeppeennddeenntt ddiiaabbeetteess mmeelllliittuuss aarriisseess aass rreessuulltt ooff aabbssoolluuttee iinnssuulliinn iinnssuuffffiicciieennccyy..  IItt iiss ddeessccrriibbeedd bbyy iinnssuulliinnooppeenniiaa aanndd bbyy iinncclliinnaattiioonn ttoo kkeettooaacciiddoossiiss..  TThhiiss ddiiaabbeetteess ooccccuurr mmoorree ffrreeqquueennttllyy iiss iinn cchhiillddrreenn aanndd yyoouunngg ppeeoopplleess ((ttiillll 3300 yyeeaarrss))..  IInnssuulliinn iiss nneeeeddeedd ffoorr ssuusstteennttaattiioonn ooff ppaattiieenntt lliiffee.. AAttttaacchheedd ttoo iitt’’ss aabbsseennccee kkeettooaacciiddiicc ccoommaa ddeevveellooppss..
    • 36. Carbohydrate metabolism in normal conditions and diabetes mellitus INSULIN 1. Increase in permeability of myocyte and adipocyte membranes for glucose (Glut-4) 2. Increase glycolysis, pentose-IIMMPPAAIIRRMMEENNTT in activity of glucokinase, glycogen-sythetase, aerobic phosphate shunt and Krebs cycle enzymes 3. Increased rate of glycogen synthesis in liver 4. Increase in synthesis of lipids from glucose 5. Inhibition of gluconeogenesis HHYYPPEERRGGLLYYCCEEMMIIAA
    • 37. FFoorrmmss ooff iinnssuulliinn--ddeeppeennddeenntt ddiiaabbeetteess mmeelllliittuuss  AAuuttooiimmmmuunnee –– DDRR33  VViirruuss--iinndduucceedd –– DDRR44
    • 38. MMaattuurriittyy--oonnsseett ddiiaabbeetteess ooff tthhee yyoouunngg · CChhrr.. –– 22 HHNNFF44aa ((MMOODDYY II ) -- HHeeppaattiicc NNuucclleeaarr ffaaccttoorr 44 a ggeennee · CChhrr..--77 gglluuccookkiinnaassee ((MMOODDYY II II ) · CChhrr..--1111,, 1122 HHNNFF11aa ((MMOODDYY II II II ) -- HHeeppaattiicc NNuucclleeaarr ffaaccttoorr mmuuttaattiioonn · MMiittoocchhoonnddrriiaall DDNNAA mmuuttaattiioonnss,, ootthheerr ggeenneettiicc ddeeffeeccttss
    • 39. GGeenneettiicc HHLLAA--DDRR33//44 EEnnvviirroonnmmeenntt VViirraall iinnffee....?? AAuuttooiimmmmuunnee IInnssuulliittiiss AAbb ttoo ßß cceellllss//iinnssuulliinn ß cell Destruction 11.. DDrruuggss,, cchheemmiiccaallss ((ssttrreeppttoozzoottoocciinn,, aallllooxxaannee,, ppeennttaammiiddiinnee) 22.. DDiieettaarryy ((ccooww mmiillkk,, hhiigghh nniittrroossaammiinnee lleevveellss) 33.. VViirruusseess ((CCooxxssaacckkiiee,, mmeeaasslleess) ((mmoolleeccuullaarr mmyymmiiccrryy)) TTyyppee II // IIDDDDMM IInnssuulliinn ddeeffiicciieennccyy
    • 40. PATHOGENESIS OF DDIIAABBEETTEESS MMEELLLLIITTUUSS IInnssuulliinn iinnssuuffffiicciieennccyy FFaattttyy aacciiddss ­ KKeettoonnee bbooddiieess ­ b -- hhyyddrrooxxyybbuuttiirraattee,, aacceettooaacceettaattee aaccccuummuullaattiioonn iinn bblloooodd MMeettaabboolliicc aacciiddoossiiss KKeettoonnuurriiaa KKuussssmmaauull''ss rreessppiirraattiioonn CCNNSS ddeepprreessssiioonn BBlloooodd gglluuccoossee lleevveell ­ gglluuccoossuurriiaa ppoollyyuurriiaa ddeehhyyddrraattiioonn® tthhiirrsstt ­ SSHHOOCCKK HHyyppoovvoolleemmiiaa PPoollyy-- ddiippssiiaa
    • 41.  AAuuttooiimmmmuunnee iinnssuulliinn--ddeeppeennddeenntt ddiiaabbeetteess aarriisseess iinn ppeerrssoonnss wwiitthh ggeennoommee DDRR33.. IItt iiss aassssoocciiaatteedd wwiitthh ootthheerr aauuttooiimmmmuunnee eennddooccrriinnooppaatthhiieess,, ffoorr eexxaammppllee,, wwiitthh iillllnneesssseess ooff tthhyyrrooiidd ggllaanndd ((aauuttooiimmmmuunnee tthhyyrrooiiddiittiiss,, ddiiffffuussee ttooxxiicc ggooiitteerr)),, aaddrreennaall ggllaanndd ((AAddddiissoonn’’ss ddiisseeaassee))..  TThhiiss ddiiaabbeetteess ttyyppee ddeevveellooppss iinn aannyy aaggee mmoorree ffrreeqquueenntt iinn wwoommeenn..  AAuuttooiimmmmuunnee iiss ddiiaabbeetteess ddeessccrriibbeedd bbyy pprreesseennccee iinn bblloooodd ooff ppaattiieenntt aauuttooaannttiibbooddiieess aaggaaiinnsstt ooff LLaannggeerrggaannss iisslleettss..
