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Organisation of the Body

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Stress   A change that disturbs or threatens to disturb homeostasis Physical - trauma, infection, intense heat or cold, starvation, surgery, severe blood loss, pain, dehydration Psychological - anxiety, depression  
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Arterial supply   Adrenal arteries branch from the aorta, renal , inferior phrenic arteries Same on both sides Superior suprarenal arteries etc High blood supply ensures hormones are readily perfused into systemic circulation  
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Venous drainage   Left adrenal vein drains to left renal vein Right adrenal vein drains to IVC  
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Adrenal gland capillaries   Arteriole supply - widely networked capillaries Moves out to inside Enters via the capsule Branch into capillaries Move through cortex into medulla where enter central adrenal vein  
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Development of the adrenal glands   Medulla - neural crest cells Cortex - mesoderm Fetal adrenal cortex has two zones = Fetal zone which regresses after birth and definitive zone that forms the adult cortex Shows importance of adrenal in development  
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Adrenal medulla   Preparation for emergency activity Fight or flight Via adrenaline and noradrenaline  
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Stimulation of adrenal medulla   Anything that activates the SNS like pain, low BP etc Increases stimulation of medulla oblongata Sympathetic presynaptic neuron releases ACh onto medulla Medulla acts as postsynaptic nerve to release adrenaline and noradrenaline  
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Action of adrenaline   Fight or flight response Rapid release - seconds Short half life - 10 secs Rapid action - secs Depletes only a small fraction of stored catecholamine so adequate stores remain to respond to subsequent stress  
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Adrenaline synthesis   Tyrosine - L-dopa by tyrosine hydroxylase to Dopamine by dopa decarboxylase Transported into vesicle and forms noradrenaline by dopamine hydroxylase Transported out of vesicles to form adrenaline by phenyl N methyl transferase  
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Action of the adrenal medulla   Preparation for emergency activity Increased adrenaline secretion from the adrenal medulla causes changes which increase circulation, increase the availability of energy substrates and decreases non-essential activities  
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Sympathetic activity in stress via adrenergic receptors   Increases lipolysis Increased glycogenolysis Increased skeletal muscle twitch Dilates arteries in muscle Constricts arteries elsewhere Constricts veins Increases rate and force of heart contraction Dilates bronchi  
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Phaeochromocytoma   Tumour arising from chromaffin cells Uncontrolled secretion of adrenaline and noradrenaline symptoms - hypertension, tachycardia, hyperstimulation of CNS  
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Adrenal cortex   Maintenance of essential processes in chronic stress Capsule - protection Zona glomerulosa - aldosterone Zona fasciculata - cortisol Zona reticularis - androgens All steroid hormones, lipid soluble and derived from cholesterol  
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Synthesis of steroid hormones   Made rapidly from cholesterol via enzymes in mitochondria and SER in response to stress NOT STORED Lots of hydroxylases 3 main pathways - one for each  
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Plasma transport of adrenal steroids   Plasma albumin binds all steroids with low affinity Cortisol - cortisol binding globulin Aldosterone - no high affinity binding protein Adrenal androgens - sex steroid binding globulins  
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Breakdown of steroids   Liver converts steroids to hydrophilic metabolites Liver damage e.g. cirrhosis leads to increased plasma steroids  
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The Hypothalamo-pituitary adrenal axis   Stress detected by hypothalamus - releases CRH Acts on pituitary which releases ACTH Acts on adrenal cortex which releases cortisol All controlled by a negative feedback system to prevent the system becoming harmful  
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Cortisol secretion in response to the stress of an operation   Minor surgery - smaller release and resolved within a day Major surgery - larger release and levels remain elevated  
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Glucocorticoids   Preserve glucose for the brain Accelerate gluconeogenesis and lipid/protein catabolism CNS activity e.g. increase appetite Increased RBC production Maintenance of circulation Reduce inflammation and immune response  
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Mechanism of steroid action   Via activation of intracellular receptors that control transcription Receptor hormone complex enters nucleus HPA axis cortisol is switched on immediately in stress but acts slowly Genomic action - 10% of genes regulated Epigenetic changes  
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Clinical uses of glucocorticoids   Inflammatory disorders Arthritis Asthma Eczema Inhibit transplant rejection Chemo Antenatal to mature the lungs in fetus threatening preterm labour  
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Lipid messengers in inflammation   Inflammation usually caused by prostaglandins Cortisol inhibits phospholipase A2 and cyclooxygenase to reduce synthesis of prostaglandins  
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Causes of excess glucocorticoid secretion   Pituitary tumour secreting ACTH-High ACTH and cortisol in Cushings disease Excess glucocorticoids for other reasons - cushings disease Adrenal cortex tumour excreting excess cortisol Ectopic secretion of ACTH by neoplasma e.g. small cell lung carcinoma  
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Side effects of glucocorticoids   Buffalo hump fat pads Thin skin Hypertension Thin arms and legs Osteoporosis Infertility Poor wound healing Trunkal obesity Bruising Moon face  
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Chronic stress in utero   Stress of undernourishment or poor oxygen results in low birth weight Highly correlated with hypertension, diabetes, lower life expectancy, mental health disorders Maladaptation to stress  
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Chronic stress in childhood   Chronic stress leads to retarded growth  
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Chronic stress in adulthood   Continuing psychological stress is a major factor in mental health, obesity, CVD and T2 diabetes E.g. due to modern day work styles like shift work  
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Aldosterone   Class of steroids that regulate salt and water balance Stimulates reabsorption of Na in the distal nephron Acts via nuclear mineralocorticoid receptors to increase transcription of ENaC and Na/K ATPase Stimulates reabsorption of NA in the kidney  
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Stimulation of renin-angiotensin system   Decreased blood pressure detected by kidney Secretes renin Breaks down angiotensinogen into angiotensin 1 Converted into angiotensin 2 in lungs Stimulates adrenal cortex to release aldosterone Increases water reabsorption and decreased urine volume  
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Hypoaldosteronism   Sodium loss Low blood volume Low blood pressure  
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Hyperaldosteronism   Excess sodium retention Water retention Increased blood pressure  
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Spironolactone   A MR antagonist is a diuretic drug used an an anti hypertensive  
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Adrenal androgens   Minor component of adrenal secretion in adults Weak androgen DHEA Stimulates pubertal hair growth and secondary sexual characteristic development Large amounts produced in fetus - converted by mother into oestrogen needed for pregnancy maintenance  
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Congenital adrenal hyperplasia   Inherited defect of steroid synthesis in the adrenals Excessive secretion of adrenal androgens Results in masculinisation of females, precocious puberty in males Mutation in 21-hydroxylase - not used in androgen synthesis so all cholesterol sent here  
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Addisons disease   Lack of cortisol results in loss of negative feedback so high ACTH and MSH High circulating levels cause hyperpigmentation of skin-stimulates MC1 melanocortin receptors Short synacthen test-no increase from baseline cortisol Treated with hydrocortisone  
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