Post on 20-Feb-2020
transcript
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Pathophysiology of lipid metabolism
Kiril Terziyski, MD, PhDPathophysiology Dept.
Medical University - Plovdiv
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Keystones
• Dyslipidemias• Atherosclerosis• Obesity
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Why do we need lipids?
• Highest energy value• Compact storage• Thermoregulation
– Thermal insulator– Thermoproduction
(brown adipose tissue)
• Fat-soluble vitamins (A, D, E, K)• Plastic function (phospholipids)
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Digestion and Absorption
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What may go wrong?
• Insufficient bile in duodenum (cholecystitis, cholelithiasis)
• Insufficient pancreatic lipase in duodenum (pancreatitis)
• Food, rich in Ca2+ and Mg2+ salts • Stomach hyperacidity (decreased lipase activity)• Increased intestinal passage• Hyponatriemia, e.g. Adison’s diasease ($α-GlyceroP)• Hypoproteinemia, hypovitaminosis A, B, C (decreased
chylomicron synthesis)
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Further logistics
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How the lungs digest lipids...and more
The LipoProtein Lipase (LPL) requires ApoC-II as a co-factor
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Liver Almighty
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Under Apo-control
ØApoA – Activates Lecitine-Cholesterol Acyl-Transferase (LCAT)
ØApoB – Binding to cellular receptors
ØApoC – Activates LPL
ØApoE – Binding of other lipoproteins to LDL
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Scavengers
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Lipid metrics
“Keep your cholesterol ratio5-to-1 or lower”.
AHA
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A blood too fat
Phenotype/ relative frequency
Lipoprotein(s)elevated
SerumChol.Conc.
SerumTGConc.
Etiology
I <1% Chylomicrons Normal to # #### Defficiency in LPL or apoCII
IIa 10% LDL ## Normal $ or no functional LDL-R
IIb 40% LDL and VLDL ## ## Overproduction of VLDL by liver
III <1% IDL ## ### Abnormal apoE
IV 45% VLDL Normal to # ## Overproduction and/or impaired catabolism of VLDL
V 5% VLDL and chylomicrons
# to ## #### Increased production or decreased clearance of VLDL and chylomicrons
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Acquired hyperlipemias
LPL - inhibitors• NaCl• Biliary salts (cholestasis)• Pancreatic LPL-inhibitor• Circadian genesHypoalbuminemia
Cholesterol
Food
Synthesis
Bile
Sterols
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Low HDL is even worse
Indipendent predictor of CAD!Causes:• Insulin resistance• Physical inactivity• Diabetes mellitus type 2• Smoking• High CH intake• Drugs (anabolic steroids, contraceptives, β-
blockers, diuretics)
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Look at the cholesterol… it matters!
Corneal opification
Corneal arcus Xantomas
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AtherosclerosisDefinition and risk factors
• Modifiable– Diabetes mellitus– Dyslipoproteinemia– Tobacco smoking– C-reactive protein– Vitamin B6 deficiency– Hypothyroidism
•Nonmodifiable• Advanced age• Male sex• Genetics
• Uncertain• Obesity• Postmenopausal estrogen deficiency• Saturated fat• Trans fat• High carbohydrate intake• Short sleep duration• Chlamydia pneumoniae
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Step by step
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From cradle to grave
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Sometimes it gets complicated
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The new Pandemic
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Etiology
ØGenetic predispositionüMonogeneticüPolygenetic
ØMaternal diabetes during pregnancyØAgeØLifestyleüSedentaryüOvereating/ Junk foodüSmoking cessationüSocio-economic status
ØMedical treatmentØViruses?
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Obesity metrics
How is body fat percentage measured?
Obesity is a medical condition in which excess body fat …
ØUnderwater weighingØWhole-body air displacement plethysmographyØDual energy X-ray absorptiometryØBioelectrical impedance analysisØSkinfolds
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Birthdays come with an extra… fat
Lower basal metabolic rate Insulin resistanceLower muscle mass Sedentarism
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Keep it as simple as possible!
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Types of obesity
Ø30% less Ins-RØ“Active fat”
FOFIFOTITOFITOTI
Life issue vs Wife issue
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Some more metrics
Males Females
Waist >94 cm >80 cm
Waist/Hip ratio >0.90 >0.85
Shirt size >43 (XL)
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Too many or too big
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Classification
• Primary– Alimentary– Regulatory– Metabolic
• Secondary– Endocrine– Iatrogenic
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Alimentary…not elementary
Energyinput
Energy expenditure
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Hunger or Appetite
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Leptin resistance
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Metabolic obesity
ØDecreased Basal Metabolic Rate (BMR)
ØTendency towards lipogenesis
ØMore efficient E- production
ØMore efficient energy expenditure
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Regulatory obesity
Hypothalamic damage
ØTumorØTraumaØHaemmorhageØInfection
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Secondary obesity
• Endocrine– Hypogonadism– Hypothyroidism– Adreno-genital syndromes– Hyperglucocorticism– Polycystic ovaries (PCOS)– Pregnancy (progesterone, leptin)
• Iatrogenic– CS, Antidepresants …
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The Endocrine Adipocyte
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Morbidity and mortality
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The Metabolic Syndrome
Add-ons•Hyperuricemia•Obstructive Sleep Apnea•hsCRP•PCOS
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Tilt the scales
Energyinput
Energy expenditure
1. Eat less, but don’t starve2. Frequent meals (5/day)3. More fibers4. Less CH with high GI
1. Exercise more (5x45)2. Exercise aerobic
$Insulin
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Giuseppe Arcimboldo