![Page 1: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/1.jpg)
![Page 2: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/2.jpg)
![Page 3: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/3.jpg)
![Page 4: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/4.jpg)
CHOLESTEROL METABOLISM
![Page 5: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/5.jpg)
![Page 6: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/6.jpg)
STRUCTURE OF CHOLESTEROL
![Page 7: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/7.jpg)
CHOLESTEROL-STRUCTURE
![Page 8: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/8.jpg)
CHOLESTEROL-STRUCTURE
• Steroid alcohol
• Steroid nucleus with 4 fused rings + 8C branched chain attached to C 17
• Ring A has alcohol at C3
• Ring B has a double bond between C5=C6
![Page 9: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/9.jpg)
FUNCTIONS
• Cholesterol performs these main functions:
1. It helps make the outer coating of cells (membrane) and keeps it fluid. Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction.
2. In many neurons, a myelin sheath, rich in cholesterol provides insulation for more efficient conduction of impulses.
3. It makes up the bile acids that work to digest food in the intestine.
4. It allows the body to make Vitamin D
5. It allows the body to make steroid hormones, like estrogen in women and testosterone in men.
![Page 10: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/10.jpg)
HIGH CHOLESTEROL FOOD
![Page 11: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/11.jpg)
CHOLESTEROL METABOLISM
![Page 12: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/12.jpg)
CHOLESTEROL METABOLISM
![Page 13: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/13.jpg)
CHOLESTEROL LEVEL IN BLOOD
• Normal = 150-200 mg%
• Hypercholesterolemia:-
Diabetes Mellitus (↑Lipolysis→↑FFA →↑β Oxid →↑AcetylCoA)
Hypothyroidism (↓LDL Receptor→ ↓ LDL Clearance)
Obstructive Jaundice (↓ excretion)
Nephrotic Syndrome (↑Apo B 100 →↑VLDL →↑LDL →↑Cholesterol)
Primary HyperLipoproteinemia Type II (↓ Receptor)
Smoking
Alcohol intoxication (↑NADH/NAD ratio → ↓TCA →↑Acetyl CoA)
![Page 14: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/14.jpg)
CHOLESTEROL LEVEL IN BLOOD
LDL cholesterol Optimal: less than 100 mg/dL Near-optimal: 100 to 129 mg/dL Borderline high: 130 to 159 mg/dL High: 160 to 189 mg/dL Very high: 190 mg/dL and above. Guidance is also set out for the other measures in the lipid profile:6 Total cholesterol Desirable: less than 200 mg/dL Borderline high: between 200-239 mg/dL High: 240 mg/dL or above. HDL cholesterol Low: below 40 mg/dL High: 60 mg/dL or above.
![Page 15: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/15.jpg)
ATHEROSCLEROSIS • ↑Plasma Cholesterol
→deposition of Cholesterol in the endothelial lining of blood vessels
→plaque
→Atherosclerosis
→Narrowing of blood vessels
→ ↑risk of Cardiovascular / Cerebrovascular
/ Peripheral vascular diseases
→Life threatening
![Page 16: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/16.jpg)
CHOLESTEROL HOMEOSTASIS
• Cholesterol pool in liver
• Source:-
(a) Diet
(b) De Novo synthesis in Liver
(c) De Novo synthesis in all extrahepatic tissues :-specially adrenal cortex, reproductive tissue, (ovaries,testes,placenta), intestine
• Elimination:-
(a) Cholesterol in bile
(b) Bile salts
(c) Plasma lipoproteins (VLDL) → peripheral tissue
![Page 17: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/17.jpg)