    • 42. • Virus-induced insulin-dependent diabetes mellitus binded with genome DR4 and different from autoimmune on mechanisms of development. In this case there are no autoantibodies against islets of pancreas. Its certainly can appear in blood but rapidly (pending of year) disappear. They do not perform essential role in pathogenesis of illness. • Development of this diabetes type frequently precede from viral infectious epidemic parotitis, german measles, measles, viral hepatitis. • Pathogenic viruses action is not specific. It consists in development of inflammatory process in Langergans islets. Insulitis arises. Lymphoid infiltration of damaged islets develops at first after then destruction.
    • 43. • Sometimes the specific (immune) destruction mechanisms of β- cells are linked. The viruses pervert antigen membranes properties of affected β-cells and are followed with attack of autoimmune mechanisms. • There is one more possibility. Membrane β-cells is lightly damaged by much chemical substances even in insignificant concentrations. • Such substances are called β-cytotoxic. They are, for example, alloxane and streptosocine. They create a favourable background for immediate viruses action on membrane of β-cells. • Virus-induced diabetes arises early before 30 years of life. It is identically widespread and among males, both among women.
    • 44. Insulin-independent ddiiaabbeetteess mmeelllliittuuss  TThhiiss ddiiaabbeetteess ttyyppee pprriinncciippllee ddiiffffeerrss ffrroomm tthhee ffiirrsstt..  PPaattiieennttss,, aass aa rruullee ddoonn’’tt nneeeedd ttoo eexxooggeenniicc iinnssuulliinn..  MMeettaabboolliicc ddiissoorrddeerrss aattttaacchheedd ttoo tthhiiss ddiiaabbeetteess aarree mmiinniimmaall.. DDiieett tthheerraappyy aanndd ppeerr oorraall gglluuccoossee ddeeccrreeaassiinngg mmeeddiicciinneess aarree ssuuffffiicciieennttllyy ffoorr tthheeiirr ccoommppeennssaattiioonn..  OOnnllyy iinn ssttrreessss ((ttrraauummaa aaccttiioonn,, sshhaarrpp iinnffeeccttiioonn)) ccoonnddiittiioonnss ppaattiieenntt uussee iinnssuulliinn..  IIllllnneessss ccaann ccoouurrssee ffoorr yyeeaarrss wwiitthhoouutt hhyyppeerrggllyycceemmiiaa.. SSoommeettiimmeess iitt iiss ddiisscclloosseedd iinn aaggee mmoorree 4400 yyeeaarrss..  TThheerree aarree tthhrreeee ffaaccttoorrss ggrroouupp,, wwhhiicchh ppllaayy aa ddeecciissiivvee rroollee iinn ffoorrmmiinngg ooff tthhiiss ddiiaabbeetteess ttyyppee.. HHeerree aarree:: the genetic factors functional disturbance of β-cells insulin resistance
    • 45.  GGeenneettiicc ffaaccttoorrss determine hereditary liability to disease. Specific genetic marker (special diabetogenic gene) is not found. It is known only, that inclination to insulin-independent diabetes is not coupled with major complex of histocompatibility.  FFuunnccttiioonn ooff ββ--cceellllss of patient with insulin-independent diabetes is violated. Amount of them is diminished. Attached to loading by glucose they do not multiply insulin secretion in necessary amount. Diabetologist connects these violations with amyloidosis of Langergans islets.
