#13344 - Endocrine Adrenal Gland - Organisation of the Body

THE ADRENAL GLAND: response to stress, acute and chronic

Acute stressors: trauma/infection/intense heat or cold/starvation/surgery/sever blood/pain/dehydration

Chronic stress: anxiety, depression

Development and gross anatomy

-adrenal glands located medial to the upper pole of each kidney- identified as a seprate organ at 2 months gestation

-during fetal development the adrenal cortex consists of a fetal zone and a definitive zone

-the fetal zone of the adrenal cortex is very prominent in the fetus but it regresses after birth-the fetal zone produces androgens which the placenta aromatises to oestrogens

-the definitive zone is similar to the adrenal cortex

outercortex:

-develops from the mesoderm close to the mesonephros

-sheets of cells surrounded by capillaries and are arranged in three zones

-secretes steroid hormones

-zona glomerulosa (outer zone)- secretes aldosterone (mineralocorticoid)- electron microscope- cells arranged in irregular ovoid clusters separated by delicate fibrous trabeculae. Cytoplasm has large amount of SER, mitachondria

-zona fasciulata (middle zone) – secretes cortisol – broadest of the three, narrow coloumns parallel cords of secretory cells disposed at right angles to the capsule. Sepearted by strands of collagen, wide bore capillaries, lipid droplets present

-zona reticularis (inner zone)-secretes small amount of androgens- thin innermost layer of adrenal cortex, irregular network of branching cords, clusters of glandular cells small closely packed cells arranged in irregular cords

-light microscope- cells are surrounded by fenestrated capillaries and there memabrane has microvillous projections. There are many lipid droplets, mitochondria, golgi, SR

inner medulla:

-develops from the neural crest tissue

-adrenal medulla made up of groups of chromaffin cells, packed with catecholamine granules- seen with H $ E stain, appear basophilic -these store large amount of adrenaline and noradrenaline- secretes catecholamines- noradrenaline, adrenaline

-reinforce the action of the sympathetic nervous system under conditions of stress- rapid response

Blood supply to the adrenal gland

-richly vascularised supplied by the superior, middle and inferior suprarenal arteries- these form a plexus under the capsule of the gland

-the cortex has an anastomosing network of capillary sinusoids- branches of the subcapsular plexus- short cortical arteries- these descend into lower zones and drain into the smaller venules which converge into the central vein of the medulla. Central medullary vein has longitunal bundles of smooth muscle between which cortical venules enter- contraction of the smooth muscle dam back cortical blood and regulates flow

-medulla is supplied by long cortical arteries- these descend from the subscapular plexus- through the cortex into the medulla- ramify into a rich network of dilated capillaries- drain into central vein of the medulla

-the central adrenal vein splits into the left adrenal vein which into the renal vein and the right adrenal vein which drains into the inferior vena cava

-the blood supply is not reduced in stress

Innervation

-mostly the medulla is innervated

-thoracic preganglionic sympathetic fibres secrete ACH-act on nicotinic receptors

THE ADRENAL MEDULLA: RESPONSE TO ACUTE STRESS

Stimulus to release adrenaline

-stressful stimuli which activates the sympathetic nervous system. E.g- low blood pressure, haemorrhage, pain, low blood glucose, exercise, surgery, asphyxia

-this leads to the activation of preganglionic sympathetic fibres which release ACH, act on nictonic receptors

-stress results in a very rapid increase in adrenaline and noradrenaline concentrations but when stress is removed the concentrations of adrenaline and noradrenaline decreases rapidly

-rapid responses are due to large reserves of the catecholamines

Synthesis of adrenaline

-occurs in the cytoplasm of the chromaffin cells

-tyrosine is converted to DOPA by tyrosine hydroxylase. DOPA is converted to dopamine by DOPA decarboxylase- dopamine is then pumped into granules and is converted into noradrenaline by B hydroxylase

-noradrenaline is stored or pumped out of the granule for conversion to adrenaline (80% of the total) by phenyl-N-methyltransferase in the cytoplasm

-adrenal is then pumped into granules for storage and release

Actions

-preperation for emergency physical activity

-adrenal medulla contributes to 10% of total sympathetic nervous system response to stress

Stress: change that disturbs or threatens to disturb homeostasis

Receptors:

-adrenaline and noradrenaline act at adrenergic receptors. But the potency on different receptors vary

-alpha receptors: PLC coupled (noradrenaline > adrenaline)

-a1: all blood vessels (vasoconstrictor), gut sphincters

-a2: presynaptic terminals:

-Beta receptors: Camp coupled

-b1: heart, fat (adrenaline = noradrenaline)