![Page 18: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/18.jpg)
CHOLESTEROL SYNTHESIS
![Page 19: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/19.jpg)
CHOLESTEROL SYNTHESIS
• Takes place in all tissues
• Specially important:- liver, Adrenal cortex,Ovaries, Testes, Placenta, Intestine
![Page 20: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/20.jpg)
CHOLESTEROL SYNTHESIS REQUIREMENTS
• Acetate→ All C atoms
• NADPH → Reducing equivalents
• ATP →ADP + Pi + energy
• Acetyl CoA→ hydrolysis of high energy thioester bonds → energy
• Enzymes in cytosol and membrane of SER
• Regulatory mechanisms to balance
Rate of synthesis: Rate of excretion
![Page 21: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/21.jpg)
1. SYNTHESIS OF HMG CoA
• 2 Acetyl CoA condense → Acetoacetyl CoA
• Acetyl CoA + Acetoacetyl CoA → HMG CoA(6C)
• Enzyme = HMG CoA Synthase
2 isoenzymes:-
(a) Cytosolic → Cholesterol synthesis
(b) Mitochondrial → Ketone body synthesis
![Page 22: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/22.jpg)
SYNTHESIS OF HMG CoA
![Page 23: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/23.jpg)
2. SYNTHESIS OF MEVALONATE • HMG CoA (reduced) → 6 C Mevalonate
• HMG CoA Reductase (ER membrane protein with catalytic domain in cytosol)
• It is the rate limiting and regulated step
• 2 NADPH = reducing agent
• Releases CoA (action becomes irreversible)
![Page 24: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/24.jpg)
SYNTHESIS OF 6 C MEVALONATE
![Page 25: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/25.jpg)
HMG CoA REDUCTASE
![Page 26: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/26.jpg)
3. SYNTHESIS OF SQUALENE
a. Mevalonate + ATP → + ATP → 5-pyrophosphate mevalonate
• Enzyme= Kinase
![Page 27: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/27.jpg)
SYNTHESIS OF SQUALENE
b. 5-pyrophosphomevalonate is decarboxylated →Isopentenyl pyrophosphate (IPP) 5 C
(an isoprenoid)
• Enzyme= Decarboxylase
![Page 28: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/28.jpg)
SYNTHESIS OF SQUALENE
c. IPP isomerized → 5 C
DPP
(Dimethylallyl
Pyrophosphate)
• Enzyme = Isomerase
![Page 29: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/29.jpg)
SYNTHESIS OF SQUALENE
d. IPP + DPP condense → 10 C GPP
(Geranyl pyrophosphate )
• Enzyme = Transferase
![Page 30: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/30.jpg)
SYNTHESIS OF SQUALENE
e. IPP + GPP → FPP
( 15 C Farnesyl pyrophosphate)
• Enzyme = Transferase
![Page 31: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/31.jpg)
SYNTHESIS OF SQUALENE
f. 2 FPP condense and reduce → PPi + SQUALENE (30 C)
• 6 IPP required
• 18 ATP required ( 3 ATP/ Mevalonate →IPP)
• Enzyme = Squalene synthase
![Page 32: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/32.jpg)
SYNTHESIS OF SQUALENE
![Page 33: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/33.jpg)
SYNTHESIS OF LANOSTEROL • Squalene is hydroxylated
→cyclization →Lanosterol
• ER associated enzymes
• O2, NADPH needed
![Page 34: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/34.jpg)
SYNTHESIS OF CHOLESTEROL
• Many enzymes involved
• ER associated pathway
a)30 C chain→ 27 C
b)2 Methyl groups at C 4 removed
c)Double bond migrates from C8→C5
d)Double bond between C24 and 25 reduced
→ Cholesterol
![Page 35: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/35.jpg)
SYNTHESIS OF CHOLESTEROL
![Page 36: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/36.jpg)
