2 Salma Marji

النسخ

1 2 Salma Marji

2 بسم هللا الرحمن الرحيم Subject Lecture # Date : #/#/2021 Subject Uptake by this mechanism does not regulate C synthesis by the cells. The macrophages become overloaded with C and are transformed into foam cells. These cells die under the intima of arteries, causing deposition of CE, leading to atherosclerosis. المشكلة بأخذ ال macrophages ل LDL النه doesn t regulate cholesterol ( c) synthesis by cells احنا قلنا في الوضع الطبيعي اول ما ال tissuesتاخد ال LDL ويصير liberation لل, c ال free cholesterol بنظم عملية ال further uptake of LDL اما هون فش تنظيم لتصنيع ال c جوا الخلية ف ال macrophage رح تكون مليانة ب cوفش اي تنظيم يعني اللي بده يدخل يدخل وبتروح ال macrophageتتحول ل foam cells فيها intima في ال foamبتموت cells وبعدين هاي lipid and cholesterol a lot ويخرج منها ال c فبصير عنا depositionلل cholesterol esters في ال intima وبالتالي A) atherosclerosis ( Accumulated foam cells in arterial walls also stimulate release of growth factors and proliferation of smooth فريق يقين 2

3 muscles and formation of plaque (atheroma). These produce narrowing of blood vessels and predispose to thrombosis. اللي بزود ال A اكتر هو انه وجودها في ال arterialبعملstimulation wall smooth muscle cells will go اللي رح تخلي ال growth factors arteries ال proliferationوبتخ ن ل The incidence of cronary atherosclerosis is directly related to the concentration of LDL in the blood plasma. عشان هيك الدكاترة اول اشي بطلعوا عليه هو ال حدوث ال A اعلى.. LDLالنه كل ما كان اعلى بتكون نسبة Antioxidants like vitamin C and E decrease the incidence of atherosclerosis. احنا قلنا من االشياء اللي بتصير لل LDL هي ال Peroxidation فعشان هيك بياخدوا antioxidantعشان اهون الموضوع واحاول اعمل modification for LDL وبالتالي بقل خطورة االصابة بال A الرسمة توضيح للي حكيناه اذا بدكم ترجعولها عند الدقيقة 53:13 فريق يقين 3

4 Role of lipoprotein (a) in heart disease: Lipoprotein (a), or lp(a), is a particle that when present in large quantities in the plasma, is associated with an increased risk of cronary heart disease. Lipoprotein (a) is nearly identical in structure to an LDL particle. Its distinguishing feature is the presence of an additional apolipoprotein molecule, apo (a), that is covalently linked at a single site to apo B 100. apo B اضافية ماسكة بال apo(a) عنده lp(a) انه ال LDL و lp(a) الفرق الوحيد بين ال فريق يقين

5 apo apo a LDL lp a الدائرة الزرقاء هي b 100 وكونلي ال الحظوا االشي االصفر اللي بشبه الدودة ارتبط مع ال LP (a) plasma levels are determined by genetic factors. However, factors as diet may play some role as trans fatty acids have been shown to increase LP (a) and estrogen decrease both LDL & LP (a). في عنا عوامل جينية بتحدد كمية ال lp a في الجسم, غير طبعا عن الدايت النه الناس اللي بتاحد لقينا انه بزود ال (a) lp فبالتالي امراض القلب رح تزيد.. ولقينا trans fatty acid كمان ان االستروجين بقلل ال ال LDL and lp a فهاد االشي منيح وعشان هيك بنشوف 2 انه النساء اقل عرضة من الرجال باالصابة بامرتض القلب ولكن اذا صاب النساؤ امراض القلب فالموضوع بكون خطير جدا Apo (a) is a highly homologous to plasminogen, the precursor of blood protease (plasmin) which causes fibrinolysis. It is hypothesized that elevated LP (a) slows the breakdown of blood clots that trigger heart attacks because it competes with plasminogen for the binding of plasminogen activators. مشكلة ال انه ال apoالي a فيها كتير بشبه ال plasminogin اللي بتحول ل LP a blood clot وهاد ال بكسر ال fibrinوبالتالي plasmin يحمينا من حدوث ال plasmin فريق يقين 5