    • 46. Pathogenesis of Type II DM GGeenneettiicc // ßß cceellll ddeeffeecctt IIDDDDMM OObbeessiittyy // LLiiffee ssttyyllee ?? ßß cceellll eexxhhaauussttiioonn AAbbnnoorr.. SSeeccrreettiioonn IInnssuulliinn RReessiissttaannccee Relative Insulin Def. TTyyppee IIII NNIIDDDDMM
    • 47. Insulin-resistance • Insulin-resistance arises or on genetic base or as result of influence of external factors (risk factors). Biological insulin action is mediated over receptors. They are localized on cells-targets membranes (myocytes, lypocytes). Interaction of insulin and receptor is followed with changes of physical state of cells-targets membrane. • As result of this transport system is activated, which carries glucose over cellular membrane. • Transmembrane moving of glucose is provided by proteins-transmitters. • Amount of glucose carried in cell depends on closeness of insulin receptors on membrane and on receptor affinity to insulin. These parameters depend on insulin level in blood. • Hyperinsulinemia diminishes amount of receptors and their affinity to insulin. Hypoinsulinemia on the contrary multiplies amount of receptors and their affinity to insulin.
    • 48. • Chronic resistance ooff iinnssuulliinn rreecceeppttoorrss causes a chronic hyperfunction of β-cells and surplus production of insulin. This in turn raises receptor resistance. Thus arises a vicious circle. Protracted loading of β-cells conduces to exhaustion of their functions.
    • 49. About 4% pregnant women develop DM due to metabolic changes during pregnancy. Although they revert back to normal glycaemia after delivery, these women are prone to develop DM later in their life. Mitochondrial DNA is inherited maternally and encodes several genes in the oxidative phosphorylation pathway, ribosomal RNAs, and 22 transfer RNAs (tRNAs). In rare cases, (<1%), diabetes is associated with point mutations in a mitochondrial tRNA gene, tRNALeu(UUR). Mitochondrial diabetes is caused by a primary defect in β-cell function. Recall that ATP is required for insulin secretion in β cells, and impairment of mitochondrial ATP synthesis results in decreased insulin secretion.
    • 50. 2. Genetic ddeeffeeccttss iinn iinnssuulliinn pprroocceessssiinngg oorr iinnssuulliinn aaccttiioonn:: • DDeeffeeccttss iinn pprrooiinnssuulliinn ccoonnvveerrssiioonn • IInnssuulliinn ggeennee mmuuttaattiioonnss • IInnssuulliinn rreecceeppttoorr mmuuttaattiioonnss 33.. EExxooccrriinnee ppaannccrreeaattiicc ddeeffeeccttss • CChhrroonniicc ppaannccrreeaattiittiiss • PPaannccrreeaatteeccttoommyy • NNeeooppllaassiiaa • CCyyssttiicc ffiibbrroossiiss • HHeemmaacchhrroommaattoossiiss • FFiibbrrooccaallccuulloouuss ppaannccrreeaattooppaatthhyy 55.. EEnnddooccrriinnooppaatthhiieess • AAccrroommeeggaallyy • CCuusshhiinngg ssyynnddrroommee • HHyyppeerrtthhyyrrooiiddiissmm • PPhheeoocchhrroommooccyyttoommaa • GGlluuccaaggoonnoommaa 11.. GGeenneettiicc ddeeffeeccttss ooff bb--cceellll ffuunnccttiioonn MMaattuurriittyy--oonnsseett ddiiaabbeetteess ooff tthhee yyoouunngg ((MMOODDYY)),, ccaauusseedd bbyy mmuuttaattiioonnss iinn:: • HHeeppaattooccyyttee nnuucclleeaarr ffaaccttoorr 44aa [[HHNNFF--44aa]] ((MMOODDYY11)) • GGlluuccookkiinnaassee ((MMOODDYY22)) • HHeeppaattooccyyttee nnuucclleeaarr ffaaccttoorr 11aa [[HHNNFF--11aa]] ((MMOODDYY33)) • IInnssuulliinn pprroommootteerr ffaaccttoorr [[IIPPFF--11]] ((MMOODDYY44)) • HHeeppaattooccyyttee nnuucclleeaarr ffaaccttoorr 11bb [[HHNNFF--11bb]] ((MMOODDYY55)) • NNeeuurrooggeenniicc ddiiffffeerreennttiiaattiioonn ffaaccttoorr 11 [[NNeeuurroo DD11]] ((MMOODDYY66)) • MMiittoocchhoonnddrriiaall DDNNAA mmuuttaattiioonnss 77.. IInnffeeccttiioonnss • CCyyttoommeeggaalloovviirruuss • CCooxxssaacckkiiee vviirruuss BB 44.. DDrruuggss • GGlluuccooccoorrttiiccooiiddss • TThhyyrrooiidd hhoorrmmoonnee • αα--iinntteerrffeerroonn • PPrrootteeaassee iinnhhiibbiittoorrss • ββ--aaddrreenneerrggiicc aaggoonniissttss • TThhiiaazziiddeess • NNiiccoottiinniicc aacciidd • PPhheennyyttooiinn 66.. GGeenneettiicc ssyynnddrroommeess aassssoocciiaatteedd wwiitthh ddiiaabbeetteess • DDoowwnn ssyynnddrroommee • KKlleeiinnffeelltteerr ssyynnddrroommee • TTuurrnneerr ssyynnddrroommee 88.. GGeessttaattiioonnaall DDiiaabbeetteess MMeelllliittuuss • DDiiaabbeetteess aassssoocciiaatteedd wwiitthh pprreeggnnaannccyy
    • 51. IMPAIRMENT OF LIPID METABOLISM IN DIABETES MELLITUS Insulin deficiency Decreased glucose utilization Decreased lipogenesis Mobilization of fats to depoes Hyperlipidemia Metabolic acidosis Increased ketogenesis and cholesterol productoin Ketonemia and hypercholesterolemia Ketonuria Loss of Na+ Keto-acidotic coma
    • 52. IIMMPPAAIIRRMMEENNTT OOFF PPRROOTTEEIINN MMEETTAABBOOLLIISSMM IINN DDIIAABBEETTEESS MMEELLLLIITTUUSS Decreased gglluuccoossee uuttiilliizzaattiioonn IInnccrreeaassee iinn pprrootteeoollyyssiiss AAmmiinnaacciiddeemmiiaa,, iinnccrreeaasseedd uuppttaakkee ooff aammiinnooaacciiddss bbyy tthhee lliivveerr 11.. AAccttiivvaattiioonn ooff gglluuccoonneeooggeenneessiiss 22.. IInnccrreeaasseedd rreemmoovvaall ooff nniittrrooggeenn vviiaa uurreeaa LLoossss ooff ppoottaassssiiuumm aanndd ootthheerr iioonnss bbyy tthhee cceellllss DDeehhyyddrraattiioonn ooff tthhee cceellllss PPoottaassssiiuumm lloossss bbyy tthhee oorrggaanniissmm IInnssuulliinn ddeeffiicciieennccyy
    • 53. Symptoms of diabetes mellitus Major symptoms are: • hyperglycemia, • glucosuria and • polyuria.
    • 54. Pathogenesis of diabetes mellitus symptoms
    • 55. GGlluuccoossuurriiaa  IInn hheeaalltthhyy mmaann pprraaccttiiccaallllyy hhaass nnoott gglluuccoossee iinn uurriinnee.. IItt iiss eexxccrreeaatteedd iinn aammoouunntt nnoott mmoorree 11 gg.. AAttttaacchheedd ttoo ssuuggaarr ddiiaabbeetteess aammoouunntt ooff eexxccrreetteedd gglluuccoossee iinnccrreeaasseess rreeppeeaatteeddllyy..  IIff gglluuccoossee ccoonncceennttrraattiioonn iinn bblloooodd aanndd pprriimmaarryy uurriinnee ddooeess nnoott eexxcceeeedd 99 mmmmooll//ll,, eeppiitthheelliiuumm ooff ccaannaalliiccuullii rreeaabbssoorrbbeedd iitt.. TThhiiss mmaaxxiimmuumm ccoonncceennttrraattiioonn iiss ccaalllleedd nneepphhrriittiicc tthhrreesshhoolldd.. 10 mmol/L  IIff aa gglluuccoossee ccoonncceennttrraattiioonn eexxcceeeeddss aa nneepphhrriittiicc tthhrreesshhoolldd ((99 mmmmooll//ll)),, ppaarrtt ooff gglluuccoossee ggooeess iinn sseeccoonnddaarryy uurriinnee ((gglluuccoossuurriiaa))..
