Guyton Chapter 77

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Guyton Chapter 77

• Adrenal Cortical Hormones

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Adrenal Glands

• Two Adrenal Glands (SupraRenal Glands)
• Adrenal Medulla
• Central 20
• Related to Sympathetic Nervous System (sometimes
  head ganglion of sympathetic n.s.)
• Secretes Catecholamines
• Epinephrine Norepinephrine

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Adrenal Glands

• Two Adrenal Glands (SupraRenal Glands)
• Adrenal Cortex (surrounds medulla)
• Secretes corticosteroids
• Synthesized from cholesterol
• Mineralcorticoids (e.g. principally aldosertone)
• Glucocorticoids (e.g. principally cortisol)
• Sex hormones (e.g. androgens)

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Adrenal Cortex

• Go Find Rex gt Make Good Sex
• Zona Glomerulosa gt Mineralcorticoids
• Zona Fasciculata gt Glucocorticoids
• Zona Reticularis gt Sex Hormones

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Zona Glomerulosa

• Outer Layer of Adrenal Cortex
• Secretes aldosterone
• Contains aldosterone synthase
• Aldosterone secretion stimulated by
• Angiotension II
• Potassium

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Zona Fasciculata

• Middle layer of adrenal cortex
• Secretes cortisol corticosterone
• ( small amounts of androgens estrogens )
• Secretion controlled primarily by
• ACTH from anterior pituitary

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Zona Reticularis

• Secretes adrenal androgens
• DHEA (dehydroepiandrosterone)
• Androstenedione
• Small amounts of
• Estrogens
• Glucocorticoids
• Secretion primarily stimulated by ACTH (however
  control is not so well understood)

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Angiotensin II

• Stimulates secretion of aldosterone and causes
  hypertrophy of zona glomerulosa
• Little or no effect on
• Zona fasciculata
• Zona reticularis

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ACTH

• Stimulates secretion of cortisol and adrenal
  androgens and hypertrophy of
• Zona fasciculata
• Zona reticularis
• Little or no effect on
• Zona glomerulosa

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Mineral Corticoids

• Aldosterone (90 of all m.c. activity)
• Desoxycorticosterone (1/30 potent lt aldo)
• Very slight / minor m.c. activity
• Corticosterone
• Cortisol
• Corticosterone
• Synthetic
• 9alpha-Fluorocortisol (gtpotent than aldo)

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Glucocorticoids

• Cortisol (95 of g.c. activity)
• Corticosterone (4 of g.c. activity)
• Synthetics (potency)
• Cortisone (1X cortisol)
• Prednisone (4X cortisol)
• Methylprednisone (5X cortisol)
• Dexamethasone (30X cortisol)

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m.c. g.c. cross react

• m.c. g.c. have cross reactive functions
• each can weakly trigger other function
• m.c. triggers slight g.c. activity
• g.c. triggers slight m.c. activity

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Plasma proteins

• Adrenalcortical hormones bind to
• Cortisol-binding globulin (transcortin)
• Albumin
• Bound cortisol 90 to 95
• long half life (60 to 90 minutes)
• Free aldosterone 40
• short half life (20 minutes)
• Bound hormone serves as a reservoir buffering
  hormone for use as needed

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Aldosterone (primary m.c.)

• 90 of m.c. acitivity
• 3000 more potent than cortisol
• Cortisol significant m.c. activity
• cortisol has 2000 higher concentration

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Aldosterone

• ? Aldosterone (in renal tubules)
• ? Na absorption (conserves Na)
• ? K secretion (wastes K ? urine)
• (esp. collecting tubules)
• ? Aldosterone (in renal tubules)
• ? Na absorption (wastes Na ? urine)
• ? K secretion (conserves K)
• (see summary sheet)

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Aldosterone Deficiency

• Death within 3 days to 2 weeks unless
• Tx 1 ? extensive salt therapy
• Tx 2 ? m.c. injection (aldosterone or other)
• Untreated
• ? K ? Na ? Cl
• ECF Blood volume drops precipitously
• ? C.O. ? Circulatory Shock ? Death
• Hyperkalemia ? Cardiac toxicity
• Weak contractions ? arrhythmia ? heart failure

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Aldosterone Excess

• Increases Na H2O in ECF
• H2O Reabsorbed from tubules via osmosis
• Increased thirst H2O intake
• Increased arterial pressure
• Aldosterone Escape
• Pressure natriuresis
• Pressure diuresis
• ? K ? severe muscle weakness
• ? H ? mild alkalosis

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Aldosterone Mechanism of Action

• Just like any other steroid
• Intracellular receptor
• Binds to DNA
• Makes RNA
• Makes Protein

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Aldosterone Regulation

• Potent
• ? K ? ? Aldo secretion
• ? renin-angiotensin system (angiotensin II) ? ?
  Aldo secretion
• Weak
• ? Na ? very slight ? Aldo secretion
• ACTH is necessary for Aldo secretion (however
  little effect on rate of secretion)

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Glucocorticoids (Main Cortisol)

• ? Gluconeogenesis
• ? enzymes to convert a.a. ? glucose
• ? mobilization of a.a. from extrahepatic tissue
• Mainly from muscles
• ? glycogen storage in liver
• ? glucose utilization by cells
• ? blood glucose (adrenal diabetes)
• Not well understood insulin not so effective here

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Cortisol

• Reduces protein stores in almost all cells
• decreased protein synthesis
• increased catabolism of protein
• EXCEPT in liver cells
• Increases liver plasma proteins
• Increases blood a.a.
• Decreases transport into extrahepatic cells
• Increases transport into hepatic cells

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Cortisol

• Mobilizes fatty acids from adipose cells
• Increases oxidation of fatty acids
• Helps shift from glucose to fat metabolism during
  times of starvation or stress
• Conserves body glucose glycogen
• Obesity buffalo torso round moon face

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Cortisol

• Helps in resisting stress and inflammation
• (study details in the text pp. 953-954)

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Cortisol Mechanism of Action

• Just like any other steroid
• Intracellular receptor
• Binds to DNA
• Makes RNA
• Makes Protein

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Cortisol Regulation

• Almost entirely CRF ? ACTH
• ACTH ? Cortisol secretion via cAMP
• Some ? due to physiological stress
• Neg feedback to hypothalamus (?CRF)
• Neg feedback to ant pituitary (?ACTH)
• Co-Secreted via POMC with MSH, Lipotropin
  Endorphins

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Sex Hormones

• Adrenal androgens
• Dehydropiandrosterone
• In men
• In women

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Hypoadrenal cortical

• Addisons atrophy of adrenal cortices
• Autoimmune?
• T.b.
• Cancer
• Obvious effects m.c. g.c. deficiency
• Melanin pigmentation of mucous tissues
• Tx ? sm amts m.c. g.c.

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Hyper adrenal cortical

• cushings

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Hyper aldosterone

• Conns syndrome

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