The Adrenal Glands. The Adrenal Glands - Structure

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Transcript of The Adrenal Glands. The Adrenal Glands - Structure

  • The Adrenal Glands

  • The Adrenal Glands - Structure

  • Adrenal cortexDerived from same embryological tissue that gave rise to gonads(mineralocorticoids)(glucocorticoids)(gonadocortocoids)

  • Synthesis17

  • Develops from ectoderm, the same embryological tissue that gives rise to the nervous system; 2 hormones - epinephrine and norepinephrine; Stimulated directly by sympathetic division of nervous system

  • Epinephrine (E): 80% Norepinephrine (NE): 20% Adrenomedullin

  • Synthesis of Catecholamines (DA, NE, E)

  • Functions of E and NECardiovascular effects

    Metabolic effects Glucose production BMR

    Stress response

  • The Adrenal cortex

  • Synthesis of the different steroids is not uniformly distributed through the cortex.

    The outermost group of cells (zona glomerulosa) synthesizes aldosterone, but essentially no cortisol nor androgens, because those cells do not express the enzyme 17-alpha-hydroxylase which is necessary for synthesis of 17-hydroxypregnenolone and 17-hydroxyprogesterone.

    That enzyme is however present in cells of the inner zones of the cortex (zonae fasiculata and reticularis), which are the major sites of cortisol production. 17

    SteroidRepresentativeEffectsMineralocorticoidsAldosteroneNa+, K+ and water homeostasis

    GlucocorticoidsCortisolGlucose homeostasis and many othersSex steroidAndrogens

  • The Adrenal Glands - Production of Hormones

  • MineralocorticoidsAldosterone: the most common mineralocorticoid, accounts for about 90% of all mineralocorticoid activity

    About 60% are bound to plasma proteins, half life is about 20 min

    Aldosterone increases Na+ retention in kidney, sweat glands, and salivary glands, which also increases water retention

    Increases K+ and H+ secretion in kidney

    Save Na+, lose K+: Renal reabsorption of Na+ in the principal cells of the collecting tubules, the distal tubules and collecting ducts; excretion of K+ and hydrogen ions in the distal tubules and collecting ducts

  • Regulation of aldosterone secretionIncreased K; Increased activity of Renin-angiotensin system; Increased sodium through renin; ACTH

  • The Adrenal Glands - CortisolCRH

  • GlucocorticoidsCortisol (hydrocortisone) : the most common glucocorticoid, 95% of all glucocorticoid activity,

    involved with glucose metabolism,

    protects against low blood glucose levels, or hypoglycemia;

    Others: Cortisone (synthetic, as potent as cortisol); Dexamethasone (synthetic, 30 times as potent as cortisol)

  • GlucocorticoidsMetabolism: catabolic hormone causing the breakdown of complex molecules to be used for energy

    Proteins: increases protein breakdown, releasing amino acids into blood

    Lipids: mobilizes fatty acids from adipose tissue

    Carbohydrates: increases blood glucose levels and gluconeogenesis

    Large amounts of cortisol decreases inflammation, suppresses immune system, slows healing

  • The Adrenal Glands---Cortisol

  • Effects on blood cellsRBC, neutrophils, monocytes and plateletsLymphocytes, eosinophils and basophilsEffects on Vascular SystemPermissive action through inhibition of enzyme (e.g. COMT) that degrades norepinephrine at sympathetic nerve endings- optimize vascular responses to catecholamines cortisol is needed for maintaining blood pressure

    Helps to maintain blood volume by decreasing the permeability of the vascular endothelium

  • Effect on bone formation-inhibition reduce the synthesis of type I collagen (the fundamental component of bone matrix)

    decreases absorption of calcium from the viscera

    calcium excretion via glomerular filtration rate in the kidney

    the rate of bone resorption (excess cortisol osteoporosis) Excitability of CNS - alters mood and behavior, insomnia, strikingly depress or elevate moodsEffects on nervous system

  • Anti-inflammatory effectsSuppress the immune response (stabilizing lysosomes)

    Widely used in therapy:

    - to reduce the inflammatory destruction of rheumatoid arthritis and other autoimmune diseases

    to prevent the rejection of transplanted organs

    to control asthmaEffects on digestive system Digestive secretions

  • Mechanism of actionBinds to cytosolic receptor - Cortisol-receptor complex migrates to nucleus and transferred to nuclear binding site - interacts with DNA -Increase RNA synthesis

  • Regulation of cortisol secretion the HPA axis

  • ACTH (corticotropin, adrenocorticotropin) Cortisol secretion

    Cause hypertrophy or proliferation of the adrenocortical cells

    Secretion with MSH

    Diurnal rhythm

  • Transport of Adrenocorticosteroids 75% of cortisol bound to corticosteroid-binding globulins (CBG, transcortin)

    15% of cortisol bound to Albumin

    10% free

  • Abnormalities of adrenocortical secretionHypoadrenalism, Also called Addisons diseaseClinical features

    excessive urinary loss of Na and Cl ions (dehydration)

    Hypoglycaemia

    Muscle weakness

    Skin pigmentation (due to ACTH)

    Hypotension

    Inability to withstand stress

    Autoimmune disease

    Cannot use lipid reserves for ATP production,

    K+ buildup, acidosis, etc.

  • Hyperadrenalism Cushings syndromeFat deposits in cheeks - moon face, plethora (reddish face & neck), trunk obesity

    Purple abdominal striae (loss of collagen in subcutaneous tissue and increases tearing), thin skin, resulting in easy bruisabilitySkin pigmentation (due to ACTH)Poor wound healing

    Hypertension (mineral effects of cortisol)

    HyperglycaemiaOsteoporosis (loss of protein in bone)

    Muscular weakness

    Mental abnormalities

    Hirsutism (due to adrenal androgens)

  • The amount of androgen secreted by adrenal cortex is too low to have much effect under normal circumstances

  • Stress Response and the HPA axisStress can be productive (for example, appropriate levels of short term stress can help you respond to a crisis) or non-productive (for example, long term stress due to a job you hate can suppress the immune system)

    Alarm phaseFight or flight, adrenal medulla, E and NE

    Resistance phaseGlucocorticoids mobilize energy reserves, but saves glucose for nervous system

    Exhaustion phase Mineralocorticoids - gastritis, ulcers, irritable bowel syndrome, depression, etc.

  • Stress and the HPA axisStress overrides negative feed-back i.e. cortisol secretion is stimulated even though cortisol level is high, but gradually it is diminished

    Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus

    Result of stressStart of stress

  • Schematic representation of the interactions between the HPAl axis and the reproductive and growth axes. Chronic hyperactivation of the stress system may lead to osteoporosis and metabolic syndrome. SmC: somatomedin C. Activation is represented by solid green lines and inhibition by dashed red lines.

  • Schematic representation of the interactions between the HPA axis and the thyroid and immune function.

  • Schematic representation of the detrimental effects of chronic stress on adipose tissue, bone and muscle metabolism.

  • Schematic representation of the effects of stress on gastrointestinal function. LC: locus ceruleus.

  • Schematic representation of the interactions between the HPA axis, the adipose tissue and the hypothalamic appetite-satiety centers. ARC: arcuate nucleus, PVN: paraventricular nucleus, LHA: lateral hypothalamic area, NPY: neuropeptide Y AgRP: agouti related peptide, Y1: neuropeptide Y receptor type 1, MC4R: melanocortin receptor type 4, MCH: melanin concentrating hormone.

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