DMBMS

1. Cholesterol
BY
dr: Mohammed Bahgat Mohammed Sofyan
Assistant lecturer of medical biochemistry,
Faculty of medicine, Al-Azhar university
(Assiut branch)
1

2. 2

3. 3

4. ‫صورة‬ ‫كل‬ ‫على‬ ‫اضغط‬
‫الشاش‬ ‫عرض‬ ‫وضع‬ ‫في‬
‫ة‬
‫قنواتنا‬ ‫على‬ ‫وادعمنا‬
‫اإلنترنت‬ ‫على‬

5. ‫على‬ ‫ملفي‬ ‫في‬ ‫هنا‬ ‫أرفعها‬ ‫التي‬ ‫شرائحي‬ ‫ومذاكرة‬ ‫بالتعلم‬ ‫وأسعد‬ ‫وأرحب‬ ‫أسمح‬
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‫من‬
‫نسخ‬
‫شريحة‬
‫او‬
‫اثنين‬
‫عند‬
‫الضرورة‬
،
‫وال‬
‫مانع‬
‫من‬
‫شرح‬
‫البوربو‬
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‫بي‬
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‫عدم‬
‫إزالة‬
‫اسمي‬
‫من‬
‫البوربوينت‬
،
‫فال‬
‫أسمح‬
‫أبدا‬
‫بإزالة‬
‫اسمي‬
‫من‬
‫على‬
‫الباوربوينت‬
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‫بدال‬
‫منه‬
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‫وكأنك‬
‫من‬
‫صممتها‬
‫فهذه‬
‫سرقة‬
‫ال‬
‫أسمح‬
‫بها‬
‫وتضييع‬
‫لحق‬
‫من‬
‫تعب‬
‫في‬
‫عملها‬
.
‫وفقكم‬
‫هللا‬
‫وإياي‬
‫للتعلم‬
‫ونفع‬
‫اآلخرين‬
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theft that I do not allow and a waste of the right of those who are
tired in this work. May God bless you and me for learning and
benefiting others
5

6. Cholesterol
•
‫وجوده‬
:
•
‫في‬ ‫خاصة‬ ‫األكل‬ ‫في‬ ‫يوجد‬
• Forms
•
‫تصنيعه‬ ‫من‬ ‫عليه‬ ‫بنحصل‬ ‫الكوليسترول‬ ‫أكثر‬ ‫لكن‬ ‫ضئيلة‬ ‫بكميات‬ ‫األكل‬ ‫من‬ ‫عليه‬ ‫بنحصل‬
‫سيتوبالزم‬ ‫داخل‬
‫الخاليا‬
NB:
• Plasma cholesterol synthesized from liver
6

7. STEPS
7

8. Steps :
1_ acetyl CoA combine with another acetyl CoA
to gives Acetoacetyle CoA by thiolase enzyme
2_ Acetoacetyle coA combine with another
acetyl CoA to gives B hydroxy methyl C0A
( BHMG CoA)
3_ BHMG coA convert to mevalonate by BHMG
CoA reductase
4_ mevalonate ➡ sequaline ➡ lanosterol ➡
desmosterol ➡ cholesterol.
8

9. Regulation of
cholesterol
synthesis :
HMG CoA reductase is the key enzymes
• 1_ Insulin ➡ stimulate HMG CoA reductase ➡
stimulate cholesterol synthesis
_Glucagon hormones➡ Inhibit HMG CoA
reductase➡ inhibit cholesterol synthesis
• 2_ ⬆cholesterol ➡ feedback inhibition of HMG CoA
reductase
• 3_ Drugs as statin ➡ inhibit HMG CoA reductase
9

10. FUNCTION OF CHOLESTEROL
• 1_ Formation of the cell membrane
10

11. FUNCTION OF CHOLESTEROL
2_ Formation of lipoproteins
11

12. FUNCTION OF CHOLESTEROL
3_ synthesis of Vit D3 :
Cholesterol ➡ 7 dehydrocholesterole ➡
25 hydroxyvit D ( Vit D 3)( liver) ➡
1,25 D OH Vit D 3 (kidney)
12