    • 56. Chronic hyperglycemia Increased RBF (hyperperfusion) Renal vasodilation Protein glycation Hypertension Increased intraglomerular capillary pressure Increased protein excretion Glomerular damage • Loss of negative charge • Glomerulosclerosis • Thickening of basement membrane • Mesangial expansion Increased GFR Microalbuminuria Macroalbuminuria RBF - Renal blood flow Decreased GFR and renal failure GFR - Glomerular filtration rate
    • 57. Polyuria • Glucose is osmotic active substance. • Increasing of it’s concentration in primary urine raises osmotic pressure. • Water is exuded from organism together with glucose (osmotic diuresis). • Patient excretes 3-4 L of urine per day, sometimes till 10 L.
    • 58. PATHOGENESIS OF HYPERGLYCEMIC CCOOMMAA Insulin deficiency Decreased glucose utilization Increased glucose production Hyperglycemia Glucosuria Osmotic diuresis Hyperosmolarity and dehydration DIC syndrome C O M A DEATH SHOCK
    • 59. Complication of diabetes mellitus The very frequent diabetes complications are following: ¨ketoacidosis, ¨macroangiopathy, ¨microangiopathy, ¨neuropathy. angiopathy
    • 60.  KKeettooaacciiddoossiiss.. IInn hheeaalltthhyy ppeeoopplleess ssyynntthheessiiss ooff kkeettoonnee bbooddiieess iinn lliivveerr iiss ssttrriiccttllyy ccoonnttrroolleedd.. MMaaiinn rreegguullaattoorryy mmeecchhaanniissmm iiss aacccceessss lliimmiittaattiioonn ooff ffaatt aacciiddss iinn mmyyttoocchhoonnddrriieess ooff hheeppaattooccyytteess.. OOvveerr hheeaadd ppeerrmmiissssiibbllee ccoonncceennttrraattiioonn lliimmiitt ooff kkeettoonnee bbooddiieess iinn bblloooodd iiss aapppprrooxxiimmaatteellyy 00,,11 mmmmooll//LL..  IInn ccaassee ooff eexxcceeeeddiinngg tthhiiss lleevveell rreegguullaattoorryy mmeecchhaanniissmmss aarree ssttaatteedd.. FFoorreemmoosstt kkeettoonnee bbooddiieess ppuutt ssppeecciiffiicc rreecceeppttoorrss bbaacckk uupp oonn mmeemmbbrraannee ββ--cceellllss ooff LLaannggeerrggaann’’ss iisslleettss.. IInnssuulliinn eexxccrreettiioonn iinn bblloooodd iinnccrreeaasseess.. IInnssuulliinn ssttiimmuullaatteess rreessyynntthheessiiss ooff ffaatt aacciiddss.. FFiirrsstt ssttaaggee ooff rreessyynntthheessiiss iiss ddeerriivvaattiioonn ooff mmaalloonniill-- CCооАА.. SSuurrpplluuss aammoouunntt ooff mmaalloonniill--CCооАА oopppprreesssseess ppeenneettrraattiioonn ooff ffaatt aacciiddss iinn mmyyttoocchhoonnddrriieess.. SSyynntthheessiiss ooff kkeettoonnee bbooddiieess sslloowwss..  AAttttaacchheedd ttoo ddiiaabbeetteess mmeelllliittuuss ddiissttuurrbb mmeecchhaanniissmm ooff bbootthh ssyynntthheessiiss rreegguullaattiioonn ooff kkeettoonnee bbooddiieess –– bbootthh oonn lleevveell ooff ββ--cceellllss,, aanndd oonn lleevveell ooff hheeppaattooccyytteess.. RReecceeppttoorr ssttiimmuullaattiioonn ooff ββ--cceellllss bbyy kkeettoonnee bbooddiieess ddooeess nnoott ccaauussee iinnccrreeaasseedd eexxccrreettiioonn iinnssuulliinn iinn bblloooodd..  IInn ccoonnddiittiioonnss ooff iinnssuulliinnooppeenniiaa ffaatt aacciiddss ppeenneettrraattee iinn hheeppaattooccyytteess iinn uunnrreessttrriicctteedd aammoouunntt.. LLiivveerr ssyynntthheessiizzeess mmaannyy kkeettoonnee bbooddiieess.. EExxttrraahheeppaattiicc ttiissssuueess ccaann nnoott uuttiilliizzee tthheemm.. AAmmoouunntt ooff kkeettoonnee bbooddiieess iinn bblloooodd iinnccrreeaasseess.. MMeettaabboolliicc aacciiddoossiiss ooccccuurr.. IItt ccaann ccoommpplleettee bbyy kkeettooaacciidd ccoommaa..  SSeellddoomm aattttaacchheedd ttoo ddiiaabbeetteess mmeelllliittuuss llaaccttooaacciiddoossiiss ooccccuurr.. IItt iiss aattttaacchheedd ttoo iinnssuulliinn--iinnddeeppeennddeenntt ddiiaabbeetteess mmeelllliittuuss,, aattttaacchheedd ttoo ccoommbbiinnaattiioonn ooff ddiiaabbeetteess wwiitthh hhyyppooxxiiaa,, sseeppssiiss,, sshhoocckk..