-b2: bronchi, blood vessels (vasodilator skeletal muscle) (adrenaline > noradrenaline)

Effect of adrenaline

a) cardiovascular system

-increases the heart rate and force of contraction via B1 receptors

-stimulates vasodilation in skeletal muscle (B2), vasoconstriction in the skin (a1)

-increases the mean arterial pressure through vasoconstriction

b) Respiratory system

-increases the dilation of the bronchi and bronchioles via B2 receptors

-increase respiratory rate through effects on CNS

c) GI Tract

-inhibition of peristalsis-relaxation of gut smooth muscle

-contraction of gut sphincter-act on A1receptors

-vasoconstriction a1 of gut vasculature

d) Metabolic substrate metabolism

-adrenaline increases metabolite availability

-liver – promotes glycogenolysis, gluconeogenesis, release of glucose into circulation

-skeletal muscle: promotes glycogenolysis and lactic acid formation

-fat: stimulates lipolysis to release free fatty acids and glycerol

e) Central nervous system

-causes arousal through actions on the brainstem, produces coarse tremor

Pathology of the adrenal medulla

-if the adrenal medulla is removed – the stress response is compensated for by the reaminder of the sympathetic system

-tumours of the adrenal medulla (phaechromocytoma)- constantly secrete catecholamines- hypertension, foreceful heart beat, tremor, anxiety

ADRENAL CORTEX-MAINTAINENCE OF ESSENTIAL PROCESSES IN CHRONIC STRESS

-Adrenal cortex produces steroid hormones made from cholesterol: cortisol (glucocorticoid), aldosterone (mineralocorticoid) but also a small amount of androgens from cholesterol

Synthesis of steroid hormones

-the cholesterol circulating in blood in association with LDL- the LDL is taken up by LDL receptors through receptor mediated endocytosis into clathrin coated vesicles

-the cholesterol within the LDL are stored as free cholesterol or as cholesterol esters within lipid droplets. Lysosomal hydrolases act on cholesterol esters to release free cholesterol

-the side chain of the taken up or synthesized cholesterol is cleaved by cytochrome P450 side chain cleaving enzyme to yield prenenolone- common precursor of all steroid hormones- rate limiting step

-steroid hormones are not stored in vesicles- so the synthesis and secretion are closely linked

-ACTH stimulation- increases the rate of the rate limiting step

-enzymes which convert pregnenolone to glucocorticoids and mineralocorticoids are located in the mitochondria and smooth ER.

-The steroid synthesized in not stored in the cell and rapidly diffuses out of the cel

-therefore the steroids are made on demand

Transport of adrenal steroid hormones

Cortisol: binds to cortisol binding globulin in plasma with a high affinity and to albumin with low affinity

Aldosterone: no high affinity binding protein is present in plasma so binds weakly to albumin and has shorter half life than cortisol as a result.

-binding of the protein prolongs the half life of the steroid in circulation. The binding globulin proteins protects tissue from excess exposure to steroids.

-These binding proteins are synthesized in the liver so in liver failure there are high concentrations of steroid. In males with liver cirrhosis there is an increase in free plasma oestrogen concentrations which leads to excess breast deveopment

Metabolism of steroid hormones

-kidney filters free steroid but reabsorbs 90%.

-Liver converts steroid hormones hydrophilic metabolites by hydroxylation and conjugation reactions. In liver damage- cirrhosis in alcoholics the levels of cortisol build up.

A) CORTISOL

Control of glucocorticoid output:

-nerve terminals of the hypothalamus releases corticotrophin releasing factor in response to stress (inhibited by cortisol negative feeback)- enters the capillary plexus of the internal carotid artery

-Enters the anterior pituitary via the hypothalamus- hypophyseal portal veins (Indian ink experiment)

-Corticotroph releasing factor act on anterior pituitary corticotrophs to stimulate Adrenocorticotroph hormone production and release into the jugular vein. -The CRH also stimulates division of the corticotroph cells

-Pulsatile secretion of corticotrophin releasing hormone from hypothalamus- receives input from retina- very high concentration of ACTH early in the morning and diminishes throughout the day- so secretion of ACTH is diurnal

-CRH secretion is also stimulated by stress so increased ACTH with stress

-Vasopressin hormone synthesised in the hypothalamus- induces release of adrenocorticotrophin hormone

-ACTH (Peptide hormone)- binds to MC2R on the plasma membrane of all three steroid secreting cell types. Only cells in the fasciculate and reticularis layers have the 17 alpha hydroxylase needed for synthesizing...