Biochemistry of special situations

1. Biochemistryofspecialsituations Zuzana Chmátalová

2. Pregnancyandlactation

3. Placentalhormones • Gestagens: • Decrease uterine contractility and promote the development of lobulo-alveolar syst. • The need of cholesterol intake • Estrogens: • Estriol dominates • Potentiation of proliferative processes, water retention and elasticity of the symphysis • Block the binding of prolactin to the receptor

4. Humanchorionic gonadotropin (hCG): • Glycoproteinmaintainingthe corpus luteum • Peakproduction in themiddleofthefirsttrimester • Itstimulatestheproductionof testosterone in male fetuses • Placentallactogen (hCS) • Chorionicsomatomammotropin / pl. growth hormone • Mobilizationof free MK frommother´s fatstores • Increasesperipheralmotherstissueresistance to insulin • Relaxin • Inhibitionofmyometrialcontractions • Angiogenicandvasodilatoryeffect on bloodvessels • GnRH, TRH, CRH, ACTH, somatostatin, dopamine, endorphins

5. Physiologicalchanges in pregnancy • Metabolicdemandes • Increase in BMR • Interindividualdefferences (210 - 570 kcal/den ) • Necessityofa balanced varied diet, quality proteins, vitamins, minerals, calcium... • Increase in: • oxygen consumption, minuteventilation, tidal volume... • heartrateandstroke volume • glomerularfiltrationrate, creatininclearance • Changes in concentrationofhemocoagulationcascademediators

6. Postpartumcomlications • „baby blues“ or „blue blues“ • Occurrence in 50-75 % ofwoman • Earlyonsetafterparturition • Depression, sadness, tearfulness... • Postpartumdepression • Occurence in 10-13 % ofwoman • Depression, insomnia, lackofappetite... • Lasts 14 daysatleast • Necessityofmedication • Postpartumpsychosis • Occurence in 0,2 % ofwoman • Earlyand rapid onset • Depression, isolation, confusion, catatonia, hallucinations, self-harm, inability to take care of yourself and baby ... • Necessityofmedication

7. Risk ofincompatibility • ABO system incompatibility is present in a one-third of pregnancies • Hemolysis does not lead to severe fetal anemia • Dangerous in case of persisting antibodies • Partial protection against sensitization in Rh • Rh incompatibility system • Rh-mother and Rh + fetus • Anti-D penetrate the placenta • Hemolytic disease of the newborn

8. Risksassociatedwith... • Smoking • Low birth weight • Possibility of intrauterine growth retardation • Spontaneous abortion • Premature birth, stillbirth • Sudden Infant Death Syndrome • Alcohol use • Spontaneous abortion, growth retardation, low birth weight • Decreased Apgar score • Lower IQ, hyperactivity, learning disability • Fetal alcohol syndrome

9. Eating disorders • Premature birth, cesarean section • Low birth weight, smaller head circumference • Risks associated with the disease • Increased occurrence of PP depression • Obesity • GDM • Preeclampsia • Premature birth, stillbirth • Obstetric complications (induction of labor, dystocia, cesarean section) • Macrosomia

10. Lactation • Glandular, adipose and connective tissue • Myoepithelial cells are surrounded by secretory cells • Progesterone: alveoli • Estrogens: collecting system • Prolactin: milk production • Oxytocin: the release of milk • Ejection reflex ("let-down" reflex)

11. Benefitsofbreastfeeding • Smaller postpartum blood loss • Lower incidence of Amenia • Protection against breast cancer, ovarian cancer and osteoporosis • Contraceptive effect • Supporting motherliness • Returns figures • Protection against diarrhea, infections and otitis DC • Lower risk of obesity, diabetes, allergies • Stronger bones in adulthood and old age • Mental development For mother For child

12. humoralmanifestationsofmalignancies

13. Ectopic Hormone secretion • „ectopicsecretion“ • Syndromes of hormone overproduction in most neoplasms • Productionof peptide hormonesmainly • 1,25(OH)2D3 isexception • Products oftumors are qualitatively different from the products of endocrine glands • Productionis not supressible • Reduced biological activity • Homologue of hormones