    • 61. MMaaccrrooaannggiiooppaatthhyy  MMaaccrrooaannggiiooppaatthhyy iiss vveesssseellss aatthheerroosscclleerroossiiss ooff cceerreebbrruumm,, hheeaarrtt,, kkiiddnneeyyss,, lleeggss.. DDiiaabbeetteess lleeaadd ttoo aatthheerroosscclleerroossiiss ddeevveellooppmmeenntt..  TThheerree aarree tthhrreeee aacccceelleerraattiioonn wwaayy ooff aatthheerrooggeenneessiiss iinn ppaattiieennttss wwiitthh ddiiaabbeetteess.. IInn ccoonnddiittiioonnss ooff iinnssuulliinn iinnssuuffffiicciieennccyy ggrroowwtthh hhoorrmmoonnee ssyynntthheessiiss iinnccrreeaasseess.. HHeerree uuppoonn pprroolliiffeerraattiioonn ooff ssmmooootthh mmyyoocciitteess aacccceelleerraatteess kkeeyy ssttaaggee ooff aatthheerrooggeenneessiiss.. AAttttaacchheedd ttoo ddiiaabbeetteess vveesssseellss eennddootthheelliiuumm ddaammaaggeess..  SSyynntthheessiiss ooff tthhrroommbbooxxaannee iinnccrreeaassee,, aanndd tthhiiss hheellppss ttoo aaddhheessiioonn ooff tthhrroommbbooccyytteess.. TThhrroommbbooccyytteess eexxccrreett mmiittooggeennee tthhrroommbbooccyyttiicc ggrroowwtthh ffaaccttoorr ((TTGGFF)).. IItt aallssoo ssttiimmuullaatteess pprroolliiffeerraattiioonn ooff ssmmooootthh mmyyooccyytteess..  AAttttaacchheedd ttoo ddiiaabbeetteess ccoonncceennttrraattiioonn ooff lliippoopprrootteeiiddss llooww ddeennssiittyy,, iinnccrreeaassee ccoonncceennttrraattiioonn ooff lliippoopprrootteeiiddss ooff hhiigghh ddeennssiittyy..
    • 62. • Microangiopathy develop in shallow vessels – arterials, venues, capillaries. Two process form their pathogenic base – thickining of basal membrane and reproduction endothelium. • Direct cause of microangiopathy is hyperglycemia and synthesis of glycoproteids in basal membrane. • There are two main clinical forms microangiopathy: diabetic retinopathy diabetic nephropathy
    • 63. A composite photograph showing a pretreatment fundus photograph (A), and a photograph demonstrating radiation retinopathy at 24 months (B). A fluorescein angiogram demonstrates intraretinal microangiopathy next to the tumour (C), and regression to chorioretinal scar after laser photocoagulation (D).
    • 64. Neuropathy • Neuropathy manifest by violation of nerves function sensible, motor, vegetative. Essence of these decreases is demyelinisation of nervous fibres, decrease of axoplasmatic flow.
    • 65. • This is hereditary illness. In it’s base lies an blockade of galactose metabolism. In organism intermediate metabolits accumulate. • There are two the main forms of galactosemia on base of:  transferase insufficiency and galactokinase insufficiency.