6 fibrin هأل لما نيجي نالقي ال lp a زاد بالجسم, اللي رح يصير فعليا انه بقل تكسير ال يعني بصير عنا clotsوامراض بالقلب طيب ليش النه مش قلنا ال apo a كتير بشبه ال? plasminogen ف اكيد رح يتنافس معه على نفس plasminogen activator ال receptor اللي هو ال وكونه نسبة ال apoاعلى a ف clots اكيد رح يفوز وهيك رح يبطئ شغل ال plasminogenوما رح يتكسر ال وبالتالي antagonist apo a رح تزيد نسبة حدوث االمراض يعني كأنه ال اشتغل ومنع عمل ال plasminogen او قلل عمله.. Metabolism of (HDL) They are formed by liver cells and small intestine as discoidal HDL which are mainly formed of PL bilayer, free C, and apolipoproteins (A,C,D,E) then accept free C from extrahepatic tissues, where it is esterified by LCAT (This enzyme is secreted by the liver and binds to HDL and is activated by apo A-I present in HDL). LCAT catalyzes the transfer of acyl group from position 2 of lecithin to C to form CE and lysolecithin. هأل ال HDL اول ما يطلع بكون discoidalيعني شبه القرص مش منفوخ وبفرق عن الباقي انه phospholipid is bilayer وال HDLماشية بتاخد ال Free c من ال extrahepatic tissue وبتعمله esterification عن طريق ال LCAT enzyme اللي بنعمله activationعن طريق apo a 1 موجود عند ال HDL فريق يقين 6

7 LCAT: lethicin cholesterol acyl transferase يعني LCATحيعمل transfer لل fatty acid من ال الليثيسين للكوليسترول الليثيسين هو phospholipid ولما ناخد ال fattyتبعته acid من ال position 2 يتحول الى lysolecithin رح CE form a central hydrophobic core that pushes the PL bilayer apart and converts the discoidal HDL into the spherical HDL 3. CE النها تعب ت من ال spherical discoidalالى هون بتبلش تتحول من وصارتHDL3. HDL 3 also receives excess surface lipids, C, PL from CM and VLDL when broken by LPL enzyme. HDL 3 now becomes HDL 2. طبعا طول ما هي ماشية بتاخد Lipids سواء من ال CM or VLDL وهدول ال lipids بتكسروا وال HDL3 becomes HDL2 Hepatic lipase hydrolyzes and removes part of the TAG, CE, PL from HDL 2 reforming HDL 3. TAG على اشياء تانية HDL2 يشيلك شوية هاد االنزيم برضه رح يشتغلك على ويحولها يرجع الى HDL3 LDL كانت tissues بينما ال HDL منيحة النه بتلملي الكوليسترول من ال ال تحطلي كوليسترول في ال tissues ف نسبة ال HDL لما تكون عالية هاد اشي منيح فريق يقين 7

8 HDL act as reservoir for different apoproteins (C,E), which are important for metabolism of CM and VLDL. عشان هيك اذا كان ال HDL مش مزبوط.. رح تكون ال METABOLISMل بعض ال plasma lipoprotein مش مزبوطة.. HDL by the mean of CETP (apo D) provide CE to CM remnants and LDL in exchange with TAG. ال CETP بساعد بعملية تبادل ال TAG And CE بين HDL و CM و VLDL CETP : cholesterol ester transverse protein HDL are endocytosed by liver cells, where CE are hydrolyzed. The free C released is either repacked into lipoproteins or converted to bile acids to be secreted in bile. So, HDL are important for removal of C from tissues to the liver (reverse C transport) and high levels of HDL protect against atherosclerosis. اهمية ال HDL تكمن في ازالة الكوليسترول من ال Tissues reverse C transport. واوديها لل liver ف عملنا فريق يقين 8

9 الدكتورة حكت بكل الرسمات انه اهتموا بس بالكالم اللي مكتوب بالساليدات *ال PCAT اللي بالرسمة نفسها ال.LCAT Notes: While some components of the Lipid Profile (Total Cholesterol and HDL Cholesterol) are not impacted by food, others, particularly the triglyceride level, can be. ال HDL and Total cholesterol ما بيتأثروا باالكل عشان هيك لما بدك تعمل فحص الهم فش داعي تصوم اما اذا بدك تعمل لل TAG الزم تصوم النه بيختلف تركيزه لما تاكل كونه االكل معظمه TAG فريق يقين 9

10 The LDL cholesterol is a value often obtained by a calculated method that relies on the accurate measurement of triglycerides. For this reason, a nonfasting sample can raise triglycerides and yield an inaccurate LDL cholesterol calculation. وكمان عندك ال LDL الزم تصوم النه بحساب ال LDL TAG وهي المعادلة تحت في معادلة بتعتمد برضه على ال There is no simple, direct way to measure VLDL cholesterol. VLDL cholesterol is usually estimated as a percentage of your triglyceride value. LDL cholesterol (mg/dl) = total cholesterol HDL cholesterol (triglycerides/5) VLDL اذا بدك تحسب ال LDL بتجيب ال total وبتطرح منه ال HDL ما الها طريقة مباشرة للحساب ف هي نفسها ال TAG/5 VLDL وال.. هسا ال where triglycerides/5 is used to represent very low density lipoprotein-c (VLDL-C) فريق يقين 10

