M4: Adrenal Steroids Flashcards
Adrenal Glands
- located on the top of each kidney
- divided into: outer cortex, inner medulla
- modified sympathetic ganglion
- innervated by preganglionic sympathetic nerve fibres
- responds to SNS under stress conditions
- secretes catecholamines: (E) epinephrine & (N) norepinephrine
Effects of Catecholamines
INCREASES:
- mental alertness
- metabolic rate
- heart rate, contractility, BP
- resp rate
- bronchodilation
- mydraisis (pupil dilation)
DECREASES:
- digestive and urinary functions
3 Regions of the Adrenal Cortex
- Zona Glomerulosa (outermost):
- secretes mineralcorticoids (aldosterone) - Zona Fasciculata (middle)
- secretes glucocorticoids (hydrocortisone) - Zona Reticularis (innermost)
- secretes sex hormones (testosterone, estrogen)
Role of Aldosterone
- stimulates renal tubules: DCT & CD
- retains Na+ and water
- # excretion of K+
- increase in Na and decreases K in blood
- increase blood volume and blood pressure
Factors That Stimulate Aldosterone Secretion
- hyperkalemia
- hyponatremia
- hypovolemia
- hypotension
- renin-angiotensis-aldosterone system (RAAS)
GLUCOCORTICOIDS:
- Regulation of Secretion
- Mechanism of Action
REGULATION OF SECRETION:
Corticotropin releasing hormone (CRH) → increases Adrenocorticotropic hormone (ACTH) → increases glucocorticoids →
ACTH stimulates:
- Synthesis and secretion of glucocorticoids
- Growth of the adrenal gland
Negative Feedback
MECHANISM OF GLUCOCORTICOIDS ACTION:
- Glucocorticoids cross cell membrane by diffusion
- Bind to receptors in cytoplasm or nucleus
- Activate or inactivate specific genes
- Alter rate of DNA transcription in nucleus:
Change patterns of protein synthesis - Directly affect metabolic activity and structure of target cell
Effects of Glucocorticoids
- Metabolic Effect:
Carbohydrate metabolism:
Increase blood glucose level due to:
- Increase gluconeogenesis
- Decrease glucose uptake and utilization by cells
Protein Metabolism:
- Increase mobilization of proteins and amino acids →
- Increase protein catabolism
Lipid Metabolism:
- Increase mobilization of peripheral fat
- Redistribution of fat from limbs to face and trunk
Anti-insulin action
Anti-Inflammatory & Immunosuppressive:
- Decrease number &/or activities of white blood cells and other components of immune system
- Stabilize lysosomal membranes
Effect on Blood Cells:
- Increase number of RBCs and neutrophils
- Decrease number of lymphocytes and eosinophils
Mineralocorticoids-Like Action:
- Na+ & water retention & K+ excretion
- Increase blood volume & blood pressure
- Decrease bone formation → osteoporosis
Effect on GIT: mucosal ulceration
Increase CNS excitability → mood changes
Therapeutic Indications of Glucocorticoids
Adrenal Hypofunction:
- Replacement therapy
Bronchial asthma
Allergic Reactions:
- Simple as eczema or severe as anaphylaxis
Autoimmune Diseases:
- e.g., rheumatoid arthritis, SLE
Organ Transplantation:
- Immunosuppressive to inhibit rejection
Malignancies:
- e.g., acute leukemia (chemotherapy)
Different Inflammatory Conditions: e.g.,
- Inflammatory bowel disease
- Renal disease: e.g., nephrotic syndrome
- Facial palsy
Glucocorticoids & Therapy and Route of Admission
Equivalent Glucocorticoids Concentrations:
Hydrocortisone 20mg ✓
Prednisolone 5mg ✓
Betamethasone 750 mcg ✓
Dexamethasone 750 mcg ✓
Route of Admission:
Topical, oral, inhalation, injection – IM, IV, SC, intralesional, intra-articular,
Adrenal Gland Disorders
- Adrenocortical Hypofunction:
Addison’s Disease (Panhypocorticism): Hypofunction of all zones of adrenal cortex
Causes:
(1) Primary (adrenal gland disorder):
- Autoimmune destruction (80%)
- Tuberculosis (20%)
- Infections: e.g., cytomegalovirus (CMV)
- Bilateral adrenalecteomy
(2) Secondary (pituitary gland disorder):
(Inadequate secretion of ACTH)
- Destruction of pituitary gland e.g., trauma, tumor
- Sudden withdrawal of prolonged steroid therapy
Clinical Manifestations:
- Fatigue and muscle weakness
- Hypotension
- Anorexia, nausea, vomiting, abdominal pain
- Weight loss
- Hyperpigmentation
- Mental depression
- Acute severe conditions → (Addisonian crisis): severe hypotension = shock
- Adrenocortical Hyperfunction:
(1) Conn’s Syndrome:
- Increase aldosterone secretion without activation of RAAS
Causes:
- Adrenal hyperplasia
- Adrenal tumors: adenoma, carcinoma
Main Features:
- Hypertension
- Hypokalemia
- Decrease renin level
- Alkalosis
Treatment:
Surgical &/or medical
(2) Cushing’s Syndrome:
Increase glucocorticoids secretion
Causes:
- Latrogenic (most common): Glucocorticoids or ACTH therapy
Spontaneous:
- Adrenal: hyperplasia or tumor
- Pituitary: adenoma excess ACTH secretion
- Ectopic ACTH/CRH secretion: e.g., some tumors
Clinical Manifestations:
- Obesity (moon face and buffalo hump)
- Myopathy
- Hypertension
- Hyperglycemia → diabetes mellitus
- Recurrent infections
- Thin atrophic skin with bruises
- Osteoporosis
- Psychosis
- BIG:
B =
- Blood pressure →hypertension
Bone → osteoporosis
I = Immunosuppression → Infection
G = Glucose → Diabetes Mellitus
- Obesity – Fat Distribution – Edema
- Loss of Diurnal Variation
Treatment: of the cause
(3) Congenital Adrenal Hyperplasia:
- Congenital metabolic disorder: Autosomal recessive
Due to enzymatic defect:
Most common is: 21-hydroxylase enzyme deficiency
Effects:
- Increase adrenal androgens
- Decrease cortisol and aldosterone
Clinical Manifestations:
Female = masculinization
Male = precocious puberty
