ADRENAL GLAND

PHYSIOLOGY

AnatomyAnatomy

Adrenal CortexAdrenal Cortex

phenylethanolamine-N-

methyltransferase

Norepinephrine Epinephrine

Adrenal Medulla

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

Steroidogenesis3 dehydrogenase

Steroidogenesis 17 hydroxylase

Steroidogenesis 21- hydroxylase

Steroidogenesis 11- hydroxylase

Steroidogenesis

Synthesis & ReleaseSynthesis & Release

Transport Proteins

Corticosteroid-binding globulin (CBG)

Albumin

Transport & MetabolismTransport & Metabolism

Cortisol Aldosterone

80% bound to CBG 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 & MetabolismTransport & Metabolism

Transport & Metabolism

Hypothalamus

CRH

Pituitary

ACTH

Adrenal Cortex

CORTISOL

Regulation - GlucocorticoidsRegulation - Glucocorticoids

Regulation - Glucocorticoids

Regulation - Glucocorticoids

Regulation-Glucocorticoids

Regulation-Glucocorticoids

Mechanism of Action-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-GlucocorticoidsBiologic Actions-Glucocorticoids

Interaction of Hormones in Metabolism

long-term starvation: normal levels of counter-regulatory

hormones

ketogenesis

protein degradation

gluconeogenesis

BMR

Biologic Actions-GlucocorticoidsBiologic 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-GlucocorticoidsBiologic 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; cell killing

Biologic Actions-GlucocorticoidsBiologic Actions-Glucocorticoids

BBaacckk ttoo HHuummaann PPhhyyssiioollooggyy hhoommee ppaaggee

BBaacckk ttoo lliisstt ooff cchhaapptteerrss         

FFiigguurree 1122..11         

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Biologic Actions-Glucocorticoids

Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Pathophysiology

Regulation-MineralocorticoidsRegulation-Mineralocorticoids

Stimuli for Renin Secretion

blood pressure

serum Na

blood volume

4. ANS stimulation

Regulation-MineralocorticoidsRegulation-Mineralocorticoids

Regulation-Mineralocorticoids

Actions of Angiotensin II

1. Direct arteriolar vasoconstrictor

2. Stimulus to aldosterone secretion

Regulation-Mineralocorticoids

Regulation-Mineralocorticoids

Aldosterone

MOA: transcription of enzymes and proteins

Major actions: Na reabsorption in distal tubule

Extrarenal effects: Na reabsorption in saliva, sweat, stool

Biologic Actions-MineralocorticoidsBiologic Actions-Mineralocorticoids

Hypersecretion of Aldosterone

1o aldosteronism – Conn’s syndrome

2o aldosteronism – liver/kidney disease

SXS: hypertension

hypokalemia

metabolic alkalosis

PathophysiologyPathophysiology

Primary Hyperaldosteronism

ECF volume Aldosterone Na retention + Renin

Renal perfusion pressure

Secondary Hyperaldosteronism

Na retention Renal perfusion Renin Aldosterone + pressure ECF volume

PathophysiologyPathophysiology

Hyposecretion of Aldosterone

1o hyposecretion – Addisons’ dse

2o hyposecretion – kidney damage

SXS: hypovolemia

hyponatremia

hyperkalemia

PathophysiologyPathophysiology

Happy New Year!!!

Anatomy

AnatomyAnatomy

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Figure 12.1     

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Figure 12.21     

Figure 12.22     

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Figure 12.25     

Figure 12.26

Synthesis & Release

Epinephrine Norepinephrine

t½ < 10 sec t½ < 15 sec

levels 20-50ng/ml 100-350 ng/ml

Transport & MetabolismTransport & Metabolism

Transport & Metabolism

Stimuli for Catecholamine Secretion

1.exercise, stress and anxiety

2. hypoglycemia

3. emergency situations

4. decreased blood pressure

5. decreased oxygen availability

RegulationRegulation

Mechanism of Action of Catecholamines

receptors : stimulates adenylate cyclase

receptors : inhibits adenylate cyclase

Biologic ActionsBiologic Actions

Biologic Actions

Factors Involved in Activation of Sympathetic Response

Sympathoadrenal System Sympathetic Nervous System

Signal Input Ach from preganglionic n Ach from preganglionic neuron

Major Secretory Epinephrine Norepinephrine product

Stimuli for psychological stress, anxiety cold stress, exercise, activation hypoxia, hypoglycemia postural hypotension

Major PSIO first line of defense vs first line of defense vs stress effect stress (fight or flight) normal homeostatic

maintenance of CV sympathetic tone

Hormonal kidney and liver presynaptic neuron (reuptake) metabolism (metabolism)

Biologic ActionsBiologic Actions

Major Physiologic Effects:

cardiac output

2. respiration

3. blood flow to heart, muscles, brain, lungs

4. alertness

5. circulating glucose, FFA, lactic acid

Biologic ActionsBiologic 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 preferential shunting of smooth muscle flow blood

Skeletal contraction locomotion muscle

Liver glycogenolysis glucose to tissues

Adipose tissuelipolysis FFA to tissues

Biologic ActionsBiologic Actions

Disorders of Adrenal Medulla

hyposecretion – hypofunction of adrenal gland

hypersecretion – benign pheochromocytoma; malignant neuroblastoma

SXS: hypertension tremors tachycardia anxiety headache sweating

PathophysiologyPathophysiology

Therapeutic Uses of Catecholamines

Agonists Antagonists

Parkinson’s disease hypertension clinical depression hyperthyroidism shock cardiac arrhythmia asthma angina pectoris allergic reactions nasal congestion

PathophysiologyPathophysiology

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