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10/15/2014 1 Pathophysiology of lipid metabolism Kiril Terziyski, MD, PhD Pathophysiology Dept. Medical University - Plovdiv
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Page 1: Pathophysiology of lipid metabolism printoutpathophysiology.info/Lectures/Dentistry/English... · Pathophysiology of lipid metabolism Kiril Terziyski, MD, PhD Pathophysiology Dept.

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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


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