REGULATION OF CHOLESTEROL SYNTHESIS
(HMG CoA REDUCTASE) 1. Sterol levels in cell control gene expression
2. Sterols reduce enzyme activity
3. AMPK(AMP activated protein kinase) inactivates the enzyme by phosphorylation.
Phosphatase activates it by dephosphorylation
(↑ATP→↑Cholesterol synthesis)
4. Insulin/Thyroxine→↑HMG CoA reductase gene
Glucagon/Glucocorticoids→↓gene
5. Statin drugs→structural analogs of HMG CoA
→Competitive inhibitors of HMG CoA reductase
→used to ↓plasma Cholesterol level
![Page 37: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/37.jpg)
DEGRADATION OF CHOLESTEROL
• Cholesterol ring cannot be opened
• Intact sterol nucleus →eliminated in feces as
(a) Bile acids and Bile salts
(b) Cholesterol→reduced by intestinal bacteria →Coprostanol and Cholestanol
![Page 38: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/38.jpg)
DEGRADATION OF CHOLESTEROL
![Page 39: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/39.jpg)
BILE ACIDS AND BILE SALTS
• Bile = Dilute solution of Cholesterol,
Bile salts + Lecithin (Phosphatidyl choline)
• Synthesized in liver → Common Bile duct
→stored in Gall bladder
→secreted into duodenum
![Page 40: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/40.jpg)
BILE ACIDS
• 24 C
• 2-3 OH groups
• Side chain ends at Carboxyl group (i.e. acids)
• Amphipathic because of OH group and methyl group→polar and non polar faces
( Oh groups lie below plane of ring and CH3 groups above the plane of ring)
→emulsifying agents in intestine
→ prepare lipids for hydrolytic enzymes
![Page 41: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/41.jpg)
BILE ACIDS
![Page 42: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/42.jpg)
SYNTHESIS OF BILE ACIDS
• Liver (has enzyme 7αHydroxylase)
• Multistep
• Multiorganelle
• OH groups inserted
• Double bond reduced
• Hydrocarbon chain shortened by 3C
• Carboxyl group added at the end of chain
• →Primary Bile acids ( triol = Cholic acid + diol = ChenodeoxyCholic acid)
![Page 43: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/43.jpg)
SYNTHESIS OF CHOLIC ACID
![Page 44: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/44.jpg)
SYNTHESIS OF BILE SALTS
• In liver →Bile acids → Bile salts
• Bile acids → conjugated with Glycine / Taurine
( derived from Cysteine) →Bile salts
• Carboxyl group of Bile acid forms amide bond with amino group of amino acid
• →Glycocholic / Glycochenodeoxycholic acids
Taurocholic/ Taurochenodeoxycholic acids
• 3 Glycine : 1 Taurine
• Bile salts are more amphipathic (additional acid /SO4
group at the end)
→↑effective detergents than Bile acids
• Mechanism for Cholesterol excretion
![Page 45: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/45.jpg)
BILE SALTS
![Page 46: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/46.jpg)
ACTION OF INTESTINAL FLORA ON BILE SALTS
• Bile salts in intestine
→ Bacteria remove Glycine/ Taurine
→Primary Bile acids
→Remove hydroxyl group from primary Bile acids
→Secondary Bile acids
(Cholic acid→Deoxy Cholic acid
Chenodeoxycholic acid →Lithocholic acid)
![Page 47: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/47.jpg)
ENTEROHEPATIC CIRCULATION • Bile salts secreted in intestine
→95% reabsorbed →reused
→Liver conjugates primary and secondary Bile acids with Glycine/Taurine→Bile→GI
→Bile acids + bile salts absorbed in ileum
(By Na:Bile salt Cotransporter)
(Lithocolic acid is poorly reabsorbed)
→ Portal blood ( carried by Albumin)
→Liver ( mixture of Bile acids and salts)
→ 15-30 gm Bile salts secreted daily
→ 0.5 gm (3%)lost in feces
→0.5 gm synthesized from Cholesterol in liver
![Page 48: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/48.jpg)
TREATMENT OF HYPERCHOLESTEROLEMIA
Cholestyramine/Fiber
→ bind Bile acids in GIT
→prevent reabsorption
→ ↑excretion
→ relieves inhibition of Bile acid synthesis in liver
→ ↑Cholesterol changes to Bile acids
→ ↓ Hypercholesterolemia
Plant sterols
→ ↓ absorption of dietary Cholesterol
(by competition for absorption)
![Page 49: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/49.jpg)
ENTEROHEPATIC CIRCULATION
![Page 50: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/50.jpg)
CHOLELITHIASIS (GALL STONES)
• Cholesterol in Bile must be accompanied with Phopholipids and Bile salts →solubilization
• If ↑Cholesterol →precipitates →Gall stones
(85% of Gall stones- rest are mixed/Bilirubin)
• Causes:-
(a) Ileal disease→malabsorption of Bile acids
(b) Obstruction of Biliary tract→↓enterohepatic circulation
(c) Hepatic dysfunction→↓synthesis of Bile salts
(d) ↓Bile acid synthesis
(e) ↑Biliary Cholesterol
![Page 51: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/51.jpg)
GALL STONES
![Page 52: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/52.jpg)
NORMAL PLASMA CHOLESTEROL • 150-200 mg / dl
![Page 53: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/53.jpg)
CURRENT RECOMMENDATION
![Page 54: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/54.jpg)
HYPERCHOLESTEROLEMIA CAUSES • Environmental + Genetic factors →Hypercholesterolemia • Environmental factors → Obesity/ Dietary choices. • Genetic factors→ additive effects of multiple genes / single gene
defect (e.g. familial hypercholesterolaemia) • Secondary causes:- diabetes mellitus type 2 obesity alcohol dialysis nephrotic syndrome obstructive jaundice Hypothyroidism/ Cushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta
blockers, retinoic acid).