13. 13

14. FUNCTION OF CHOLESTEROL
4_ synthesis of bile acids and bile salt :
‫بتحتاج‬ ‫دي‬ ‫العملية‬ ‫ان‬ ‫تعرف‬ ‫لكن‬ ‫بتاعها‬ ‫المخطط‬ ‫انظر‬
• Vit C, thyroid hormones especially in the conversation of cholesterol to 7
hydroxy cholesterol by 7 hydroxylase .
‫هنسخدم‬ ‫اننا‬ ‫تعرف‬ ‫الزم‬ ‫كمان‬
NADPH+H
‫هينتج‬ ‫اآلخر‬ ‫في‬
bile acids and salts
14

15. 15

16. FUNCTION OF CHOLESTEROL
5_synthesis of steroid hormones as corticosteroids,
mineralosteroids, and sex hormones ( male sex
hormones as testosterone and female sex hormones
as estrogen and progesterone)
16

17. 17

18. Mech
Mechanism of atherosclerosis of
atherosclerosis :
High-level LDL or modified LDL ( by cigarette,
Alcohol,...) are uptaken by macrophage
precipitate under intima
of blood vessels proliferation of smooth muscle
of blood vessels hypertrophy narrowing of
blood vessels atherosclerosis
18

19. 19

20. 20

21. 21

22. Results of
atherosclerosis
over the years
1_ angina and M.I.
2_ stroke
3_ peripheral vascular disease (PVD)
22

23. Markers of
Atherosclerosis
?????????
23

24. 24

25. 25

26. speciment
Serum
or according
to pamphlet
26

27. Preanalytical procedures :
1
-
‫قاعد‬ ‫وهو‬ ‫الدهون‬ ‫نقيس‬
2
-
‫شديدة‬ ‫تمارين‬ ‫عمل‬ ‫عدم‬ ‫يشترط‬
3
-
‫عمل‬ ‫عدم‬ ‫يشترط‬
diet
4
-
‫يوضع‬ ‫ال‬
tornique
‫طويلة‬ ‫لفترة‬
5
-
‫صيام‬ ‫من‬ ‫البد‬
12
‫قياس‬ ‫عند‬ ‫ساعة‬
• lipid profile generally
•
‫الصيام‬ ‫يشترط‬ ‫فال‬ ‫الكوليسترول‬ ‫باستثناء‬
6
-
‫الح‬ ‫تقييم‬ ‫ويتم‬ ‫أسبوع‬ ‫كل‬ ‫القياس‬ ‫يتم‬ ‫شهرين‬ ‫خالل‬ ‫في‬ ‫التحليل‬ ‫تكرار‬ ‫من‬ ‫بد‬ ‫ال‬ ‫العالج‬ ‫اعطاء‬ ‫قبل‬
‫ذلك‬ ‫على‬ ‫بناء‬ ‫الة‬
7
-
‫واإلسترويدات‬ ‫الحمل‬ ‫أدوية‬ ‫مثل‬ ‫أدوية‬ ‫أخذ‬ ‫عدم‬ ‫مراعاة‬ ‫ينبغي‬
.
27

28. •
‫هي‬ ‫الكوليسترول‬ ‫بيها‬ ‫بنقيس‬ ‫اللي‬ ‫الطريقة‬
• Enzymatic method
•
‫ال‬ ‫انزيم‬ ‫فيها‬ ‫بنستخدم‬
peroxidase
‫ال‬ ‫بيحول‬ ‫اللي‬
• H2O2 ➡ H2O + O
• O oxidized non coloured chromagen into coulerd chromagen
• SO reduced substances as
Hyperbiluribinaemia, hyperuricemia, ⬆Vit C, Hb,and tetracycline ➡ compete
with chromagen for O ➡ false low results of cholesterol.
28

29. Reactions :
Cholesterol ester + H2O ➡ Cholesterol + fatty acids
By cholesterol esterase enzyme
Cholesterol + O2 ➡4-Cholestenona + H2O2
By cholesterol oxidase enzyme
2 H2O2 + Phenol + 4-AP➡4H2O + Quinonimine ( red colour read at wavelength 500_530 nm)
By peroxidase enzyme
29

30. ‫البامفلت‬ ‫في‬ ‫موجوده‬ ‫الخطوات‬ ‫طبعا‬
• As pamphlet
• EX
is added to 10 micron of ( blank, standard and
serum)
• Wait for 15 minutes at 37'C.
• Then reads Absorbance at WL 530 nm or as pamphlet say.
30