14. hypercalcemia • The most common paraneoplastic endocrine syndrome • Very common in patientswithlung cancer and multiple myeloma • Rare in GIT adenocarcinoma or sarcoma • Indicates advanced tumorswith poor prognosis • Excessive bone resorption induced by mediators of tumor • Production of different factors increasingkalcemiaand the participation of prostaglandin E • The possible contribution of reduced renal excretion

15. Solid tumors • Characteristic hypercalcemic syndrome • Hypophosphatemia and nephrogenic cAMP • The production of PTH-like proteins • Multiple Myeloma • Cytokines locally produced by myeloma cells • TNF-β, IL-1

16. Adhhypersecretion • Carcinomaofthelung, prostateand duodenum • Waterintoxicationandhyponatremia • Synthesisofmoleculessimilar to ADH, oxytocin andneurophysins • Pituitaryproductionremainsintact • Weakness, somnolence, convulsions, coma ...

17. ACTH hypersecretion • The most common in patientswithlungcancer • Tumorscontainsproopiomelanocortin • Different processing • ​​Larger molecule • Lesserbiological activity • Elevated cortisol concentrations without the characteristic clinical symptoms

18. Other hormones produced by tumors • Growth-hormone-releasing hormone andgrowth hormone • Gonadotropinsandglycoproteinhormones • hCG - tumorsofthelung, breast, GIT, ovary • Calcitonin • Erythropoetin • Renin

19. Sport exercise

20. Smooth, skeletalandcardiacmuscles • ATP isexclusivesourceofenergy • Skeletalmuscles: type I andIIb • Type I (slow-twitch) • Mitochondriaand myoglobin • Oxidativephosphorylation • Type IIb (fast-twitch) • Rich in glycogen • Prone to fatigue • Type IIa • Fast-oxidativeglycolyticfibers

21. ATP • Creatinephosphate (CP) • Glycogen • Free fattyacids (FFA) • Ketones • Aminoacids (AA) • Alanine, aspartate, glutamate, ¨valine, leucine, isoleucine

22. Fuelutilisation in skeletalmuscle • CP donates a phosphate to ADP to generate ATP • CP issmallreservoirofhigh-energyphosphate • Glycolysis • Aerobic • Anaerobic • Oxidativephosphorylation

23. Anaerobicglycolysis • At the onset of the exercise • Demand for ATP increases • Conversion of glycogen to lactate • In the type IIb fibres • Low oxidative capacity • Main source of ATP in these muscle fibres • During strenuous activity • ATP demand exceeds the oxidative capacity of the tissue

24. Short-term high-intensity exercise • Maximalmitochondrialmetabolism • AMP starts to accumulate • Activationofphosphofructokinase-1 andglycogenolysis • Additional ATP fromanaerobicglycolysis • Glycolysiscontinues • Lactateisused by restingmusclesor by theheartorcanbetransported to the liver

25. long-term mild to modarate-intensity exercise • Lowlactateproduction • Bloodglucose as a fuel • Glycogenolysisandgluconeogenesis • Influence ofhormonalchanges • FFA as a sourceof ATP • mainlyskeletalmuscle type I • Branched-chain AA as a sourceof ATP • The purine nucleotidecycle, acetate

26. preferentialutiliZationofffaoverglucose • Availibility of FFA in the blood • Inhibition of glycolysis by products of FFA oxidation • Reduced glucose transport during long-term exercise

27. energysubstratesduringexercise • ATP, CP • ATP, CP, anaerobic glycolysis • glucosis from glycogen • anaerobic and aerobic glycolysis

28. aerobic glycolysis • aerobic glycolysis • lipolysis • aerobic glycolysis • beta oxidation • participation of AA and gluconeogenesis

29. metaboliceffectsoftraining • Increased muscle glycogen stores • Increasd number and size of mitochondria • Increased protein synthesis in muscles and reduced protein turnover • Improved strenth, power and endurance of muscle performance

30. Thank you for your attention