![Page 55: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/55.jpg)
CHOLESTEROL LEVEL IN BLOOD
• Normal = 150-200 mg%
• Hypercholesterolemia:-
Diabetes Mellitus (↑Lipolysis→↑FFA →↑β Oxid →↑AcetylCoA)
Hypothyroidism (↓LDL Receptor→ ↓ LDL Clearance)
Obstructive Jaundice (↓ excretion)
Nephrotic Syndrome (↑Apo B 100 →↑VLDL →↑LDL →↑Cholesterol)
Primary HyperLipoproteinemia Type II (↓ Receptor)
Smoking
Alcohol intoxication (↑NADH/NAD ratio → ↓TCA →↑Acetyl CoA)
![Page 56: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/56.jpg)
HYPERCHOLESTEROLEMIA SIGNS AND SYMPTOMS • Hypercholesterolemia → asymptomatic
• Chronic ↑serum cholesterol→ atherosclerosis.
• Over a period of decades→↑serum cholesterol →atheromatous plaques in the arteries
→ progressive stenosis (narrowing)
/ complete occlusion (blockage) of the involved arteries
• Smaller plaques may rupture→clot→obstructs blood flow
• Sudden occlusion of a coronary artery→myocardial infarction
• Occlusion of an artery supplying the brain→ stroke.
![Page 57: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/57.jpg)
HYPERCHOLESTEROLEMIA SIGNS AND SYMPTOMS • Gradual stenosis/occlusion →slow↓blood supply to the
tissues and organs →↓organ function becomes impaired→ tissue ischemia (restriction in blood supply)→specific symptoms.
• Temporary ischemia of the brain (Transient ischemic attack)→ temporary loss of vision, dizziness and impairment of balance, aphasia (difficulty speaking), paresis (weakness) and paresthesia (numbness or tingling), usually on one side of the body.
• Insufficient blood supply to the heart→ chest pain
• Ischemia of the eye →transient visual loss in one eye.
• Insufficient blood supply to the legs→calf pain when walking,
• Intestinal ischemia→abdominal pain after eating a meal
![Page 58: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/58.jpg)
HYPERCHOLESTEROLEMIA SIGNS AND SYMPTOMS
Some types of hypercholesterolemia lead to specific physical findings.
• Familial hypercholesterolemia (Type IIa hyperlipoproteinemia) may be associated with xanthelasma palpebrarum (yellowish patches underneath the skin around the eyelids),arcus senilis (white or gray discoloration of the peripheral cornea),and xanthomata (deposition of yellowish cholesterol-rich material) of the tendons, especially of the fingers.
• Type III hyperlipidemia may be associated with xanthomata of the palms, knees and elbows
![Page 59: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/59.jpg)
HYPERCHOLESTEROLEMIA CAUSES
![Page 60: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/60.jpg)
HYPERCHOLESTEROLEMIA CAUSES
![Page 61: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/61.jpg)
HYPERCHOLESTEROLEMIA CAUSES
![Page 62: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/62.jpg)
HYPERCHOLESTEROLEMIA CAUSES
![Page 63: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/63.jpg)
HYPERCHOLESTEROLEMIA PATHOPHYSIOLOGY
![Page 64: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/64.jpg)
HYPERCHOLESTEROLEMIA SIGNS AND SYMPTOMS
![Page 65: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/65.jpg)
HYPERCHOLESTEROLEMIA COMPLICATIONS (M.I.)
![Page 66: PowerPoint Presentation Lecture... · obstructive jaundice Hypothyroidism/ ushing’s syndrome anorexia nervosa medications (thiazide diuretics, ciclosporin, glucocorticoids, beta](https://reader034.vdocuments.site/reader034/viewer/2022042105/5e8424f450e88070e9486933/html5/thumbnails/66.jpg)
HYPERCHOLESTEROLEMIA COMPLICATIONS ( STROKE)