Adrenal Gland Physiology (dr

ADRENAL GLAND PHYSIOLOGY

Anatomy

Adrenal Cortex

Adrenal Medulla

phenylethanolamine-Nmethyltransferase

Norepinephrine

Epinephrine

Steroidogenesis

Steroidogenesis

Steroidogenesis

Steroidogenesis

Steroidogenesis

Congenital Adrenal Hyperplasia - autosomal recessive disorder due to deficiency or lack of an enzyme in the synthesis of cortisol

Steroidogenesis

Steroidogenesis

3β dehydrogenase

Steroidogenesis

17α hydroxylase

Steroidogenesis

21- hydroxylase

Steroidogenesis

11- hydroxylase

Steroidogenesis

Synthesis & Release

Transport & Metabolism

Transport Proteins  Corticosteroid-binding globulin (CBG)  Albumin

Transport & Metabolism

Cortisol 80% bound to CBG

Aldosterone 60% bound to albumin

15% bound to albumin 5% free

40% free

t½ 90 mins

t ½ 30 mins

Serum levels: 10-25μg/dl

2-10 ng/dl

Transport & Metabolism

Regulation - Glucocorticoids

Hypothalamus

CRH Pituitary

ACTH Adrenal Cortex

CORTISOL

Regulation - Glucocorticoids

Regulation - Glucocorticoids

Regulation-Glucocorticoids

Regulation-Glucocorticoids

Mechanism of Action-Glucocorticoids

Biologic Actions-Glucocorticoids

Biologic Actions-Glucocorticoids

Interaction of Hormones in Metabolism post-prandial: regulatory hormone (insulin)  cellular glucose uptake early fasting: counter-regulatory hormones (E,G,GH,C)  glycogenolysis; minimal glycolysis late fasting: counter-regulatory hormones (E,G,GH,C)  gluconeogenesis; lipolysis; protein degradation long-term starvation  ketogenesis

Biologic Actions-Glucocorticoids

Interaction of Hormones in Metabolism long-term starvation: normal levels of counterregulatory hormones  ketogenesis   protein degradation   gluconeogenesis   BMR

Biologic Actions-Glucocorticoids

Biologic Actions-Glucocorticoids

Biologic Actions-Glucocorticoids

Physiologic Effects 1. hepatic glucose production 2. protein catabolism 3. fat catabolism 4. increased bone resorption 5. altered mood 6. increased gastric acidity 7. PNMT synthesis

Biologic Actions-Glucocorticoids

Therapeutic Effects 1. prevents vascular collapse during stress 2. anti-inflammatory effect Capillary dilation; prostaglandin/leukotriene production; Leukocyte migration; stabilzation of lysosomal membrane

3. invoking immunosuppression - T cell proliferation; complement synthesis; β cell killing

Biologic Actions-Glucocorticoids

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Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Regulation-Mineralocorticoids

Regulation-Mineralocorticoids

Stimuli for Renin Secretion  blood pressure  serum Na  blood volume •

ANS stimulation

Regulation-Mineralocorticoids

Regulation-Mineralocorticoids

Actions of Angiotensin II 2. Direct arteriolar vasoconstrictor 3. Stimulus to aldosterone secretion

Regulation-Mineralocorticoids

Biologic Actions-Mineralocorticoids

Aldosterone MOA: transcription of enzymes and proteins

Major actions: Na reabsorption in distal tubule

Extrarenal effects: Na reabsorption in saliva, sweat, stool

Pathophysiology

Hypersecretion of Aldosterone 1o aldosteronism – Conn’s syndrome 2o aldosteronism – liver/kidney disease SXS: hypertension hypokalemia metabolic alkalosis

Pathophysiology

Primary Hyperaldosteronism  ECF volume

Aldosterone   Na retention 



+  Renin  Renal perfusion pressure

Secondary Hyperaldosteronism  Na retention Renal perfusion   Renin   Aldosterone 

pressure

+  ECF volume

Pathophysiology

Hyposecretion of Aldosterone 1o hyposecretion – Addisons’ dse 2o hyposecretion – kidney damage SXS: hypovolemia hyponatremia hyperkalemia

Happy New Year!! !

Anatomy

Anatomy

Synthesis & Release

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Transport & Metabolism

Epinephrine t½ < 10 sec

Norepinephrine t½ < 15 sec

levels

20-50ng/ml

100-350 ng/ml

Transport & Metabolism

Regulation

Stimuli for Catecholamine Secretion 2. exercise, stress and anxiety 3. hypoglycemia 4. emergency situations 5. decreased blood pressure 6. decreased oxygen availability

Biologic Actions

Mechanism of Action of Catecholamines

β receptors : stimulates adenylate cyclase α receptors : inhibits adenylate cyclase

Biologic Actions

Biologic Actions Factors Involved in Activation of Sympathetic Response

Signal Input

Sympathoadrenal System

Sympathetic Nervous System

Ach from preganglionic n

Ach from preganglionic neuron

Major Secretory Epinephrine product

Norepinephrine

Stimuli for activation

psychological stress, anxiety cold stress, exercise, hypoxia, hypoglycemia postural hypotension

Major PSIO effect

first line of defense vs stress (fight or flight)

first line of defense vs stress normal homeostatic maintenance of CV sympathetic tone

Hormonal metabolism

kidney and liver (metabolism)

presynaptic neuron (reuptake)

Biologic Actions

Major Physiologic Effects: cardiac output • respiration • blood flow to heart, muscles, brain, lungs •  alertness •  circulating glucose, FFA, lactic acid

Biologic Actions

Sympathetic Response “Fight of Flight” Tissue

Direct Response

Physiological Outcome

Lungs

respiration

O2 to heart

Heart

cardiac output

blood/O2 to tissues

Vascular +/- regional blood smooth muscle flow

preferential shunting of blood

Skeletal muscle

contraction

locomotion

Liver

glycogenolysis

glucose to tissues

Adipose tissuelipolysis

FFA to tissues

Pathophysiology

Disorders of Adrenal Medulla hyposecretion – hypofunction of adrenal gland hypersecretion – benign pheochromocytoma; malignant neuroblastoma SXS: hypertension tachycardia headache

tremors anxiety sweating

Pathophysiology

Therapeutic Uses of Catecholamines Agonists Parkinson’s disease clinical depression shock asthma allergic reactions nasal congestion

Antagonists hypertension hyperthyroidism cardiac arrhythmia angina pectoris

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