31. Measurment of cholesterole
•
‫ال‬ ‫بجهاز‬ ‫يقاس‬
spectrophotometer
•
‫ال‬ ‫علي‬ ‫ونحصل‬ ‫ونفصلها‬ ‫الدم‬ ‫عينة‬ ‫بنجيب‬
serum
‫عليه‬ ‫نضع‬
kits of cholesterol
‫لون‬ ‫وينتج‬ ‫الدم‬ ‫في‬ ‫الكوليسترول‬ ‫مع‬ ‫يتحد‬ ‫يقوم‬
...
‫ال‬ ‫مع‬ ‫طرديا‬ ‫يتناسب‬ ‫اللون‬ ‫هذا‬
• Concentration of cholesterol in the sample
•
‫ال‬ ‫نحسب‬
absorption of sample
•
‫وباستخدام‬
standar
‫له‬ ‫نقيس‬ ‫التركيز‬ ‫معلوم‬
absorption
•
‫معايا‬ ‫يبقي‬ ‫كده‬
• Concentration of stander ( C st)
• Absorption of stander (A st)
• Absorption of sample (As)
‫معلومة‬ ‫قيم‬ ‫كلهم‬ ‫ودول‬
•
‫فاضل‬ ‫يبقي‬
• Concentration of sample ( Cs)
‫المعادلة‬ ‫من‬ ‫يتحسب‬
• Cs = As X ( Cst / Ast )
•
‫الدم‬ ‫في‬ ‫الكوليسترول‬ ‫جميع‬ ‫يقاس‬ ‫هنا‬ ‫ملحوظة‬
• Free or esterified cholesterol or combined with VLDL, LDL, HDL, chylomicron.
31

32. REFERENCE Values
Less than 200
mg/dl ➡ Normal
( desired )
200_ 239
➡ Borderline
240 and above
➡High
32

33. ‫علي‬ ‫الدم‬ ‫في‬ ‫بيحمل‬ ‫الكوليسترول‬ ‫إن‬ ‫تعرف‬ ‫الزم‬
lipoproteins as Chylomicrons, VLDL, IDL,LDL and
lipoprotein a
Total cholesterol = VLDLc + LDLc + HDLc
‫علي‬ ‫الموجود‬ ‫الكوليسترول‬ ‫إهمال‬ ‫مع‬
Chylomicrons and lipoprotein a
‫لصغرهما‬
.
33

34. •
‫الدم‬ ‫في‬ ‫والدهون‬ ‫الكوليسترول‬ ‫يزود‬ ‫اللي‬ ‫بقي‬ ‫ايه‬
‫كلمة‬
[
‫دهن‬
]
DOHN
4D
1_ Diet rich in fat(especially saturated F.A) or carbohydrate
2_ D.M
3_ Drinking coffee ☕ smoking 🚬or alcohol
4_ Drugs as contraceptive, anabolic,steroids corticosteroids, thiazide, BB and anticonvulsant.
34

35. •
‫الدم‬ ‫في‬ ‫والدهون‬ ‫الكوليسترول‬ ‫يزود‬ ‫اللي‬ ‫بقي‬ ‫ايه‬
‫كلمة‬
[
‫دهن‬
]
DOHN
3O
1_ Obesity
2_ Obstructive jundice
3_ Others as pregnancy
35

36. •
‫الدم‬ ‫في‬ ‫والدهون‬ ‫الكوليسترول‬ ‫يزود‬ ‫اللي‬ ‫بقي‬ ‫ايه‬
‫كلمة‬
[
‫دهن‬
]
DOHN
2H
1_ Hypothyroidism
2_ Hyperlipoproteinaemia
1N
1_Nephrotic syndrome (nephritic syndrome ) and CRF
36

37. To investigate a case of Hyperlipidaemia :
for exclude secondary causes :
a_ blood sugar to exclude DM
b_ TSH to exclude hypothyroidism
c_ ALP, gamma GT to exclude obstructive jaundice
d_ protein in urine and kidney function tests to exclude nephrotic syndrome
e_ history of( obesity, diet, drugs as alcohol, coffee, thiazide)
If all normal Exclude genetic causes as a history of Hyperlipidaemia in family familial
screening...... etc.
37

