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Adrenal Cortex. Prof. K. Sivapalan. Structure of Steroid Hormones. Classification of steroids. Mineralocorticoids- aldesteron Glucocorticoids- cortizol Sex hormones androgens estrogens. Mechanism of Action of Steroids. Transport- bound to globulin- Transcortin.
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Adrenal Cortex Prof. K. Sivapalan
Structure of Steroid Hormones. Adrenal Cortex.
Classification of steroids • Mineralocorticoids- aldesteron • Glucocorticoids- cortizol • Sex hormones • androgens • estrogens Adrenal Cortex.
Mechanism of Action of Steroids. • Transport- bound to globulin- Transcortin. • Binds to receptors in cytozol, transported to Nucleus and act on transcription. • Direct action on membrane and enzymes. Adrenal Cortex.
Glucocorticoids. • Half-life- 60-90 minutes Adrenal Cortex.
Effects on Carbohydrarte Metabolism. • In Liver, increases gluconeogenesis. • Increase transport of AA into cells of liver. • Gluconeogenic enzymes increased in liver. • Entry of AA into other tissues prevented. • Reduces glucose utilization by cells. • The above changes are not seen in Heart, Brain, and red cells. • Increases blood glucose level. Adrenal Cortex.
Effects on Protein Metabolism. • Reduce protein synthesis. • Increase catabolism of cellular protein. • Reduce RNA in muscles and lymphoid tissue. • Increase blood Amino acids. • Increase protein synthesis in liver, plasma proteins. Adrenal Cortex.
Effects on Fat Metabolism. • Increased lypolysis from adipose tissue in limbs. • Fat storage increased in face and trunk. • Increased plasma FFA. Adrenal Cortex.
Other Effects of Glucocorticoids. • Permissive action: • Catacholamines- calorigenesis, lypolytic action, pressure responses, bronchodilation. • Glucagon- same as above. • Vascular reactivity: • Smooth muscle tone requires steroids. • Capillaries require steroids for normal permeability [absence increases permeability] • Essential for life. Adrenal Cortex.
Other Effects of Glucocorticoids • Nervous system: • Reduction results in personality changes- irritability, apprehension and inability to concentrate. • Electroencephalogram changes: slower than normal A rhythm. • Increase results in reduced threshold for convulsions. • Water Metabolism: • Deficiency leads to inability to excrete water. Increased ADH and reduced GFR observed which are repaired by glucocorticoids only. Adrenal Cortex.
Other Effects of Glucocorticoids • Bone- reduce protein matrix and causes osteoporosis. • Blood and Immunity: • Increased RBC, nutrophils, platelets. • Reduced eosinophils, basophils, lympho cytes and all immune responses at high doses. • Use as anti-inflammatory drug. • Resistance to stress: • High levels of corticoids needed to cope with stressful conditions. [Essential for life] Adrenal Cortex.
Effects of Mineralocorticoids. • Half life- 20 minutes. • Distal tubule of kidney- sodium absorption in exchange of potassium and hydrogen. Blood volume cannot be maintained without this action. • *Essential for life. • Similar action seen in sweat glands, salivary glands and gastric glands. Adrenal Cortex.
Effects of Sex Hormones • Secretion increases at puberty. • Androgens are responsible for acne in males and females. • All other actions done by sex hormones secreted by testis and ovary. Adrenal Cortex.
Regulation of secretion. • Corticotrophin Releasing hormone [CRH] stimulates ACTH which stimulates glucorticoids. • Renin- angeotensin system regulates aldesteron secretion. Adrenal Cortex.
Diurnal Variation of Secretion. Adrenal Cortex.
Other factors that stimulate CRH • Trauma- nociceptive pathways • Emotion- lymbic system • Emotional stresses, fear, anxiety, apprehension • Baro receptors throw Nucleus Tractus Solitarius inhibit. Adrenal Cortex.
Stimuli that increase aldesteron secretion. • Glucorticoid also increased, • Surgery. • Anxiety. • Physical trauma. • Haemorrhage. • Glucocorticoid unaffected: • High potassium intake. • Low sodium intake. • Inferior vena cava constriction in throax. • Standing. • Secondary to congestic cardiac failure, cirrhosis, nephrosis. Adrenal Cortex.
Adreno Cortical Insufficiency. • Acute- adrenal crisis: • Head ache, lassitude, confusion, restlessness, vomiting, abdominal or costo-vertibral pain, circulatory collapse, unconsciousness, death. • Chronic- Addison’s disease. • Mineralocorticoid insufficiency alone is rare. • Mixed insufficiency is common. Adrenal Cortex.
Addison’s disease. • Weakness and fatigability. • Weight loss and dehydration.- • Increased sodium excretion, water diuresis, reduced appetite and GIT function. • Hypotension and small heart- dizziness, syncopal attacks. • GIT- reduced acid secretion, reduced motility. • Nervousness and mental symptoms. • Precipitation of crisis in stress. • Pigmentation- depends on the cause. Adrenal Cortex.
Pigmentation due to ACTH. Adrenal Cortex.
Hyper Aldesteronism. • Primary hyper aldesteronism- • tumor- Conn’s Syndrom. • Secondary Aldesteronism- • Cardiac failure, renal disease, cirrhosis. • Hypokalaemia. • Slight increase in ECF and blood volume. • Slight increase in plasma sodium. • Hypertension. Adrenal Cortex.
Hyper Adrenalism- Cushings Disease. • Redistribution of fat- • Moon face. • Fat pads of neck. • Pendulous abdomen. • Buffalo hump. • Striae in skin. • Thin extremities. Adrenal Cortex.
MOON Face. Same person before and after treatment. Twin sisters with and without moon face. Adrenal Cortex.
Other Features of Increased Glucocorticoids. • Red face- polycythaemia. • Thin skin, wasting of muscles, osteoporosis- weakness and backache. • Poorly healing wounds. • Systolic hypertension- sodium retention, angeotensin increase or direct effect. • Diabetes mellitus. • Mood changes- increased appetite, insomnia, euphoria, toxic psychosis. • Hypokalaemia- mineralocorticoid action. • Hirsutism- increased androgens. Adrenal Cortex.
Effects if increased Androgens. • Female fetus- male type of genitalia. • Male fetus- facilitated development of genitalia. • In childhood- stimulation of growth but early closure of epiphysis and short stature. • Prepubertal boys- precautious puberty without testicular development. • Adult male- no significant changes. • Pubertal and adult females- male features. Adrenal Cortex.