Adrenal gland

ADRENAL GLANDS

• Objectives
• At the end of this lecture, the student should be able to:
• Describe the physiology of adrenal hormones secretion.
• Determine the synthesis of adrenal hormones.
• Recognize the functions of the adrenal hormones.
• State the pharmacological actions and therapeutic principles of corticosteroids.
• Identify the side effects of steroid abuse.
• State the importance of steroid tapering after prolonged use.

About 5x3 cm in size, combined weight in an adult human ranges from

7 to 10 grams.

Anatomy and Function

Capsule
Cortex (outer) has 3 zones:
1- Zona glomerulosa : mineralocorticoids, mainly aldosterone, responsible for the regulation of BP. It affects the distal convoluted tubule and collecting duct of the kidney
(increased reabsorption of Na + and excretion of
both K + and H + ions).
2- Zona fasciculata: glucocorticoids, such as
11-deoxycorticosterone, corticosterone, and
cortisol.

3- Zona reticularis: produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.

Medulla (core of the gland)

It secretes norepinephrine and epinephrine. Catecholamines (aa tyrosine ), water-soluble, the major hormones underlying the fight-or-flight response.
Receives input from the sympathetic nervous system through preganglionic fibers originating in the thoracic spinal cord from T5–T11.
Cortisol also promotes epinephrine synthesis.

History

1855 – Addison's disease



1856 – Adrenal glands essential for life


1930 – Cortex > medulla


1932 – Cushing’s syndrome


1949 – Steroids in rheumatoid arthritis


1952 – Aldosterone

• Basal secretions

• Group
• Hormone
• Daily secretions
• Glucocorticoids
• Cortisol
• 5 – 30 mg
• Mineralocorticoids
• Aldosterone
• 5 – 150 mcg
• Sex Hormones
• Androgen
• Progestogen
• Oestrogen
• DHEA
• Progesterone
• Oestradiol
• 15 – 30 mg
• 0.4 – 0.8 mg
• Trace
From Essential of Pharmacotherapeutics, ed. FSK Barar. P.351

Cholesterol

Pregnenolone
Progesterone

Corticosterone

11-Desoxy-corticosterone
18-Hydroxy- corticosterone
ALDOSTERONE

17-α- Hydroxy pregnenolone

11- Desoxy- cortisol
17- Hydroxy progesterone
21,β hydroxylase

CORTISOL

11,β hydroxylase


Dehydro-epi androsterone
Andro-stenedione

Oestrone

Oestriol

TESTOSTERONE

OESTRADIOL

ACTH

Pharmacological Actions
• Carbohydrate
• Protein
• Lipid
• Electrolyte & water
• CVS
• Sk. Muscle
• CNS
• Stomach
• Blood
• Anti-inflammatory
• Immunosuppressant
• Respiratory system
• Growth & Cell Division
• Calcium metabolism


Actions: Carbohydrate and protein metabolism
Gluconeogenesis
- In the liver (synthesis of glucose from aa and glycerol ).
- Mobilization of amino acids from extrahepatic tissues as substrates for gluconeogenesis.
- Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy and the released glycerol provide another substrate for gluconeogenesis.
Peripheral utilization of glucose
- Inhibition of glucose uptake in muscle and adipose tissue

Glycogen deposition in liver

(activation of hepatic glycogen synthase)

Negative nitrogen balance & hyperglycemia

Redistribution of Fat
Buffalo hump
Supraclavicular fat
Moon face

Promote adipokinetic agents activity

(glucagon, growth hormone, adrenaline, and
thyroxin)
Actions: Lipid metabolism


Aldosterone is more important, acts on D.T. & C.D. of kidney
Na+ reabsorption
Urinary excretion of K+ and H+
Glucocorticoids assist in the normalization of extracellular fluid volume by regulating body’s action to atrial natriureteric peptide.
Cortisol reduces the capacity of osteoblasts to produce new bone tissue and decreases the absorption of calcium in the GIT.
Actions: Electrolyte and water balance

Restrict capillary permeability

Maintain tone of arterioles
Myocardial contractility
Actions: Cardiovascular system
Mineralocorticoids induced hypertension
Na+ sensitize blood vessels to the action of
catecholamines & angiotensin

Addison's disease: weakness & fatigue is due to

Prolonged use:

Actions: Skeletal Muscles

Needed for maintaining the normal function of Sk. muscle
inadequacy of circulatory system
Steroid myopathy, weakness, reduced muscle mass and
repair


Direct:
Mood (euphoria)
Behavior, psychosis
Brain excitability
Significant impact on vigilance (attention deficit disorder) and cognition (memory).

Actions: CNS

ICP (pseudotumor cerebri)

Aggravate peptic ulcer. May be due to

Acid & pepsin secretion

immune response to H.Pylori

Actions: Stomach

RBC: Hb & RBC content

(erythrophagocytosis )

WBC: Lymphocytes, eosinophils, monocytes,

basophils

Actions: Blood

Recruitment of WBC & monocyte- macrophage
into affected area & elaboration of chemotactic
substances
Lipocortin
TNF from phagocytic cells
IL1 from monocyte-macrophage
Formation of Plasminogen Activator
Fibroblastic activity
Expression of cyclooxygenase II

Actions: Anti-inflammatory

Phospholipids
Arachidonic acids
lipoxygenase
Cycylooxygenase
Leukotriene
Prostaglandins,
Thromboxane
Prostacyclins
Suppress Phospholipase A2
Lipocortin- 1
Corticosteroids


PAF by lipocortin

Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

Immunosuppressive & anti-allergic actions

Suppresses all types of hypersensitivity & allergic phenomenon.
At High dose: Interfere with all steps of immunological response.
Causes greater suppression of CMI (graft rejection & delayed hypersensitivity).
Transplant rejection: antigen expression from grafted tissues, delay revascularization, sensitization of T lymphocytes.

Main pathogens of concern in glucocorticoid-induced immunodeficiency:

Legionella micdadei, Listeria monocytogenes, Mycobacterium tuberculosis, Nocardia
asteroides, Salmonella species, Staphylococcus aureus, Streptococci


Aspergillus, Blastomyces, Candida albicans and nonalbicans species, Coccidioides
immitis, Cryptococcus neoformans , Histoplasma capsulatum. Penicillium marneffei,
Pseudallescheria boydii, Zygomycosis

Adenovirus, Cytomegalovirus, Herpes simplex virus, Human papillomavirus,

Influenza/parainfluenza, Respiratory syncytial virus, Varicella zoster

Other

Cryptosporidiosis/lsospora belli
Pneumocystis carinii
Strongyloides stercoralis
Toxoplasma gondii

Inhibit cell division or synthesis of DNA.

Delay the process of healing.
Retard the growth of children.
Delay puberty

Actions: Growth & Cell division

Intestinal absorption


Renal excretion

Excessive loss of calcium from spongy bones (e.g., vertebrae, ribs )

Actions: Calcium metabolism

Not bronchodilators

Most potent and most effective anti-inflammatory.
Effects not seen immediately (delay 6 or more hrs).
Inhaled corticosteroids are used for long term control.

Actions: Respiratory system