Endocrine pathophysiology. Doc. MUDr. Ing. RNDr. Peter Celec, DrSc., MPH

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1 Endocrine pathophysiology Doc. MUDr. Ing. RNDr. Peter Celec, DrSc., MPH

2 Cell-cell communicabon Neurocrine (neurotransmiders) Endocrine (hormones) Paracrine (cytokines) Autocrine (various)

3 Hormones Proteins / pepbdes Preprohormone (ER, GA, secrebon granules) Steroids Cholesterol Amines Tyrosine

4 Endocrine regulabon NegaBve feedback PosiBve feedback ProducBon (endocrine gland) Transport (binding proteins in plasma) Target Bssue (receptors on cells)

5 Endocrine glands

6

7 Endocrine disorders Physiology & OverproducBon Insufficiency Resistance

8 Hypothalamus Neural regulabon of the autonomic nervous system - adrenal medulla ProducBon of ADH and oxytocin RegulaBon of the pituitary

9 Hypothalamus Liberins CRH (ACTH), TRH (TSH), GHRH (GH), GnRH (LH, FSH), Salsolinol (PRL) StaBns SomatostaBn (GH), Dopamine (PRL)

10 Hypothalamus Hypothalamic - pituitary axis Control of the producbon and release of pituitary hormones Pulse secrebon Specific membrane receptors Second messenger AutoregulaBon

11 Pituitary Anterior pituitary Adenohypophysis ACTH, TSH, FSH, LH, PRL, GH, MSH Endocrine regulabon Posterior pituitary Neurohypophysis ADH, Oxytocin Neural regulabon of hormone release

12

13 Hypopituitarism General SelecBve InfecBons, infarcbons, cysts, tumors, injuries, iatrogenic, Sheehan syndrome FerBlity, Growth... Therapy - supplementabon

14 GH disorders GH overproducbon GiganBsm Before puberty Acromegaly AXer puberty

15

16 GH disorders GH insufficiency Nanism Before puberty GH insufficiency syndrome AXer puberty Somatopause

17 ADH disorders ADH insufficiency Diabetes insipidus Polydipsia, polyuria OverproducBon ADH Syndrome of IADH Hypoosmolarity of plasma, hyponatriemia, oliguria

18 Thyroid gland physiology AcBons of the thyroid Controls body temperature How body burns calories Controls how fast food moves through digesbve tract Muscle strength Thyroid hormones T4-thyroxine T3-triiodothyronine Calcitonin

19 Specifics Iodine is rare Ubiquitary receptors Highly potent acbon Very common disorders 5% women 0,5% men

20 Iodine intake 150 ug daily intake of iodine 125 ug taken up by the thyroid gland Iodine in the soil region dependent Iodide supplementabon of salt

21 T4:T3 15:1 TBG Peripheral conversion T4 receptor... T3:T4 15:1 5mg T4 per gland InflammaBon and trauma lead to thyreotoxicosis

22 AcBon Increase of number and size of mitochondria Synthesis of respiratory chain enzymes Na+ K+ ATPase Uncloupling proteins Increase in resbng metabolic acbvity

23

24 Grave s disease Grave s Basedow trias Goiter Exophtalmus Hyperthyroidism Autoimmune disease AnB-TSH receptor

25 Calcitonin Parafollicular C cells in the thyroid gland Unknown physiological funcbons Inhibits absorpbon from the gut Inhibits osteoclasts Inhibits food intake (sabety hormone?) Inhibits phosphate reabsorpbon Procalcitonin Marker of sepsis

26 Parathyroid glands

27 Parathyroid glands Parathyroid hormone An antagonist of calcitonin Increase in plasma Ca 2+

28 Hyperparathyroidism Primary (4/100000; women; age>45) Parathyroid glands Secondary Kidneys TerBary From secondary autonomy of the parathyroid glands Bone resorpbon

29 Adrenal glands Cortex Zona glomerulosa (mineralocorbcoids) Zona fasciculata (glucocorbcoids) Zona rebcularis (androgens) Medulla catecholamines

30

31

32 Disorders of the adrenal glands Insufficiency Primary Addison's disease Autoimmune, tuberculosis, hemorrhage (Waterhouse- Friderichsen syndrome in meningococcal infecbons) Secondary pituitary disorders, disconbnuabon of glucocorbcoid therapy

33 Addison's disease Aldosterone insufficiency Hypotension, hyponatremia, hyperkalemia Skin pigmentabon Pro-Opio-Melano-CorBco-Tropin ACTH increased (dif-dg secondary adrenal insufficiency)

34 Conn's disease Primary hyperaldosteronism Mostly unilateral endocrine acbve tumor Hypertension Hypernatremia Hypokalemia

35 Cushing's syndrome HypercorBsolism Primary Adrenal adenoma Secondary Cushing's disease - overproducbon of ACTH Ectopic producbon - lung ca Iatrogenic

36 Cushing's syndrome Central obesity Hypertension Osteoporosis Reduced growth Mental changes HirsuBsm, acne, oligomenorrhea

37 Models Surgical models Pharmacological models ImmunizaBon Hormonal subsbtubon Receptor gene ko mice

38 Tasks What is the cause of PCOS? How to treat acute hypercalcemia? What are the symptoms of oxytocin insufficiency? What are the consequences of GnRH modulabon?

39

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