11 Non-HDL cholesterol, another calculated measure, does not rely on triglycerides, however, and can be done as a nonfasting sample. في اشي تاني بقدروا يقيسوا.. انه ليش ما نقيس ال Non-HDL يعني اقيس ال VLDL and LDL وهاد احسنلي النه هيك بقدر اتنبأ المرض بشكل افضل وكمان فش داعي يكون الشخص صايم النه فعليا انت بتطرح ال total cholesterol من ال HDL ف بالتالي فش عندي TAG النه انا حسبت ال VLDL and LDL مع بعض كأنهم واحد ف ما احتجت TAGيعني فش داعي للصيام Furthermore, the non-hdl cholesterol value reflects all of the major lipoproteins linked with a higher risk of cardiovascular disease. ال NON-HDL مش بس بعطيك معلومات عن LDL عشان اقيس كل المخاطر ال كمان عن ال VLDLوهاد احسن Some lipid experts experts argue that the non-hdl cholesterol value is better than the LDL cholesterol value for predicting heart disease. Your non-hdl cholesterol result refers to your total cholesterol value minus your HDL cholesterol. For these reasons, if one desires an accurate triglyceride and calculated LDL cholesterol level, it is ideal to fast for 8-12 hours prior to the test. However, if this is not the case, total cholesterol, HDL cholesterol and non-hdl cholesterol cholesterol values may still be obtained obtained accurately, and will be useful. فريق يقين 11

12 *LDL composition changes as they circulate in the blood. Some molecules are removed and others are added, resulting in lipoprotein particles whose properties vary from large and fluffy to small and dense. Traditional lipid testing measures the amount of LDL cholesterol (LDL- C) present in the blood, but it does not evaluate the number of particles of LDL (LDL-P). Some studies have shown that increased numbers of small, dense LDL particles (sdldl ) are associated with inflammation and are more likely to dense LDL particles (sdldl ) are associated with inflammation and are more likely to cause atherosclerosis than fewer light, fluffy LDL particles. Researchers think that the presence of an increased number of sdldl could be one of the reasons that some people have heart attacks even though their total cholesterol and LDL cholesterol concentrations are not particularly high. هاد الساليد نطت عنه الدكتورة *Studies indicate that the risk for atherosclerosis is more related to the number of LDL particles (LDL-P) than the total amount of cholesterol within these particles. فريق يقين 12

13 *It is also important to remember that LDL particles carry other molecules than cholesterol. For example, triglycerides (TG) are also carried within LDL-particles. TG molecules are larger than cholesterol ester molecules. LDL يعني الخطورة مش بكمية الكوليسترول ال انما بعدد ال LDL الموجودة النه ال فيها TAG مش بس الكوليسترول واكتشفوا انه TAGكمان حيأثر علي اكبر من الكوليسترول.. طيب ايش If the number of TG molecules in an LDL-particle is high, there will be less space for cholesterol molecules. Therefore, if triglycerides are high, it may take many more LDL particles to carry a given amount of cholesterol. هأل اذا كان العدد تبع TG اعلى معناته فش وسع لكوليسترول كتير صح فريق يقين 13

14 12 TG 2 يعني مثال انا عندي LDL وفيهم كمية عالية جدا وعندي كوليسترول الزم يدخلوا جوا هدول ال 2 LDL طيب يا عمي ما في وسع كيف بدكم تدخلوا بهاي الحالة انا بحتاج ل اكتر عشان اوزع عليهم باقي ال 12 كوليسترول LDL Therefore high LDL particle count may be associated with small, cholesterol depleted, triglyceride rich particles. TG معناها عندي LDLعالي عالي يعني فش مساحة للكوليسترول ( CHOLESTROL وبالتالي ال LDLرح particle تكون صغنونة DEPLETED) Research has shown that high levels of triglycerides are associated with small LDL particle size. (There is an inverse correlation between blood levels of triglycerides and LDL particle size. Thus, the higher your triglycerides, the greater the number of small LDL particles. Conversely, the lower your triglycerides, the higher the number of large, fluffy LDL particles) انه يكون عندي LDLكبيرة يعني مليانة كوليسترول ارحم من انه يكون LDLصغيرة ويكون عددها كتير كبير. فريق يقين 14