    • 66. Deficit of glucose-1-phosphat uridyltransferase. • This enzyme converts galactose-1-phosphate in glucose-1-phosphate. Attached to it’s insufficiency galactose-1-phosphate and sugar alcohol of galactose (galactit) accumulates in tissues lens of the eye, liver, brain, kidneys. Mammal and cow milk contains lactose. • Therefore the illness symptoms appear with first days of child life. • Diarrhea, vomiting, dehydrotation occur. • Liver increases (splenomegalia). Hepatocytes lose ability to conjugate bilirubine. Children become yellowish. • Affection of kidneys displays in proteinuria, aminoaciduria and acidosis. • For galactosemia cataract is very typical. Their beginnings related to accumulation of osmotic active galactite in vitreous bodies of eyes. Galactite absorb in water, and water breaks tissues. • Dangerous consequences arise in the brain. This foremost is delay of mental development. • Mortal end is possible. • Cure method is diet without galactose.
    • 67. DDeeffiicciitt ooff ggaallaaccttookkiinnaassee..  AAttttaacchheedd ttoo tthhiiss iillllnneessss vvaarriiaanntt aa pprroocceessss ooff pphhoosspphhoorriillaattiioonn ooff ggaallaaccttoossee iiss bblloocckkeedd,, tthhaatt iiss ttrraannssffoorrmmaattiioonn ooff ggaallaaccttoossee iinn ggaallaaccttoossee--11--pphhoosspphhaatt.. IIllllnneessss ddiissppllaayyss iinn ccaattaarraaccttss..  OOtthheerr ssyymmppttoommss aarree aabbsseenntt oorr mmiinnoorr.. CCuurree iiss ddiieett wwiitthhoouutt ggaallaaccttoossee..
    • 68. GGLLYYCCOOGGEENNOOSSIISS  TTyyppee ІІ ––GGiirrkkee ddiisseeaassee.. DDeeffiicciitt ooff gglluuccoossoo--66-- pphhoosspphhaattaassee  TTyyppee ІІІІ ––PPoommppee ddiisseeaassee.. DDeeffiicciitt ooff aacciiddiicc mmaallttaassee ((αα--11,,44--gglluuccoossiiddaassee))  TTyyppee ІІІІІІ ––CCoorrii ddiisseeaassee,, FFoorrbbss ddiisseeaassee.. DDeeffiicciitt ooff aammyylloo--11,,66-- gglluuccoossiiddaassee  TTyyppee ІІVV ––AAnnddeerrssoonn ddiisseeaassee.. DDeeffiicciitt ooff aammyylloo-- 11,,44,,11,,66--ttrraannssgglluuccoossiiddaassee  TTyyppee VV ––MMccAArrddeell ddiisseeaassee DDeeffiicciitt ooff pphhoosspphhoorriillaassee ooff mmyyooccyytteess  ТТyyppee VVІІ ––HHeerrss ddiisseeaassee.. DDeeffiicciitt ooff pphhoosspphhoorriillaassiicc ccoommpplleexx iinn lliivveerr  ТТyyppee VVІІІІ.. DDeeffiicciitt ooff mmuussccllee pphhoosspphhooffrruuccttookkiinnaassee
    • 69. • Simple carbohydrates deposit in organism as polysaccharides. • In muscles and liver accumulates glycogen. It consist of 4 % of liver weight and 2 % of muscles weight. • Muscles glycogen is used as of ready fuel source for immediate guaranteeing by energy. Liver – without interruption provides cerebrum and erythrocytes with glucose . • Synthesis and splitting of glycogen are exactly adjusted and coordinated processes. Attached to immediate need in glucose α–cells of pancreas secret glucagone. It activates adenylatcyclase of hepatic cells. • Adenilatcyclase stimulates derivation of cAMP. Under action of cAMP takes place activation of proteinkinase and this enzyme raises activity glycogenphosphorilase and oppresses activity of glucogensynthase. Here upon starts intensive glycogenolysis. Supplementary amount of glucose is secreted in blood. • In other situation after consuming of carbohydrates in blood accumulates surplus of glucose. β-cells of pancreas multiply insulin synthesis. Insulin raises activity of glycogensyntase. Active glucogenesis starts too. Surplus of glucose reserves in appearance of glucogen in liver and muscles. • There are illnesses in base of which is accumulation of glycogen in organs. They are called ggllyyccooggeennoosseess. All of them are hereditary enzymopathy. There are seven main types of glycogenoses.
