5. Fisiopatología Células neuronales modificadas. Secreción de Adrenalina (80%) y Noradrenalina (20%) Contracción de vasos sanguíneos. Aumenta actividad cardíaca. Inhibe el T. digestivo. Dilata pupilas. Misma acción, duración prolongada. Estímulo Directo: a través de n. simpáticos. Indirecto: a través de hormonas propias.
10. Potasio en LECEje hipotálamo-hipófisis-suprarrenal (HHS) ->ACTH H. Corticotropa E. de Andrógenos ACTH
11. COLESTEROL A: 3β-deshidrogenasa B: 17α-hidroxilasa C:21β-hidroxilasa PREGNENOLONA D: 11β-hidroxilasa E: 18-hidroxilasa A B Progesterona 17α-hidroxipregnenolona B C 11-desoxicorticosterona DHEA 17α-hidroxiprogesterona A C D Corticosterona 11-desoxicortisol Androstenediona Estrona D E Testosterona Estradiol CORTISOL Aldosterona
12. Colesterol De novo (a partir de acetato) A partir de LDL (80%) Receptores específicos en membrana celular. Endocitosis (depresiones revestidas) Lisosomas ACTH y ATII: Incrementan el número de receptores. Aumento de actividad enzimática liberadora. Estimulan la conversión a pregnenolona.
20. Tasa de secreción: 0.15mg/díaMineralocorticoides Afectanglucemia. Control: EjeHipotálamo – Hipófisis – Suprarrenal (HHS) ACTH 90% unida a globulinafijadora, transcortina, albúmina. V½ = 60’-90’ En sangre: 12μg/100mL Tasa de secreción: 15-20mg/día Glucocorticoides
21. Metabolismo Forma con ácido glucurónico: Sulfatos 25% bilis -> heces ~80% conjugados inactivos -> sangre Orina (Excreción)
22. MINERALOCORTICOIDES Aldosterona (90% de toda la actividad) Desoxicorticosterona (1/30) Corticosterona(ligera actividad) 9α-fluorocortisol(sintético, algo más potente) Cortisol(mínima pero se secreta en grandes cantidades) Cortisona (sintético, actividad mínima)
23. GLUCOCORTICOIDES Cortisol (muy potente, 95%) Corticosterona (4%, mucho menos potente) Cortisona (sintética, casi tan potente) Prednisona (sintética, 4 veces más potente) Metilprednisona (sintética, 5 veces más potente) Dexametasona (sintética, 30 veces más potente)
39. Primaria Destrucción (Enfermedad de Addison) Secundaria Hipopituitarismo Extirpación quirúrgica de hipófisis Alteración del eje HHS Terciaria: Trastorno hipotalámico Suspensión brusca de tratamiendo con glucocorticoides
52. Deficiencia de glucocorticoides Hipoglicemia Letargia Debilidad Fiebre GI: Anorexia, náuseas, vómitos y pérdida de peso. Aumenta sensibilidad a infecciones
71. Manifestaciones Clínicas Movilización de grasa periférica y deposito en: Región torácica y superior de abdómen “Espalda de búfalo” Cara redonda y pletórica “Cara de luna” Hipertensión (acción mineralocorticoide) Potencia andrógena: acné e hirsutismo Hiperglicemia (pospandrial) Glucogenogenesis Menor utilización de glucosa Catabolismo de proteínas (plasma normal) Supresión del sistema inmunitario Estrías purpúreas Osteoporosis grave
86. Fig.1. Bloodeosinophilcounts in theuntreatedpatientwithAddison’sdisease. Theraisedcountswerenotreducedby ACTH analog, butaftercortisonethecountfellrapidlyto normal.
87. BIOQUÍMICA Glucosa: 60mg/dL Tolerancia a la Glucosa Basal: 58mg/dL 1h: 90mg/dL 2h: 87mg/dL 3h: 85mg/dL Electrolitos en suero Na: 123mmol/L K: 5.8mmol/L Cortisol plasmático 8am: 2mg/dL (N = 5-25) 5pm: 0.7mg/dL (N = 2-12) Electrolitos en orina Na: 210mmol/24h VN: 40 a 210mmol/24h K: 90mmol/24h VN: 25 a 125mmol/24h Volumen: 2500mL/24h 17 cetoesteroides: 4mg/24h VN: 3 a 8mg/24h 17 OH esteroides: 0.5mg/24h VN: 6 a 20mg/24h Prueba de ACTH Ausencia de elevación de cortisol
88. GLUCOSE TOLERANCE TEST (GTT) In a healthy individual, the insulin response to a large oral glucose dose is almost immediate. It peaks in 30 to 60 minutes and returns to normal levels within 3 hours when sufficient insulin is present to metabolize the glucose ingested at the beginning of the test. Indications for Test Family history of diabetes Obesity Unexplained episodes of hypoglycemia History of recurrent infections (boils and abscesses) In women, history of delivery of large infants, stillbirths, neonatal death, premature labor, and spontaneous abortions Transitory glycosuria or hyperglycemia during pregnancy, surgery, trauma, stress, MI, and ACTH administration
89. NORMAL Basal: 110 mg/dLor 6.1 mmol/L 30-minute: 110 a 170 mg/dLor 6.1 a 9.4 mmol/L 1-hour: <184 mg/dLor <10.2 mmol/L 2-hour : <138 mg/dLor <7.7 mmol/L 3-hour : 70 a 120 mg/L or 3.9 a 6.7 mmol/L Allfourbloodvaluesmustbewithin normal limitstobeconsidered normal.