15 Now, what does all this mean? It means that one person (person A) may have large cholesterol rich LDL particles, while another (person B) may have smaller cholesterol depleted particles. These two persons may have the same LDL-C concentration. However, person B will have higher LDL particle particle number (LDL-P). Despite similar levels of LDL-C, person B is at higher risk for future cardiovascular events. Furthermore, person B will have more small LDLparticles. طيب هاد االشي شو بفسرلي large cholesterol rich LDL a انه لما يكون شخصين مختلفين واحد عنده والتانيb smaller cholesterol depleted with more particles عنده particles LDL b LDL-C concentration عندهم نفس وال 2 بس اللهم عند متوزعة على اكتشفوا انه b عنده خطورة ال cardiovascular event اعلى particleاكتر. فريق يقين 15

16 Hyperlipoproteinemias Type I (Hyperchylomicronemia): - The familial type is due to deficiency of lipoprotein lipoprotein lipase or deficiency deficiency of apo CII - Increased plasma levels of chylomicrons and VLDL - Increased plasma level of triacylglycerols and slight increase in plasma cholesterol. (VLDL) ف البالزما بتبين TAG كتر ما فيها -من So, the plasma is turbid. عكرة Type II (Hyperbetalipoproteinemia): -The familial type is due to defective LDL receptor or mutation in ligand region of apo B The acquired type occurs in hypothyroidism as T3 increases the sensitivity of LDL receptor to LDL. ليش ال hypothyroidism بتكون مرتبطة ب hyperbetalipoproteinemia? النه ال T3 بتزود ال sensitivityتبعت ال LDLلل receptor LDL ف لو ما فيش T3 يبقى ال receptorمش حيكون sensitive انه يعمل uptakeلل LDL ف بتزيد ال LDLعندهم فريق يقين 16

17 * A T3 test is most often used to diagnose hyperthyroidism, a condition in which the body makes too much thyroid hormone. There are two subtypes of hyperbetalipoproteinemia: 1) Type IIa: It is characterized by increased plasma LDL without increase in VLDL. So, the plasma is clear. 2) Type IIb: It is characterized by increased plasma LDL with a slight increase in plasma VLDL. So, the plasma is slightly turbid. There is marked hypercholesterolemia which if familial called familial hyper cholesterolemia. Also, there is a slight increase in plasma triglycerides levels " especially in type IIb. Atherosclerosis & coronary heart disease were sequelae of elevated LDL & Type III (Dysbetalipoproteinemia): - The familial type is due to abnormality in apo E leading to the defective uptake of chylomicrons & VLDL remnants by apo E receptor. -Increase chylomicron remnants & VLDL remnants in plasma. فريق يقين 17

18 Type IV (Hyperprebetalipoproteinemia): - It is characterized by increased plasma VLDL & triacylglycerols and some increase in plasma cholesterol. - The familial type (famelial hypertriacylglycerolemia ) which is the most common familial lipid abnormality is often associated associated with hyperinsulinemia hyperinsulinemia and poor glucose tolerence -The acquired type is due to type II diabetes mellitus, obesity, alcoholism and administration of progestational hormones. TG مشكلة المجموعة الرابعة انهم بكونوا VLDL كتير النه ال LIVERبكون عنده poor glucose tolerance? كتير.. شو عالقة ال hyperinsulinemiaوال ال بتكون relatedالى hyperinsulinemia حد ما بأن االمسولين تبعهم مش شغال type 2 كويس يعني عندهم insulin resistance يعني زي كأنك بتحكي diabetes ف لما يكون عنا insulinيعني resistance وي كأنه فش انسولين فعليا, البنكرياس بفكر الخلل منه وبصير يفرز انسولين بكمية اكبر.. والفكرة انه عند عدم احساس الجسم باالنسولين بيبقة مش عارفين نحرق ال glucoseف بنروح نحرق TAG اللي موجودة بال VLDL ويطلع ال يروح لل liver ويطلعلي FFA adipose tissue فريق يقين 18

19 TypeV (Hyperchylomicronemia& Hyperprebetalipoproteinemia): The cause is unknown السبب مش معروف لهاد النوع بس يقال انه الجين المسؤول عن تصنيع ال assembly شغال بطريقة عالية وهاد بساعد او بعمل inductionلل apolipoprotein VLDL CM بتاع هدول ال lipoprotein particles يعني ال assemblyلل وال Hyperchylomicronemia & اعلى وبالتالي بصير Hyperprebetalipoproteinemia Type VI (Hyperalphalipoproteinemia): -It is due to familial increase in HDL concentration. -It occurs during estrogen therapy. -There is reduced risk of atherosclerosis. هاد اللي بنطمح اله انه يكون عناال HDLاعلى.. بالتوفيق... فريق يقين 19