• Peak cortisol secretion occurs early in the morning, between the 6th and 8th hours of sleep. The secretion then gradually declines throughout the day and reaches a low point late in the evening.

1. Metabolic effects:

A. Carbohydrates (Hyperglycemic & Diabetogenic):

• Cortisol raises blood glucose levels, providing more glucose for nervous tissue. This occurs through two mechanisms: o Cortisol inhibits glucose uptake in most tissues, such as muscle, lymphoid, and fat. o Cortisol increases hepatic output of glucose via gluconeogenesis from amino acids in particular (not from liver glycogenolysis).
• It also has an anti-insulin action, leading to hyperglycemia (Diabetogenic).

B. Fat (Lipolytic & Ketogenic):

• Cortisol has a lipolytic action as it increases the activity of hormone-sensitive lipase in adipose tissue. This enzyme breaks down stored triglycerides into glycerol and fatty acids.
• In cases of insulin deficiency, as in diabetics, cortisol increases ketone body formation (ketogenic).

C. Protein (Catabolic):

• Cortisol reduces protein stores in all body cells, except liver cells, through:
• Decreased protein synthesis.
• Increased catabolism of proteins already in cells.
• Cortisol inhibits amino acid transport into extrahepatic cells while stimulating amino acid transport into liver cells.

1. Permissive action: Cortisol enhances the capacity of glucagon and catecholamines, hence the term "permissive" describes many of the actions of cortisol.

• Glucagon promotes glycogenolysis in the liver. Without cortisol, fasting hypoglycemia rapidly develops.
• Cortisol also increases vascular reactivity to catecholamines. Without cortisol, blood pressure decreases.

1. H2O & Electrolytes:

   • Promotes H2O excretion by:
     • Decreasing ADH, accelerating its inactivation by the liver.
     • Increasing GFR by enhancing glomerular plasma flow.
   • Exhibits slight mineralocorticoid activity leading to Na retention & K excretion.

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2. Blood Cells:

   • Decreases the number of Eosinophils & Lymphocytes:

     • Cortisol reduces the count of eosinophils by inducing their apoptosis and by increasing their sequestration in the spleen.
     • It inhibits lymphocyte mitosis, thereby reducing the number of T lymphocytes.

   • Increases Neutrophils:

     • Cortisol stimulates the release of neutrophils from bone marrow, increasing their quantity but suppressing their function.
     • It inhibits WBC adhesion, leading to neutrophilia.

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3. Stress:

• Physical or mental stress can include trauma, pain, infection, surgery, anxiety, and shock.
• Stressful stimuli increase the secretion of ACTH, which in turn elevates the cortisol level in the blood. Most of these stimuli also activate the sympathetic nervous system. Cortisol is required for catecholamines to exert their actions, known as permissive action.
• Both glucocorticoids and catecholamines increase free fatty acids (FFAs) as an energy source and raise the blood glucose level to ensure a steady supply of glucose to vital organs.
• Cortisol also escalates the level of plasma amino acids, which are used for gluconeogenesis and the formation of new proteins by damaged tissues.

1. Bone: - Cortisol inhibits bone formation through several mechanisms: o It reduces the synthesis of type 1 collagen, which is the main component of the bone matrix. o It slows down the formation rate of active osteoblasts. o It decreases the absorption of Ca and PO4 from the intestine due to its anti-vitamin D action, and increases the renal excretion of these ions. This results in less calcium available for bone mineralization. o Cortisol also increases the rate of bone resorption, that’s why osteoporosis is a major side effect of cortisol.

1. Anti-inflammatory: Inflammation refers to various responses to tissue injury, characterized by local redness, heat, swelling, pain, and loss of function. High levels of cortisol, whether secreted naturally or injected, decrease the synthesis, secretion, and action of IL1. This can:

• Block the early stages of the inflammatory process before inflammation begins.
• If inflammation has already started, cortisol promotes rapid resolution of inflammation.

1. Anti-allergic: Certain antibodies, when combined with their antigens, lead to the release of histamine and leukotrienes from mast cells, causing many allergy symptoms. Glucocorticoids don't affect the combination of antigen and antibody, but they prevent histamine release and block the formation of leukotrienes. Administering glucocorticoids can relieve symptoms of asthma, delayed hypersensitivity reactions, and many other allergic conditions.

1. Immunity: High concentrations of glucocorticoids interfere with antibody production from B lymphocytes, reducing circulating levels of immunoglobulins and suppressing humoral immunity. Excess glucocorticoids suppress cellular immunity by blocking lymphocyte IL2 production, which decreases T-lymphocytes proliferation.

• It also decreases T-lymphocyte production of interferon and so decreases the destruction of viruis infected T-lymphocytes and tumor cells. - The ability of glucocorticoids to suppress immunity makes it double weapons: o Useful in prevention of immunological rejection of transplanted organs. o Injurious by fulminating old infections and tumorigenic.

Physiological effect of Aldosterone

1. Aldosterone primarily targets the kidney, where it significantly increases Na+ reabsorption by the principal cells of the kidney's collecting ducts. Since water is reabsorbed alongside Na+, aldosterone can be perceived as controlling the amount of Na+ rather than its concentration in the ECF.