90. CLINICAL IMPLICATIONS Thepresence of abnormal GTT values (decreasedtolerancetoglucose) isbasedonthe International Classificationfor Diabetes Mellitus. Diagnosis of gestational diabetes mellitus (GDM) Decreasedglucosetoleranceoccurswithhighglucosevalues in thefollowingconditions: Diabetes mellitus Postgastrectomy Hyperthyroidism Excessglucoseingestion Hyperlipidemiatypes III, IV, and V Hemochromatosis Cushing'sdisease (steroideffect) CNS lesions Pheochromocytoma von Gierke'sdisease, severeliverdamage, orincreasedepinephrinelevels (withhypoglycemia) Increasedglucosetolerancewith flat curve occurs in thefollowingconditions: Pancreaticisletcellhyperplasiaor tumor Poor intestinal absorptioncausedbydiseasessuch as sprue, celiacdisease, orWhipple'sdisease Hypoparathyroidism Addison'sdisease Liverdisease Hypopituitarism, hypothyroidism
91.
92.
93. CLINICAL IMPLICATIONS Decreased cortisol levels: Adrenal hyperplasia Addison's disease Anterior pituitary hyposecretion (pituitary destruction) Hypothyroidism (hypopituitarism) Increased cortisol levels: Hyperthyroidism Stress (trauma, surgery) Carcinoma (extreme elevation in the morning and no variation later in the day) Cushing's syndrome (high on rising but no variation later in the day) Overproduction of ACTH due to tumors (oat cell cancers) Adrenal adenoma Obesity
94. CORTISOL SUPPRESSION (DEXAMETHASONE SUPPRESSION) The DST helps to differentiate causes of elevated cortisol. Cortisol levels <15 µg/dL (<41.4 nmol/L) is an indication of adrenal cortisol insufficiency. Normal values: <5 µg/dL or <138 nmol/L ClinicalImplications Suppressionoccurs in personswith: Cushing'ssyndrome (>10 µg/dLor >276 nmol/L) Endogenousdepression (50% of cases) No suppressionoccurs in: Adrenal adenoma, carcinoma Ectopic ACTH-producingtumors
95. ADRENOCORTICOTROPIN HORMONE (ACTH) STIMULATION This detects adrenal insufficiency after Cortrosyn administration. Cortrosyn is a synthetic subunit of ACTH that exhibits the full corticosteroid-stimulating effect of ACTH in healthy persons. Failure to respond is an indication of adrenal insufficiency. Normal: Cortisol: >20 µg/dL (>552 nmol/L) riseafterCortrosynadministration Clinical implications: Absentorblunted response tocortisolstimulation: Addison'sdisease (adrenal insufficiency) Hypopituitarism (secondary adrenal insufficiency) Adrenal carcinoma, adenoma Response tocortisolstimulation: adrenal hyperplasia
Notes de l'éditeur
4 – 5gr. cada una. Retroperitoneales.
La proporción varía según condiciones fisiológicas.Duración 5 a 10 veces más. Desaparecen con lentitud (2 a 4min)Estímulo directo e indirecto, se potencian y pueden sustituirse entre sí.
Adrenalina: metabolismo hasta un 100% por encima de lo normal.Glucogenólisis hepática y muscular.
Mineralocorticoides. Glucocorticoides. Andrógenos.ATII↑: aldosterona↑: hipertrofia de z. glomerularACTH↑: cortisol↑ y andrógenos↑: hipertrofia de z. fascicular y reticular
Mitocondria: glucocorticoidesRetículo endoplásmico: mineralocorticoides y h. sexuales
Entran a hígadocombinadas o libres, se combinan con proteínaspara:ReservorioparareducirfluctuacionesrápidasDistribuciónrelativamenteuniforme
It plays an important role in regulating the extracellular fluid (ECF) and blood volumes and in maintaining K+ balance. When ECF and blood volumes are reduced (hemorrhage, diarrhea), renin is released from the kidney, which in turn increases angiotensin II levels. Angiotensin II is a potent stimulator of aldosterone secretion by the adrenal gland. Aldosterone acts on a number of organs, causing the retention of Na+ and water, a response that serves to increase ECF and blood volume. The kidney is the most important organ in this response. When the ECF and blood volumes are increased (congestive heart failure), atrialnatriuretic peptide is secreted and acts on the adrenal cortex to inhibit aldosterone secretion. An increase in the [K+] of the ECF (hyperkalemia) also stimulates aldosterone secretion by the adrenal cortex. Aldosterone acts primerily on the kidney to stimulate K+ excretion. Finally, aldosterone increases urinary H+ excretion.
Hipófisis anterior*
Cortisol has many direct and indirect actions. It causes muscle wasting, fat deposition, hyperglycemia, insulin resistance, osteoporosis, suppression of the immune response (anti-inflammatory), and reduced production of connective tissue that can lead to poor wound healing. At high levels, it can exhibit mineralocorticoid actions and cause Na+ retention and enhanced K+ and H+ excretion by the kidneys. Cortisol is also necessary for the normal production of epinephrine by the adrenal medulla.Disminuye IL-1
Aumenta en primerashoras de la mañana, disminuye en últimashoras de la tarde.
The adrenal androgens, dehydroepiandrosterone (DHEA) and androstenedione, do not have major effects in males, where the actions of testosterone predominate. In females, the adrenal glands are the primary source of circulating androgens. These adrenal androgens are responsible for the growth of both pubic and axillary hair. In both sexes, adrenal androgens play an important role in puberty. In early puberty, the adrenal androgens contribute to development of the external genitalia and other secondary sexual characteristics (adrenarche). The general effects of androgens are anabolic, leading to increased muscle mass and bone formation. They also cause sebaceous gland hypertrophy, hairline recession, and growth of facil hair.