38. Treatment
• 1- Avoid risk factors
• 2- reduction of weight
• 3- increase physical activity
• 4- decrease diet rich in saturated fat , lipids,
cholesterol and carbohydrates.
• 5- drugs
38

39. Ator ( statin) ➡ HMGcoA reductase inhibitors
cholesterol absorption inhibitors ➡ as Ezetimibe
39

40. 40

41. 41

42. Norma
lrange
42

43. 43
CERTIFICATE
of Participation
TO CERTIFY THAT
Has attended and listened to this lecture
carefully
Date Signature
Dr: Mohammed Bahgat Sofyan
November 6, 2021
Dr:

44. 44
Before After

45. REFERENCES :
• _ https://labtestsonline.org
• _ https://www.medscape.com
• _ https://www.wikipedia.org
• _ https ps://www.labcorp.com
• _ https://www.uptodate.com
• _ https://www.ncbi.nlm.nih.gov Home - PubMed – NCBI
• _TIETZ TEXTBOOK OF CLINICAL CHEMISTRY AND MOLECULAR DIAGNOSTICS, SIXTH EDITION 2018.
• _Essential of clinical pathology book; 1st edition; Shirish M Kawthalkar; 2010.
• _Essential of biochemistry book ;1st edition; 2012.
• _ ABC of clinical hematology ; 4th edition ; Drew Provan; 2018.
• _ Harper's illustrated biochemistry 30th edition 2015.
• _ Lippincott's illustrated review of biochemistry sixth edition 2014.
• _ Lecturea Notes Clinical Biochemistry, 9th Edition Walker, Simon, 2103.
• _Some audios and videos from Well-known, trusted professors who study from accredited
books.
45

46. ‫اليوتيوب‬ ‫علي‬ ‫البحث‬ ‫أو‬ ،‫اليوتيوب‬ ‫علي‬ ‫قناتي‬ ‫دي‬
‫د‬ ‫باسم‬
.
‫سفيان‬ ‫بهجت‬ ‫محمد‬
،
‫هللا‬ ‫شاء‬ ‫إن‬ ‫نستمر‬ ‫حتى‬ ‫بالقناة‬ ‫وتشتركوا‬ ‫تتابعوني‬ ‫ياريت‬
https://www.youtube.com/channel/UCaYs1d8s0ntZvteHS3mMmGA
‫ب‬ ‫الفيس‬ ‫في‬ ‫البحث‬ ‫أو‬ ،‫انضمامكم‬ ‫يشرفنا‬ ‫الفيسبوك‬ ‫علي‬ ‫بتاعتي‬ ‫الصفحة‬ ‫دي‬
DMBMS2018
،
‫هللا‬ ‫شاء‬ ‫إن‬ ‫نستمر‬ ‫حتى‬ ‫تتابعوني‬ ‫ياريت‬
https://www.facebook.com/DMBMS2018/
‫باسم‬ ‫التلجرام‬ ‫علي‬ ‫قناتي‬ ‫ودي‬
ِ ‫للناس‬ ‫أنفعهم‬ ‫الناس‬ ‫خير‬
📚
‫هللا‬ ‫شاء‬ ‫إن‬ ‫نستمر‬ ‫حتى‬ ‫تتابعوني‬ ‫ِريت‬‫ا‬‫ي‬
https://t.me/DMBMS2020
‫على‬ ‫بروفايلي‬
‫لينكيدإن‬
‫وتعملولي‬ ‫تتابعوني‬ ‫ياريت‬
endorsement
‫مهاراتي‬ ‫على‬
https://www.linkedin.com/in/mohammed-bahgat-sofyan-8ba012142/
‫موقع‬ ‫على‬ ‫بروفايلي‬ ‫وده‬
SlideShare
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‫وده‬
‫بروفايلي‬
‫الشخصي‬
‫الفيسبوك‬ ‫علي‬
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‫الفيسبوك‬ ‫على‬ ‫بنا‬ ‫الخاص‬ ‫اللوجوا‬ ‫وده‬
#
‫دمحمد‬
_
‫بهجت‬
_
‫سفيان‬
_
medical_biochimestry 46

47. THANK YOU
meet on the
best later, God
willing
47