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Chol- TG- HDL- LDL. The most important lipids in human body are TG and Chol Chol is the component of cell membrane and TG is the most important source of energy for cells Chol and TG don’t transport as free molecules in plasma and transport as a component of LP. Major lipoproteins.
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Chol- TG- HDL- LDL The most important lipids in human body are TG and Chol Chol is the component of cell membrane and TG is the most important source of energy for cells Chol and TG don’t transport as free molecules in plasma and transport as a component of LP
Major lipoproteins LP classified according to density , size , chemical contents , and electrophoretic movement Chylomicron VLDL LDL HDL
According to function , we can classified LP in 2 groups: 1-Particle with lower density that distribute TG and Chol to peripheral tissues (CM-VLDL-LDL) 2-Higher density particle (HDL) , plays a key role in reverse Chol transport High serum HDL decrease CHD
LDL Constitues about 50% of total LP mass in plasma Don’t scatter light or alter the clarity of plasma Relative to other LP LDL have a higher content of Chol Is the most atherogenic LP
HDL Is involved in reverse Chol transport , the process by which excess Chol is returned from tissues to the liver The lab measurement of such particles may eventually prove to be clinically useful
LP measurement 1-particle mass (TG and Chol and pr) 2-measurement of LP Chol
Blood sampling Chol have higher physiological CV related to other lipids thus measurement must be made in several blood samples taken at least a week Chol levels rises with age starting in early adulthood in both sexes F have lower level than M Chol levels are slightly higher in winter Ideally patients should fast for 12h before venipuncture but fasting for at least 9 h before blood specimens are acceptable Generally TC and HDL-c levels can be measured in nonfasting individuals Posture……
Medications and dis that alterate lipid plasma: OCP Postmenopausal estrogen Anti HTN drugs Thyroid dis Liver dis Kidney dis Recent Mi –stroke-cardiac catheterization-trauma-acute infection-pregnancy
Chol and TG measurement: 1-Enzymatic 2-Chemical
HDL measurement 1-ultracentrifuge 2-electrophoresis 3-percipitation 4-homogenous assay
LDL measurement 1-ultracentrifuge 2-electrophoresis 3-homogenous assay 4-friedwald calculation
For screening , we check Chol , TG , LDL , HDL Testing should be performed in all adults age 20 or older and should be repeated at least once every 5 years If a children has 1-familial history of immature CHD or 2-at least one parents with hypercholesterolemia screening initiate in 2 Y
Total Chol <200 Desirable 200-239 Borderline high ≥ 240 High
LDL-Chol <100 Optimal 100-129 Near optimal 130-159 Borderline high 160-189 High ≥190 Very high
HDL-Chol <40 Low ≥ 60 High
TG <150 Normal 150-199 Borderline high 200-499 High ≥ 500 Very high
Major risk factor • Smoking • HTN • HDL<40 • FH of premature CHD • Age(M>=45 , F>=55) • Diabetes • CHD
Dyslipidemia • Primary • Secndary: • Obesity • Immobility • Smoking • High carbohydrate intake • High alcohol intake • Dis
T3-T4-TSH The normal thyroid gland weighs 15-25 g For normal thyroid hormone synthesis need to intact hypothalamic-pituitary-thyroid axis and iodide
Hypothalamic-Pituitary-Thyroid AxisNegative Feedback Mechanism
Thyroxine(T4) 100% of circulating T4 is of thyroid origin 70% bind to TBG , 20% transthyretin , 10% alb 0.03% of T4 remains unbound to pr Pr bound T3 , T4 don,t inter cells and are considered to be biologically inert Reference range is 5-12.5 microg/dl in adults and slightly lower in pediatrics
Triiodothyronine(T3) Only 20% of T3 is of thyroid origin , 80% produced in nonthyroid tissue from T4 Most of circulating T3 bound to TBG 0.3% of T3 remains unbound to pr Reference range is 60-160 microg/dl T3 measurement is helpful in confirming the diagnosis of hyperthyroidism The measurement of serum T3 is not helpful in evaluating patients suspected of hypothyroidism
TSH Is the most important thyroid function test TSH results within the reference interval usually exclude thyroid dysfunction Normal range is 0.5-5 mIU/L
TRH Synthesized in hypothalamus Stimulate TSH secretion from hypophysis Lab tests for serum TRH are not useful for thyroid disorders because it is difficult to develop specific Ab
Hyperthyroidism Symptoms: Weight loss-sweating-heat intolerance-palpitation-insomnia- increased bowel movement-tremors-infertility-amenorrhea Lab tests: T3 ↑ –T4 ↑ -TSH↓
T3 thyrotoxicosis: T4 normal –T3 ↑ -TSH↓ Etiology: Toxic adenoma Toxic nodular goiter In region of iodine deficiency In patients with hyperthyroidism early in the course of treatment with antithyroid drugs or during relapse after treatment
T4thyrotoxicosis: • T3 normal –T4 ↑ -TSH↓ • Etiology: • Iodide induced thyrotoxicosis • Drugs • NTI
Hypothyroidism Symptomps: Cold intolerance-constipation-water retention-hypercholesterolemia-depression-pretibial myxedema periorbital edema Lab tests: T3 ↓ –T4 ↓ -TSH↑
Subclinical Hypothyroidism T3 normal-T4 normal-TSH ↑
↑or↓ Thyroid tests without concomitant change in metabolic state have been reported in: Pregnancy NTI Drugs
Pregnancy Estrogen>>>TBG ↑ >>>>T3&T4 ↑ HCG(TSH)>>>Free T3&T4 ↑>>>TSH↓
NTI • During acute illness: • Low or low normal TSH • Low or Low normal T4 • Very low t3 • Resoloution of illness • Normal or above normal TSH
Drugs Estrogen Glucocorticoides Dopamine Iode Lithium Phenytoin Carbamazepin Furosemide Heparin Phenobarbital Rifampin
Physiologic effect on TFT • Age • Sex • Season • Menstrual period • Smoking • exercise • fasting
screening • After 35y each 5y • For patients that receive constant dose of L-thyroxin TFT each 1y
Biochemical markers of bone metabolism • The skeleton is a metabolically active organ that undergoas remodelling throughtout life • Remodelling is necessary: • 1-To maintain the structural integrity of the skeleton • 2-to fulfill its metabolic functions as a storehouse of Ca and P
Types of bone • 1-Cortical(compact) • 2-Cancellous(Trabecular)
Cortical bone • Supportive , protective , mechanical function • Shaft of long bone and outer envelope of all bones • Constitues 80% of skeletal mass • 90% bone and 10% space
Cancellous bone • Repository for hematopoitic cells , short term mineral exchange • End of long and short bones , medullary cavities of vertebral bodies and flat bones • Constitues 20% of skeletal mass • 25% bone and 75% space
Calcium • Is the most prevalent cation in the human body • A healthy adult contains approximately 1-1/3Kg Ca • 99% is in the skeleton
Serum calcium • 1-Free(ionized): • Active form • 50% of total serum Ca • 2-Complexed • Bound to anions (bicarbonate , lactate , phosphate) • 10% of total serum Ca • 3-Pr bound: • Alb • 40% of total serum Ca
Ca function: • 1-skeletal mineralization • 2-blood coagulation • 3-neural transmission • 4-plasma buffering capacity • 5-enzyme activity • 6-maintenance of normal muscle tone
Recommends that all adults have a daily intake of at least 1200mg/d of Ca
Lactating females and postmenopausal womens not given exogenous estrogen should have at least 1500mg/d