    • 70. Glycogenosis type I – Girke’s disease. • Girke’s disease cause deficit of glucose-6-phosphatase. This enzyme provides 90 % of glucose which disengages in liver from glycogen. It play central role in normal glucose homeostasis. Glucose which disengages attached to disintegration of glycogen or is derivated in process of gluconeogenesis obligatory goes over stage of glucose-6-phosphate. • Enzyme glucose-6-phosphatase tears away a phosphate group from glucose. There free glucose is formed it goes out in blood. Attached to Girke’s disease stage of tearing phosphate group is blocked. There are no free glucose hypoglycemia occur. Hypoglycemia arises. Attached to Girke’s disease glycogen is deposed in liver and kidneys.
    • 71. Glycogen Storage Disorders: • Type 1= Von Gierke’s: – Shortly after birth: Severe lifethreatening Hypoglycemia – Lactic acidosis –due to isolated glycolysis of G6Po – Hyper-uricemia, hhyyppeerr lliippiiddeemmiiaa – Increased association with epistaxis – *HHeeppaattoommeeggaallyy – **AAddvveerrssee rreessppoonnssee ttoo GGlluuccaaggoonn wwiitthh wwoorrsseenniinngg LLaaccttiicc aacciiddoossiiss • Management requires IV glucose, and then as output, close NG corn-starch or glucose solution administration to achieve close to nl glucose homeostasis. • Frequent snacks and meals. Continuous nighttime glucose infusions up to the age of 2.
    • 72. Type ІІ glycogenosis – Pompe’s disease. • Illness is related to deficit of lysosomal enzyme – sour maltase, or α-1,4- glucosidase. • This enzyme slits glycogene to glucose in digestive vacuoles. Attached to it’s deficit glycogen accumulates at first in lysosomes and then in cytosole of hepatocytes and myocytes.
    • 73. Type 2- Pompe’s disease: • Normal Glucose • Do to an accumulation of glycogen in lysosomes. • **Ancient city of Pompeii was destroyed by Mt. Vesuvius- 79 AD** • Manifested by massive Cardiomegaly, Hepatomegaly, Macroglossia. • Fatal If results in CHF. • Limited therapies in Neonatal Variant. – Attempts at enzyme replacement ongoing.
    • 74. Glycogen in the Liver (left stained to show glycogen, right normal) Glycogen in Muscle Cells Type ІІІ glycogenosis – Cori’s disease, Forbs’ disease  This illness is named limited ecstrinosis. In it’s base lies a deficit of amylo-1,6-glucosidase.  Degradation of glycogen pauses in sites of branching.  Glycogen accumulates in liver and muscles. Cure is diet with big proteins maintenance.
    • 75. Type ІV glycogenosis – Anderson’s disease. • It is called by deficit of amilo- 1,4,1,6-transglucosidase (branching enzyme). • As result of this there is derivated anomalous glycogen with very long branches and rare points of branching. It is not exposed to degradation and accumulates in liver, heart, kidneys, spleen, lymphatic nods, skeletal muscles.
    • 76. • It’s cause is deficit of phosphorilase of myocytes. Typical pain displays in muscles after physical loading. • Glycogene does not slit only in muscles. Here it accumulates. In liver mobilization of glycogen comes normal.
    • 77. • Illness arises as result of insufficiency of hepatic phosphorilase complex. • Glycogen accumulates in liver. • Typical sign is hepatomegalia.
    • 78. • TTyyppee VVІІІІ ggllyyccooggeennoossiiss.. IIllllnneessss eesssseennccee iiss iinn oopppprreessssiioonn ooff mmuussccllee pphhoosspphhooffrruuttkkiinnaassee.. SSyymmppttoommss aarree ssiimmiillaarr ttoo MMccAArrddlleess ddiisseeaassee.
    • 79. 1. ROBBINS BASIC PATHOLOGY / [edited by] Vinay Kumar, Abul K. Abbas, Jon C. Aster. – 9th ed. – 2013. 2. Kathryn L. McCance . Pathophysiology: the biologic basis for disease in adults and children / [edited by] Kathryn L. McCance, Sue E. Huether; section editors, Valentina L. Brashers, Neal S. Rote - 6th ed. – 2010. 3. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasic // Elsevier Inc. – 2010. 4. General and clinical pathophysiology. Edited by prof. A.V. Kubyskin. Simferopol. – 2011. 5. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin.– New York, Milwaukee. – 2009. 6. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams & Wilkins), Trade paperback (2003) / Carol Mattson Porth, Kathryn J. Gaspard. Chapter 32 7. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart. New York. – 2000. 8. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. – 2010.