RESPIRATION AND ENDOCRINOLOGY

RESPIRATION AND ENDOCRINOLOGY

Sri KadarsihBagian Ilmu Faal

Hormone plays a vital role in normal fetal lung maturation, -----> endocrine disease exert profound effects on the respiratory system

Influence of hormone on fetal lung maturation and surfactant systemThe mature function of surfactant is to reduce the surface tension.

The normal maturation of the pneumocytes and the synthesis and secretion of surfactant is influenced by several hormones

Neonates who lack a mature complete surfactant system or who have a deficient of specific component develop a neonatal respiratory distress syndrome (NRDS).

GLUCOCORTICOIDSThe important physiologic role that glucocorticoid play in the regulation of the fetal surfactant system is suggested by the observation in human:

A surge in cortisol level in amniotic fluid before the maturation of the surfactant systemAn inverse relationship between cortisol level in cord blood and NRDS.Administration of glucocorticoid at antepartum accelerates maturation of the surfactant system with a decrease in the incidence of NRDS in high-risk pregnancyreceptors of glucocorticoid present in the lung

THYROID HORMONESThyroid hormones influence the maturation of the fetal lung and regulate surfactant synthesis

Low level of thyroid hormones in cord blood have been found in neonates who develop NRDS. In the pneumocytes have nuclear receptors for T3

ESTROGENIn human, plasma estrogen levels are decreased in infants with NRDS

In animal studies, the administration of estrogen to mothers produces the following effects in the fetus accelerated morphologic maturation of the lung.

These effects are mediated by estrogen-binding macromolecular in the cytosol of lung cells and not by classic estrogen receptors.

PROLACTINReceptors of prolactin are present in the fetal lung

The presence of low cord blood prolactin, which is found in infants with NRDS.INSULINThe incidence of NRDS is increase 6-fold in infants of mother with diabetes because of delay in the maturation of the lung and the surfactant system.

Insulin receptors are present in the fetal lung.

Glucose freely crosses the placenta from mother to fetus and induces the fetal pancreas to produce more insulin

OTHER HORMONESThyrotropin and corticotropin accelerates in the maturation of the surfactant system.

Epidermal growth factor (EGF) also may play a role in lung maturationThe lung secretes many hormones that act on cells and tissues within the lung and also influence other tissues (amines: serotonin, dopamine, nor-epinephrine, epinephrine, and histamine), prostaglandin.

Hormones may stimulate, or inhibit their effector cells.The hormones, within the lung may effect regional blood flow, dilate or contract bronchial smooth muscle, influence mucous gland activity, change vascular permeability, influence cellular proliferation.

Most of the amines can act as neurotransmitter that detectable in blood of normal persons and are increased in various pathologic conditions.

Intrapulmonary sources of several amines are the pulmonary neuroendocrine (PNE) cells.

The PNE cells are situated near the basement membrane of the epithelium of the entire respiratory airway (larynx, trachea, bronchi, bronchioles)

The large number of PNE cells in the fetus and newborn suggested a role in pulmonary development and in postnatal circulation

PgE2: effect on bronchial dilation effect on pulmonary vessels, often vasodilatation but can constrict other effect, systemic vasodilatation, decreases mucous secretion, inhibit platelet aggregation

PgF2a: effect on bronchial: constriction effect on pulmonary vessels : constriction other effect: variable systemic vasoconstriction, increases mucous secretion, regulate fetal lung fluid transport

Angiotensin II: location: in the lung endothelium effect: pulmonary vasoconstriction, releases pulmonary prostacyclin

Serotonin : location: PNE cells effect: pulmonary vasoconstriction, bronchial constriction

The secretion and the action of most of the pulmonary hormones depend on or are modulated by the presence or absence of other hormones

ACTH: noncompetitively inhibit the pulmonary synthesis of angiotensin II

Histamine: releases pulmonary arachidonic acid metabolites

THE CARDIOVASCULAR SYSTEM AND ENDOCRINOLOGY

Sri Kadarsih SoejonoBagian Ilmu Faal

The cardiac manifestation of acromegaly include the enlargement of the heart, hypertension, premature coronary artery disease, cardiac arrhythmia, and congestive heart failure, premature artherosclerosis.

Hormones present in acromegaly : GH, aldosterone, catecholamine, and angiotensin II

THYROID HORMONESThe effect of thyroid hormones:those that indirect effect and appear to be mediated by the sympathetic nervous systemthose that are directly mediated by thyroid hormones

The fact that the clinical manifestations of hyperthyroidism parallel with the catecholamine excess, thyroid hormone enhances the sensitivity of cardiac tissue to catecholamine.

It has been observed that b-adrenergic blocker (propranolol) improve or even eliminate many of the cardiac manifestations of hyperthyroidismExogenous T3 and T4 increases the number of b-adrenergic receptors, and an increase in b-adrenergic receptor affinity.

The direct effect of the thyroid hormones on the heart appears to be mediated in changes in the level of mRNA for specific protein. As in other tissue, thyroid hormone increases the activity of sodium pump in cardiac cells.

PARATHYROID HORMONEParathyroid hormone has a direct effect on the heart. When PTH is added to isolated heart cells, an increase of chronotropy and inotropy. The direct effect of PTH on the heart cells probably mediated by binding with the receptors, which increases entry of calcium into the myocardial cells.

ADRENAL GLANDHypertension may partly contribute the atherosclerosis, the accelerated of atherosclerosis most likely is secondary to the lipid-mobilizing effects of cortisol.

Cortisol has an effect in the lipid-mobilization, and accelerate atherosclerosis that may partly contribute to hypertension

Glucocorticoid potentiates the vascular smooth muscle response to vasoconstriction agent, or increased renin substrate and increase the blood pressure.

Angiotensin II increased sensitivity of the vascular smooth muscle to vasoactive agent, and increase the blood pressure.

STEROID HORMONESThe hypothesis, estrogens are protective against the development of atherosclerotic cardiovascular disease.

Several studies have reported that estrogens administration actually may increase cardiovascular risk.

Exogenous estrogens actually may increase the risk of atherosclerotic cardiovascular disease.

The use of oral contraceptive agents in the premenopausal woman has been associated with an increase risk of cardiovascular morbidity and mortality.This increased risk has been associated with:increased frequency of thromboembolic diseasehypertensionthe presence of DM

THE ENDOCRINE ENDOTHELIUMThe vascular endothelium is capable of generating substances that can circulate and affect neighboring smooth muscle cells and blood cells.Endothelial cells can produce and release a variety of vasoactive substancesendothelium-derived relaxing factors (e.g. NO, prostaglandins)endothelium-derived constricting factors (endothelin, cyclooxygenase-derived constracting factors)

Endothelium-derived relaxing factor:EDRF have been demonstrated in large arteries and in resistance vessel, can be release in basal conditions: in response to mechanical forces, such as shear stress, and after activation of receptor-operated mechanisms by acetylcholine, neurotransmitters, various local and circulating hormones, and substances derived from platelets and the coagulation system

Relaxing of smooth muscle cells by endothelium derived NO (EDNO) is associated with activation of soluble quanylil cyclase and an increased in intracellular (cGMP) in vascular smooth muscle.

EDNO causes vasodilatation and platelet deactivation and represents in important antithrombotic of endothelium

Prostacyclin is synthesized in the vasculature on response to shear stress, hypoxia

Prostacyclin causes relaxation by increasing cAMP in smooth muscle and platelets, it also inhibit platelet aggregation.

Endothelium-derived constricting factorThe cyclooxygenase pathway produces a variety of endothelium-derived constricting factor, their release particularly prominent in the veins and in the cerebral and ophthalmic circulation.Endothelin-1 is a potent vasoconstrictor. Endothelin causes vasodilatation in lower concentrationIn the heart this may lead to ischemia, arrhythmia, and death.

Possible pathway involved in regulating the mechanism of endothelin production are:cGMP dependentcAMP dependentan inhibitory factor produce by vascular smooth muscle cellsEndothelin can release NO and prostacyclin from endothelial cells as a negative feedback mechanism